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1.  Imaging endocervical mucus anatomy and dynamics in macaque female reproductive track using optical coherence tomography 
Endocervical mucus acts as an important barrier to block human immunodeficiency virus (HIV) infection and other sexually transmitted diseases (STDs). Disruption of the mucus layer increases the risk of infection for females. An effective method to image the mucus properties can serve as a pre-screening step to risk-stratify the susceptible population.
We proposed to use optical coherence tomography (OCT) to quantitatively measure the thickness of endocervical mucus. We used a home-built bench-top OCT system to monitor the dynamic change in mucus thickness of a cultivated sample. We also fabricated a prototype endoscopic OCT probe to demonstrate potential in situ applications.
We observed a 200% increase in the endocervical mucus thickness after cultivating in 37 °C phosphate buffered saline solution for 30 minutes. During mucus hydrolysis, we found that mucus layer thickness decreased to about 60% of its original value after applying neuraminidase. Three dimensional volumetric image of intact macaque inner vaginal wall was also acquired.
We demonstrated that OCT can quantitatively measure the endocervical mucus thickness and its dynamics in ex vivo experiments. Endoscopic OCT has the potential to resolve fine structures inside macaque female reproductive track (FRT) for in vivo applications.
PMCID: PMC4312293
Human immunodeficiency virus (HIV); endocervical mucus; optical coherence tomography (OCT)
2.  Extensive calcifications in portal venous system in a patient with hepatocarcinoma 
World Journal of Gastroenterology : WJG  2014;20(43):16377-16380.
Calcification of the portal venous system is a rare entity that can be incidentally discovered during computed tomography (CT). We describe a case of extensive calcifications in the portal venous system in a middle-aged male patient with hepatocellular carcinoma (HCC). This patient presented with epigastric pain that had no obvious origin prior to admission. Laboratory examinations were positive for hepatitis B surface antigen and α-fetoprotein, and severe esophageal and gastric varices were detected during gastroscopy. Abdominal X-ray plain film showed well-defined linear and track-like calcification, with irregular margins directed along the course of the portal venous system. CT revealed extensive calcifications along the course of the portal, splenic, superior mesenteric and gastroesophageal veins. He underwent splenectomy 22 years ago due to splenomegaly and partial hepatectomy seven months before because of HCC of low-grade differentiation, confirmed by pathology. Finally, the patient was diagnosed with postoperative recurrent HCC and extensive portal venous system calcification after selective hepatic angiography under digital subtraction angiography.
PMCID: PMC4239534  PMID: 25473200
Portal vein; Calcification; Portal hypertension; Hepatocarcinoma; Hepatocellular carcinoma
3.  Characterization of the shrimp neuroparsin (MeNPLP): RNAi silencing resulted in inhibition of vitellogenesis 
FEBS Open Bio  2014;4:976-986.
•This is the first comprehensive study of a neuroparsin in a decapod.•Expression of shrimp neuroparsin (MeNPLP) is different after serotonin (5-HT) treatment.•MeNPLP is most likely a secretary product.•MeNPLP is involved in an early stage of vitellogenesis.
The full-length Metapenaeus ensis neuroparsin (MeNPLP) cDNA was cloned which encodes a shrimp protein homologous to the insect neuroparsin and vertebrate insulin-like growth factor binding protein (IGFBP). MeNPLP cDNA is 1389 bp in length and the longest open reading frame is 303 bp in length. The first 27 aa are predicted to be the signal peptide and aa 28–101 is the mature peptide with an estimated molecular weight of 7.83 kDa and pI of 5. It shows high amino acid sequence similarity (42–68%) to the neuroparsin of insects and N-terminal end of the IGFBP of vertebrates. The cysteine residues in MeNPLP responsible for disulfide bond formation are conserved as in other neuroparsin-like proteins. The expression level of MeNPLP is the highest in the hepatopancreas, followed by the nerve cord, brain, heart, ovary, and muscle. However, it was not expressed in the testis. Using an insect neuroparsin antibody, MeNPLP could only be detected in the hepatopancreatic tubules, suggesting that MeNPLP may be a secretary product. Although MeNPLP expression was stimulated in the ovary, it was inhibited in the hepatopancreas after treatment with neurotransmitter serotonin (5-HT). In vivo gene silencing of MeNPLP could cause a significant decrease of vitellogenin transcript level in the hepatopancreas and ovary. As a result, a corresponding decrease in vitellogenin protein level was observed in the hemolymph and ovary. In conclusion, this study has provided the first evidence that MeNPLP is involved in the initial stage of ovary maturation in shrimp.
PMCID: PMC4244560  PMID: 25431753
5-HT, serotonin; CHH, crustacean hyperglycemic hormone; EST, expressed sequence tag; GSI, gonadosomatic index; IGFBP, insulin-like growth factor binding protein; ITP, ion transport peptide; MeNPLP, Metapenaeus ensis neuroparsin; NP, neuroparsin; Shrimp; Neuroparsin; IGF-like binding protein; RNA interference; Vitellogenin
4.  Relationship between melatonin receptor 1B and insulin receptor substrate 1 polymorphisms with gestational diabetes mellitus: a systematic review and meta-analysis 
Scientific Reports  2014;4:6113.
Studies have investigated the relationship between genetic variants and risk of gestational diabetes mellitus (GDM). However, the results remain inconclusive. The aim of this study was to investigate the association of rs10830963 and rs1387153 variants in melatonin receptor 1B (MTNR1B) and rs1801278 variant in insulin receptor substrate 1 (IRS1) with GDM susceptibility. Electronic database of PubMed, Medline, Embase, and CNKI (China National Knowledge Infrastructure) were searched for relevant studies between 2005 and 2014. The odds ratio (OR) with its 95% confidence interval (CI) were employed to estimate the association. Total ten case-control studies, including 3428 GDM cases and 4637 healthy controls, met the inclusion criteria. Our results showed a significant association between the three genetic variants and GDM risk, rs10830963 with a P-value less than 0.0001, rs1387153 with a P-value of 0.0002, and rs1801278 with a P-value of 0.001. Furthermore, all the genetic models in these three polymorphisms were associated with increased risks of GDM as well (P< = 0.009). In conclusion, our study found that the genetic polymorphisms rs10830963 and rs1387153 in MTNR1B and rs1801278 in IRS1 were associated with an increased risk of developing GDM. However, further studies with gene-gene and gene-environmental interactions should be considered.
PMCID: PMC4141258  PMID: 25146448
5.  BMPRIA Mediated Signaling Is Essential for Temporomandibular Joint Development in Mice 
PLoS ONE  2014;9(8):e101000.
The central importance of BMP signaling in the development and homeostasis of synovial joint of appendicular skeleton has been well documented, but its role in the development of temporomandibular joint (TMJ), also classified as a synovial joint, remains completely unknown. In this study, we investigated the function of BMPRIA mediated signaling in TMJ development in mice by transgenic loss-of- and gain-of-function approaches. We found that BMPRIA is expressed in the cranial neural crest (CNC)-derived developing condyle and glenoid fossa, major components of TMJ, as well as the interzone mesenchymal cells. Wnt1-Cre mediated tissue specific inactivation of BmprIa in CNC lineage led to defective TMJ development, including failure of articular disc separation from a hypoplastic condyle, persistence of interzone cells, and failed formation of a functional fibrocartilage layer on the articular surface of the glenoid fossa and condyle, which could be at least partially attributed to the down-regulation of Ihh in the developing condyle and inhibition of apoptosis in the interzone. On the other hand, augmented BMPRIA signaling by Wnt1-Cre driven expression of a constitutively active form of BmprIa (caBmprIa) inhibited osteogenesis of the glenoid fossa and converted the condylar primordium from secondary cartilage to primary cartilage associated with ectopic activation of Smad-dependent pathway but inhibition of JNK pathway, leading to TMJ agenesis. Our results present unambiguous evidence for an essential role of finely tuned BMPRIA mediated signaling in TMJ development.
PMCID: PMC4122352  PMID: 25093411
6.  Studies of Efficacy and Liver Toxicity Related to Adeno-Associated Virus–Mediated RNA Interference 
Human Gene Therapy  2013;24(8):739-750.
Adeno-associated virus (AAV)–mediated RNA interference shows promise as a therapy for chronic hepatitis B virus (HBV) infection, but its low efficacy and hepatotoxicity pose major challenges. We have generated AAV vectors containing different promoters and a panel of HBV-specific short hairpin RNAs (shRNAs) to investigate factors that contribute to the efficacy and pathogenesis of AAV-mediated RNA interference. HBV transgenic mice injected with high doses of AAV vectors containing the U6 promoter produced abundant shRNAs, transiently inhibited HBV, but induced severe hepatotoxicity. Sustained HBV suppression without liver toxicity can be achieved by lowering the dose of AAV-U6 vectors. AAVs containing the weaker H1 promoter did not cause liver injury, but their therapeutic efficacy was highly dependent on the sequence of the shRNA. Mice treated with the toxic U6-promoter-driven shRNA showed little change in hepatic microRNA levels, but a dramatic increase in hepatic leukocytes and inflammatory cytokines and chemokines. Hepatotoxicity was completely absent in immunodeficient mice and significantly alleviated in wild-type mice depleted of macrophages and granulocytes, suggesting that host inflammatory responses are the major cause of liver injury induced by the overexpressed shRNAs from AAV-U6 vectors. Our results demonstrate that selection of a highly potent shRNA and control its expression level is critical to achieve sustained HBV suppression without inducing inflammatory side effects.
Sun and colleagues generate a panel of AAV vectors containing various promoters and hepatitis B virus (HBV)-specific short hairpin RNAs (shRNAs) to investigate factors that contribute to the efficacy and pathogenesis of AAV-mediated RNA interference. They show that injecting HBV transgenic mice with high doses of AAV vectors containing the U6 promoter produce abundant shRNAs, transiently inhibit HBV, but induce severe hepatotoxicity. By contrast, AAVs containing the weaker H1 promoter do not cause liver injury, but their therapeutic efficacy is highly dependent on the sequence of the shRNA.
PMCID: PMC3747597  PMID: 23829557
7.  Biological pattern and transcriptomic exploration and phylogenetic analysis in the odd floral architecture tree: Helwingia willd 
BMC Research Notes  2014;7:402.
Odd traits in few of plant species usually implicate potential biology significances in plant evolutions. The genus Helwingia Willd, a dioecious medical shrub in Aquifoliales order, has an odd floral architecture-epiphyllous inflorescence. The potential significances and possible evolutionary origin of this specie are not well understood due to poorly available data of biological and genetic studies. In addition, the advent of genomics-based technologies has widely revolutionized plant species with unknown genomic information.
Morphological and biological pattern were detailed via anatomical and pollination analyses. An RNA sequencing based transcriptomic analysis were undertaken and a high-resolution phylogenetic analysis was conducted based on single-copy genes in more than 80 species of seed plants, including H. japonica. It is verified that a potential fusion of rachis to the leaf midvein facilitates insect pollination. RNA sequencing yielded a total of 111450 unigenes; half of them had significant similarity with proteins in the public database, and 20281 unigenes were mapped to 119 pathways. Deduced from the phylogenetic analysis based on single-copy genes, the group of Helwingia is closer with Euasterids II and rather than Euasterids, congruent with previous reports using plastid sequences.
The odd flower architecture make H. Willd adapt to insect pollination by hosting those insects larger than the flower in size via leave, which has little common character that other insect pollination plants hold. Further the present transcriptome greatly riches genomics information of Helwingia species and nucleus genes based phylogenetic analysis also greatly improve the resolution and robustness of phylogenetic reconstruction in H. japonica.
PMCID: PMC4083144  PMID: 24969969
Biological pattern; Helwingia Willd; Phylogenetic analysis; Transcriptome
8.  Hellbender Genome Sequences Shed Light on Genomic Expansion at the Base of Crown Salamanders 
Genome Biology and Evolution  2014;6(7):1818-1829.
Among animals, genome sizes range from 20 Mb to 130 Gb, with 380-fold variation across vertebrates. Most of the largest vertebrate genomes are found in salamanders, an amphibian clade of 660 species. Thus, salamanders are an important system for studying causes and consequences of genomic gigantism. Previously, we showed that plethodontid salamander genomes accumulate higher levels of long terminal repeat (LTR) retrotransposons than do other vertebrates, although the evolutionary origins of such sequences remained unexplored. We also showed that some salamanders in the family Plethodontidae have relatively slow rates of DNA loss through small insertions and deletions. Here, we present new data from Cryptobranchus alleganiensis, the hellbender. Cryptobranchus and Plethodontidae span the basal phylogenetic split within salamanders; thus, analyses incorporating these taxa can shed light on the genome of the ancestral crown salamander lineage, which underwent expansion. We show that high levels of LTR retrotransposons likely characterize all crown salamanders, suggesting that disproportionate expansion of this transposable element (TE) class contributed to genomic expansion. Phylogenetic and age distribution analyses of salamander LTR retrotransposons indicate that salamanders’ high TE levels reflect persistence and diversification of ancestral TEs rather than horizontal transfer events. Finally, we show that relatively slow DNA loss rates through small indels likely characterize all crown salamanders, suggesting that a decreased DNA loss rate contributed to genomic expansion at the clade’s base. Our identification of shared genomic features across phylogenetically distant salamanders is a first step toward identifying the evolutionary processes underlying accumulation and persistence of high levels of repetitive sequence in salamander genomes.
PMCID: PMC4122941  PMID: 25115007
transposable element; genome size evolution; Cryptobranchus; indels; age distribution; phylogeny
9.  A transparent broadband ultrasonic detector based on an optical micro-ring resonator for photoacoustic microscopy 
Scientific Reports  2014;4:4496.
Photoacoustic microscopy (PAM) does not rely on contrast agent to image the optical absorption contrast in biological tissue. It is uniquely suited for measuring several tissue physiological parameters, such as hemoglobin oxygen saturation, that would otherwise remain challenging. Researchers are designing new clinical diagnostic tools and multimodal microscopic systems around PAM to fully unleash its potential. However, the sizeable and opaque piezoelectric ultrasonic detectors commonly used in PAM impose a serious constraint. Our solution is a coverslip-style optically transparent ultrasound detector based on a polymeric optical micro-ring resonator (MRR) with a total thickness of 250 μm. It enables highly-sensitive ultrasound detection over a wide receiving angle with a bandwidth of 140 MHz, which corresponds to a photoacoustic saturation limit of 287 cm−1, at an estimated noise-equivalent pressure (NEP) of 6.8 Pa. We also established a theoretical framework for designing and optimizing the MRR for PAM.
PMCID: PMC3968454  PMID: 24675547
10.  Billions of basepairs of recently expanded, repetitive sequences are eliminated from the somatic genome during copepod development 
BMC Genomics  2014;15:186.
Chromatin diminution is the programmed deletion of DNA from presomatic cell or nuclear lineages during development, producing single organisms that contain two different nuclear genomes. Phylogenetically diverse taxa undergo chromatin diminution — some ciliates, nematodes, copepods, and vertebrates. In cyclopoid copepods, chromatin diminution occurs in taxa with massively expanded germline genomes; depending on species, germline genome sizes range from 15 – 75 Gb, 12–74 Gb of which are lost from pre-somatic cell lineages at germline – soma differentiation. This is more than an order of magnitude more sequence than is lost from other taxa. To date, the sequences excised from copepods have not been analyzed using large-scale genomic datasets, and the processes underlying germline genomic gigantism in this clade, as well as the functional significance of chromatin diminution, have remained unknown.
Here, we used high-throughput genomic sequencing and qPCR to characterize the germline and somatic genomes of Mesocyclops edax, a freshwater cyclopoid copepod with a germline genome of ~15 Gb and a somatic genome of ~3 Gb. We show that most of the excised DNA consists of repetitive sequences that are either 1) verifiable transposable elements (TEs), or 2) non-simple repeats of likely TE origin. Repeat elements in both genomes are skewed towards younger (i.e. less divergent) elements. Excised DNA is a non-random sample of the germline repeat element landscape; younger elements, and high frequency DNA transposons and LINEs, are disproportionately eliminated from the somatic genome.
Our results suggest that germline genome expansion in M. edax reflects explosive repeat element proliferation, and that billions of base pairs of such repeats are deleted from the somatic genome every generation. Thus, we hypothesize that chromatin diminution is a mechanism that controls repeat element load, and that this load can evolve to be divergent between tissue types within single organisms.
PMCID: PMC4029161  PMID: 24618421
Chromatin diminution; Genome size; Transposable elements; Germline-soma differentiation; Copepod
11.  The expression of aquaporins 1 and 5 in rat lung after thoracic irradiation 
Journal of Radiation Research  2014;55(4):683-689.
Radiation-induced lung toxicity (RILT), leading to radiation pneumonia or fibrosis, is a primary problem of radiation therapy. The pathogenesis of RILT remains unclear. In this study, we used a rat model of RILT to examine the expression of aquaporins (AQPs) after radiation injury. Sprague Dawley rats were given a single dose of 17 Gy (dose rate of 3.0 Gy/min) of X-irradiation to the thorax. Rats that survived acute pneumonitis (at 1–4 weeks) were evaluated weekly for the expression of AQP1 and AQP5 in the lung by immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR) analyses. Immunohistochemical analysis showed that AQP1 protein was expressed in the capillary endothelium, and its level was significantly decreased after irradiation. AQP5 protein was expressed in the alveolar epithelium, and its level was increased between Days 7 and 14 after irradiation but decreased at Day 28, compared with the sham group. The RT-PCR results were consistent with the immunohistochemical analysis results. In summary, this study provides the first report of AQP1 and AQP5 expression in a model of radiation-induced pulmonary inflammation and edema. Decreased levels of AQP1 and AQP5 after irradiation suggest that these proteins play a role in the pathogenesis of RILT.
PMCID: PMC4100000  PMID: 24570172
radiation-induced lung toxicity; AQP1; AQP5
Nature medicine  2011;17(3):356-365.
To date, our understanding of the role of X-Box Binding Protein 1 (XBP1) in metabolic processes was limited to its ability to up-regulate ER folding capacity and thereby, to increase insulin sensitivity. Here, we demonstrate that XBP1s interacts with Forkhead box O1 (FoxO1) transcription factor and directs it to proteasome-mediated degradation. Our results provide the first evidence that, in addition to its regulatory effects on the ER system and insulin sensitivity, XBP1s can independently regulate glucose homeostasis through its interaction with FoxO1. Indeed, a DNA binding defective mutant of XBP1s, which does not have the ability to increase ER folding capacity, is still capable of reducing blood glucose levels and increasing glucose tolerance in the severely obese and diabetic ob/ob mice. XBP1-mediated degradation of FoxO1 might lead to development of new therapeutic approaches for treatment of type 2 diabetes.
PMCID: PMC3897616  PMID: 21317886
13.  C-Terminal Domain of ICA69 Interacts with PICK1 and Acts on Trafficking of PICK1-PKCα Complex and Cerebellar Plasticity 
PLoS ONE  2013;8(12):e83862.
PICK1 (protein interacting with C-kinase 1) is a PKC (protein kinase C)-binding protein, which is essential for synaptic plasticity. The trafficking of PKCα-PICK1 complex to plasma membrane is critical for the internalization of GluR2 and induction of long-term depression. ICA69 (islet cell autoantigen 69 kDa) is identified as a major binding partner of PICK1. While heteromeric BAR domain complex is suggested to underlie the interaction between PICK1 and ICA69, the role of C-terminal domain of ICA69 (ICAC) in PICK1-ICA69 complex is unknown.
Methodology/Principal Findings
We found that ICAC interacted with PICK1 and regulated the trafficking of PICK1-PKCα complex. ICAC and ΔICAC (containing BAR domain) might function distinctly in the association of ICA69 with PICK1. While ΔICAC domain inclined to form clusters, the distribution of ICAC was diffuse. The trafficking of PICK1 to plasma membrane mediated by activated PKCα was inhibited by ICA69. This action might ascribe to ICAC, because overexpression of ICAC, but not ΔICAC, interrupted PKCα-mediated PICK1 trafficking. Notably, infusion of maltose binding protein (MBP) fusion protein, MBP-ICA69 or MBP-ICAC, in cerebellar Purkinje cells significantly inhibited the induction of long-term depression at parallel fiber- and climbing fiber-Purkinje cell synapses.
Our experiments showed that ICAC is an important domain for the ICA69-PICK1 interaction and plays essential roles in PICK1-mediated neuronal plasticity.
PMCID: PMC3865253  PMID: 24358315
14.  20-Hydroxyeicosatetraenoic Acid Contributes to the Inhibition of K+ Channel Activity and Vasoconstrictor Response to Angiotensin II in Rat Renal Microvessels 
PLoS ONE  2013;8(12):e82482.
The present study examined whether 20-hydroxyeicosatetraenoic acid (HETE) contributes to the vasoconstrictor effect of angiotensin II (ANG II) in renal microvessels by preventing activation of the large conductance Ca2+-activated K+ channel (KCa) in vascular smooth muscle (VSM) cells. ANG II increased the production of 20-HETE in rat renal microvessels. This response was attenuated by the 20-HETE synthesis inhibitors, 17-ODYA and HET0016, a phospholipase A2 inhibitor AACOF3, and the AT1 receptor blocker, Losartan, but not by the AT2 receptor blocker, PD123319. ANG II (10-11 to 10-6 M) dose-dependently decreased the diameter of renal microvessels by 41 ± 5%. This effect was blocked by 17-ODYA. ANG II (10-7 M) did not alter KCa channel activity recorded from cell-attached patches on renal VSM cells under control conditions. However, it did reduce the NPo of the KCa channel by 93.4 ± 3.1% after the channels were activated by increasing intracellular calcium levels with ionomycin. The inhibitory effect of ANG II on KCa channel activity in the presence of ionomycin was attenuated by 17-ODYA, AACOF3, and the phospholipase C (PLC) inhibitor U-73122. ANG II induced a peak followed by a steady-state increase in intracellular calcium concentration in renal VSM cells. 17-ODYA (10-5 M) had no effect on the peak response, but it blocked the steady-state increase. These results indicate that ANG II stimulates the formation of 20-HETE in rat renal microvessels via the AT1 receptor activation and that 20-HETE contributes to the vasoconstrictor response to ANG II by blocking activation of KCa channel and facilitating calcium entry.
PMCID: PMC3853207  PMID: 24324797
15.  Quantitative Imaging of Rapidly Decaying Evanescent Fields Using Plasmonic Near-Field Scanning Optical Microscopy 
Scientific Reports  2013;3:2803.
Non-propagating evanescent fields play an important role in the development of nano-photonic devices. While detecting the evanescent fields in far-field can be accomplished by coupling it to the propagating waves, in practice they are measured in the presence of unwanted propagating background components. It leads to a poor signal-to-noise ratio and thus to errors in quantitative analysis of the local evanescent fields. Here we report on a plasmonic near-field scanning optical microscopy (p-NSOM) technique that incorporates a nanofocusing probe for adiabatic focusing of propagating surface plasmon polaritons at the probe apex, and for enhanced coupling of evanescent waves to the far-field. In addition, a harmonic demodulation technique is employed to suppress the contribution of the background. Our experimental results show strong evidence of background free near-field imaging using the new p-NSOM technique. Furthermore, we present measurements of surface plasmon cavity modes, and quantify their contributing sources using an analytical model.
PMCID: PMC3786296  PMID: 24076563
16.  Sequencing of Culex quinquefasciatus establishes a platform for mosquito comparative genomics 
Arensburger, Peter | Megy, Karine | Waterhouse, Robert M. | Abrudan, Jenica | Amedeo, Paolo | Antelo, Beatriz | Bartholomay, Lyric | Bidwell, Shelby | Caler, Elisabet | Camara, Francisco | Campbell, Corey L. | Campbell, Kathryn S. | Casola, Claudio | Castro, Marta T. | Chandramouliswaran, Ishwar | Chapman, Sinéad B. | Christley, Scott | Costas, Javier | Eisenstadt, Eric | Feshotte, Cedric | Fraser-Liggett, Claire | Guigo, Roderic | Haas, Brian | Hammond, Martin | Hansson, Bill S. | Hemingway, Janet | Hill, Sharon | Howarth, Clint | Ignell, Rickard | Kennedy, Ryan C. | Kodira, Chinnappa D. | Lobo, Neil F. | Mao, Chunhong | Mayhew, George | Michel, Kristin | Mori, Akio | Liu, Nannan | Naveira, Horacio | Nene, Vishvanath | Nguyen, Nam | Pearson, Matthew D. | Pritham, Ellen J. | Puiu, Daniela | Qi, Yumin | Ranson, Hilary | Ribeiro, Jose M. C. | Roberston, Hugh M. | Severson, David W. | Shumway, Martin | Stanke, Mario | Strausberg, Robert | Sun, Cheng | Sutton, Granger | Tu, Zhijian (Jake) | Tubio, Jose Manuel C. | Unger, Maria F. | Vanlandingham, Dana L. | Vilella, Albert J. | White, Owen | White, Jared R. | Wondji, Charles S. | Wortman, Jennifer | Zdobnov, Evgeny M. | Birren, Bruce | Christensen, Bruce M. | Collins, Frank H. | Cornel, Anthony | Dimopoulos, George | Hannick, Linda I. | Higgs, Stephen | Lanzaro, Gregory C. | Lawson, Daniel | Lee, Norman H. | Muskavitch, Marc A. T. | Raikhel, Alexander S. | Atkinson, Peter W.
Science (New York, N.Y.)  2010;330(6000):86-88.
Culex quinquefasciatus (the Southern house mosquito) is an important mosquito vector of viruses such as West Nile virus and St. Louis encephalitis virus as well of nematodes that cause lymphatic filariasis. It is one species within the Culex pipiens species complex and enjoys a distribution throughout tropical and temperate climates of the world. The ability of C. quinquefasciatus to take blood meals from birds, livestock and humans contributes to its ability to vector pathogens between species. We describe the genomic sequence of C. quinquefasciatus, its repertoire of 18,883 protein-coding genes is 22% larger than Ae. aegypti and 52% larger than An. gambiae with multiple gene family expansions including olfactory and gustatory receptors, salivary gland genes, and genes associated with xenobiotic detoxification.
PMCID: PMC3740384  PMID: 20929810
17.  Reductive Degradation of Tetrabromobisphenol Using Iron–Silver and Iron–Nickel Bimetallic Nanoparticles with Microwave Energy 
Environmental Engineering Science  2012;29(6):453-460.
In this work, a novel combined system by Fe-Ag or Fe-Ni nanoparticles and microwave (MW) radiation were used for the debromination of tetrabromobisphenol A (TBBPA) in aqueous solutions. Core-shell structure bimetallic nanoparticles were prepared by replacement reaction in liquid phase and then characterized by X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy techniques. MW radiation can enhance the degradation of TBBPA by Fe-Ag or Fe-Ni observably. The rate of reduction reactions for bimetallic nanoparticles under MW were first compared with those under conventional heating conditions. Compared with nano-iron, the deposition of Ag or Ni also accelerated the debromination, and Fe-Ag was more reactive than Fe-Ni toward TBBPA reduction. Removal efficiencies increased with increasing Fe-Ag dosage and MW energy level. Major reduction products of TBBPA identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) were tri-BBPA, di-BBPA, mono-BBPA, and BPA, which indicated a stepwise debromination process. It provides an effective technology for TBBPA laden wastewater treatment.
PMCID: PMC3363012  PMID: 22693414
debromination; TBBPA; bimetallic; nanoparticles; microwave radiation
18.  NK cells in immunotolerant organs 
Cellular and Molecular Immunology  2013;10(3):202-212.
Organs such as the liver, uterus and lung possess hallmark immunotolerant features, making these organs important for sustaining self-homeostasis. These organs contain a relatively large amount of negative regulatory immune cells, which are believed to take part in the regulation of immune responses. Because natural killer cells constitute a large proportion of all lymphocytes in these organs, increasing attention has been given to the roles that these cells play in maintaining immunotolerance. Here, we review the distribution, differentiation, phenotypic features and functional features of natural killer cells in these immunotolerant organs, in addition to the influence of local microenvironments on these cells and how these factors contribute to organ-specific diseases.
PMCID: PMC4012777  PMID: 23563087
immunotolerance; liver; lung; natural killer cell; uterus
19.  NMR Studies of Localized Water and Protein Backbone Dynamics in Mechanically Strained Elastin 
The journal of physical chemistry. B  2011;115(47):13935-13942.
We report on measurements of the dynamics of localized waters of hydration and the protein backbone of elastin, a remarkable resilient protein found in vertebrate tissues, as a function of the applied external strain. Using deuterium 2D T1–T2 NMR, we separate four reservoirs in the elastin–water system characterized by water with distinguishable mobilities. The measured correlation times corresponding to random tumbling of water localized to the protein is observed to decrease with increasing strain and is interpreted as an increase in its orientational entropy. The NMR T1 and T1ρ relaxation times of the carbonyl and aliphatic carbons of the protein backbone are measured and indicate a reduction in the correlation time as the elastomer strain is increased. It is argued, and supported by MD simulation of a short model elastin peptide [VPGVG]3, that the observed changes in the backbone dynamics give rise to the development of an entropic elastomeric force that is responsible for elastins’ remarkable elasticity.
PMCID: PMC3622950  PMID: 22017547
20.  Complete genome sequencing and analysis of six enterovirus 71 strains with different clinical phenotypes 
Virology Journal  2013;10:115.
Hand, foot and mouth diseases (HFMD) caused by enterovirus 71(EV71) presents a broad spectrum of clinical manifestations ranging from mild febrile disease to fatal neurolocal disease. However, the mechanism of virulence is unknown.
We isolated 6 strains of EV71 from HFMD patients with or without neurological symptoms, and sequenced the whole genomes of the viruses to reveal the virulence factors of EV71.
Phylogenetic tree based on VP1 region showed that all six strains clustered into C4a of C4 sub-genotype. In the complete polypeptide, 298 positions were found to be variable in all strains, and three of these positions (ValP814/IleP814 in VP1, ValP1148/IleP1148 in 3A and Ala P1728/Cys P1728/Val P1728 in 3C) were conserved among the strains with neurovirulence, but variable in strains without neurovirulence. In the 5′-UTR region, it showed that the first 10 nucleotides were mostly conserved, however from the 11th nucleotide, nucleotide insertions and deletions were quite common. The secondary structure prediction of 5′-UTR sequences showed that two of three strains without neurovirulence (SDLY11 and SDLY48) were almost the same, and all strains with neurovirulence (SDLY96, SDLY107 and SDLY153) were different from each other. SDLY107 (a fatal strain) was found different from other strains on four positions (CP241/TP241, AP571/TP571, CP579/TP579 in 5′-UTR and TP7335/CP7335 in 3′-UTR).
The three positions (ValP814/IleP814 in VP1, ValP1148/IleP1148 in 3A and Ala P1728/Cys P1728/Val P1728 in 3C), were different between two phenotypes. These suggested that the three positions might be potential virulent positions. And the three varied positions were also found to be conserved in strains with neurovirulence, and variable in strains without neurovirulence. These might reveal that the conservation of two of the three positions or the three together were specific for the strains with neurovirulence. Varation of secondary structure of 5′-UTR, might be correlated to the changes of viral virulence. SDLY107 (a fatal strain) was found different from other strains on four positions, these positions might be related with death.
PMCID: PMC3669102  PMID: 23577963
Enterovirus 71; Virulent determinant; Hand, foot and mouth disease
21.  Genome-wide identification, classification and expression profiling of nicotianamine synthase (NAS) gene family in maize 
BMC Genomics  2013;14:238.
Nicotianamine (NA), a ubiquitous molecule in plants, is an important metal ion chelator and the main precursor for phytosiderophores biosynthesis. Considerable progress has been achieved in cloning and characterizing the functions of nicotianamine synthase (NAS) in plants including barley, Arabidopsis and rice. Maize is not only an important cereal crop, but also a model plant for genetics and evolutionary study. The genome sequencing of maize was completed, and many gene families were identified. Although three NAS genes have been characterized in maize, there is still no systematic identification of maize NAS family by genomic mining.
In this study, nine NAS genes in maize were identified and their expression patterns in different organs including developing seeds were determined. According to the evolutionary relationship and tissue specific expression profiles of ZmNAS genes, they can be subgrouped into two classes. Moreover, the expression patterns of ZmNAS genes in response to fluctuating metal status were analysed. The class I ZmNAS genes were induced under Fe deficiency and were suppressed under Fe excessive conditions, while the expression pattern of class II genes were opposite to class I. The complementary expression patterns of class I and class II ZmNAS genes confirmed the classification of this family. Furthermore, the histochemical localization of ZmNAS1;1/1;2 and ZmNAS3 were determined using in situ hybridization. It was revealed that ZmNAS1;1/1;2, representing the class I genes, mainly expressed in cortex and stele of roots with sufficient Fe, and its expression can expanded in epidermis, as well as shoot apices under Fe deficient conditions. On the contrary, ZmNAS3, one of the class II genes, was accumulated in axillary meristems, leaf primordia and mesophyll cells. These results suggest that the two classes of ZmNAS genes may be regulated on transcriptional level when responds to various demands for iron uptake, translocation and homeostasis.
These results provide significant insights into the molecular bases of ZmNAS in balancing iron uptake, translocation and homeostasis in response to fluctuating environmental Fe status.
PMCID: PMC3637603  PMID: 23575343
Maize; Nicotianamine synthase; Gene family; Iron uptake and homeostasis; Subcellular localization; Expression profiling; In situ hybridization
22.  Thermal hysteresis in the backbone and side chain dynamics of the elastin mimetic peptide [VPGVG]3 revealed by 2H NMR 
We report on experimental measurements of the backbone and side chain dynamics of the elastin mimetic peptide [VPGVG]3 by 2H NMR echo spectroscopy and 2D T1-T2 correlation relaxometry. The T1 and T2 relaxation times of the Gly α-deuterons and Val α-, β- and γ- deuterons of a hydrated sample reveal a thermal hysteresis when the temperature is raised from −10°C to 45°C and then subsequently cooled back to −10°C. In addition, near 30°C we observe a reduction in the slope of the T1(T) and T2(T) heating curves, indicating a structural change that appears to be correlated well to the known inverse temperature transition of this peptide. The thermal dependence of the correlation times of the Gly α-deuterons are well fit by an Arrhenius Law, from which we have measured Eact =(20.0 ± 3.1) kJ/mol when the sample is heated, and Eact =(10.9 ± 2.8) kJ/mol when cooled. Molecular dynamics simulations support the notion that the measured activation energy is determined largely by the extent of localized water, which is observed to decrease with increasing temperature from approximately 25°C to 42°C.
PMCID: PMC3257400  PMID: 22142235
23.  Highly Efficient Light-Trapping Structure Design Inspired By Natural Evolution 
Scientific Reports  2013;3:1025.
Recent advances in nanophotonic light trapping open up the new gateway to enhance the absorption of solar energy beyond the so called Yablonovitch Limit. It addresses the urgent needs in developing low cost thin-film solar photovoltaic technologies. However, current design strategy mainly relies on the parametric approach that is subject to the predefined topological design concepts based on physical intuition. Incapable of dealing with the topological variation severely constrains the design of optimal light trapping structure. Inspired by natural evolution process, here we report a design framework driven by topology optimization based on genetic algorithms to achieve a highly efficient light trapping structure. It has been demonstrated that the optimal light trapping structures obtained in this study exhibit more than 3-fold increase over the Yablonovitch Limit with the broadband absorption efficiency of 48.1%, beyond the reach of intuitive designs.
PMCID: PMC3535673  PMID: 23289067
24.  Slow DNA Loss in the Gigantic Genomes of Salamanders 
Genome Biology and Evolution  2012;4(12):1340-1348.
Evolutionary changes in genome size result from the combined effects of mutation, natural selection, and genetic drift. Insertion and deletion mutations (indels) directly impact genome size by adding or removing sequences. Most species lose more DNA through small indels (i.e., ∼1–30 bp) than they gain, which can result in genome reduction over time. Because this rate of DNA loss varies across species, small indel dynamics have been suggested to contribute to genome size evolution. Species with extremely large genomes provide interesting test cases for exploring the link between small indels and genome size; however, most large genomes remain relatively unexplored. Here, we examine rates of DNA loss in the tetrapods with the largest genomes—the salamanders. We used low-coverage genomic shotgun sequence data from four salamander species to examine patterns of insertion, deletion, and substitution in neutrally evolving non-long terminal repeat (LTR) retrotransposon sequences. For comparison, we estimated genome-wide DNA loss rates in non-LTR retrotransposon sequences from five other vertebrate genomes: Anolis carolinensis, Danio rerio, Gallus gallus, Homo sapiens, and Xenopus tropicalis. Our results show that salamanders have significantly lower rates of DNA loss than do other vertebrates. More specifically, salamanders experience lower numbers of deletions relative to insertions, and both deletions and insertions are skewed toward smaller sizes. On the basis of these patterns, we conclude that slow DNA loss contributes to genomic gigantism in salamanders. We also identify candidate molecular mechanisms underlying these differences and suggest that natural variation in indel dynamics provides a unique opportunity to study the basis of genome stability.
PMCID: PMC3542557  PMID: 23175715
indel spectrum; insertion; deletion; mutation; genome size; transposable element
25.  Correction: Cytosolic Phospholipase A2 alpha/Arachidonic Acid Signaling Mediates Depolarization-Induced Suppression of Excitation in the Cerebellum 
PLoS ONE  2012;7(11):10.1371/annotation/d08032c8-4a27-4c9c-8ef7-b3ec64351cde.
PMCID: PMC3552745

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