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1.  The Common Marmoset Genome Provides Insight into Primate Biology and Evolution 
Worley, Kim C. | Warren, Wesley C. | Rogers, Jeffrey | Locke, Devin | Muzny, Donna M. | Mardis, Elaine R. | Weinstock, George M. | Tardif, Suzette D. | Aagaard, Kjersti M. | Archidiacono, Nicoletta | Rayan, Nirmala Arul | Batzer, Mark A. | Beal, Kathryn | Brejova, Brona | Capozzi, Oronzo | Capuano, Saverio B. | Casola, Claudio | Chandrabose, Mimi M. | Cree, Andrew | Dao, Marvin Diep | de Jong, Pieter J. | del Rosario, Ricardo Cruz-Herrera | Delehaunty, Kim D. | Dinh, Huyen H. | Eichler, Evan | Fitzgerald, Stephen | Flicek, Paul | Fontenot, Catherine C. | Fowler, R. Gerald | Fronick, Catrina | Fulton, Lucinda A. | Fulton, Robert S. | Gabisi, Ramatu Ayiesha | Gerlach, Daniel | Graves, Tina A. | Gunaratne, Preethi H. | Hahn, Matthew W. | Haig, David | Han, Yi | Harris, R. Alan | Herrero, Javier M. | Hillier, LaDeana W. | Hubley, Robert | Hughes, Jennifer F. | Hume, Jennifer | Jhangiani, Shalini N. | Jorde, Lynn B. | Joshi, Vandita | Karakor, Emre | Konkel, Miriam K. | Kosiol, Carolin | Kovar, Christie L. | Kriventseva, Evgenia V. | Lee, Sandra L. | Lewis, Lora R. | Liu, Yih-shin | Lopez, John | Lopez-Otin, Carlos | Lorente-Galdos, Belen | Mansfield, Keith G. | Marques-Bonet, Tomas | Minx, Patrick | Misceo, Doriana | Moncrieff, J. Scott | Morgan, Margaret B. | Muthuswamy, Raveendran | Nazareth, Lynne V. | Newsham, Irene | Nguyen, Ngoc Bich | Okwuonu, Geoffrey O. | Prabhakar, Shyam | Perales, Lora | Pu, Ling-Ling | Puente, Xose S. | Quesada, Victor | Ranck, Megan C. | Raney, Brian J. | Deiros, David Rio | Rocchi, Mariano | Rodriguez, David | Ross, Corinna | Ruffier, Magali | Ruiz, San Juana | Sajjadian, S. | Santibanez, Jireh | Schrider, Daniel R. | Searle, Steve | Skaletsky, Helen | Soibam, Benjamin | Smit, Arian F. A. | Tennakoon, Jayantha B. | Tomaska, Lubomir | Ullmer, Brygg | Vejnar, Charles E. | Ventura, Mario | Vilella, Albert J. | Vinar, Tomas | Vogel, Jan-Hinnerk | Walker, Jerilyn A. | Wang, Qing | Warner, Crystal M. | Wildman, Derek E. | Witherspoon, David J. | Wright, Rita A. | Wu, Yuanqing | Xiao, Weimin | Xing, Jinchuan | Zdobnov, Evgeny M. | Zhu, Baoli | Gibbs, Richard A. | Wilson, Richard K.
Nature genetics  2014;46(8):850-857.
A first analysis of the genome sequence of the common marmoset (Callithrix jacchus), assembled using traditional Sanger methods and Ensembl annotation, has permitted genomic comparison with apes and that old world monkeys and the identification of specific molecular features a rapid reproductive capacity partly due to may contribute to the unique biology of diminutive The common marmoset has prevalence of this dizygotic primate. twins. Remarkably, these twins share placental circulation and exchange hematopoietic stem cells in utero, resulting in adults that are hematopoietic chimeras.
We observed positive selection or non-synonymous substitutions for genes encoding growth hormone / insulin-like growth factor (growth pathways), respiratory complex I (metabolic pathways), immunobiology, and proteases (reproductive and immunity pathways). In addition, both protein-coding and microRNA genes related to reproduction exhibit rapid sequence evolution. This New World monkey genome sequence enables significantly increased power for comparative analyses among available primate genomes and facilitates biomedical research application.
doi:10.1038/ng.3042
PMCID: PMC4138798  PMID: 25038751
2.  Sub1 and Maf1, Two Effectors of RNA Polymerase III, Are Involved in the Yeast Quiescence Cycle 
PLoS ONE  2014;9(12):e114587.
Sub1 and Maf1 exert an opposite effect on RNA polymerase III transcription interfering with different steps of the transcription cycle. In this study, we present evidence that Sub1 and Maf1 also exhibit an opposite role on yeast chronological life span. First, cells lacking Sub1 need more time than wild type to exit from resting and this lag in re-proliferation is correlated with a delay in transcriptional reactivation. Second, our data show that the capacity of the cells to properly establish a quiescent state is impaired in the absence of Sub1 resulting in a premature death that is dependent on the Ras/PKA and Tor1/Sch9 signalling pathways. On the other hand, we show that maf1Δ cells are long-lived mutant suggesting a connection between Pol III transcription and yeast longevity.
doi:10.1371/journal.pone.0114587
PMCID: PMC4273968  PMID: 25531541
3.  The Influence of Social Factors and Health on Depressive Symptoms and Worry: A Study of Older Vietnamese Adults 
Aging & mental health  2012;16(6):780-786.
Objectives
Vietnam has a growing older population, many of whom experienced war and social upheavals in their lives. Prior research has described the health of the older population, but little work has explored mental health. The current study examines the frequency and correlates of two mental health indicators: depressive symptoms and worry.
Method
A representative sample of 600 adults 55 and older stratified by gender (50% women), age (mean = 70.33), and rural/urban (50% rural) was recruited in Da Nang, Vietnam and surrounding rural districts. Participants were interviewed in their homes by trained interviewers. Dependent variables were a Vietnamese version of the CES-D and a culturally specific worry scale.
Results
Forty-seven percent of the sample had scores above the cut-off for clinical depression and scores on the worry scale were high. Using multiple linear regressions we found that women, the less educated and individuals with more material hardship had higher depressive symptoms whereas rural residents, women, married, and young-old individuals were more worried. Pain, ADL assistance and emotional support were significant predictors of both depressive symptoms and worry, though the direction of the association for emotional support differed. Illnesses were only a predictor of depressive symptoms.
Conclusion
The high reports of depressive symptoms and worry suggests the need for incorporating mental health screening as part of health programs for older adults in Vietnam. Attention to factors associated with depressive symptoms and worry, such as economic hardship, health problems and lack of emotional support, may contribute to alleviation of symptoms.
doi:10.1080/13607863.2012.667780
PMCID: PMC4233407  PMID: 22486622
depression; worry; older adults; Vietnam
4.  Toxic detection in mine water based on proteomic analysis of lysosomal enzymes in Saccharomyces cerevisiae 
Objectives
Lysosome is the cell-organelle which is commonly used as biomonitoring tool in environmental pollution. In this study, the lysosomal proteomic of the yeast Saccharomyces cerevisiae was analyzed for utilization in the detection of toxic substances in mine water samples.
Methods
This work informs the expression of lysosomal proteomic in yeast in response with toxic chemicals, such as sodium meta-arsenite and tetracycline, for screening specific biomarkers. After that, a recombinant yeast contained this biomarker were constructed for toxic detection in pure toxic chemicals and mine water samples.
Results
Each chemical had an optimal dose at which the fluorescent protein intensity reached the peak. In the case of water samples, the yeast showed the response with sample 1, 3, 4, and 5; whereas there is no response with sample 2, 6, and 7.
Conclusions
The recombinant yeast showed a high ability of toxic detection in response with several chemicals such as heavy metals and pharmaceuticals. In the case of mine water samples, the response varied depending on the sample content.
doi:10.5620/eht.e2014019
PMCID: PMC4243728  PMID: 25384384
Heavy metals; Lysosomal proteomic; Lysosomal response; Mine water; Pharmaceuticals
5.  Multilocus Sequence Typing of Mycoplasma hyorhinis Strains Identified by a Real-Time TaqMan PCR Assay 
Journal of Clinical Microbiology  2014;52(5):1664-1671.
A real-time TaqMan PCR assay based on the gene encoding the protein p37 was developed to detect Mycoplasma hyorhinis. Its specificity was validated with 29 epidemiologically unrelated M. hyorhinis strains (28 field strains and one reference strain) and other mycoplasma species or with other microorganisms commonly found in pigs. The estimated detection limit of this qPCR assay was 125 microorganism equivalents/μl. The same 29 epidemiologically unrelated M. hyorhinis strains and four previously fully sequenced strains were typed by two portable typing methods, the sequencing of the p37 gene and a multilocus sequence typing (MLST) scheme. The first method revealed 18 distinct nucleotide sequences and insufficient discriminatory power (0.934). The MLST scheme was developed with the sequenced genomes of the M. hyorhinis strains HUB-1, GDL-1, MCLD, and SK76 and based on the genes dnaA, rpoB, gyrB, gltX, adk, and gmk. In total, 2,304 bp of sequence was analyzed for each strain. MLST was capable of subdividing the 33 strains into 29 distinct sequence types. The discriminatory power of the method was >0.95, which is the threshold value for interpreting typing results with confidence (D = 0.989). Population analysis showed that recombination in M. hyorhinis occurs and that strains are diverse but with a certain clonality (one unique clonal complex was identified). The new qPCR assay and the robust MLST scheme are available for the acquisition of new knowledge on M. hyorhinis epidemiology. A web-accessible database has been set up for the M. hyorhinis MLST scheme at http://pubmlst.org/mhyorhinis/.
doi:10.1128/JCM.03437-13
PMCID: PMC3993664  PMID: 24622092
6.  Complex Actions of Thyroid Hormone Receptor Antagonist NH-3 on Gene Promoters in Different Cell Lines 
It is desirable to obtain new antagonists for thyroid hormone (TRs) and other nuclear receptors (NRs). We previously used X-ray structural models of TR ligand binding domains (LBDs) to design compounds, such as NH-3, that impair coactivator binding to activation function 2 (AF-2) and block thyroid hormone (triiodothyronine, T3) actions. However, TRs bind DNA and are transcriptionally active without ligand. Thus, NH-3 could modulate TR activity via effects on other coregulator interaction surfaces, such as activation function (AF-1) and corepressor binding sites. Here, we find that NH-3 blocks TR-LBD interactions with coactivators and corepressors and also inhibits activities of AF-1 and AF-2 in transfections. While NH-3 lacks detectable agonist activity at T3-activated genes in GC pituitary cells it nevertheless activates spot 14 (S14) in HTC liver cells with the latter effect accompanied by enhanced histone H4 acetylation and coactivator recruitment at the S14 promoter. Surprisingly, T3 promotes corepressor recruitment to target promoters. NH-3 effects vary; we observe transient recruitment of N-CoR to S14 in GC cells and dismissal and rebinding of N-CoR to the same promoter in HTC cells. We propose that NH-3 will generally behave as an antagonist by blocking AF-1 and AF-2 but that complex effects on coregulator recruitment may result in partial/mixed agonist effects that are independent of blockade of T3 binding in some contexts. These properties could ultimately be utilized in drug design and development of new selective TR modulators.
doi:10.1016/j.mce.2008.09.016
PMCID: PMC4180716  PMID: 18930112
7.  Parameter estimations of sigmoidal models of cancer 
BMC Bioinformatics  2014;15(Suppl 10):P15.
doi:10.1186/1471-2105-15-S10-P15
PMCID: PMC4196032
8.  Report of four new patients with protein-truncating mutations in C6orf221/KHDC3L and colocalization with NLRP7 
To date, two maternal-effect genes have been shown to have causative roles in recurrent hydatidiform moles (RHMs); NLRP7 that is mutated in 48–60% of patients with RHMs and C6orf221 (HUGO-approved nomenclature is now KHDC3L), a recently identified gene, that is mutated in 14% of patients with RHMs who are negative for NLRP7 mutations. We sequenced KHDC3L in 97 patients with RHMs and reproductive loss who are mostly negative for NLRP7 mutations. We identified three unrelated patients, each homozygous for one of the two protein-truncating mutations, a novel 4-bp deletion resulting in a frameshift, c.299_302delTCAA, p.Ile100Argfs*2, and a previously described 4-bp deletion, c.322_325delGACT, p.Asp108Ilefs*30, transmitted on a shared haplotype to three patients from different populations. We show that five HM tissues from one of these patients are diploid and biparental similar to HMs from patients with two defective NLRP7 mutations. Using immunofluorescence, we show that KHDC3L protein displays a juxta perinuclear signal and colocalizes with NLRP7 in lymphoblastoid cell lines from normal subjects. Using cell lines from patients, we demonstrate that the KHDC3L mutations do not change the subcellular localization of the protein in hematopoietic cells. Our data highlight the similarities between the two causative genes for RHMs, KHDC3L and NLRP7, in their subcellular localization, the parental contribution to the HM tissues caused by them, and the presence of several founder mutations and variants in both of them indicating positive selection and adaptation.
doi:10.1038/ejhg.2012.274
PMCID: PMC3746251  PMID: 23232697
KHDC3L; 4-bp deletion; diploid biparental hydatidiform mole; NLRP7; colocalization
9.  The relationship between Agent Orange and prostate specific antigen: a comparison of a hotspot and a non-sprayed area in Vietnam 
Objectives
The aim of this study was to explore the impact of Agent Orange exposure for prostate cancer with a comparison of the prostate specific antigen (PSA) levels between a hotspot and a non-sprayed area.
Methods
The study was conducted in Phu Cat district (hotspot) and Kim Bang district (non-sprayed), with a total of 101 men in the hotspot and 97 men in the non-sprayed area older than 50 years of age. About 5 mL of whole blood and a health status questionnaire were collected from each subject in August 2009–2011.
Results
The mean age of the subjects in the hotspot (68.0 years old) was significantly higher than that of those in the non-sprayed area (65.0 years old). No significant difference was found between the hotspot area (0.93 ng/mL) and the non-sprayed area (0.95 ng/mL) in terms of PSA levels. Likewise, this was not statistically significant after adjusting for age. The prevalence of high PSA levels (>3 ng/mL) did not differ significantly between the hotspot (14 men; 13.9 %) and non-sprayed area (9 men; 9.3 %). No significant difference was found between the hotspot area and the non-sprayed area in terms of occupation (farmer and others). In control subjects, no significant difference was found between the PSA levels in subjects exposed to Agent Orange and non-exposed subjects. Likewise, no significant difference was found between the PSA levels of combatants and civilians.
Conclusion
The PSA levels were not significantly different between the hotspot and the non-sprayed area.
doi:10.1007/s12199-013-0330-1
PMCID: PMC3773094  PMID: 23526145
Agent Orange; PSA (prostate specific antigen); Prostate cancer; Hotspot; Vietnam
10.  LMA Supreme for neonatal resuscitation: study protocol for a randomized controlled trial 
Trials  2014;15:285.
Background
The most important action in the resuscitation of a newborn in the delivery room is to establish effective assisted ventilation. The face mask and endotracheal tube are the devices used to achieve this goal. Laryngeal mask airways that fit over the laryngeal inlet have been shown to be effective for ventilating newborns at birth and should be considered as an alternative to facemask ventilation or endotracheal intubation among newborns weighing >2,000 g or delivered ≥34 weeks’ gestation. A recent systematic review and meta-analysis of supraglottic airways in neonatal resuscitation reported the results of four randomized controlled trials (RCTs) stating that fewer infants in the group using laryngeal mask airways required endotracheal intubation (1.5%) compared to the group using face masks (12.0%). However, there were methodological concerns over all the RCTs including the fact that the majority of the operators in the trials were anesthesiologists.
Our hypothesis is based on the assumption that ventilating newborns needing positive pressure ventilation with a laryngeal mask airway will be more effective than ventilating with a face mask in a setting where neonatal resuscitation is performed by midwives, nurses, and pediatricians. The primary aim of this study will be to assess the effectiveness of the laryngeal mask airway over the face mask in preventing the need for endotracheal intubation.
Methods/design
This will be an open, prospective, randomized, single center, clinical trial. In this study, 142 newborns weighing >1,500 g or delivered ≥34 weeks gestation needing positive pressure ventilation at birth will be randomized to be ventilated with a laryngeal mask airway (LMA SupremeTM, LMA Company, UK - intervention group) or with a face mask (control group). Primary outcome: Proportion of newborns needing endotracheal intubation. Secondary outcomes: Apgar score at 5 minutes, time to first breath, onset of the first cry, duration of resuscitation, death or moderate to severe hypoxic-ischemic encephalopathy within 7 days of life.
Trial registration
ClinicalTrials.gov identifier: NCT01963936 (October 11, 2013).
doi:10.1186/1745-6215-15-285
PMCID: PMC4223364  PMID: 25027230
Laryngeal mask; Resuscitation; Positive pressure ventilation; Newborn infant
11.  Evaluating Proton Stereotactic Body Radiotherapy to Reduce Chest Wall Dose in the Treatment of Lung Cancer 
Purpose
Stereotactic body radiotherapy (SBRT) can produce excellent local control of several types of solid tumor; however, toxicity to nearby critical structures is a concern. We found previously that in SBRT for lung cancer, the chest wall (CW) volume receiving 20, 30, or 40 Gy (V20, V30, or V40) was linked with the development of neuropathy. Here we sought to determine whether the dosimetric advantages of protons could produce lower CW doses than traditional photon-based SBRT.
Methods
We searched an institutional database to identify patients treated with photon SBRT for lung cancer with tumors within <2.5 cm of the CW. We found 260 cases; of these chronic grade ≥2 CW pain was identified in 23 patients. We then selected 10 representative patients from this group and generated proton SBRT treatment plans, using the identical dose of 50 Gy in 4 fractions, and assessed potential differences in CW dose between the two plans.
Results
The proton SBRT plans reduced the CW doses at all dose levels measured. The median CW V was 364.0 cm320 for photons and 160.0 cm3 for protons (P<0.0001); V30 was 144.6 cm3 for photons vs. 77.0 cm3 for protons (P=0.0012); V was 93.9 cm335 for photons vs. 57.9 cm3 for protons (P=0.005); V40 was 66.5 cm3 for photons vs. 45.4 cm3 for protons (P=0.0112); and mean lung dose was 5.9 Gy for photons vs. 3.8 Gy for protons (P=0.0001). Coverage of the planning target volume was comparable between the two sets of plans (96.4% for photons and 97% for protons).
Conclusions
From a dosimetric standpoint, proton SBRT can achieve the same coverage of the PTV while significantly reducing the dose to the CW and lung relative to photon SBRT and therefore may be beneficial for the treatment of lesions close to critical structures.
doi:10.1016/j.meddos.2013.08.001
PMCID: PMC4086145  PMID: 24200220
Stereotactic body radiation therapy; protons; normal tissue toxicity; lung cancer
12.  Epidemiological and clinical characteristics of children who died from hand, foot and mouth disease in Vietnam, 2011 
BMC Infectious Diseases  2014;14:341.
Background
In 2011, a large outbreak of hand, foot and mouth disease (HFMD) in Vietnam resulted in 113,121 children seeking medical attention, of whom170 died. Understanding the epidemiology of fatal HFMD may improve treatment and help targeting prevention activities for vulnerable populations. We describe epidemiological and clinical characteristics of children who died from HFMD in Vietnam in 2011.
Methods
Clinical data were obtained through reviewing medical records of the deaths occurring from January through December 2011 in all hospitals in Vietnam. Hospitals reported any deaths among patients with laboratory-confirmed enterovirus (EV) infection to the Ministry of Health. Data were extracted from the national database.
Results
Of the 169 deaths reviewed for whom records were available, 87% were 3-year-old or younger, 69% were male, 18% attended daycare, 89% lived in Southern Vietnam, and 85% of the deaths occurred between May-October 2011. One hundred thirty (77%) cases sought treatment in a hospital within three days of onset of illness. Symptoms at admission included fever (98%), myoclonus (66%), vomiting (53%), oral ulcers (50%) and vesicular erythema (50%). One hundred six (75%) cases had leukocytosis and 91 (54%) had hyperglycemia. One hundred three (61%) tested positive for EV, of which 84 (82%) were positive for EV71.
Conclusions
Deaths associated with HFMD occurred throughout 2011 among males three years or younger who were cared for at home. The HFMD control program should focus on interventions at the household level. Clinicians should be alerted to symptoms suggestive of severe HFMD including fever, myoclonus, vomiting, oral ulcers and vesicles with high white blood cell count especially in young children.
doi:10.1186/1471-2334-14-341
PMCID: PMC4068316  PMID: 24942066
Hand foot and mouth disease; Clinical manifestation; Enterovirus; Vietnam
13.  The relationship between dioxins and salivary steroid hormones in Vietnamese primiparae 
Objective
Nearly 40 years after Agent Orange was last sprayed, we conducted a cross-sectional study to evaluate the impact of dioxin exposure on salivary hormones in Vietnamese primiparae. Our previous studies found higher levels of salivary cortisol and cortisone in one of the most highly dioxin-contaminated areas, known as a “hot-spot”, than in a non-exposed area. As a result, we suggested that further research with a larger number of participants would be needed to confirm whether dioxin affects steroid hormone levels in Vietnamese primiparae.
Methods
The concentration of steroid hormones in saliva was determined by liquid chromatography (electrospray ionization tandem mass spectrometry), whereas the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in breast milk were determined by gas chromatography-high resolution mass spectrometry, for a sample of the population from a “hot-spot” (n = 16) and a non-exposed area (n = 10). All subjects were aged between 20 and 30 years and had children aged between 4 and 16 weeks.
Results
The mean toxic equivalence of PCDDs, PCDFs and PCDDs + PCDFs in breast milk in the hot-spot area was found to be significantly higher than in the non-exposed area (p < 0.001). Likewise, salivary cortisol, cortisone and dehydroepiandrosterone (DHEA) levels were significantly higher in the hotspot area than in the non-exposed area (p < 0.05). As a result, herein we report, for the first time, that salivary DHEA levels in primiparae are higher in a hot-spot than in a non-exposed area, and that this may be the result of dioxin exposure.
Conclusions
Our findings highlight the long-term effects of Agent Orange/dioxin on steroid hormones in Vietnamese primiparae in the post-war period.
doi:10.1007/s12199-012-0310-x
PMCID: PMC3650178  PMID: 23114996
Dioxin; Breast milk; Saliva; Steroid hormone; Vietnam
14.  The Relationship between Dioxin Congeners in the Breast Milk of Vietnamese Women and Sister Chromatid Exchange 
The aim of this study was to clarify the relationship between dioxin concentrations in breast milk and the sister chromatid exchange (SCE) frequency in women from herbicide-sprayed and non sprayed areas. Blood samples were taken from 21 women with high TCDD (tetrachlorodibenzo-p-dioxin) levels from sprayed areas, 23 women with moderate TCDD levels from sprayed areas, and 19 women from non sprayed areas to determine their SCE frequency. The SCE frequencies for the high and moderate TCDD groups from the sprayed area and for the non sprayed area group were 2.40, 2.19, and 1.48 per cell, respectively. Multiple regression analysis showed that the standardized β values for 1,2,3,6,7,8-hexaCDD (β = 0.60), 1,2,3,4,6,7,8-heptaCDD (β = 0.64), and octaCDD (β = 0.65) were higher than those for TCDD (β = 0.34) and 1,2,3,7,8-pentaCDD (β = 0.42). The adjusted R2 value for polyCDDs (R2 = 0.38) was higher than that for polyCDD toxic equivalents (TEQ (toxic equivalents); R2 = 0.23). This study therefore shows that levels of hexa-, hepta-, and octaCDD, which were previously regarded as being less toxic than TCDD, are closely related to SCE frequency and that the level of dioxin (pg/g lipid) is potentially more useful as an indicator than TEQ value for explaining SCE frequency.
doi:10.3390/ijms15057485
PMCID: PMC4057685  PMID: 24786289
dioxins; furans; congener; sister chromatid exchange; Vietnam
15.  Mammary ductal elongation and myoepithelial migration are regulated by the composition of the extracellular matrix 
Journal of microscopy  2013;251(3):212-223.
Summary
Mammary branching morphogenesis occurs over a period of weeks deep inside an adipocyte-rich stroma. The adipocytes contain light-scattering lipid droplets that limit the depth of penetration of visible light. Organotypic culture methods were developed to enable high-resolution optical monitoring of branching morphogenesis ex vivo. A challenge has been to identify the best culture conditions to model specific developmental events. We recently demonstrated that collagen I induces protrusive invasion in both normal and neoplastic mammary epithelium. In this study, we observed that the abundance of collagen I fibrils correlated strongly with invasive behaviour, even when the collagen I concentration was identical. We found that the extent of fibril assembly was experimentally manipulable by varying the incubation time at 4°C following pH neutralization. We next tested the capacity of collagen I fibrils to induce invasive behaviour when presented in combination with basement membrane proteins (Matrigel). We found that epithelial organoids in mixed gels of collagen I and basement membrane proteins exhibited more extensive branching morphogenesis but did not initiate protrusions into the matrix. Organoids in pure Matrigel produced many small epithelial buds that were bare of myoepithelial cells. Surprisingly, organoids in mixed gels of collagen I and Matrigel produced fewer epithelial buds, the buds elongated further, and the elongating buds remained covered by myoepithelial cells. Our mixed gels therefore provide a more physiologically accurate model of mammary branching morphogenesis. Our results also suggest that changes in the composition of the extracellular matrix could induce migration of epithelial cells past myoepithelial coverage.
doi:10.1111/jmi.12017
PMCID: PMC3978143  PMID: 23432616
Basement membrane; collagen I; extracellular matrix; mammary branching morphogenesis
16.  Study on antibacterial activity of silver nanoparticles synthesized by gamma irradiation method using different stabilizers 
Nanoscale Research Letters  2014;9(1):162.
Colloidal solutions of silver nanoparticles (AgNPs) were synthesized by gamma Co-60 irradiation using different stabilizers, namely polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), alginate, and sericin. The particle size measured from TEM images was 4.3, 6.1, 7.6, and 10.2 nm for AgNPs/PVP, AgNPs/PVA, AgNPs/alginate, and AgNPs/sericin, respectively. The influence of different stabilizers on the antibacterial activity of AgNPs was investigated. Results showed that AgNPs/alginate exhibited the highest antibacterial activity against Escherichia coli (E. coli) among the as-synthesized AgNPs. Handwash solution has been prepared using Na lauryl sulfate as surfactant, hydroxyethyl cellulose as binder, and 15 mg/L of AgNPs/alginate as antimicrobial agent. The obtained results on the antibacterial test of handwash for the dilution to 3 mg AgNPs/L showed that the antibacterial efficiency against E. coli was of 74.6%, 89.8%, and 99.0% for the contacted time of 1, 3, and 5 min, respectively. Thus, due to the biocompatibility of alginate extracted from seaweed and highly antimicrobial activity of AgNPs synthesized by gamma Co-60 irradiation, AgNPs/alginate is promising to use as an antimicrobial agent in biomedicine, cosmetic, and in other fields.
doi:10.1186/1556-276X-9-162
PMCID: PMC3977955  PMID: 24708872
Silver nanoparticles; Gamma irradiation; Antibacterial; E. coli; Handwash
17.  Retardation of arsenic transport through a Pleistocene aquifer 
Nature  2013;501(7466):204-207.
Groundwater drawn daily from shallow alluvial sands by millions of wells over large areas of South and Southeast Asia exposes an estimated population of over 100 million to toxic levels of arsenic (1). Holocene aquifers are the source of widespread arsenic poisoning across the region (2, 3). In contrast, Pleistocene sands deposited in this region more than ~12,000 years ago mostly do not host groundwater with high levels of arsenic. Pleistocene aquifers are increasingly used as a safe source of drinking water (4) and it is therefore important to understand under what conditions low levels of arsenic can be maintained. Here we reconstruct the initial phase of contamination of a Pleistocene aquifer near Hanoi, Vietnam. We demonstrate that changes in groundwater flow conditions and the redox state of the aquifer sands induced by groundwater pumping caused the lateral intrusion of arsenic contamination over 120 m from Holocene aquifer into a previously uncontaminated Pleistocene aquifer. We also find that arsenic adsorbs onto the aquifer sands and that there is a 16–20 fold retardation in the extent of the contamination relative to the reconstructed lateral movement of groundwater over the same period. Our findings suggest that arsenic contamination of Pleistocene aquifers in South and Southeast Asia as a consequence of increasing levels of groundwater pumping have been delayed by the retardation of arsenic transport.
doi:10.1038/nature12444
PMCID: PMC3772538  PMID: 24025840
18.  Diabetes Mellitus Accelerates Cartilaginous Metaplasia and Calcification in Atherosclerotic Vessels of LDLr Mutant Mice 
Background
Vascular calcification is highly prevalent in patients with type II diabetes mellitus (T2DM). Little is known about whether T2DM is causative.
Methods
Low density lipoprotein receptor mutant (LDLr−/−) mice were fed with customized diabetogenic and/or procalcific diets to induce atherosclerosis, cartilaginous metaplasia and calcification, along with obesity, hyperglycemia, hyperinsulinemia, and hypercholesterolemia at various levels, and euthanized for study after 18–24 weeks on diet.
Results
We found that T2DM accelerated cartilaginous and calcific lesion development by ~3- and 13-folds as determined by incidence of vascular cartilaginous metaplasia and calcification in LDLr−/− mice. Lowering dietary fat from ~60% to ~40% kcal reduced body weight and serum glucose and insulin levels, leading to a 2-fold decrease in aortic calcium content. Correlation analysis of calcium content with a calculated insulin resistance index, HOMA-IR, showed a positive correlation of insulin resistance with vascular calcification. Finally, we used genetic fate mapping strategy to trace cells of SM origin in these animals. Vascular SMCs were found to be a major cell source contributing to osteochondrogenic differentiation and calcification. Receptor for advanced glycation end-products (RAGE) was up-regulated, co-localizing with osteochondrogenic SMCs.
Conclusions
Through quantitative measure of aortic calcium content, we provided experimental findings that LDLr−/− mice, like T2DM patients, are predisposed to vascular calcification. Our study is also the first to establish a distinct role of hyperglycemia and hypercholesterolemia in osteochondrogenic differentiation of SMCs and determined these cells as a major source contributing to cartilaginous and calcifying lesions of T2DM blood vessels, possibly mediated by RAGE.
doi:10.1016/j.carpath.2012.06.007
PMCID: PMC3481013  PMID: 22818582
atherosclerosis; receptor for glycation end-products; smooth muscle cells; type 2 diabetes mellitus; vascular calcification
19.  Patellar dislocation due to iatrogenic quadriceps fibrosis: results of operative treatment in 54 cases 
Objective
To evaluate the clinical and functional results of a surgical treatment of patellar dislocation whose etiology was iatrogenic quadriceps fibrosis in children.
Materials and methods
A prospective study was undertaken from February 2004 to December 2009. The study included 54 pediatric patients (56 knees) that had developed dislocation of the patella after repeated intramuscular injections of antibiotic(s) into the quadriceps muscle. There were 11 males (20.4 %) and 43 females (79.6 %). The patients’ mean age at surgery was 7 years, 9 months (range 6 years, 4 months to 12 years, 6 months). A complete history of each patient was recorded. The affected knees were evaluated preoperatively and postoperatively on the basis of the symptoms, signs, and roentgenographic findings. Patellar dislocation was classified according Bensahel’s criteria. All patients had a three-part surgical procedure that combined capsulorrhaphy, quadricepsplasty, and transfer of the vastus medialis oblique to the superior border of the patella.
Results
There has been no poor postsurgical result or recurrence so far; we have noted an ugly scar in nine knees (16.1 %), limitation of the knee flexion in five knees (8.9 %), and loss of extension of 5 °–20 ° in four knees (7.1 %). Overall, we attained excellent results in 39 knees (69.7 %), good results in 13 knees (23.2 %), and fair results in four knees (7.1 %).
Conclusion
In our cases of pediatric dislocation of the patella caused by iatrogenic quadriceps fibrosis, the introduced three-part surgical procedure has shown great success in restoring the realignment mechanism of the patella. The technique is simple, safe, and effective in skeletally immature children.
doi:10.1007/s11832-014-0564-5
PMCID: PMC3935028  PMID: 24510420
Patellar instability; Patellar dislocation; Iatrogenic quadriceps fibrosis; Surgical treatment; Quadricepsplasty; Capsulorrhaphy; Subluxation of the patella; Developmental dysplasia of the patella (DDP); Malformative dislocation
20.  Draft Genome Sequence of Pseudomonas nitroreducens Strain TX1, Which Degrades Nonionic Surfactants and Estrogen-Like Alkylphenols 
Genome Announcements  2014;2(1):e01262-13.
Pseudomonas nitroreducens TX1 ATCC PTA-6168 was isolated from rice field drainage in Taiwan. The bacterium is of special interest because of its capability to use nonionic surfactants (alkylphenol polyethoxylates) and estrogen-like compounds (4-t-octylphenol and 4-nonylphenol) as a sole carbon source. This is the first report on the genome sequence of P. nitroreducens.
doi:10.1128/genomeA.01262-13
PMCID: PMC3907738  PMID: 24482523
21.  Randomised Pharmacokinetic Trial of Rifabutin with Lopinavir/Ritonavir-Antiretroviral Therapy in Patients with HIV-Associated Tuberculosis in Vietnam 
PLoS ONE  2014;9(1):e84866.
Background
Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured.
Methods
This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir.
Results
Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 – 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations.
Conclusions
Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis.
Trial Registration
ClinicalTrials.gov NCT00651066
doi:10.1371/journal.pone.0084866
PMCID: PMC3898920  PMID: 24465443
22.  Targeting Cancer Cells with Reactive Oxygen and Nitrogen Species Generated by Atmospheric-Pressure Air Plasma 
PLoS ONE  2014;9(1):e86173.
The plasma jet has been proposed as a novel therapeutic method for cancer. Anticancer activity of plasma has been reported to involve mitochondrial dysfunction. However, what constituents generated by plasma is linked to this anticancer process and its mechanism of action remain unclear. Here, we report that the therapeutic effects of air plasma result from generation of reactive oxygen/nitrogen species (ROS/RNS) including H2O2, Ox, OH−, •O2, NOx, leading to depolarization of mitochondrial membrane potential and mitochondrial ROS accumulation. Simultaneously, ROS/RNS activate c-Jun NH2-terminal kinase (JNK) and p38 kinase. As a consequence, treatment with air plasma jets induces apoptotic death in human cervical cancer HeLa cells. Pretreatment of the cells with antioxidants, JNK and p38 inhibitors, or JNK and p38 siRNA abrogates the depolarization of mitochondrial membrane potential and impairs the air plasma-induced apoptotic cell death, suggesting that the ROS/RNS generated by plasma trigger signaling pathways involving JNK and p38 and promote mitochondrial perturbation, leading to apoptosis. Therefore, administration of air plasma may be a feasible strategy to eliminate cancer cells.
doi:10.1371/journal.pone.0086173
PMCID: PMC3897664  PMID: 24465942
23.  Genetics and Epigenetics of Recurrent Hydatidiform Moles: Basic Science and Genetic Counselling 
Gestational trophoblastic disease (GTD) is a group of conditions that originate from the abnormal hyperproliferation of trophoblastic cells, which derive from the trophectoderm, the outer layer of the blastocyst that would normally develop into the placenta during pregnancy. GTDs encompass hydatidiform mole (HM) (complete and partial), invasive mole, gestational choriocarcinoma, placental-site trophoblastic tumor, and epithelioid trophoblastic tumor. Of these, the most common is HM, and it is the only one that has been reported to recur in the same patients from independent pregnancies, which indicates the patients’ genetic predisposition. In addition, HM is the only GTD that segregates in families according to Mendel’s laws of heredity, which made it possible to use rare familial cases of recurrent HMs (RHMs) to identify two maternal-effect genes, NLRP7 and KHDC3L, responsible for this condition. Here, we recapitulate current knowledge about RHMs and conclude with the role and benefits of testing patients for mutations in the known genes.
doi:10.1007/s13669-013-0076-1
PMCID: PMC3920063  PMID: 24533231
NLRP7; KHDC3L; Recurrent hydatidiform moles; Genetics; Epigenetics; DNA methylation; GTD; Live birth; Recurrent HMs (RHMs); Gestational choriocarcinoma; Gestational trophoblastic disease; Management of gestational trophoblastic diseases
24.  Rapid and Quantitative Detection of Zoonotic Influenza A Virus Infection Utilizing Coumarin-derived dendrimer-based Fluorescent Immunochromatographic Strip Test (FICT) 
Theranostics  2014;4(12):1239-1249.
Great efforts have been made to develop robust signal-generating fluorescence materials which will help in improving the rapid diagnostic test (RDT) in terms of sensitivity and quantification. In this study, we developed coumarin-derived dendrimer-based fluorescent immunochromatographic strip test (FICT) assay with enhanced sensitivity as a quantitative diagnostic tool in typical RDT environments. The accuracy of the proposed FICT was compared with that of dot blot immunoassay techniques and conventional RDTs. Through conjugation of coumarin-derived dendrimers with latex beads, fluorescent emission covering broad output spectral ranges was obtained which provided a distinct advantage of easy discrimination of the fluorescent emission of the latex beads with a simple insertion of a long-pass optical filter away from the excitation wavelength. The newly developed FICT assay was able to detect 100 ng/10 μL of influenza A nucleoprotein (NP) antigen within 5 minutes, which corresponded to 2.5-fold higher sensitivity than that of the dot blot immunoassay or conventional RDTs. Moreover, the FICT assay was confirmed to detect at least four avian influenza A subtypes (H5N3, H7N1, H7N7, and H9N2). On applying the FICT to the clinical swab samples infected with respiratory viruses, our FICT assay was confirmed to differentiate influenza H1N1 infection from other respiratory viral diseases. These data demonstrate that the proposed FICT assay is able to detect zoonotic influenza A viruses with a high sensitivity, and it enables the quantitation of the infection intensity by providing the numerical diagnostic values; thus demonstrating enhanced detectability of influenza A viruses.
doi:10.7150/thno.10255
PMCID: PMC4184001  PMID: 25285172
Avian influenza A subtype; Fluorescent immunochromatographic strip test (FICT); Conjugation; Latex; Coumarin-derived dendrimer; Dot blot immunoassay.
25.  Processed Vietnamese ginseng: Preliminary results in chemistry and biological activity 
Journal of Ginseng Research  2013;38(2):154-159.
Background
This study was carried out to investigate the effect of the steaming process on chemical constituents, free radical scavenging activity, and antiproliferative effect of Vietnamese ginseng.
Methods
Samples of powdered Vietnamese ginseng were steamed at 120°C for various times and their extracts were subjected to chemical and biological studies.
Results
Upon steaming, contents of polar ginsenosides, such as Rb1, Rc, Rd, Re, and Rg1, were rapidly decreased, whereas less polar ginsenosides such as Rg3, Rg5, Rk1, Rk3, and Rh4 were increased as reported previously. However, ocotillol type saponins, which have no glycosyl moiety at the C-20 position, were relatively stable on steaming. The radical scavenging activity was increased continuously up to 20 h of steaming. Similarly, the antiproliferative activity against A549 lung cancer cells was also increased.
Conclusion
It seems that the antiproliferative activity is closely related to the contents of ginsenoside Rg3, Rg5, and Rk1.
doi:10.1016/j.jgr.2013.11.015
PMCID: PMC3986633  PMID: 24748840
antiproliferation; ginsenoside; Panax vietnamensis; steaming; Vietnamese ginseng

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