Fan, Song | Lu, Hongyan | Ma, Xiaoyan | Sun, Yanming | He, Xiong | Li, Chunmei | Raymond, H.F. | McFarland, Willi | Sun, Jiangping | Ma, Wei | Jia, Yujiang | Xiao, Yan | Shao, Yiming | Ruan, Yuhua
Abstract
We assessed HIV prevalence and associated behaviors and risk factors among men who have sex with men (MSM) in Beijing, China. Five hundred MSM were recruited for a biological and behavioral survey using respondent-driven sampling (RDS) in 2009. Serologic specimens were tested for markers of HIV and syphilis infection. A computer-assisted personal interview (CAPI) administered questionnaire gathered information including demographic characteristics, sexual behaviors, HIV testing, and social norms concerning condom use. The adjusted HIV prevalence was 8.0%, syphilis 22.0%. HIV testing and disclosure was low; only 39.3% had HIV tested in the past 12 months, 49.7% knew their own HIV status and 22.8% knew their last male partner's HIV status. HIV infection was associated with syphilis, ever having sex with a woman, not knowing the HIV status of the most recent male partner, and never buying condoms in the past 12 months. Stronger endorsement of positive social norms around condom use strongly and predicted lower prevalence of HIV infection. Compared to surveys of similar design in the recent past, HIV continues to spread rapidly among Beijing's MSM. Our results identify points of intervention that, if addressed in time, may still alter the course of the epidemic including the promotion of HIV testing and partner disclosure, syphilis control and particularly changing social norms around condom use.
doi:10.1089/apc.2011.0277
PMCID: PMC3326445
PMID: 22248333
Change detection is a classic paradigm that has been used for decades to argue that working memory can hold no more than a fixed number of items (“item-limit models”). Recent findings force us to consider the alternative view that working memory is limited by the precision in stimulus encoding, with mean precision decreasing with increasing set size (“continuous-resource models”). Most previous studies that used the change detection paradigm have ignored effects of limited encoding precision by using highly discriminable stimuli and only large changes. We conducted two change detection experiments (orientation and color) in which change magnitudes were drawn from a wide range, including small changes. In a rigorous comparison of five models, we found no evidence of an item limit. Instead, human change detection performance was best explained by a continuous-resource model in which encoding precision is variable across items and trials even at a given set size. This model accounts for comparison errors in a principled, probabilistic manner. Our findings sharply challenge the theoretical basis for most neural studies of working memory capacity.
Author Summary
Working memory is a fundamental aspect of human cognition. It allows us to remember bits of information over short periods of time and make split-second decisions about what to do next. Working memory is often tested using a change detection task: subjects report whether a change occurred between two subsequent visual images that both contain multiple objects (items). The more items are present in the images, the worse they do. The precise origin of this phenomenon is not agreed on. The classic theory asserts that working memory consists of a small number of slots, each of which can store one item; when there are more items than slots, the extra items are discarded. A modern model postulates that working memory is fundamentally limited in the quality rather than the quantity of memories. In a metaphor: instead of watering only a few plants in our garden, we water all of them, but the more plants we have, the less water each will receive on average. We show that this new model does much better in accounting for human change detection responses. This has consequences for the entire field of working memory research.
doi:10.1371/journal.pcbi.1002927
PMCID: PMC3585403
PMID: 23468613
Orientation tuning has been a classic model for understanding single neuron computation in the neocortex. However, little is known about how orientation can be read out from the activity of neural populations, in particular in alert animals. Our study is a first step towards that goal. We recorded from up to 20 well-isolated single neurons in the primary visual cortex of alert macaques simultaneously and applied a simple, neurally plausible decoder to read out the population code. We focus on two questions: First, what are the time course and the time scale at which orientation can be read out from the population response? Second, how complex does the decoding mechanism in a downstream neuron have to be in order to reliably discriminate between visual stimuli with different orientations? We show that the neural ensembles in primary visual cortex of awake macaques represent orientation in a way that facilitates a fast and simple read-out mechanism: with an average latency of 30–80 ms, the population code can be read out instantaneously with a short integration time of only tens of milliseconds and neither stimulus contrast nor correlations need to be taken into account to compute the optimal synaptic weight pattern. Our study shows that – similar to the case of single neuron computation – the representation of orientation in the spike patterns of neural populations can serve as an exemplary case for understanding of the computations performed by neural ensembles underlying visual processing during behavior.
doi:10.1523/JNEUROSCI.1335-12.2012
PMCID: PMC3506189
PMID: 22855811
Multiple properties of plasmonic assemblies are determined by their geometrical organization. While high degree of complexity was achieved for plasmonic superstructures based on nanoparticles (NPs) little is known about the stable and structurally reproducible plasmonic assemblies made up from geometrically diverse plasmonic building blocks. Among other possibilities they open the door for the preparation of regiospecific isomers of nanoscale assemblies significant both from fundamental point of view and optical applications. Here we present a synthetic method for complex assemblies from NPs and nanorods (NRs) based on selective modification of NRs with DNA oligomers. Three types of assemblies denoted as End, Side, and Satellite isomers which display distinct elements of regiospecificity, were prepared with the yield exceeding 85%. Multiple experimental methods independently verify various structural features, uniformity, and stability of the prepared assemblies. The presence of interparticle gaps with finely controlled geometrical parameters and inherently small size comparable with those of cellular organelles fomented their study as intracellular probes. Against initial expectations SERS intensity for End, Side, and Satellite isomers was found to be dependent primarily on the number of the NPs in the superstructures rationalized with the help of electrical field simulations. Incubation of the label-free NP-NR assemblies with HeLa cells indicated sufficient field enhancement to detect structural lipids of mitochondria and potentially small metabolites. This provided the first proof-of-concept data for the possibility of real-time probing of local organelle environment in live cells. Further studies should include structural optimization of the assemblies for multitarget monitoring of metabolic activity and further increase in complexity for applications in transformative optics.
doi:10.1021/ja2088713
PMCID: PMC3277787
PMID: 22192084
nanoparticles; nanorods; plasmons; intracellular; SERS; metabolism; biosensor
Zhang, Xuan | Huang, Ya Ping | Gao, Hai Nv | Yang, Mei Fang | Zhao, Hong | Hu, Jian Hua | Chen, Xiao Ming | Ma, Wei Hang | Fan, Jun | Costa, Cristina
Based on sequence variation in the N-terminus of the UL55 gene, which encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gBn genotypes. We assessed the distribution of CMV gBn genotypes and the correlation between CMV gBn DNA (detected by real-time PCR) and CMV-positive pp65 cells (identified by immunohistochemical staining) in a cohort of hematopoietic stem cell transplant patients. The distribution of gB genotypes was as follows: gBn1, 60% of patients; gBn2, 13.3%; mixed gBn1 and gBn3 infection, 26.7%; and gBn4 and other mixed infections, 0%. CMV gBn1 was the most common genotype. The detected level of CMV gB DNA correlated well with the number of CMV-positive pp65 cells detected by immunostaining (r = 0.585).
doi:10.1371/journal.pone.0051224
PMCID: PMC3519544
PMID: 23251460
Xu, Xiao-Ling | Ma, Wei | Zhu, Yu-Bo | Wang, Chao | Wang, Bing-Yuan | An, Na | An, Lei | Liu, Yan | Wu, Zhong-Hong | Tian, Jian-Hui | Wang, Haibin
The microtubule-associated protein ASPM (abnormal spindle-like microcephaly-associated) plays an important role in spindle organization and cell division in mitosis and meiosis in lower animals, but its function in mouse oocyte meiosis has not been investigated. In this study, we characterized the localization and expression dynamics of ASPM during mouse oocyte meiotic maturation and analyzed the effects of the downregulation of ASPM expression on meiotic spindle assembly and meiotic progression. Immunofluorescence analysis showed that ASPM localized to the entire spindle at metaphase I (MI) and metaphase II (MII), colocalizing with the spindle microtubule protein acetylated tubulin (Ac-tubulin). In taxol-treated oocytes, ASPM colocalized with Ac-tubulin on the excessively polymerized microtubule fibers of enlarged spindles and the numerous asters in the cytoplasm. Nocodazole treatment induced the gradual disassembly of microtubule fibers, during which ASPM remained colocalized with the dynamic Ac-tubulin. The downregulation of ASPM expression by a gene-specific morpholino resulted in an abnormal meiotic spindle and inhibited meiotic progression; most of the treated oocytes were blocked in the MI stage with elongated meiotic spindles. Furthermore, coimmunoprecipitation combined with mass spectrometry and western blot analysis revealed that ASPM interacted with calmodulin in MI oocytes and that these proteins colocalized at the spindle. Our results provide strong evidence that ASPM plays a critical role in meiotic spindle assembly and meiotic progression in mouse oocytes.
doi:10.1371/journal.pone.0049303
PMCID: PMC3496685
PMID: 23152892
Lu, Qiulun | Yao, Yihong | Yao, Yufeng | Liu, Shizhi | Huang, Yuan | Lu, Shan | Bai, Ying | Zhou, Bisheng | Xu, Yan | Li, Lei | Wang, Nan | Wang, Li | Zhang, Jie | Cheng, Xiang | Qin, Gangjian | Ma, Wei | Xu, Chengqi | Tu, Xin | Wang, Qing | Katare, Rajesh Gopalrao
Background
Peripheral arterial disease (PAD) is a common disease accounting for about 12% of the adult population, and causes significant morbidity and mortality. Therapeutic angiogenesis using angiogenic factors has been considered to be a potential treatment option for PAD patients. In this study, we assessed the potential of a new angiogenic factor AGGF1 for therapeutic angiogenesis in a critical limb ischemia model in mice for PAD.
Methods and Results
We generated a unilateral hindlimb ischemia model in mice by ligation of the right common iliac artery and femoral artery. Ischemic mice with intrasmuscular administration of DNA for an expression plasmid for human AGGF1 (AGGF1 group) resulted in increased expression of both AGGF1 mRNA and protein after the administration compared with control mice with injection of the empty vector (control group). Color PW Doppler echocardiography showed that the blood flow in ischemic hindlimbs was significantly increased in the AGGF1 group compared to control mice at time points of 7, 14, and 28 days after DNA administration (n = 9/group, P = 0.049, 0.001, and 0.001, respectively). Increased blood flow in the AGGF1 group was correlated to increased density of CD31-positive vessels and decreased necrosis in muscle tissues injected with AGGF1 DNA compared with the control tissue injected with the empty vector. Ambulatory impairment was significantly reduced in the AGGF1 group compared to the control group (P = 0.004). The effect of AGGF1 was dose-dependent. At day 28 after gene transfer, AGGF1 was significantly better in increasing blood flow than FGF-2 (P = 0.034), although no difference was found for tissue necrosis and ambulatory impairment.
Conclusions
These data establish AGGF1 as a candidate therapeutic agent for therapeutic angiogenesis to treat PAD.
doi:10.1371/journal.pone.0046998
PMCID: PMC3479102
PMID: 23110058
Ma, Wei | Raymond, H Fisher | Wilson, Erin C | McFarland, Willi | Lu, Hongyan | Ding, Xianbin | Lu, Rongrong | Ma, Xiaoyan | Xia, Dongyan | Xu, Jing | He, Xiong | Feng, Liangui | Fan, Song | Li, Xuefeng | Sun, Jiangping | Jia, Yujiang | Shao, Yiming | Ruan, Yuhua | Xiao, Yan
Background
Although various HIV prevention programs targeting men who have sex with men (MSM) are operating in China, whether and how these programs are being utilized is unclear. This study explores participation of HIV prevention programs and influencing factors among MSM in two cities in China.
Methods
This is a mixed-method study conducted in Beijing and Chongqing. A qualitative study consisting of in-depth interviews with 54 MSM, 11 key informants, and 8 focus group discussions, a cross-sectional survey using respondent-driven sampling among 998 MSM were conducted in 2009 and 2010 respectively to elicit information on MSM’s perception and utilization of HIV prevention programs. Qualitative findings were integrated with quantitative multivariate factors to explain the quantitative findings.
Results
Fifty-six percent of MSM in Chongqing and 75.1% in Beijing ever participated in at least one type of HIV prevention program (P=0.001). Factors related to participation in HIV prevention programs included age, ethnicity, income, HIV risk perception, living with boyfriend, living in urban area, size of MSM social network, having talked about HIV status with partners, and knowing someone who is HIV positive. Reasons why MSM did not participate in HIV prevention programs included logistical concerns like limited time for participation and distance to services; program content and delivery issues such as perceived low quality services and distrust of providers; and, cultural issues like HIV-related stigma and low risk perception.
Conclusions
The study shows that there is much room for improvement in reaching MSM in China. HIV prevention programs targeting MSM in China may need to be more comprehensive and incorporate the cultural, logistic and HIV-related needs of the population in order to effectively reach and affect this population’s risk for HIV.
doi:10.1186/1471-2458-12-847
PMCID: PMC3570394
PMID: 23039880
MSM; HIV prevention programs; Utilization; Participation; China
Optimal nitrogen (N) supply is critical for achieving high grain yield of maize. It is well established that N deficiency significantly reduces grain yield and N oversupply reduces N use efficiency without significant yield increase. However, the underlying proteomic mechanism remains poorly understood. The present field study showed that N deficiency significantly reduced ear size and dry matter accumulation in the cob and grain, directly resulting in a significant decrease in grain yield. The N content, biomass accumulation, and proteomic variations were further analysed in young ears at the silking stage under different N regimes. N deficiency significantly reduced N content and biomass accumulation in young ears of maize plants. Proteomic analysis identified 47 proteins with significant differential accumulation in young ears under different N treatments. Eighteen proteins also responded to other abiotic and biotic stresses, suggesting that N nutritional imbalance triggered a general stress response. Importantly, 24 proteins are involved in regulation of hormonal metabolism and functions, ear development, and C/N metabolism in young ears, indicating profound impacts of N nutrition on ear growth and grain yield at the proteomic level.
doi:10.1093/jxb/ers187
PMCID: PMC3430998
PMID: 22936831
C/N metabolism; hormonal metabolism; maize ear; nitrogen deficiency; nitrogen oversupply
Qin, Xianhui | Li, Jianping | Zhang, Yan | Ma, Wei | Fan, Fangfang | Wang, Binyan | Xing, Houxun | Tang, Genfu | Wang, Xiaobin | Xu, Xin | Xu, Xiping | Huo, Yong | Zhang, Cuilin
Objective
This study examined the prevalence of impaired fasting glucose (IFG) and diabetes and their associated factors in 17,184 Chinese hypertensive adults aged 45–75 years.
Methods
A cross-sectional investigation was carried out in a rural area of Lianyungang, China. Previously undiagnosed diabetes [fasting plasma glucose (FPG) ≥7.0mmol/l] and IFG (6.1–6.9mmol/l) were defined based on FPG concentration. Previously diagnosed diabetes was determined on the basis of self-report. Total diabetes included both previously diagnosed diabetes and previously undiagnosed diabetes.
Results
The prevalence of previously diagnosed diabetes, undiagnosed diabetes, and IFG were 3.4%, 9.8%, and 14.1%, respectively. About 74.2% of the participants with diabetes had not previously been diagnosed. In the multivariable logistic-regression model, older age, men, antihypertensive treatment, obesity (BMI ≥25kg/m2), abdominal obesity (waist circumference ≥90cm for men and ≥80cm for women), non-current smoking, a family history of diabetes, higher heart rate, lower physical activity levels, and inland residence (versus coastal) were significantly associated with both total diabetes and previously undiagnosed diabetes. Furthermore, methylene- tetrahydrofolate reductase (MTHFR) 677 TT genotype was an independent associated factor for total diabetes, and current alcohol drinking was an independent associated factor for previously undiagnosed diabetes. At the same time, older age, men, abdominal obesity, non-current smoking, current alcohol drinking, a family history of diabetes, higher heart rate, and inland residence (versus coastal) were important independent associated factors for IFG.
Conclusion
In conclusion, we found a high prevalence of diabetes in Chinese hypertensive adults. Furthermore, about three out of every four diabetic adults were undiagnosed. Our results suggest that population-level measures aimed at the prevention, identification (even if only based on the FPG evaluation), and treatment of diabetes should be urgently taken to overcome the diabetes epidemic in Chinese hypertensive adults.
doi:10.1371/journal.pone.0042538
PMCID: PMC3411819
PMID: 22880024
A key function of the brain is to interpret noisy sensory information. To do so optimally, observers must, in many tasks, take into account knowledge of the precision with which stimuli are encoded. In an orientation change detection task, we find that encoding precision does not only depend on an experimentally controlled reliability parameter (shape), but also exhibits additional variability. In spite of variability in precision, human subjects seem to take into account precision near-optimally on a trial-to-trial and item-to-item basis. Our results offer a new conceptualization of the encoding of sensory information and highlight the brain’s remarkable ability to incorporate knowledge of uncertainty during complex perceptual decision-making.
doi:10.1371/journal.pone.0040216
PMCID: PMC3387023
PMID: 22768258
Background
YKL-40, a proposed marker of inflammation and endothelial dysfunction, is associated with atherosclerosis and an increased cardiovascular mortality in the general population. However, the relationship between YKL-40 and arterial stiffness in hypertensive patients has not been adequately assessed.
Methods
The relationship between serum levels of YKL-40 and arterial stiffness was evaluated in 93 essential hypertensive subjects and 80 normal subjects. Essential hypertensive subjects were divided into two groups based upon urinary albumin-to-creatinine ratio (ACR): nonmicroalbuminuric group, (ACR <30 mg/g, n = 50) and microalbuminuric group (ACR ≥30 mg/g, n = 43). Large artery wall stiffness was assessed by measuring femoral arterial stiffness and carotid-femoral pulse wave velocity (cf-PWV). Serum levels of YKL-40 were determined by enzyme-linked immunosorbent assay (ELISA).
Results
The study demonstrated that YKL-40,cf-PWV and femoral arterial stiffness were increased significantly (P<0.05) in the hypertensive group compared with normal controls. These measurements were also increased significantly ( P<0.05) in the microalbuminuric group compared with the nonmicroalbuminuric group. YKL-40 was positively correlated with cf-PWV( r = 0.44, P = 0.000) and femoral arterial stiffness ( r = 0.42, P =0.001). Multiple linear stepwise regression analysis showed that YKL-40 was the impact factor of arterial stiffness ( P<0.05).
Conclusion
YKL-40 levels are elevated in essential hypertension subjects with an independent association between increasing YKL-40 levels and increasing arterial stiffness. The study suggests it played a positive role of YKL-40 in the progressing vascular complications in patients with essential hypertension.
doi:10.1186/1471-2261-12-35
PMCID: PMC3438025
PMID: 22642467
Li, Shengqing | Bode, Ann M. | Zhu, Feng | Liu, Kangdong | Zhang, Jishuai | Kim, Myoung Ok | Reddy, Kanamata | Zykova, Tatyana | Ma, Wei-ya | Carper, Andria L. | Langfald, Alyssa K. | Dong, Zigang
In addition to capsaicin, a transient receptor potential channel vanilloid subfamily 1 (TRPV1) agonist, two kinds of antagonists against this receptor are used as therapeutic drugs for pain relief. Indeed, a number of small molecule TRPV1 antagonists are currently undergoing Phase I/II clinical trials to determine their effect on relieving chronic inflammatory pain and migraine headache pain. However, we previously reported that the absence of TRPV1 in mice results in a striking increase in skin carcinogenesis, suggesting that chronic blockade of TRPV1 might increase the risk of tumor development. In this study, we found that a typical TRPV1 antagonist, AMG9810, promotes mouse skin tumor development. The topical application of AMG9810 resulted in a significant increase in the expression level of the epidermal growth factor receptor (EGFR) and its downstream Akt/mammalian target of rapamycin (mTOR)-signaling pathway. This increase was not only observed in AMG9810-treated tumor tissue but was also found in skin tissue treated with AMG9810. In telomerase-immortalized primary human keratinocytes, AMG9810 promoted proliferation that was mediated through the EGFR/Akt/mTOR-signaling pathway. In summary, our data suggest that the TRPV1 antagonist, AMG9810, promotes mouse skin tumorigenesis mediated through EGFR/Akt/mTOR signaling. Thus, the application of this compound for pain relief might increase the risk of skin cancer.
