Rudimentary G-Quadruplex-Based Telomere Capping In Saccharomyces Cerevisiae

Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show that protein-bound G4 DNA at a 3\u27 overhang inhibits 5\u27-\u3e 3\u27 resection of a paired strand by exonuclease I. These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo

Current status of haploidentical stem cell transplantation for leukemia

Haploidentical hematopoietic stem cell transplantation has made tremendous progress over the past 20 years and has become a feasible option for leukemia patients without a HLA identical sibling donor. The early complications of severe graft-versus-host disease (GVHD), graft failure and delayed engraftment, as well as disease recurrence have limited the use of this approach. Newer strategies have been applied and overcome some of the problems, including the use of T-cell depleted graft, "mega" dose of stem cells, intensive post-transplant immunosuppression and manipulation of the graft. These have decreased the transplant related mortality and GVHD associated with haploidentical transplantation, however, the major problems of disease relapse and infection, which related to late immune reconstitution, limit the development of haploidentical HSCT. Future challenges remain in improving post-transplant immune reconstitution and finding the best approach to reduce the incidence and severity of GVHD, while preserving graft-versus-leukemia effect to prevent the recurrence of underlying malignancy

Parents' psychological adjustment in families of children with Spina Bifida: a meta-analysis

BACKGROUND: Spina Bifida (SB) is the second most common birth defect worldwide. Since the chances of survival in children with severe SB-forms have increased, medical care has shifted its emphasis from life-saving interventions to fostering the quality of life for these children and their families. Little is known, however, about the impact of SB on family adjustment. Reviewers have struggled to synthesize the few contradictory studies available. In this systematic review a new attempt was made to summarize the findings by using meta-analysis and by delimiting the scope of review to one concept of family adjustment: Parents' psychological adjustment. The questions addressed were: (a) do parents of children with SB have more psychological distress than controls? (b) do mothers and fathers differ? and (c) which factors correlate with variations in psychological adjustment? METHODS: PsycInfo, Medline, and reference lists were scanned. Thirty-three relevant studies were identified of which 15 were eligible for meta-analysis. RESULTS: SB had a negative medium-large effect on parents' psychological adjustment. The effect was more heterogeneous for mothers than for fathers. In the reviewed studies child factors (age, conduct problems, emotional problems, and mental retardation), parent factors (SES, hope, appraised stress, coping, and parenting competence), family factors (family income, partner relationship, and family climate), and environmental factors (social support) were found to be associated with variations in parents' psychological adjustment. CONCLUSION: Meta-analysis proved to be helpful in organizing studies. Clinical implications indicate a need to be especially alert to psychological suffering in mothers of children with SB. Future research should increase sample sizes through multi-center collaborations

A Differentiation-Based Phylogeny of Cancer Subtypes

Histopathological classification of human tumors relies in part on the degree of differentiation of the tumor sample. To date, there is no objective systematic method to categorize tumor subtypes by maturation. In this paper, we introduce a novel computational algorithm to rank tumor subtypes according to the dissimilarity of their gene expression from that of stem cells and fully differentiated tissue, and thereby construct a phylogenetic tree of cancer. We validate our methodology with expression data of leukemia, breast cancer and liposarcoma subtypes and then apply it to a broader group of sarcomas. This ranking of tumor subtypes resulting from the application of our methodology allows the identification of genes correlated with differentiation and may help to identify novel therapeutic targets. Our algorithm represents the first phylogeny-based tool to analyze the differentiation status of human tumors

The influence of organizational culture and climate on entrepreneurial intentions among research scientists

Over the past decades, universities have increasingly become involved in entrepreneurial activities. Despite efforts to embrace their ‘third mission’, universities still demonstrate great heterogeneity in terms of their involvement in academic entrepreneurship. This papers adopts an institutional perspective to understand how organizational characteristics affect research scientists’ entrepreneurial intentions. Specifically, we study the impact of university culture and climate on entrepreneurial intentions, including intentions to spin off a company, to engage in patenting or licensing and to interact with industry through contract research or consulting. Using a sample of 437 research scientists from Swedish and German universities, our results reveal that the extent to which universities articulate entrepreneurship as a fundamental element of their mission fosters research scientists’ intentions to engage in spin-off creation and intellectual property rights, but not industry-science interaction. Furthermore, the presence of university role models positively affects research scientists’ propensity to engage in entrepreneurial activities, both directly and indirectly through entrepreneurial self-efficacy. Finally, research scientists working at universities which explicitly reward people for ‘third mission’ related output show higher levels of spin-off and patenting or licensing intentions. This study has implications for both academics and practitioners, including university managers and policy makers

Myocardial ischemia and reperfusion: The role of oxygen radicals in tissue injury

Thrombolytic therapy has gained widespread acceplance as a means of treating coronary artery thrombosis in patients with acute myocardial infarction. Although experimental data have demonstrated that timely reperfusion limits the extent of infarction caused by regional ischemia, there is growing evidence that reperfusion is associated with an inflammatory response to ischemia that exacerbates the tissue injury. Ischemic myocardium releases archidonate and complement-derived chemotactic factors, e.g., leukotriene B 4 and C 5a , which attract and activate neutrophils. Reperfusion of ischemic myocardium accelerates the influx of neutrophils, which release reactive oxygen products, such as superoxide anion and hydrogen peroxide, resulting in the formation of a hydroxyl radical and hypochlorous acid. The latter two species may damage viable endothelial cells and myocytes via the peroxidation of lipids and oxidation of protein sulfhydryl groups, leading to perturbations of membrane permeability and enzyme function. Neutrophil depletion by antiserum and inhibition of neutrophil function by drugs, e.g., ibuprofen, prostaglandins (prostacyclin and PGE 1 ), or a monoclonal antibody, to the adherence-promoting glycoprotein Mo-1 receptor, have been shown to limit the extent of canine myocardial injury due to coronary artery occlusion/reperfusion. Recent studies have challenged the hypothesis that xanthine-oxidase-derived oxygen radicals are a cause of reperfusion injury. Treatment with allopurinol or oxypurinol may exert beneficial effects on ischemic myocardium that are unrelated to the inhibition of xanthine oxidase. Furthermore, the human heart may lack xanthine oxidase activity. Further basic research is needed, therefore, to clarify the importance of xanthine oxidase in the pathophysiology of reperfusion injury. Current data are highly suggestive of a deleterious role of the neutrophil in organ reperfusion and justify consideration of the clinical investigation of neutrophil inhibitors in patients receiving thrombolytic agents during the evolution of an acute myocardial infarction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44595/1/10557_2004_Article_BF00133206.pd

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified