Displaying publications 1 - 20 of 46 in total

  1. Abeer MM, Mohd Amin MC, Martin C
    J. Pharm. Pharmacol., 2014 Aug;66(8):1047-61.
    PMID: 24628270 DOI: 10.1111/jphp.12234
    The field of pharmaceutical technology is expanding rapidly because of the increasing number of drug delivery options. Successful drug delivery is influenced by multiple factors, one of which is the appropriate identification of materials for research and engineering of new drug delivery systems. Bacterial cellulose (BC) is one such biopolymer that fulfils the criteria for consideration as a drug delivery material.
  2. Low WL, Kenward MAK, Amin MCIM, Martin C
    Medicines (Basel), 2016 Mar 01;3(1).
    PMID: 28930118 DOI: 10.3390/medicines3010008
    The emerging problems posed by antibiotic resistance complicate the treatment regime required for wound infections and are driving the need to develop more effective methods of wound management. There is growing interest in the use of alternative, broad spectrum, pre-antibiotic antimicrobial agents such as essential oils (e.g., tea tree oil, TTO) and metal ions (e.g., silver, Ag⁺). Both TTO and Ag⁺ have broad spectrum antimicrobial activity and act on multiple target sites, hence reducing the likelihood of developing resistance. Combining such agents with responsive, controlled release delivery systems such as hydrogels may enhance microbiocidal activity and promote wound healing. The advantages of using chitosan to formulate the hydrogels include its biocompatible, mucoadhesive and controlled release properties. In this study, hydrogels loaded with TTO and Ag⁺ exhibited antimicrobial activity against P. aeruginosa, S. aureus and C. albicans. Combining TTO and Ag⁺ into the hydrogel further improved antimicrobial activity by lowering the effective concentrations required, respectively. This has obvious advantages for reducing the potential toxic effects on the healthy tissues surrounding the wound. These studies highlight the feasibility of delivering lower effective concentrations of antimicrobial agents such as TTO and Ag⁺ in ionically crosslinked chitosan hydrogels to treat common wound-infecting pathogens.
  3. Campion KL, McCormick WD, Warwicker J, Khayat ME, Atkinson-Dell R, Steward MC, et al.
    J. Am. Soc. Nephrol., 2015 Sep;26(9):2163-71.
    PMID: 25556167 DOI: 10.1681/ASN.2014070653
    The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pHo) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pHo can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pHo from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)i) mobilization, whereas raising pHo to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)o). Similar pHo effects were observed for Ca(2+)o-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)i mobilization. Intracellular pH was unaffected by acute 0.4-unit pHo changes, and the presence of physiologic albumin concentrations failed to attenuate the pHo-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pHo sensitivity. Finally, pathophysiologic pHo elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pHo changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo.
  4. Lefoulon E, Bain O, Makepeace BL, d'Haese C, Uni S, Martin C, et al.
    PeerJ, 2016;4:e1840.
    PMID: 27069790 DOI: 10.7717/peerj.1840
    Wolbachia is an alpha-proteobacterial symbiont widely distributed in arthropods. Since the identification of Wolbachia in certain animal-parasitic nematodes (the Onchocercidae or filariae), the relationship between arthropod and nematode Wolbachia has attracted great interest. The obligate symbiosis in filariae, which renders infected species susceptible to antibiotic chemotherapy, was held to be distinct from the Wolbachia-arthropod relationship, typified by reproductive parasitism. While co-evolutionary signatures in Wolbachia-arthropod symbioses are generally weak, reflecting horizontal transmission events, strict co-evolution between filariae and Wolbachia has been reported previously. However, the absence of close outgroups for phylogenetic studies prevented the determination of which host group originally acquired Wolbachia. Here, we present the largest co-phylogenetic analysis of Wolbachia in filariae performed to date including: (i) a screening and an updated phylogeny of Wolbachia; (ii) a co-phylogenetic analysis; and (iii) a hypothesis on the acquisition of Wolbachia infection. First, our results show a general overestimation of Wolbachia occurrence and support the hypothesis of an ancestral absence of infection in the nematode phylum. The accuracy of supergroup J is also underlined. Second, although a global pattern of coevolution remains, the signal is derived predominantly from filarial clades associated with Wolbachia in supergroups C and J. In other filarial clades, harbouring Wolbachia supergroups D and F, horizontal acquisitions and secondary losses are common. Finally, our results suggest that supergroup C is the basal Wolbachia clade within the Ecdysozoa. This hypothesis on the origin of Wolbachia would change drastically our understanding of Wolbachia evolution.
  5. Low WL, Kenward K, Britland ST, Amin MC, Martin C
    Int Wound J, 2017 Apr;14(2):369-384.
    PMID: 27146784 DOI: 10.1111/iwj.12611
    The increasing occurrence of hospital-acquired infections and the emerging problems posed by antibiotic-resistant microbial strains have both contributed to the escalating cost of treatment. The presence of infection at the wound site can potentially stall the healing process at the inflammatory stage, leading to the development of a chronic wound. Traditional wound treatment regimes can no longer cope with the complications posed by antibiotic-resistant strains; hence, there is a need to explore the use of alternative antimicrobial agents. Pre-antibiotic compounds, including heavy metal ions and essential oils, have been re-investigated for their potential use as effective antimicrobial agents. Essential oils have potent antimicrobial, antifungal, antiviral, anti-inflammatory, antioxidant and other beneficial therapeutic properties. Similarly, heavy metal ions have also been used as disinfecting agents because of their broad spectrum activities. Both of these alternative antimicrobials interact with many different intracellular components, thereby resulting in the disruption of vital cell functions and eventually cell death. This review will discuss the application of essential oils and heavy metal ions, particularly tea tree oil and silver ions, as alternative antimicrobial agents for the treatment of chronic, infected wounds.
  6. Bain O, Mutafchiev Y, Junker K, Guerrero R, Martin C, Lefoulon E, et al.
    Zootaxa, 2015;3918(1):151-93.
    PMID: 25781087 DOI: 10.11646/zootaxa.3918.2.1
    Based on material deposited in museum collections, twelve species within Mansonella sensu lato were examined and their descriptions amended. Based on additional morphological details, the erection of the new monotypic subgenus Filyamagutia Bain & Uni for M. (F.) akitensis (Uni, 1983), and the new combination M. (Pseudolitomosa) musasabi (Yamaguti, 1941) Bain & Uni are proposed. A new subspecies, M. (Tetrapetalonema) atelensis amazonae Bain & Guerrero is described and a key to the seven subgenera of Mansonella is provided. Furthermore, the elevation of Sandnema to full genus rank comprising the two species S. digitatum (Chandler, 1929) n. comb. and S. sunci (Sandground, 1933) n. comb., is proposed. Host and geographic records for the species of Mansonella and Sandnema are included.
  7. Zhang C, Park JS, Grce M, Hibbitts S, Palefsky JM, Konno R, et al.
    J. Infect. Dis., 2014 Nov 15;210(10):1600-4.
    PMID: 24879800 DOI: 10.1093/infdis/jiu310
    Human papillomavirus (HPV) genotype 52 is commonly found in Asian cases of cervical cancer but is rare elsewhere. Analysis of 611 isolates collected worldwide revealed a remarkable geographical distribution, with lineage B predominating in Asia (89.0% vs 0%-5.5%; P(corrected) < .001), whereas lineage A predominated in Africa, the Americas, and Europe. We propose that the name "Asian lineage" be used to denote lineage B, to signify this feature. Preliminary analysis suggested a higher disease risk for lineage B, although ethnogeographical confounders could not be excluded. Further studies are warranted to verify whether the reported high attribution of disease to HPV52 in Asia is due to the high prevalence of lineage B.
  8. Abeer MM, Amin MC, Lazim AM, Pandey M, Martin C
    Carbohydr Polym, 2014 Sep 22;110:505-12.
    PMID: 24906785 DOI: 10.1016/j.carbpol.2014.04.052
    Acrylated abietic acid (acrylated AbA) and acrylated abietic acid-grafted bacterial cellulose pH sensitive hydrogel (acrylated AbA-g-BC) were prepared by a one-pot synthesis. The successful dimerization of acrylic acid (AA) and abietic acid (AbA) and grafting of the dimer onto bacterial cellulose (BC) was confirmed by 13C solid state NMR as well as FT-IR. X-ray diffraction analysis showed characteristic peaks for AbA and BC; further, there was no effect of increasing amorphous AA content on the overall crystallinity of the hydrogel. Differential scanning calorimetry revealed a glass transition temperature of 80°C. Gel fraction and swelling studies gave insight into the features of the hydrogel, suggesting that it was suitable for future applications such as drug delivery. Scanning electron microscopy observations showed an interesting interpenetrating network within the walls of hydrogel samples with the lowest levels of AA and gamma radiation doses. Cell viability test revealed that the synthesized hydrogel is safe for future use in biomedical applications.
  9. Gupta A, Low WL, Radecka I, Britland ST, Mohd Amin MC, Martin C
    J Microencapsul, 2016 Dec;33(8):725-734.
    PMID: 27781557 DOI: 10.1080/02652048.2016.1253796
    Wounds that remain in the inflammatory phase for a prolonged period of time are likely to be colonised and infected by a range of commensal and pathogenic microorganisms. Treatment associated with these types of wounds mainly focuses on controlling infection and providing an optimum environment capable of facilitating re-epithelialisation, thus promoting wound healing. Hydrogels have attracted vast interest as moist wound-responsive dressing materials. In the current study, biosynthetic bacterial cellulose hydrogels synthesised by Gluconacetobacter xylinus and subsequently loaded with silver were characterised and investigated for their antimicrobial activity against two representative wound infecting pathogens, namely S. aureus and P. aeruginosa. Silver nitrate and silver zeolite provided the source of silver and loading parameters were optimised based on experimental findings. The results indicate that both AgNO3 and AgZ loaded biosynthetic hydrogels possess antimicrobial activity (p 
  10. Mohamad N, Buang F, Mat Lazim A, Ahmad N, Martin C, Mohd Amin MCI
    PMID: 27690276 DOI: 10.1002/jbm.b.33776
    The use of bacterial cellulose (BC)-based hydrogel has been gaining attention owing to its biocompatibility and biodegradability. This study was designed to investigate the effect of radiation doses and acrylic acid (AA) composition on in vitro and in vivo biocompatibility of BC/AA as wound dressing materials. Physical properties of the hydrogel, that is, thickness, adhesiveness, rate of water vapor transmission, and swelling were measured. Moreover, the effect of these parameters on skin irritation and sensitization, blood compatibility, and cytotoxicity was studied. Increased AA content and irradiation doses increased the thickness, crosslinking density, and improved the mechanical properties of the hydrogel, but reduced its adhesiveness. The swelling capacity of the hydrogel increased significantly with a decrease in the AA composition in simulated wound fluid. The water vapor permeability of polymeric hydrogels was in the range of 2035-2666 [g/(m-2  day-1 )]. Dermal irritation and sensitization test demonstrated that the hydrogel was nonirritant and nonallergic. The BC/AA hydrogel was found to be nontoxic to primary human dermal fibroblast skin cells with viability >88% and was found to be biocompatible with blood with a low hemolytic index (0.80-1.30%). Collectively, these results indicate that these hydrogels have the potential to be used as wound dressings. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2553-2564, 2017.
  11. Pandey M, Mohamad N, Low WL, Martin C, Mohd Amin MC
    Drug Deliv Transl Res, 2017 02;7(1):89-99.
    PMID: 27815776 DOI: 10.1007/s13346-016-0341-8
    Burn wound management is a complex process because the damage may extend as far as the dermis which has an acknowledged slow rate of regeneration. This study investigates the feasibility of using hydrogel microparticles composed of bacterial cellulose and polyacrylamide as a dressing material for coverage of partial-thickness burn wounds. The microparticulate carrier structure and surface morphology were investigated by Fourier transform infrared, X-ray diffraction, elemental analysis, and scanning electron microscopy. The cytotoxicity profile of the microparticles showed cytocompatibility with L929 cells. Dermal irritation test demonstrated that the hydrogel was non-irritant to the skin and had a significant effect on wound contraction compared to the untreated group. Moreover, histological examination of in vivo burn healing samples revealed that the hydrogel treatment enhanced epithelialization and accelerated fibroblast proliferation with wound repair and intact skin achieved by the end of the study. Both the in vitro and in vivo results proved the biocompatibility and efficacy of hydrogel microparticles as a wound dressing material.
  12. Uni S, Bain O, Suzuki K, Agatsuma T, Harada M, Motokawa M, et al.
    Parasitol. Int., 2013 Feb;62(1):14-23.
    PMID: 22926421 DOI: 10.1016/j.parint.2012.08.004
    Acanthocheilonema delicata n. sp. (Filarioidea: Onchocercidae: Onchocercinae) is described based on adult filarioids and microfilariae obtained from subcutaneous connective tissues and skin, respectively, of Japanese badgers (Meles anakuma) in Wakayama Prefecture, Japan. No endemic species of the genus had been found in Japan. Recently, some filarioids (e.g., Acanthocheilonema reconditum, Dirofilaria spp., and Onchocerca spp.) have come to light as causative agents of zoonosis worldwide. The new species was readily distinguished from its congeners by morphologic characteristics such as body length, body width, esophagus length, spicule length, and the length of microfilariae. Based on the molecular data of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene, A. delicata n. sp. was included in the clade of the genus Acanthocheilonema but differed from two other congeneric species available for study, A. viteae and A. reconditum. Acanthocheilonema delicata n. sp. did not harbor Wolbachia. It is likely that the fauna of filarioids from mammals on the Japanese islands is characterized by a high level of endemicity.
  13. Lefoulon E, Giannelli A, Makepeace BL, Mutafchiev Y, Townson S, Uni S, et al.
    Int. J. Parasitol., 2017 07;47(8):457-470.
    PMID: 28344097 DOI: 10.1016/j.ijpara.2016.12.009
    The genus Onchocerca includes 34 described species and represents one of the largest genera of the filarial nematodes within the family Onchocercidae. Representative members of this genus are mainly parasites of ungulates, with some exceptions such as Onchocerca lupi and Onchocerca volvulus, infecting carnivores and/or humans. For a long time, the evolutionary relationships amongst onchocercids remained poorly studied, as the systematics of this genus was impaired by the high morphological variability of species included in the taxon. Although some molecular phylogenies were developed, these studies were mainly focused on bovine Onchocerca spp. and O. volvulus, including assessments of Wolbachia endosymbionts. In the present study, we analysed 13 Onchocerca spp. from a larger host spectrum using a panel of seven different genes. Analysis of the coxI marker supports its usefulness for the identification of species within the genus. The evolutionary history of the genus has been herein revised by multi-gene phylogenies, presenting three strongly supported clades of Onchocerca spp. Analyses of co-evolutionary scenarios between Onchocerca and their vertebrate hosts underline the effect of domestication on Onchocerca speciation. Our study indicates that a host switch event occurred between Bovidae, Canidae and humans. Cophylogenetic analyses between Onchocerca and the endosymbiotic bacterium Wolbachia indicate the strongest co-evolutionary pattern ever registered within the filarial nematodes. Finally, this dataset indicates that the clade composed by O. lupi, Onchocerca gutturosa, Onchocerca lienalis, Onchocerca ochengi and O. volvulus derived from recent speciation.
  14. Wong MC, Ching JY, Chiu HM, Wu KC, Rerknimitr R, Li J, et al.
    Am. J. Gastroenterol., 2016 11;111(11):1621-1629.
    PMID: 26977757 DOI: 10.1038/ajg.2016.52
    OBJECTIVES: We tested the hypothesis that the risk of colorectal cancer (CRC), advanced colorectal neoplasia (ACN), and colorectal adenoma among screening participants with different first-degree relatives (FDRs) affected by CRC was similar.

    METHODS: A multi-center, prospective colonoscopy study involving 16 Asia-Pacific regions was performed from 2008 to 2015. Consecutive self-referred CRC screening participants aged 40-70 years were recruited, and each subject received one direct optical colonoscopy. The prevalence of CRC, ACN, and colorectal adenoma was compared among subjects with different FDRs affected using Pearson's χ2 tests. Binary logistic regression analyses were performed to evaluate the risk of these lesions, controlling for recognized risk factors including age, gender, smoking habits, alcohol drinking, body mass index, and the presence of diabetes mellitus.

    RESULTS: Among 11,797 asymptomatic subjects, the prevalence of CRC was 0.6% (none: 0.6%; siblings: 1.1%; mother: 0.5%; father: 1.2%; ≥2 members: 3.1%, P<0.001), that of ACN was 6.5% (none: 6.1%; siblings: 8.3%; mother: 7.7%; father: 8.7%; ≥2 members: 9.3%, P<0.001), and that of colorectal adenoma was 29.3% (none: 28.6%; siblings: 33.5%; mother: 31.8%; father: 31.1%; ≥2 members: 38.1%, P<0.001). In multivariate regression analyses, subjects with at least one FDR affected were significantly more likely to have CRC (adjusted odds ratio (AOR)=2.02-7.89), ACN (AOR=1.55-2.06), and colorectal adenoma (AOR=1.31-1.92) than those without a family history. The risk of CRC (AOR=0.90, 95% confidence interval (CI) 0.34-2.35, P=0.830), ACN (AOR=1.07, 95% CI 0.75-1.52, P=0.714), and colorectal adenoma (AOR=0.96, 95% CI 0.78-1.19, P=0.718) in subjects with either parent affected was similar to that of subjects with their siblings affected.

    CONCLUSIONS: The risk of colorectal neoplasia was similar among subjects with different FDRs affected. These findings do not support the need to discriminate proband identity in screening participants with affected FDRs when their risks of colorectal neoplasia were estimated.

  15. Uni S, Mat Udin AS, Agatsuma T, Junker K, Saijuntha W, Bunchom N, et al.
    Parasit Vectors, 2020 Feb 06;13(1):50.
    PMID: 32028994 DOI: 10.1186/s13071-020-3907-8
    BACKGROUND: The genus Onchocerca Diesing, 1841 includes species of medical importance, such as O. volvulus (Leuckart, 1893), which causes river blindness in the tropics. Recently, zoonotic onchocercosis has been reported in humans worldwide. In Japan, O. dewittei japonica Uni, Bain & Takaoka, 2001 from wild boars is a causative agent for this zoonosis. Many filarioid nematodes are infected with Wolbachia endosymbionts which exhibit various evolutionary relationships with their hosts. While investigating the filarial fauna of Borneo, we discovered an undescribed Onchocerca species in the bearded pig Sus barbatus Müller (Cetartiodactyla: Suidae).

    METHODS: We isolated Onchocerca specimens from bearded pigs and examined their morphology. For comparative material, we collected fresh specimens of O. d. dewittei Bain, Ramachandran, Petter & Mak, 1977 from banded pigs (S. scrofa vittatus Boie) in Peninsular Malaysia. Partial sequences of three different genes (two mitochondrial genes, cox1 and 12S rRNA, and one nuclear ITS region) of these filarioids were analysed. By multi-locus sequence analyses based on six genes (16S rDNA, ftsZ, dnaA, coxA, fbpA and gatB) of Wolbachia, we determined the supergroups in the specimens from bearded pigs and those of O. d. dewittei.

    RESULTS: Onchocerca borneensis Uni, Mat Udin & Takaoka n. sp. is described on the basis of morphological characteristics and its genetic divergence from congeners. Molecular characteristics of the new species revealed its close evolutionary relationship with O. d. dewittei. Calculated p-distance for the cox1 gene sequences between O. borneensis n. sp. and O. d. dewittei was 5.9%, while that between O. d. dewittei and O. d. japonica was 7.6%. No intraspecific genetic variation was found for the new species. Wolbachia strains identified in the new species and O. d. dewittei belonged to supergroup C and are closely related.

    CONCLUSIONS: Our molecular analyses of filarioids from Asian suids indicate that the new species is sister to O. d. dewittei. On the basis of its morphological and molecular characteristics, we propose to elevate O. d. japonica to species level as O. japonica Uni, Bain & Takaoka, 2001. Coevolutionary relationships exist between the Wolbachia strains and their filarial hosts in Borneo and Peninsular Malaysia.

  16. Uni S, Mat Udin AS, Agatsuma T, Saijuntha W, Junker K, Ramli R, et al.
    Parasit Vectors, 2017 Apr 20;10(1):194.
    PMID: 28427478 DOI: 10.1186/s13071-017-2105-9
    BACKGROUND: The filarial nematodes Wuchereria bancrofti (Cobbold, 1877), Brugia malayi (Brug, 1927) and B. timori Partono, Purnomo, Dennis, Atmosoedjono, Oemijati & Cross, 1977 cause lymphatic diseases in humans in the tropics, while B. pahangi (Buckley & Edeson, 1956) infects carnivores and causes zoonotic diseases in humans in Malaysia. Wuchereria bancrofti, W. kalimantani Palmieri, Pulnomo, Dennis & Marwoto, 1980 and six out of ten Brugia spp. have been described from Australia, Southeast Asia, Sri Lanka and India. However, the origin and evolution of the species in the Wuchereria-Brugia clade remain unclear. While investigating the diversity of filarial parasites in Malaysia, we discovered an undescribed species in the common treeshrew Tupaia glis Diard & Duvaucel (Mammalia: Scandentia).

    METHODS: We examined 81 common treeshrews from 14 areas in nine states and the Federal Territory of Peninsular Malaysia for filarial parasites. Once any filariae that were found had been isolated, we examined their morphological characteristics and determined the partial sequences of their mitochondrial cytochrome c oxidase subunit 1 (cox1) and 12S rRNA genes. Polymerase chain reaction (PCR) products of the internal transcribed spacer 1 (ITS1) region were then cloned into the pGEM-T vector, and the recombinant plasmids were used as templates for sequencing.

    RESULTS: Malayfilaria sofiani Uni, Mat Udin & Takaoka, n. g., n. sp. is described based on the morphological characteristics of adults and microfilariae found in common treeshrews from Jeram Pasu, Kelantan, Malaysia. The Kimura 2-parameter distance between the cox1 gene sequences of the new species and W. bancrofti was 11.8%. Based on the three gene sequences, the new species forms a monophyletic clade with W. bancrofti and Brugia spp. The adult parasites were found in tissues surrounding the lymph nodes of the neck of common treeshrews.

    CONCLUSIONS: The newly described species appears most closely related to Wuchereria spp. and Brugia spp., but differs from these in several morphological characteristics. Molecular analyses based on the cox1 and 12S rRNA genes and the ITS1 region indicated that this species differs from both W. bancrofti and Brugia spp. at the genus level. We thus propose a new genus, Malayfilaria, along with the new species M. sofiani.

  17. Shimelis H, Mesman RLS, Von Nicolai C, Ehlen A, Guidugli L, Martin C, et al.
    Cancer Res., 2017 06 01;77(11):2789-2799.
    PMID: 28283652 DOI: 10.1158/0008-5472.CAN-16-2568
    Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR.
  18. Pereda J, Niimi G, Kaul JM, Mishra S, Pangtey B, Peri D, et al.
    Surg Radiol Anat, 2009 Sep;31 Suppl 1:49-93.
    PMID: 27392491 DOI: 10.1007/BF03371485
  19. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Phys. Rev. Lett., 2015 Mar 13;114(10):101801.
    PMID: 25815923
    Results are presented from a search for new decaying massive particles whose presence is inferred from an imbalance in transverse momentum and which are produced in association with a single top quark that decays into a bottom quark and two light quarks. The measurement is performed using 19.7  fb^{-1} of data from proton-proton collisions at a center-of-mass energy of 8 TeV, collected with the CMS detector at the CERN LHC. No deviations from the standard model predictions are observed and lower limits are set on the masses of new invisible bosons. In particular, scalar and vector particles, with masses below 330 and 650 GeV, respectively, are excluded at 95% confidence level, thereby substantially extending a previous limit published by the CDF Collaboration.
  20. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Phys. Rev. Lett., 2015 Feb 13;114(6):061801.
    PMID: 25723204
    A search for new long-lived particles decaying to leptons is presented using proton-proton collisions produced by the LHC at √[s]=8  TeV. Data used for the analysis were collected by the CMS detector and correspond to an integrated luminosity of 19.7  fb(-1). Events are selected with an electron and muon with opposite charges that both have transverse impact parameter values between 0.02 and 2 cm. The search has been designed to be sensitive to a wide range of models with nonprompt e-μ final states. Limits are set on the "displaced supersymmetry" model, with pair production of top squarks decaying into an e-μ final state via R-parity-violating interactions. The results are the most restrictive to date on this model, with the most stringent limit being obtained for a top squark lifetime corresponding to cτ=2  cm, excluding masses below 790 GeV at 95% confidence level.
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