doi:10.1093/carcin/bgr037
PMCID: PMC3086704
PMID: 21349818
Summary
The surface functionalization of inorganic nanostructures is an effective approach for enriching the potential applications of existing nanomaterials. Inorganic nanotubes attract great research interest due to their one-dimensional structure and reactive surfaces. In this review paper, recent developments in surface functionalization of an aluminosilicate nanotube, “imogolite”, are introduced. The functionalization processes are based on the robust affinity between phosphate groups of organic molecules and the aluminol (AlOH) surface of imogolite nanotubes. An aqueous modification process employing a water soluble ammonium salt of alkyl phosphate led to chemisorption of molecules on imogolite at the nanotube level. Polymer-chain-grafted imogolite nanotubes were prepared through surface-initiated polymerization. In addition, the assembly of conjugated molecules, 2-(5’’-hexyl-2,2’:5’,2’’-terthiophen-5-yl)ethylphosphonic acid (HT3P) and 2-(5’’-hexyl-2,2’:5’,2’’-terthiophen-5-yl)ethylphosphonic acid 1,1-dioxide (HT3OP), on the imogolite nanotube surface was achieved by introducing a phosphonic acid group to the corresponding molecules. The optical and photophysical properties of these conjugated-molecule-decorated imogolite nanotubes were characterized. Moreover, poly(3-hexylthiophene) (P3HT) chains were further hybridized with HT3P modified imogolite to form a nanofiber hybrid.
doi:10.3762/bjnano.3.10
PMCID: PMC3304320
PMID: 22428100
chemisorption; imogolite; inorganic nanotube; surface functionalization.
Lin28 is critical for stem cell maintenance and is also associated with advanced human malignancies. Our recent genome-wide studies mark Lin28 as a master post-transcriptional regulator of a subset of messenger RNAs important for cell growth and metabolism. However, the molecular basis underpinning the selective mRNA target regulation is unclear. Here, we provide evidence that Lin28 recognizes a unique motif in multiple target mRNAs, characterized by a small but critical ‘A’ bulge flanked by two G:C base pairs embedded in a complex secondary structure. This motif mediates Lin28-dependent stimulation of translation. As Lin28 is also known to inhibit the biogenesis of a cohort of miRNAs including let-7, we propose that Lin28 binding to different RNA types (precursor miRNAs versus mRNAs) may facilitate recruitment of different co-factors, leading to distinct regulatory outcomes. Our findings uncover a putative yet unexpected motif that may constitute a mechanistic base for the multitude of functions regulated by Lin28 in both stem cells and cancer cells.
doi:10.1093/nar/gkr1279
PMCID: PMC3333870
PMID: 22210884
The asymmetric unit of the title compound, C14H10N4O2, contains two independent molecules with similar structures. In one molecule, the tetrazole ring is oriented at dihedral angles of 17.71 (16) and 57.13 (17)°, respectively, to the central benzene ring and the terminal benzene ring; in the other molecule, the corresponding dihedral angles are 16.46 (18) and 75.87 (18)°. Intermolecular N—H⋯N hydrogen bonds and weak C—H⋯O and C—H⋯N hydrogen bonds occur in the crystal structure.
doi:10.1107/S1600536811044254
PMCID: PMC3247491
PMID: 22220109
Previous studies reveal that both Ca2+ and nitric oxide (NO) play pivotal roles in the plant senescence signaling cascade. However, not much is known about the molecular identity of the Ca2+ entry during senescence programming and its relationship to the downstream NO signal. