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1. Fulltext Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

   Phelan CM, Kuchenbaecker KB, Tyrer JP, Kar SP, Lawrenson K, Winham SJ, et al.

   Nat. Genet., 2017 May;49(5):680-691.

   PMID: 28346442 DOI: 10.1038/ng.3826

   Abstract

   To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

   MeSH terms: Alleles; Female; Genotype; Humans; Mutation; Neoplasms, Glandular and Epithelial/genetics*; Neoplasms, Glandular and Epithelial/pathology; Ovarian Neoplasms/genetics*; Ovarian Neoplasms/pathology; Risk Factors; Meta-Analysis as Topic; BRCA1 Protein/genetics; Genetic Predisposition to Disease/genetics*; Polymorphism, Single Nucleotide; BRCA2 Protein/genetics; Telomere-Binding Proteins/genetics; Genome-Wide Association Study; Genetic Loci/genetics*
2. Re: Cambareri et al.: Do Overweight and Obese Pediatric Stone Formers Have Differences in Metabolic Abnormalities Compared With Normal-weight Stone Formers? (Urology 2017;101:26-30)

   Mahakkanukrauh P, Sinthubua A, Das S

   Urology, 2017 07;105:210.

   PMID: 28412330 DOI: 10.1016/j.urology.2017.03.043
3. Melatonin receptors: distribution in mammalian brain and their respective putative functions

   Ng KY, Leong MK, Liang H, Paxinos G

   Brain Struct Funct, 2017 Sep;222(7):2921-2939.

   PMID: 28478550 DOI: 10.1007/s00429-017-1439-6

   Abstract

   Melatonin, through its different receptors, has pleiotropic functions in mammalian brain. Melatonin is secreted mainly by the pineal gland and exerts its effects via receptor-mediated and non-receptor-mediated actions. With recent advancement in neuroanatomical mapping, we may now understand better the localizations of the two G protein-coupled melatonin receptors MT1 and MT2. The abundance of these melatonin receptors in respective brain regions suggests that receptor-mediated actions of melatonin might play crucial roles in the functions of central nervous system. Hence, this review aims to summarize the distribution of melatonin receptors in the brain and to discuss the putative functions of melatonin in the retina, cerebral cortex, reticular thalamic nucleus, habenula, hypothalamus, pituitary gland, periaqueductal gray, dorsal raphe nucleus, midbrain and cerebellum. Studies on melatonin receptors in the brain are important because cumulative evidence has pointed out that melatonin receptors not only play important physiological roles in sleep, anxiety, pain and circadian rhythm, but might also be involved in the pathogenesis of a number of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Huntington's disease.
4. Fulltext Cryo-Electron Microscopy Structure of the Macrobrachium rosenbergii Nodavirus Capsid at 7 Angstroms Resolution

   Ho KL, Kueh CL, Beh PL, Tan WS, Bhella D

   Sci Rep, 2017 05 18;7(1):2083.

   PMID: 28522842 DOI: 10.1038/s41598-017-02292-0

   Abstract

   White tail disease in the giant freshwater prawn Macrobrachium rosenbergii causes significant economic losses in shrimp farms and hatcheries and poses a threat to food-security in many developing countries. Outbreaks of Macrobrachium rosenbergii nodavirus (MrNV), the causative agent of white tail disease (WTD) are associated with up to 100% mortality rates. There are no interventions available to treat or prevent MrNV disease however. Here we show the structure of MrNV virus-like particles (VLPs) produced by recombinant expression of the capsid protein, using cryogenic electron microscopy. Our data show that MrNV VLPs package nucleic acids in a manner reminiscent of other known nodavirus structures. The structure of the capsid however shows striking differences from insect and fish infecting nodaviruses, which have been shown to assemble trimer-clustered T = 3 icosahedral virus particles. MrNV particles have pronounced dimeric blade-shaped spikes extending up to 6 nm from the outer surface of the capsid shell. Our structural analysis supports the assertion that MrNV may belong to a new genus of the Nodaviridae. Moreover, our study provides the first structural view of an important pathogen affecting aquaculture industries across the world.
5. Fulltext Ancient River Inference Explains Exceptional Oriental Freshwater Mussel Radiations

   Bolotov IN, Kondakov AV, Vikhrev IV, Aksenova OV, Bespalaya YV, Gofarov MY, et al.

   Sci Rep, 2017 05 18;7(1):2135.

