OGA heterozygosity suppresses intestinal tumorigenesis in Apc min/+ mice

Emerging evidence suggests that aberrant O-GlcNAcylation is associated with tumorigenesis. Many oncogenic factors are O-GlcNAcylated, which modulates their functions. However, it remains unclear how O-GlcNAcylation and O-GlcNAc cycling enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), affect the development of cancer in animal models. In this study, we show that reduced level of OGA attenuates colorectal tumorigenesis induced by Adenomatous polyposis coli (Apc) mutation. The levels of O-GlcNAcylation and O-GlcNAc cycling enzymes were simultaneously upregulated in intestinal adenomas from mice, and in human patients. In two independent microarray data sets, the expression of OGA and OGT was significantly associated with poor cancer-specific survival of colorectal cancer (CRC) patients. In addition, OGA heterozygosity, which results in increased levels of O-GlcNAcylation, attenuated intestinal tumor formation in the Apc min/+ background. Apc min/+ OGA +/-mice exhibited a significantly increased survival rate compared with Apc min/+ mice. Consistent with this, Apc min/+ OGA +/-mice expressed lower levels of Wnt target genes than Apc min/+. However, the knockout of OGA did not affect Wnt/??-catenin signaling. Overall, these findings suggest that OGA is crucial for tumor growth in CRC independently of Wnt/??-catenin signaling.open2

Extension of non-minimal derivative coupling theory and Hawking radiation in black-hole spacetime

We study the greybody factor and Hawking radiation with a non-minimal derivative coupling between the scalar field and the curvature in the background of the slowly rotating Kerr-Newman black hole. Our results show that both the absorption probability and luminosity of Hawking radiation of the scalar field increase with the coupling. Moreover, we also find that for the weak coupling $\eta<\eta_c$, the absorption probability and luminosity of Hawking radiation decrease when the black hole's Hawking temperature decreases; while for stronger coupling $\eta>\eta_c$, the absorption probability and luminosity of Hawking radiation increase on the contrary when the black hole's Hawking temperature decreases. This feature is similar to the Hawking radiation in a $d$-dimensional static spherically-symmetric black hole surrounded by quintessence \cite{chensong}.Comment: 17 pages, 6 figures, 1 table, Title changed, Appendix changed, accepted by JHE

Fluids in cosmology

We review the role of fluids in cosmology by first introducing them in General Relativity and then by applying them to a FRW Universe's model. We describe how relativistic and non-relativistic components evolve in the background dynamics. We also introduce scalar fields to show that they are able to yield an inflationary dynamics at very early times (inflation) and late times (quintessence). Then, we proceed to study the thermodynamical properties of the fluids and, lastly, its perturbed kinematics. We make emphasis in the constrictions of parameters by recent cosmological probes.Comment: 34 pages, 4 figures, version accepted as invited review to the book "Computational and Experimental Fluid Mechanics with Applications to Physics, Engineering and the Environment". Version 2: typos corrected and references expande

Gene expression of O-GlcNAc cycling enzymes in human breast cancers

O-GlcNAcylation is an abundant, dynamic, and inducible posttranslational modification in which single β-N-acetylglucosamine residues are attached by O-glycosidic linkage to serine or treonine residues. It is suggested that abnormally regulated O-GlcNAcylation may contribute to the pathology of cancer. Cycling of O-GlcNAc residues on intracellular proteins is controlled by two enzymes, O-GlcNAc transferease (OGT), which catalyses the addition of O-GlcNAc residues and nucleocytoplasmic β-N-acetylglucosaminidase (O-GlcNAcase; encoded by MGEA5 gene), an enzyme involved in the removal of O-GlcNAc. In this study, relationship between the mRNA expressions of genes coding O-GlcNAc cycling enzymes in breast ductal carcinomas and clinicopathological parameters were analyzed. The results showed that poorly differentiated tumors (grade II and III) had significantly higher OGT expression than grade I tumors. Contrary, MGEA5 transcript levels were significantly lower in grade II and III in comparison with grade I tumors. The Spearman rank correlation showed the expressions of OGT and MGEA5 in breast cancer was negatively correlated (r = −0.430, P = 0.0002). Lymph node metastasis status was significantly associated with decreased MGEA5 mRNA expression. This result suggests that elevation in O-GlcNAc modification of proteins may be implicated in breast tumor progression and metastasis

Clinical outcome of endonasal KTP laser assisted dacryocystorhinostomy

BACKGROUND: To evaluate the clinical outcome of primary endonasal laser assisted dacryocystorhinostomy (ENL-DCR) using the potassium-titanyl-phosphate laser. METHODS: We retrospectively reviewed all primary ENL-DCRs performed within a period of twelve months by the same combined Ophthalmology and Otorhinolaringology team in Freeman Hospital, Newcastle upon Tyne, UK. The main outcome measure for success was resolution or significant improvement of epiphora. Details of surgery, intraoperative and postoperative complications, as well as pathology associated with failure were also studied. Patients were followed up for at least 12 months. RESULTS: A total of 41 consecutive ENL-DCRs on 29 patients (22 females, 7 males, mean age 75 years) were analysed. All patients had bicanalicular silicone intubation for at least 4 months. The success rate at 12 months postoperatively was 78.1%. Pathology associated with failure included: intranasal pathology (12.2%), mucocele (7.3%), and systemic sarcoidosis (2.4%). No significant intra-operative complications were recorded. CONCLUSION: The ENL-DCR with potassium-titanyl-phosphate laser can be considered as a safe and efficient primary procedure for the treatment of nasolacrimal duct obstruction

Stimulation programs for pediatric drug research – do children really benefit?

Most drugs that are currently prescribed in pediatrics have not been tested in children. Pediatric drug studies are stimulated in the USA by the pediatric exclusivity provision under the Food and Drug Administration Modernization Act (FDAMA) that grants patent extensions when pediatric labeling is provided. We investigated the effectiveness of these programs in stimulating drug research in children, thereby increasing the evidence for safe and effective drug use in the pediatric population. All drugs granted pediatric exclusivity under the FDAMA were analyzed by studying the relevant summaries of medical and clinical pharmacology reviews of the pediatric studies or, if these were unavailable, the labeling information as provided by the manufacturer. A systematic search of the literature was performed to identify drug utilization patterns in children. From July 1998 to August 2006, 135 drug entities were granted pediatric exclusivity. Most frequent drug groups were anti-depressants and mood stabilizers, ACE inhibitors, lipid-lowering preparations, HIV antivirals, and non-steroidal anti-inflammatory and anti-rheumatic drugs. The distribution of the different drugs closely matched the distribution of these drugs over the adult market, and not the drug utilization by children

Is a cooperative approach to seaweed farming effectual? An analysis of the seaweed cluster project (SCP), Malaysia

Seaweed (Kappaphycus spp.) farming has been practised in Malaysia since the late 1970s following government policy incentives (training and farming inputs). However, numerous governance, economic, environmental, technological and sociocultural challenges have limited the industry from achieving its full potential. The Seaweed Cluster Project (SCP) was introduced in 2012 to address some of these challenges. We sought to evaluate the effectiveness of the SCP in delivering its central objectives of increasing seaweed production, optimising the farming area, improving seaweed quality and farming efficiency, raising farmers’ income, and reducing the environmental impact of seaweed farming. Community and industry perceptions of the SCP were obtained from seven communities using a mixed-methods approach based on face-to-face semi-structured interviews, focus group discussions, household surveys, observation and secondary data. Views on the SCP outcomes were generally negative, including low take-up rates by indigenous people, poor stakeholder participation in decision-making, limited acceptance of new technologies, economic vulnerability, a complex marketing system, and low social cohesion of seaweed farming communities. Positive perceptions included recognition that the SCP confers high social status upon a community, reduces operating costs, and facilitates the production of certified seaweed. The SCP’s problems are linked to poor multi-level governance, weak market mechanisms and unintegrated community development. The study concludes with five recommendations to improve the SCP: promote the participation of indigenous people; legalise existing migrant farmers; strengthen local seaweed cooperative organisations; provide entrepreneurship skills to farmers; and fully integrate stakeholders into decision-making

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

The Cosmological Constant

This is a review of the physics and cosmology of the cosmological constant. Focusing on recent developments, I present a pedagogical overview of cosmology in the presence of a cosmological constant, observational constraints on its magnitude, and the physics of a small (and potentially nonzero) vacuum energy.Comment: 50 pages. Submitted to Living Reviews in Relativity (http://www.livingreviews.org/), December 199