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2.  Draft Genome Sequences of Type Strains Bacillus drentensis DSM 15600T and Bacillus novalis DSM 15603T 
Genome Announcements  2016;4(6):e01423-16.
Here, we report the draft genome sequences of Bacillus drentensis DSM 15600T and Bacillus novalis DSM 15603T with 5,305,306 bp and 5,667,584 bp, respectively, which will provide useful information for the functional gene mining and application of these two species. The average DNA G+C contents were 38.91% and 40.01%, respectively.
PMCID: PMC5159591  PMID: 27979958
3.  Association between neutrophilic granulocyte percentage and depression in hospitalized patients with heart failure 
BMC Psychiatry  2016;16:446.
Previous researches reveal that depression is associated with increased inflammatory markers. As a simple and cheap inflammatory marker, we hypothesize that neutrophilic granulocyte percentage is associated with depression in hospitalized heart failure patients, whose prevalence of depression is at a very high level.
Three hundred sixty-six cases of hospitalized heart failure patients with left ventricular ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) class II-IV were enrolled. All the enrolled patients received Hamilton Rating Scale for Depression (24-items) (HAM-D24). The demographic, clinical data, blood samples and echocardiography were documented. The Pearson simple linear correlation was performed to evaluate the confounding factors correlated with HAM-D24 depression index. The significantly correlated factors were enrolled as independent variables in Logistic regression to determine the risk or protective factors for depression, which was taken as dependent variable.
Two hundred ten cases of hospitalized heart failure patients (57.4%) had depression. Among them, 134 patients (63.8%) had mild depression, 58 patients (27.6%) had moderate depression and 18 patients (8.6%) had severe depression. Pearson simple linear correlation revealed that in hospitalized patients with heart failure, the neutrophils granulocyte percentage was positively correlated with the HAM-D24 depression index (r = .435, p < .001). After the adjustment of age, BMI, number of members of the household, smoking index, New York Heart Association (NYHA) classification, hemoglobin, TC, LDL-C, creatinine, cystatin-C, TBIL and albumin, the neutrophils granulocyte percentage is still significantly associated with depression in hospitalized heart failure patients (OR = 1.046, p < .001).
The neutrophils granulocyte percentage may be used as a new marker for depression in hospitalized heart failure patients.
PMCID: PMC5154115  PMID: 27955661
Neutrophilic granulocyte percentage; Depression; Hospitalized heart failure
4.  Channel morphology effect on water transport through graphene bilayers 
Scientific Reports  2016;6:38583.
The application of few-layered graphene-derived functional thin films for molecular filtration and separation has recently attracted intensive interests. In practice, the morphology of the nanochannel formed by the graphene (GE) layers is not ideally flat and can be affected by various factors. This work investigates the effect of channel morphology on the water transport behaviors through the GE bilayers via molecular dynamics simulations. The simulation results show that the water flow velocity and transport resistance highly depend on the curvature of the graphene layers, particularly when they are curved in non-synergic patterns. To understand the channel morphology effect, the distributions of water density, dipole moment orientation and hydrogen bonds inside the channel are investigated, and the potential energy surface with different distances to the basal GE layer is analyzed. It shows that the channel morphology significantly changes the distribution of the water molecules and their orientation and interaction inside the channel. The energy barrier for water molecules transport through the channel also significantly depends on the channel morphology.
PMCID: PMC5144085  PMID: 27929106
5.  Comparison of the first three waves of avian influenza A(H7N9) virus circulation in the mainland of the People’s Republic of China 
BMC Infectious Diseases  2016;16:734.
H7N9 human cases were first detected in mainland China in March 2013. Circulation of this virus has continued each year shifting to typical winter months. We compared the clinical and epidemiologic characteristics for the first three waves of virus circulation.
The first wave was defined as reported cases with onset dates between March 31-September 30, 2013, the second wave was defined as October 1, 2013-September 30, 2014 and the third wave was defined as October 1, 2014-September 30, 2015. We used simple descriptive statistics to compare characteristics of the three distinct waves of virus circulation.
In mainland China, 134 cases, 306 cases and 219 cases were detected and reported in first three waves, respectively. The median age of cases was statistically significantly older in the first wave (61 years vs. 56 years, 56 years, p < 0.001) compared to the following two waves. Most reported cases were among men in all three waves. There was no statistically significant difference between case fatality proportions (33, 42 and 45%, respectively, p = 0.08). There were no significant statistical differences for time from illness onset to first seeking healthcare, hospitalization, lab confirmation, initiation antiviral treatment and death between the three waves. A similar percentage of cases in all waves reported exposure to poultry or live poultry markets (87%, 88%, 90%, respectively). There was no statistically significant difference in the occurrence of severe disease between the each of the first three waves of virus circulation. Twenty-one clusters were reported during these three waves (4, 11 and 6 clusters, respectively), of which, 14 were considered to be possible human-to-human transmission.
Though our case investigation for the first three waves found few differences between the epidemiologic and clinical characteristics, there is continued international concern about the pandemic potential of this virus. Since the virus continues to circulate, causes more severe disease, has the ability to mutate and become transmissible from human-to-human, and there is limited natural protection from infection in communities, it is critical that surveillance systems in China and elsewhere are alert to the influenza H7N9 virus.
PMCID: PMC5139097  PMID: 27919225
Avian influenza; H7N9; China; Pandemic
6.  A Murine Abdominal Aortic Aneurysm Model by Orthotopic Allograft Transplantation of Elastase-treated Abdominal Aorta 
Journal of vascular surgery  2014;62(6):1607-1614.e2.
Murine models have proven instrumental in studying various aspects of abdominal aortic aneurysm (AAA) ranging from identification of underlying pathophysiology to the development of novel therapeutic strategies. In the current study, we describe a new model in which an elastase-treated donor aorta is transplanted to a recipient mouse and allowed to progress to aneurysm. We hypothesized that by transplanting an elastase-treated abdominal aorta of one genotype to a recipient mouse of a different genotype, one can differentiate pathophysiological factors that are intrinsic to the aortic wall from those stemming from circulation and other organs.
Elastase-treated aorta was transplanted to the infrarenal abdominal aorta of recipient mice by end-to-side microsurgical anastomosis. Heat inactivated elastase-treated aorta was used as a control. Syngeneic transplants were performed using 12-week-old C57BL/6 littermates. Transplant grafts were harvested from recipient mice on day 7 or 14 post-surgery. The aneurysm outcome was measured by aortic expansion, elastin degradation, pro-inflammatory cytokine expression, and inflammatory cell infiltration and compared to that produced with the established, conventional elastase-infusion model.
The surgical technique success rate was 75.6%, and the 14-day survival rate was 51.1%. By Day 14 post-surgery all of the elastase-treated transplanted abdominal aorta had dilated and progressed to AAAs defined as 100% or more increase in the maximal external diameter compared to that measured before elastase perfusion, while none of the transplanted aortas pre-treated with inactive elastase became aneurysmal (percentage increase in maximum aortic diameter: 159.36±23.27% (transplanted elastase) vs. 41.46±9.34% (transplanted inactive elastase). Aneurysm parameters, including elastin degradation, infiltration of macrophages and T lymphocytes were found to be identical to those observed in the conventional elastase model. Quantitative PCR analysis revealed similarly increased levels of pro-inflammatory cytokines (relative changes of mRNA in the conventional elastase model versus transplant model: Tumor Necrosis Factor alpha, TNF-α 1.71±0.27 vs. 2.93±0.86; Monocyte Chemoattractant Protein-1, MCP-1 2.36±0.58 vs. 2.87±0.51; Chemokine (C-C motif) ligand 5, CCL5 3.37±0.92 vs. 3.46±0.83; and Interferon gamma, IFN-γ 3.09±0.83 vs. 5.30±1.69). Utilizing Green Fluorescent Protein (GFP) transgenic mice as either donors or recipients, we demonstrated a small quantity of mononuclear leukocytes in the transplant grafts bared the genotype of the donors.
Transplanted elastase-treated abdominal aorta could develop to aneurysm in recipient mice. This AAA transplant model can be used to examine if and how the microenvironment of a transplanted aneurysmal aorta can be altered by the contributions of the ‘global’ environment of the recipient.
PMCID: PMC4277509  PMID: 24974783
7.  Expansion and Hepatic Differentiation of Adult Blood-Derived CD34+ Progenitor Cells and Promotion of Liver Regeneration After Acute Injury 
A new group of blood-derived CD34+ progenitor cells (BDPCs) with the ability to expand and differentiate into functional hepatocyte-like cells and promote liver regeneration is reported. With their ease of access, application through the peripheral blood, and the capability of rapid expansion and hepatic differentiation, BDPCs have great potential as a cell-based therapy for liver disease.
The low availability of functional hepatocytes has been an unmet demand for basic scientific research, new drug development, and cell-based clinical applications for decades. Because of the inability to expand hepatocytes in vitro, alternative sources of hepatocytes are a focus of liver regenerative medicine. We report a new group of blood-derived CD34+ progenitor cells (BDPCs) that have the ability to expand and differentiate into functional hepatocyte-like cells and promote liver regeneration. BDPCs were obtained from the peripheral blood of an adult mouse with expression of surface markers CD34, CD45, Sca-1, c-kit, and Thy1.1. BDPCs can proliferate in vitro and differentiate into hepatocyte-like cells expressing hepatocyte markers, including CK8, CK18, CK19, α-fetoprotein, integrin-β1, and A6. The differentiated BDPCs (dBDPCs) also display liver-specific functional activities, such as glycogen storage, urea production, and albumin secretion. dBDPCs have cytochrome P450 activity and express specific hepatic transcription factors, such as hepatic nuclear factor 1α. To demonstrate liver regenerative activity, dBDPCs were injected into mice with severe acute liver damage caused by a high-dose injection of carbon tetrachloride (CCl4). dBDPC treatment rescued the mice from severe acute liver injury, increased survival, and induced liver regeneration. Because of their ease of access and application through peripheral blood and their capability of rapid expansion and hepatic differentiation, BDPCs have great potential as a cell-based therapy for liver disease.
Hematopoietic stem/progenitor cell expansion and tissue-specific differentiation in vitro are challenges in regenerative medicine, although stem cell therapy has raised hope for the treatment of liver diseases by overcoming the scarcity of hepatocytes. This study identified and characterized a group of blood-derived progenitor cells (BDPCs) from the peripheral blood of an adult mouse. The CD34+ progenitor-dominant BDPCs were rapidly expanded and hepatically differentiated into functional hepatocyte-like cells with our established coculture system. BDPC treatment increased animal survival and produced full regeneration in a severe liver injury mouse model caused by CCl4. BDPCs could have potential for liver cell therapies.
PMCID: PMC4878335  PMID: 27075766
CD34+; Cellular therapy; Hepatocyte differentiation; Liver regeneration; Hematopoietic progenitors; Adult stem cells
8.  Homocysteine Activates B Cells via Regulating PKM2-Dependent Metabolic Reprogramming 
The overactivation of immune cells plays an important role in the pathogenesis of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis. Homocysteine (Hcy) activates B cell proliferation and Ab secretion; however, the underlying mechanisms for these effects remain largely unknown. Metabolic reprogramming is critical for lymphocyte activation and effector function. In this study, we showed that Hcy-activated B cells displayed an increase in both oxidative phosphorylation and glycolysis, with a tendency to shift toward the latter, as well as an accumulation of intermediates in the pentose phosphate pathway, to provide energy and biosynthetic substrates for cell growth and function. Mechanistically, Hcy increased both the protein expression and glycolytic enzyme activity of the pyruvate kinase muscle isozyme 2 (PKM2) in B cells, whereas the PKM2 inhibitor shikonin restored Hcy-induced metabolic changes, as well as B cell proliferation and Ab secretion both in vivo and in vitro, indicating that PKM2 plays a critical role in metabolic reprogramming in Hcy-activated B cells. Further investigation revealed that the Akt–mechanistic target of rapamycin signaling pathway was involved in this process, as the mechanistic target of rapamycin inhibitor rapamycin inhibited Hcy-induced changes in PKM2 enzyme activity and B cell activation. Notably, shikonin treatment effectively attenuated HHcy-accelerated atherosclerotic lesion formation in apolipoprotein E–deficient mice. In conclusion, our results demonstrate that PKM2 is required to support metabolic reprogramming for Hcy-induced B cell activation and function, and it might serve as a critical regulator in HHcy-accelerated initiation of atherosclerosis.
PMCID: PMC5164882  PMID: 27903739
9.  An intrinsic agonist mechanism for activation of glucagon-like peptide-1 receptor by its extracellular domain 
Cell Discovery  2016;2:16042-.
The glucagon-like peptide-1 receptor is a class B G protein coupled receptor (GPCR) that plays key roles in glucose metabolism and is a major therapeutic target for diabetes. The classic two-domain model for class B GPCR activation proposes that the apo-state receptor is auto-inhibited by its extracellular domain, which physically interacts with the transmembrane domain. The binding of the C-terminus of the peptide hormone to the extracellular domain allows the N-terminus of the hormone to insert into the transmembrane domain to induce receptor activation. In contrast to this model, here we demonstrate that glucagon-like peptide-1 receptor can be activated by N-terminally truncated glucagon-like peptide-1 or exendin-4 when fused to the receptor, raising the question regarding the role of N-terminal residues of peptide hormone in glucagon-like peptide-1 receptor activation. Mutations of cysteine 347 to lysine or arginine in intracellular loop 3 transform the receptor into a G protein-biased receptor and allow it to be activated by a nonspecific five-residue linker that is completely devoid of exendin-4 or glucagon-like peptide-1 sequence but still requires the presence of an intact extracellular domain. Moreover, the extracellular domain can activate the receptor in trans in the presence of an intact peptide hormone, and specific mutations in three extracellular loops abolished this extracellular domain trans-activation. Together, our data reveal a dominant role of the extracellular domain in glucagon-like peptide-1 receptor activation and support an intrinsic agonist model of the extracellular domain, in which peptide binding switches the receptor from the auto-inhibited state to the auto-activated state by releasing the intrinsic agonist activity of the extracellular domain.
PMCID: PMC5118412  PMID: 27917297
GLP-1R; class B GPCR; intrinsic agonist; glucagon-like peptide-1; exendin-4; BETP
10.  Local CXCR4 Upregulation in the Injured Arterial Wall Contributes to Intimal Hyperplasia 
Stem Cells (Dayton, Ohio)  2016;34(11):2744-2757.
CXCR4 is a stem/progenitor cell surface receptor specific for the cytokine stromal cell‐derived factor‐1 (SDF‐1α). There is evidence that bone marrow‐derived CXCR4‐expressing cells contribute to intimal hyperplasia (IH) by homing to the arterial subintima which is enriched with SDF‐1α. We have previously found that transforming growth factor‐β (TGFβ) and its signaling protein Smad3 are both upregulated following arterial injury and that TGFβ/Smad3 enhances the expression of CXCR4 in vascular smooth muscle cells (SMCs). It remains unknown, however, whether locally induced CXCR4 expression in SM22 expressing vascular SMCs plays a role in neointima formation. Here, we investigated whether elevated TGFβ/Smad3 signaling leads to the induction of CXCR4 expression locally in the injured arterial wall, thereby contributing to IH. We found prominent CXCR4 upregulation (mRNA, 60‐fold; protein, 4‐fold) in TGFβ‐treated, Smad3‐expressing SMCs. Chromatin immunoprecipitation assays revealed a specific association of the transcription factor Smad3 with the CXCR4 promoter. TGFβ/Smad3 treatment also markedly enhanced SDF‐1α‐induced ERK1/2 phosphorylation as well as SMC migration in a CXCR4‐dependent manner. Adenoviral expression of Smad3 in balloon‐injured rat carotid arteries increased local CXCR4 levels and enhanced IH, whereas SMC‐specific depletion of CXCR4 in the wire‐injured mouse femoral arterial wall produced a 60% reduction in IH. Our results provide the first evidence that upregulation of TGFβ/Smad3 in injured arteries induces local SMC CXCR4 expression and cell migration, and consequently IH. The Smad3/CXCR4 pathway may provide a potential target for therapeutic interventions to prevent restenosis. Stem Cells 2016;34:2744–2757
PMCID: PMC5113668  PMID: 27340942
CXCR4/SDF‐1α; TGFβ/Smad3; smooth muscle cell migration; smooth muscle cell specific CXCR4 knockout; intimal hyperplasia
11.  MicroRNA-93 Promotes Epithelial–Mesenchymal Transition of Endometrial Carcinoma Cells 
PLoS ONE  2016;11(11):e0165776.
MicroRNA-93, derived from a paralog (miR-106b-25) of the miR-17-92 cluster, is involved in the tumorigenesis and progression of many cancers such as breast, colorectal, hepatocellular, lung, ovarian, and pancreatic cancer. However, the role of miR-93 in endometrial carcinoma and the potential molecular mechanisms involved remain unknown. Our results showed that miR-93 was overexpressed in endometrial carcinoma tissues than normal endometrial tissues. The endometrial carcinoma cell lines HEC-1B and Ishikawa were transfected with miR-93-5P, after which cell migration and invasion ability and the expression of relevant molecules were detected. MiR-93 overexpression promoted cell migration and invasion, and downregulated E-cadherin expression while increasing N-cadherin expression. Dual-luciferase reporter assay showed that miR-93 may directly bind to the 3′ untranslated region of forkhead box A1 (FOXA1); furthermore, miR-93 overexpression downregulated FOXA1 expression while miR-93 inhibitor transfection upregulated FOXA1 expression at both mRNA and protein level. In addition, transfection with the most effective FOXA1 small interfering RNA promoted both endometrial cancer cell migration and invasion, and downregulated E-cadherin expression while upregulating N-cadherin expression. Therefore, we suggest that miR-93 may promote the process of epithelial–mesenchymal transition in endometrial carcinoma cells by targeting FOXA1.
PMCID: PMC5102435  PMID: 27829043
12.  Serum miR-95-3p is a diagnostic and prognostic marker for osteosarcoma 
SpringerPlus  2016;5(1):1947.
It has been demonstrated that microRNAs (miRNAs or miRs) can act as prognostic and diagnostic markers, and potential therapeutic targets. miR-95-3p has been reported to be downregulated in osteosarcoma tissues, but its potential as a serum biomarker has not been assessed in human osteosarcoma. The purpose of the present study was to examine the expression levels of miR-95-3p in serum of patients with osteosarcoma and to investigate the diagnostic and prognostic value of miR-95-3p. The serum levels of miR-95-3p in osteosarcoma patients were detected by a real-time quantitative reverse transcription-polymerase chain reaction assay. Associations between miR-95-3p expression and various clinicopathological characteristics were analyzed using Chi square test. Differences in patient survival were determined using the Kaplan–Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for multivariate analyses of prognostic values. Compared to healthy controls, the expression levels of miR-95-3p in serum of osteosarcoma patients were significantly decreased (P < 0.0001). Low miR-95-3p expression had significant association with clinical stage (P < 0.001) and metastasis (P < 0.001). The Kaplan–Meier curve showed that patients with high miR-95-3p expression survived significantly longer than patients with low miR-95-3p expression (P = 0.017). Multivariate analysis demonstrated that miR-95-3p expression level (P = 0.014) was an independent prognostic biomarker for overall survival. Our findings suggested that down-expression of serum miR-95-3p might be associated with poor prognosis of osteosarcoma patients, suggesting that decreased expression of serum miR-95-3p may serve as a valuable diagnostic/prognostic marker for osteosarcoma patients.
PMCID: PMC5102988  PMID: 27917340
Osteosarcoma; miR-95-3p; Serum; Diagnosis; Prognosis
13.  Abstracts from the 15th International Myopia Conference 
Benavente-Perez, Alexandra | Nour, Ann | Ansel, Tobin | Abarr, Kathleen | Yan, Luying | Roden, Keisha | Troilo, David | Lu, Chanyi | Pan, Miaozhen | Zheng, Min | Qu, Jia | Zhou, Xiangtian | Wildsoet, Christine F. | Lu, Fan | Zhou, Xiangtian | Chen, Jie | Bao, Jinhua | Hu, Liang | Wang, Qinmei | Jin, Zibing | Qu, Jia | Rucker, Frances | Britton, Stephanie | Hanowsky, Stephan | Spatcher, Molly | Kuo, Hui-Ying | Ke, Ching-Hsiu | Kuo, I-Hsin | Peng, Chien-Chun | Sun, Han-Yin | Morgan, Ian G. | Guggenheim, Jeremy A. | Shah, Rupal L. | Williams, Cathy | Yang, Jinglei | Reinach, Peter S. | Zhang, Sen | Pan, Miaozhen | Sun, Wenfeng | Liu, Bo | Li, Fen | Li, Xiaoqing | Zhao, Aihua | Chen, Tianlu | Jia, Wei | Qu, Jia | Zhou, Xiangtian | Jiang, Jun | Wu, Haoran | Lu, Fan | Tsubota, Kazuo | Ozawa, Hiroko | Torii, Hidemasa | Takamizawa, Shigemasa | Kurihara, Toshihide | Negishi, Kazuno | Graef, Klaus | Rathbun, Daniel | Schaeffel, Frank | Ghodsi, Ladan | Stell, William K. | Pardue, Machelle T. | Chakraborty, Ranjay | Park, Han na | Sidhu, Curran S. | Iuvone, P. Michael | Collins, Michael J | Srinvasalu, Nethrajeith | McFadden, Sally A. | Baird, Paul N. | Iuvone, P. Michael | Artal, Pablo | Cho, Pauline | Cheung, SW | Wu, Pei-Chang | Hoang, Quan V. | McFadden, Sally A. | Chakraborty, Ranjay | Lee, Duk C. | Landis, Erica G. | Bergen, Michael A. | Sidhu, Curran | Hattar, Samer | Iuvone, P. Michael | Stone, Richard A. | Pardue, Machelle T. | Metlapally, Ravi | Li, Ruiqin | Xu, Qinglin | Zhong, Hong | Pan, Chenglin | Lan, Weizhong | Li, Xiaoning | Chen, Ling | Yang, Zhikuan | Read, Scott A. | Saw, Seang-Mei | Weng, Shi-Jun | Wu, Xiao-Hua | Qian, Kang-Wei | Li, Yun-Yun | Xu, Guo-Zhong | Huang, Furong | Zhou, Xiangtian | Qu, Jia | Yang, Xiong-Li | Zhong, Yong-Mei | Smith, Earl L | Arumugam, Baskar | Hung, Li-Fang | Ostrin, Lisa A. | Trier, Klaus | Jong, Monica | Holden, Brien A. | Lam, Thomas Chuen | Shan, Samantha | Zuo, Bing | McFadden, Sally A. | Tse, Dennis Yan-yin | Bian, Jingfang | Li, King-Kit | Liu, Quan | To, Chi-ho | Gawne, Timothy J. | Siegwart, John T. | Ward, Alexander H. | Norton, Thomas T. | Zhou, Xiangtian | Zhang, Yan | Liu, Yue | Ho, Carol | Phan, Eileen | Hang, Abraham | Eng, Emily | Wildsoet, Christine
Eye and Vision  2016;3(Suppl 1):1-11.