   PMID: 28522869 DOI: 10.1038/s41598-017-02312-z

   Abstract

   The concept of long-lived (ancient) lakes has had a great influence on the development of evolutionary biogeography. According to this insight, a number of lakes on Earth have existed for several million years (e.g., Baikal and Tanganyika) and represent unique evolutionary hotspots with multiple intra-basin radiations. In contrast, rivers are usually considered to be variable systems, and the possibility of their long-term existence during geological epochs has never been tested. In this study, we reconstruct the history of freshwater basin interactions across continents based on the multi-locus fossil-calibrated phylogeny of freshwater mussels (Unionidae). These mussels most likely originated in Southeast and East Asia in the Jurassic, with the earliest expansions into North America and Africa (since the mid-Cretaceous) following the colonization of Europe and India (since the Paleocene). We discovered two ancient monophyletic mussel radiations (mean age ~51-55 Ma) within the paleo-Mekong catchment (i.e., the Mekong, Siam, and Malacca Straits paleo-river drainage basins). Our findings reveal that the Mekong may be considered a long-lived river that has existed throughout the entire Cenozoic epoch.
6. Surface modification of valve metals using plasma electrolytic oxidation for antibacterial applications: A review

   Rizwan M, Alias R, Zaidi UZ, Mahmoodian R, Hamdi M

   J Biomed Mater Res A, 2018 02;106(2):590-605.

   PMID: 28975693 DOI: 10.1002/jbm.a.36259

   Abstract

   Plasma electrolytic oxidation (PEO) is an advance technique to develop porous oxidation layer on light metals, primarily to enhance corrosion and wear resistance. The oxidation layer can also offer a wide variety of mechanical, biomedical, tribological, and antibacterial properties through the incorporation of several ions and particles. Due to the increasing need of antimicrobial surfaces for biomedical implants, antibacterial PEO coatings have been developed through the incorporation of antibacterial agents. Metallic nanoparticles that have been employed most widely as antibacterial agents are reported to demonstrate serious health and environmental threats. To overcome the current limitations of these coatings, there is a significant need to develop antibacterial surfaces that are not harmful for patient's health and environment. Attention of the readers has been directed to utilize bioactive glasses as antibacterial agents for PEO coatings. Bioactive glasses are well known for their excellent bioactivity, biocompatibility, and antibacterial character. PEO coatings incorporated with bioactive glasses can provide environment-friendly antimicrobial surfaces with exceptional bioactivity, biocompatibility, and osseointegration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 590-605, 2018.
7. Fulltext Nano-Formulation of Ethambutol with Multifunctional Graphene Oxide and Magnetic Nanoparticles Retains Its Anti-Tubercular Activity with Prospects of Improving Chemotherapeutic Efficacy

   Saifullah B, Maitra A, Chrzastek A, Naeemullah B, Fakurazi S, Bhakta S, et al.

   Molecules, 2017 Oct 12;22(10).

   PMID: 29023384 DOI: 10.3390/molecules22101697

   Abstract

   Tuberculosis (TB) is a dreadful bacterial disease, infecting millions of human and cattle every year worldwide. More than 50 years after its discovery, ethambutol continues to be an effective part of the World Health Organization's recommended frontline chemotherapy against TB. However, the lengthy treatment regimens consisting of a cocktail of antibiotics affect patient compliance. There is an urgent need to improve the current therapy so as to reduce treatment duration and dosing frequency. In this study, we have designed a novel anti-TB multifunctional formulation by fabricating graphene oxide with iron oxide magnetite nanoparticles serving as a nano-carrier on to which ethambutol was successfully loaded. The designed nanoformulation was characterised using various analytical techniques. The release of ethambutol from anti-TB multifunctional nanoparticles formulation was found to be sustained over a significantly longer period of time in phosphate buffer saline solution at two physiological pH (7.4 and 4.8). Furthermore, the nano-formulation showed potent anti-tubercular activity while remaining non-toxic to the eukaryotic cells tested. The results of this in vitro evaluation of the newly designed nano-formulation endorse its further development in vivo.

   MeSH terms: Animals; Antitubercular Agents/pharmacology*; Antitubercular Agents/chemistry*; Cell Survival/drug effects; Drug Carriers/chemistry; Drug Compounding*; Ethambutol/pharmacology*; Ethambutol/chemistry*; Graphite/chemistry*; Microbial Sensitivity Tests; Mycobacterium/drug effects; Oxides/chemistry*; Spectrum Analysis, Raman; X-Ray Diffraction; Drug Delivery Systems; Spectroscopy, Fourier Transform Infrared; Biofilms/drug effects; Mice; Magnetite Nanoparticles/ultrastructure; Magnetite Nanoparticles/chemistry*; Drug Liberation
8. Fulltext Novel Anti-Tuberculosis Nanodelivery Formulation of Ethambutol with Graphene Oxide

   Saifullah B, Chrzastek A, Maitra A, Naeemullah B, Fakurazi S, Bhakta S, et al.

   Molecules, 2017 Oct 12;22(10).

   PMID: 29023399 DOI: 10.3390/molecules22101560

   Abstract

   Tuberculosis (TB) is a bacterial disease responsible for millions of infections and preventable deaths each year. Its treatment is complicated by patients' noncompliance due to dosing frequency, lengthy treatment, and adverse side effects associated with current chemotherapy. However, no modifications to the half-a-century old standard chemotherapy have been made based on a nanoformulation strategy to improve pharmacokinetic efficacy. In this study, we have designed a new nanodelivery formulation, using graphene oxide as the nanocarrier, loaded with the anti-TB antibiotic, ethambutol. The designed formulation was characterized using a number of molecular analytical techniques. It was found that sustained release of the drug resulted in better bioavailability. In addition, the designed formulation demonstrated high biocompatibility with mouse fibroblast cells. The anti-TB activity of the nanodelivery formulation was determined using whole-cell resazurin microtiter plate assay, modified-spot culture growth inhibition assay, and biofilm inhibition assay. The nanodelivery formulation showed good anti-mycobacterial activity. The anti-mycobacterial activity of Ethambutol was unaffected by the drug loading and release process. The results of this study demonstrated the potential of this new nanodelivery formulation strategy to be considered for modifying existing chemotherapy to yield more efficacious antibiotic treatment against TB.

   MeSH terms: Animals; Antitubercular Agents/administration & dosage*; Drug Carriers/chemistry*; Drug Compounding*; Ethambutol/administration & dosage*; Graphite/chemistry*; Humans; Microbial Sensitivity Tests; Mycobacterium/drug effects; Mycobacterium/growth & development; Oxides/chemistry*; Spectrum Analysis, Raman; X-Ray Diffraction; Drug Delivery Systems*; Spectroscopy, Fourier Transform Infrared; Biofilms/drug effects; Mice; Nanoparticles/ultrastructure; Nanoparticles/chemistry*; Drug Liberation
9. Fulltext Association analysis identifies 65 new breast cancer risk loci

   Michailidou K, Lindström S, Dennis J, Beesley J, Hui S, Kar S, et al.

   Nature, 2017 11 02;551(7678):92-94.

   PMID: 29059683 DOI: 10.1038/nature24284

   Abstract

   Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P 

   MeSH terms: Asia/ethnology; Binding Sites/genetics; Breast Neoplasms/diagnosis; Breast Neoplasms/genetics*; Computer Simulation; Europe/ethnology; Female; Humans; Regulatory Sequences, Nucleic Acid; Transcription Factors/metabolism; Risk Assessment; Genetic Predisposition to Disease/genetics*; Multifactorial Inheritance/genetics; Polymorphism, Single Nucleotide/genetics; European Continental Ancestry Group/genetics; Asian Continental Ancestry Group/genetics; Genome-Wide Association Study*; Genetic Loci*
10. The Impact of Stress Urinary Incontinence on Individual Components of Quality of Life in Malaysian Women

    Lim R, Liong ML, Leong WS, Lau YK, Khan NAK, Yuen KH

    Urology, 2018 Feb;112:38-45.

    PMID: 29107131 DOI: 10.1016/j.urology.2017.10.019

    Abstract

    OBJECTIVE: To assess the impact of stress urinary incontinence (SUI) on individual components of quality of life (QoL) using both condition-specific and generic questionnaires, and to compare the results of the 2 instruments with a control group.

    METHODS: Women with or without SUI aged ≥21 years old were recruited. Subjects completed the International Consultation of Incontinence-Urinary Incontinence Short Form (ICIQ-UI-SF), International Consultation of Incontinence-Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol), and EQ-5D questionnaires.

    RESULTS: A total of 120 women with SUI and 145 controls participated. The ICIQ-LUTSqol total score (mean ± standard deviation) was significantly higher in the SUI group (38.96 ± 10.28) compared with the control group (20.78 ± 2.73) (P