Table of contents
O1 Changes in peripheral refraction associated with decreased ocular axial growth rate in marmosets
Alexandra Benavente-Perez, Ann Nour, Tobin Ansel, Kathleen Abarr, Luying Yan, Keisha Roden, David Troilo
O2 PPARα activation suppresses myopia development by increasing scleral collagen synthesis--a new drug target to suppress myopia development
Chanyi Lu, Miaozhen Pan, Min Zheng, Jia Qu, Xiangtian Zhou
O3 Evidence and possibilities for local ocular growth regulating signal pathways
Christine F Wildsoet
O4 Myopia researches at Eye Hospital of Wenzhou Medical University
Fan Lu, Xiangtian Zhou, Jie Chen, Jinhua Bao, Liang Hu, Qinmei Wang, Zibing Jin, Jia Qu
O5 Color, temporal contrast and myopia
Frances Rucker, Stephanie Britton, Stephan Hanowsky, Molly Spatcher
O6 The impact of atropine usage on visual function and reading performance in myopic school children in Taiwan
Hui-Ying Kuo, Ching-Hsiu Ke, I-Hsin Kuo, Chien-Chun Peng, Han-Yin Sun
O7 Increased time outdoors prevents the onset of myopia: evidence from randomised clinical trials
Ian G Morgan
O8 Environmental risk factors and gene-environment interactions for myopia in the ALSPAC cohort
Jeremy A. Guggenheim, Rupal L. Shah, Cathy Williams
O9 Retinal metabolic profiling identifies declines in FP receptor-linked signaling as contributors to form-deprived myopic development in guinea pigs
Jinglei Yang, Peter S. Reinach, Sen Zhang, Miaozhen Pan, Wenfeng Sun, Bo Liu, Xiangtian Zhou
O10 The study of peripheral refraction in moderate and high myopes after one month of wearing orthokeratology lens
Jun Jiang, Haoran Wu, Fan Lu
O11 Axial length of school children around the earth’s equatorial area and factors affecting the axial length
Kazuo Tsubota, Hiroko Ozawa, Hidemasa Torii, Shigemasa Takamizawa, Toshihide Kurihara, Kazuno Negishi
O12 Processing of defocus in the chicken retina by retinal ganglion cells
Klaus Graef, Daniel Rathbun, Frank Schaeffel
O13 Blue SAD light protects against form deprivation myopia in chickens, by local signaling within the retina
Ladan Ghodsi, William K. Stell
O14 Contributions of ON and OFF pathways to emmetropization and form deprivation myopia in mice
Machelle T. Pardue, Ranjay Chakraborty, Han na Park, Curran S. Sidhu, P. Michael Iuvone
O15 Response of the human choroid to defocus
Michael J Collins
O16 What can RNA sequencing tell us about myopic sclera?
Nethrajeith Srinvasalu, Sally A McFadden, Paul N Baird
O17 Overview of dopamine, retinal function, and myopia
P. Michael Iuvone
O18 The eye as a "robust" optical system and myopia
Pablo Artal
O19 Effect of discontinuation of orthokeratology lens wear on axial elongation in children
Pauline Cho, SW Cheung
O20 Myopia prevention in Taiwan
Pei-Chang Wu
O21 Alternatives to ultraviolet light and riboflavin for in vivo crosslinking of scleral collagen
Quan V. Hoang, Sally A. McFadden
O22 Absence of intrinsically photosensitive retinal ganglion cells (ipRGC) alters normal refractive development in mice
Ranjay Chakraborty, Duk C. Lee, Erica G. Landis, Michael A. Bergen, Curran Sidhu, Samer Hattar, P. Michael Iuvone, Richard A. Stone, Machelle T. Pardue
O23 Scleral micro-RNAs in myopia development and their potential as therapeutic targets
Ravi Metlapally
O24 Effects of the long-wavelength filtered continuous spectrum on emmetropization in juvenile guinea pigs
Ruiqin Li, Qinglin Xu, Hong Zhon, Chenglin Pan, Weizhon Lan, Xiaoning Li, Ling Chen, Zhikuan Yang
O25 Ocular and environmental factors associated with eye growth in childhood
Scott A. Read
O26 Overview- prevention and prediction of myopia and pathologic myopia
Seang-Mei Saw
O27 New insights into the roles of retinal dopamine in form-deprivation myopia and refractive development in C57BL/6 mice
Shi-Jun Weng, Xiao-Hua Wu, Kang-Wei Qian, Yun-Yun Li, Guo-Zhong Xu, Furong Huang, Xiangtian Zhou, Jia Qu, Xiong-Li Yang, Yong-Mei Zhong
O28 The effects of the adenosine antagonist, 7-methylxanthine, on refractive development in rhesus monkeys
Earl L Smith III, Baskar Arumugam, Li-Fang Hung, Lisa A. Ostrin, Klaus Trier, Monica Jong, Brien A. Holden
O29 Application of SWATH™ based next generation proteomics (NGP) in studying eye growth: opportunities and challenges
Thomas Chuen Lam, Bing Zuo, Samantha Shan, Sally A. McFadden, Dennis Yan-yin Tse, Jingfang Bian, King-Kit Li, Quan Liu, Chi-ho To
O30 How could emmetropization make use of longitudinal chromatic aberration?
Timothy J. Gawne, John T. Siegwart Jr., Alexander H. Ward, Thomas T. Norton
O31 Balance effect of dopamine D1 and D2 receptor subtype activation on refraction development
Xiangtian Zhou
O32 BMP gene expression changes in chick rpe in response to visual manipulations
Yan Zhang, Yue Liu, Carol Ho, Eileen Phan, Abraham Hang, Emily Eng, Christine Wildsoet
PMCID: PMC5123376
14.  Comparisons of volumetric modulated arc therapy (VMAT) quality assurance (QA) systems: sensitivity analysis to machine errors 
In volumetric modulated arc therapy (VMAT), gantry angles, dose rate and the MLC positions vary with the radiation delivery. The quality assurance (QA) system should be able to catch the planning and machine errors. The aim of this study was to investigate the sensitivity of three VMAT QA systems to machine errors.
Several types of potential linac machine errors unique to VMAT delivery were simulated in sinusoidal function of gantry angle, including gantry angle itself, MLC position and linac output. Two commercial QA systems, ArcCheck and Delta4, and an in-house developed EPID technique were compared in this study. Fifteen full arcs from head and neck plans were selected and modified to include five magnitudes of each type of error, resulting in measurements and γ analyses of 240 arcs on each system. Both qualitative and quantitative comparisons were performed using receiver operating characteristic (ROC), γ pass rate gradient, and overlap histogram methods.
In ROC analysis, the area under curve (AUC) represents the sensitivity and increases with the error magnitude. Using the criteria of 2 %/2 mm/2° (angle to agreement, ATA, only for EPID) and keeping AUC > 0.95, the minimum error detectable of ArcCheck, Delta4 and EPID are (2, 3, 3)° in gantry angle and (4, 2, 3) mm in MLC positions for the head and neck plans. No system is sensitive to the simulated output error, the AUC values were all below 0.70 even with 5 % output error. The γ gradient for gantry angle, MLC position and output errors are (−5.1, −2.6, −3.6)%/°, (−2.6, −7.1, −3.3)%/mm and (−0.2, −0.2, −0.3)%/% for ArcCheck, Delta4 and EPID, respectively. Therefore, these two analyses are consistent and support the same conclusion. The ATA parameter in EPID technique can be adjusted to tune its sensitivity.
We found that ArcCheck is more sensitive to gantry angle error and Delta4 is more sensitive to MLC position error. All three systems are not sensitive to the simulated output error. With additional analysis parameter, the EPID technique can be tuned to have optimal sensitivity and is able to perform QA for full field size with highest resolution. In addition, ROC analysis avoids the choice of γ pass rate threshold and is more robust compared with other analysis methods.
PMCID: PMC5100111  PMID: 27821135
Quality assurance; Volumetric modulated arc therapy; Receiver operator characteristic; Gamma analysis
15.  Interfering TAL effectors of Xanthomonas oryzae neutralize R-gene-mediated plant disease resistance 
Nature Communications  2016;7:13435.
Plant pathogenic bacteria of the genus Xanthomonas possess transcription activator-like effectors (TALEs) that activate transcription of disease susceptibility genes in the host, inducing a state of disease. Here we report that some isolates of the rice pathogen Xanthomonas oryzae use truncated versions of TALEs (which we term interfering TALEs, or iTALEs) to overcome disease resistance. In comparison with typical TALEs, iTALEs lack a transcription activation domain but retain nuclear localization motifs and are expressed from genes that were previously considered pseudogenes. We show that the rice gene Xa1, encoding a nucleotide-binding leucine-rich repeat protein, confers resistance against X. oryzae isolates by recognizing multiple TALEs. However, the iTALEs present in many isolates interfere with the otherwise broad-spectrum resistance conferred by Xa1. Our findings illustrate how bacterial effectors that trigger disease resistance in the host can evolve to interfere with the resistance process and, thus, promote disease.
The rice pathogen Xanthomonas oryzae produces TAL effectors (TALEs) that promote virulence. Here, the authors identify truncated TALEs that interfere with the function of a rice gene, Xa1, which confers resistance to all tested full-length TALEs.
PMCID: PMC5097170  PMID: 27811915
16.  Consequences of orthodontic treatment in malocclusion patients: clinical and microbial effects in adults and children 
BMC Oral Health  2016;16:112.
Malocclusion is a common disease of oral and maxillofacial region. The study was aimed to investigate levels changes of periodontal pathogens in malocclusion patients before, during and after orthodontic treatments, and to confirm the difference between adults and children.
One hundred and eight malocclusion patients (46 adults and 62 children at the school-age) were randomly selected and received orthodontic treatment with fixed orthodontic appliances. Subgingival plaques were Porphyromonas gingivalis (P.gingivalis), Fusobacterium nucleatum (F. nucleatum), Prevotella intermedia (P. intermedia) and Tannerella forsythensis (T. forsythensis) collected from the observed regions before and after treatment. Clinical indexes, including plaque index (PLI), gingival index (GI), sulcus bleeding index (SBI), probing depth (PD) and attachment loss (AL) of observed teeth were examined.
The detection rates of P.gingivalis, F. nucleatum, P. intermedia and T. forsythensis increased from baseline to the third month without significant difference, and then returned to pretreatment levels 12 month after applying fixed orthodontic appliances. Adults’ percentage contents of P.gingivalis, F. nucleatum, P. intermedia and T. forsythensis were significantly higher than those of children at baseline and the first month, but not obvious at the third month. PLI and SBI were increased from baseline to the first and to the third month both in adults and children groups. Besides, PD were increased from baseline to first month, followed by a downward trend in the third month; however, all patients were failed to detect with AL.
Periodontal and microbiological statuses of malocclusion patients may be influenced by fixed orthodontic appliances in both adults and children, more significant in children than in adults. Some microbiological indexes have synchronous trend with the clinical indexes. Long-term efficacy of fixed orthodontic appliances for malocclusion should be confirmed by future researches.
PMCID: PMC5084385  PMID: 27793138
Malocclusion; Orthodontic treatment; Fixed orthodontic appliances; Pathogens
17.  Induction of Interleukin-9-producing Mucosal Mast cells Promotes Susceptibility to IgE-mediated Experimental Food Allergy 
Immunity  2015;43(4):788-802.
Experimental IgE-mediated food allergy depends on intestinal anaphylaxis driven by interleukin (IL)-9. However, the primary cellular source of IL-9 and the mechanisms underlying the susceptibility to food-induced intestinal anaphylaxis remain unclear. Herein, we have reported the identification of multifunctional IL-9-producing mucosal mast cells (MMC9s) that can secrete prodigious amounts of IL-9 and IL-13 in response to IL-33, and mast cell protease-1 (MCPt-1) in response to antigen and IgE complex crosslinking, respectively. Repeated intragastric antigen challenge induced MMC9 development that required T cells, IL-4, and STAT6 transcription factor, but not IL-9 signals. Mice ablated of MMC9 induction failed to develop intestinal mastocytosis, which resulted in decreased food allergy symptoms that could be restored by adoptively transferred MMC9s. Finally, atopic patients that developed food allergy displayed increased intestinal expression of Il9 and MC-specific transcripts. Thus, the induction of MMC9s is a pivotal step to acquire the susceptibility to IgE-mediated food allergy.
Graphical abstract
PMCID: PMC4618257  PMID: 26410628
18.  Chemical Vapor Deposition of High‐Quality Large‐Sized MoS2 Crystals on Silicon Dioxide Substrates 
Advanced Science  2016;3(8):1500033.
Large‐sized MoS2 crystals can be grown on SiO2/Si substrates via a two‐stage chemical vapor deposition method. The maximum size of MoS2 crystals can be up to about 305 μm. The growth method can be used to grow other transition metal dichalcogenide crystals and lateral heterojunctions. The electron mobility of the MoS2 crystals can reach ≈30 cm2 V−1 s−1, which is comparable to those of exfoliated flakes.
PMCID: PMC5071677  PMID: 27818906
chemical vapor deposition; high quality; large size; molybdenum disulfide; silicon dioxide
19.  Characteristics of the Cochlear Symptoms and Functions in Meniere's Disease 
Chinese Medical Journal  2016;129(20):2445-2450.
Meniere's disease is a unique, progressive disease of the inner ear. The complex manifestation presents diagnostic challenges. The cochlear symptoms often present before vertigo and tend to be ignored. This study aimed to analyze the characteristics of cochlear symptoms and functions associated with Meniere's disease to investigate the regularity of the development of this disorder.
One-hundred fifteen patients who were diagnosed with definite unilateral Meniere's disease at the Hearing and Vestibular Clinic of the Department of Otorhinolaryngology of Beijing Tongren Hospital from August 2013 to November 2015 were recruited in this retrospective study. Initial symptoms, duration from initial symptoms to the diagnosis, hearing thresholds, audiogram patterns, and caloric test results were collected and analyzed for each patient. Data were analyzed using SPSS 13.0 statistical software by Spearman's correlation, Kruskal–Wallis H test, Chi-square test, and Fisher's exact test.
The average hearing threshold of these patients was 45.24 ± 18.40 dB HL. A majority of the patients (55.65%) were in Stage 3. The initial presentation of the disorder in 58 cases (50.43%) comprised only cochlear symptoms without vertigo. A weak, positive correlation was found between the degree of hearing loss and duration of the disease from initial symptoms to the diagnosis (rs = 0.288, P = 0.002). Upward-sloping, inverted “V,” downward-sloping, and flat pattern were the main audiometric patterns observed with a distinctive distribution between stages (P < 0.001). Based on the configurations of audiograms, the audiometric patterns had a weak correlation to the duration (rs = 0.269, P = 0.004), and there was a tendency of duration to rising from upward-sloping, inverted V, downward-sloping to flat pattern. (H = 10.024, P = 0.018). Frequencies of tinnitus in 56 patients (64.4%) were at the lowest points of the audiograms, i.e., the frequencies of the poorest hearing threshold. The patients at an advanced stage (Stage 3 [56] and Stage 4 [73]) exhibited a significantly higher abnormality of canal paresis than those at the earlier stages (Stage 1 [23] and Stage 2 [42]) (χ2 = 5.973, P = 0.015).
Patients with definite Meniere's disease always have a moderate to severe sensorineural hearing loss before diagnosis. Cochlear symptoms are the most common initial presentation. With the progression of the duration, the hearing impairment becomes more severe and the distribution of the audiometric pattern is distinctive between stages.
PMCID: PMC5072257  PMID: 27748337
Caloric Test; Hearing Loss; Meniere's disease; Tinnitus; Vertigo
20.  IGSA: Individual Gene Sets Analysis, including Enrichment and Clustering 
PLoS ONE  2016;11(10):e0164542.
Analysis of gene sets has been widely applied in various high-throughput biological studies. One weakness in the traditional methods is that they neglect the heterogeneity of genes expressions in samples which may lead to the omission of some specific and important gene sets. It is also difficult for them to reflect the severities of disease and provide expression profiles of gene sets for individuals. We developed an application software called IGSA that leverages a powerful analytical capacity in gene sets enrichment and samples clustering. IGSA calculates gene sets expression scores for each sample and takes an accumulating clustering strategy to let the samples gather into the set according to the progress of disease from mild to severe. We focus on gastric, pancreatic and ovarian cancer data sets for the performance of IGSA. We also compared the results of IGSA in KEGG pathways enrichment with David, GSEA, SPIA, ssGSEA and analyzed the results of IGSA clustering and different similarity measurement methods. Notably, IGSA is proved to be more sensitive and specific in finding significant pathways, and can indicate related changes in pathways with the severity of disease. In addition, IGSA provides with significant gene sets profile for each sample.
PMCID: PMC5072653  PMID: 27764138
21.  miR-1 Inhibits Cell Growth, Migration, and Invasion by Targeting VEGFA in Osteosarcoma Cells 
Disease Markers  2016;2016:7068986.
microRNAs (miRNAs) are small noncoding RNAs and have been shown to play a crucial role in the osteosarcoma (OS) tumorigenesis and progression. VEGFA is a key regulator of angiogenesis and plays an important role in regulation of tumor metastasis. The objective of this study was to determine whether VEGFA was involved in miR-1-mediated suppression of proliferation, migration, and invasion of OS cells. The expression levels of miR-1 were significantly lower in OS tumor tissues than those in adjacent normal tissues and in SAOS-2 and U2OS cell lines compared to a normal osteoblast (NHOst) cell line. VEGFA was upregulated in OS tumor tissues and SAOS-2 and U2OS cell lines. The results of CCK-8 assay and transwell assay showed that miR-1 acted as a tumor suppressor by inhibiting cell proliferation, migration, and invasion in U2OS cells. Dual luciferase reporter assay demonstrated that VEGFA was a direct and functional target gene of miR-1. miR-1 directly inhibits the protein expression of VEGFA via its 3′-UTR. Knockdown of VEGFA by siRNA inhibited proliferation, migration, and invasion of U2OS cells. Our study suggested the potential inhibitory function of miR-1 in OS cell proliferation, migration, and invasion via inhibiting VEGFA.
PMCID: PMC5061932  PMID: 27777493
22.  Identification of Happyhour/MAP4K as alternative Hpo/Mst-like kinases in the Hippo kinase cascade 
Developmental cell  2015;34(6):642-655.
In Drosophila and mammals, the canonical Hippo kinase cascade is mediated by Hpo/Mst acting through the intermediary kinase Wts/Lats to phosphorylate the transcriptional coactivator Yki/YAP/TAZ. Despite recent reports linking Yki/YAP/TAZ activity to the actin cytoskeleton, the underlying mechanisms are poorly understood and/or controversial. Using Drosophila imaginal discs as an in vivo model, we show that Wts, but not Hpo, is genetically indispensable for cytoskeleton-mediated subcellular localization of Yki. Through a systematic screen, we identify the Ste-20 kinase Happyhour (Hppy) and its mammalian counterpart MAP4K1/2/3/5 as an alternative kinase that phosphorylates the hydrophobic motif of Wts/Lats in a similar manner as Hpo/Mst. Consistent with their redundant function as activating kinases of Wts/Lats, combined loss of Hpo/Mst and Hppy/MAP4K abolishes cytoskeleton-mediated regulation of Yki/YAP subcellular localization, as well as YAP cytoplasmic translocation induced by contact inhibition. These Hpo/Mst-like kinases provide an expanded view of the Hippo kinase cascade in development and physiology.
Graphical Abstract
PMCID: PMC4589524  PMID: 26364751
Hpo; Yki; YAP; Happyhour; MAP4K1/2/3/5; F-actin; contact inhibition
23.  Expression of glycine receptors and gephyrin in rat medial vestibular nuclei and flocculi following unilateral labyrinthectomy 
The medial vestibular nucleus (MVN) and the cerebellar flocculus have been known to be the key areas involved in vestibular compensation (VC) following unilateral labyrinthectomy (UL). In this study, we examined the role of gephyrin and glycine receptor (GlyR) in VC using Sprague-Dawley rats, in an aim to gain deeper insight into the mechanisms responsible for VC. The expression of the α1 and β subunits of GlyR and gephyrin was immunohistochemically localized in rat MVN and flocculi. The mRNA and protein expression of GlyR (α1 and β subunits) and gephyrin was quantitatively determined by RT-qPCR and western blot analysis at 8 h, and at 1, 3 and 7 days following UL. It was found that in the ipsilateral MVN, the mRNA and protein expression of the β subunit of GlyR was significantly increased in comparison to the sham-operated (P<0.01) rats, and in comparison to the contralateral side (P<0.01) at 8 h following UL. In the ipsilateral flocculi, GlyR β protein expression was significantly elevated (P<0.01 for all), as compared to the sham-operated rats at 8 h, and at 1 and 3 days and to the contralateral side 8 h, 1 and 3 days following UL. No significant differences were observed in the mRNA and protein expression of GlyR α1 and gephyrin in the MVN or flocculi between the two sides (ipsilateral and contralateral) in the UL group, and between the sham-operated group and the UL group at any time point. The findings of our study thus suggest that GlyR plays a major role in the recovery of the resting discharge of the deafferented MVN neurons in the central vestibular system.
PMCID: PMC5065303  PMID: 28026001
flocculus; medial vestibular nucleus; gephyrin; glycine receptor; vestibular compensation
24.  Gastrodin ameliorates subacute phase cerebral ischemia-reperfusion injury by inhibiting inflammation and apoptosis in rats 
Molecular Medicine Reports  2016;14(5):4144-4152.
Gastrodin (GAS), which is extracted from the Chinese herbal medicine Gastrodia elata Blume, has long been used to improve stroke, epilepsy, dizziness and dementia. However, the effects and underlying mechanisms of GAS on subacute phase cerebral ischemia-reperfusion (I/R) injury remain unknown. The aim of the present study was to investigate the effects and mechanisms of GAS on cerebral I/R injury in rats. The rats were pretreated with GAS by gavage for 7 days followed by I/R surgery, and were then treated with GAS for 7 days after I/R surgery. Neurological deficits were assessed on days 1, 3 and 7 post-cerebral I/R injury. 2,3,5-Triphenyltetrazolium chloride staining was using to measure the infarct volume; morphological alterations were observed by hematoxylin and eosin staining under an optical microscope; apoptosis in the hippocampus and cortex was observed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining; and the level of mRNA and protein expression was tested by reverse transcription-quantitative polymerase chain reation and western blot analysis, respectively. GAS markedly attenuated I/R-induced disability and histological damage, alleviated neuronal apoptosis, and reduced the mRNA and protein expression levels of inflammatory and proapoptotic factors, including interleukin-1β, cyclooxygenase-2, inducible nitric oxide synthase and cleaved caspase-3. These findings suggested that GAS may ameliorate subacute phase cerebral I/R injury by inhibiting inflammation and apoptosis in rats; therefore, GAS may be considered a potential candidate for the treatment of cerebral ischemia.
PMCID: PMC5101922  PMID: 27748849
gastrodin; inflammation; apoptosis; neuroprotection; rat
25.  The outer membrane phospholipase A is essential for membrane integrity and type III secretion in Shigella flexneri 
Open Biology  2016;6(9):160073.
Outer membrane phospholipase A (OMPLA) is an enzyme located in the outer membrane of Gram-negative bacteria. OMPLA exhibits broad substrate specificity, and some of its substrates are located in the cellular envelope. Generally, the enzymatic activity can only be induced by perturbation of the cell envelope integrity through diverse methods. Although OMPLA has been thoroughly studied as a membrane protein in Escherichia coli and is constitutively expressed in many other bacterial pathogens, little is known regarding the functions of OMPLA during the process of bacterial infection. In this study, the proteomic and transcriptomic data indicated that OMPLA in Shigella flexneri, termed PldA, both stabilizes the bacterial membrane and is involved in bacterial infection under ordinary culture conditions. A series of physiological assays substantiated the disorganization of the bacterial outer membrane and the periplasmic space in the ΔpldA mutant strain. Furthermore, the ΔpldA mutant strain showed decreased levels of type III secretion system expression, contributing to the reduced internalization efficiency in host cells. The results of this study support that PldA, which is widespread across Gram-negative bacteria, is an important factor for the bacterial life cycle, particularly in human pathogens.
PMCID: PMC5043575  PMID: 27655730
Shigella flexneri; phospholipase A; cell membranes; host cell invasion

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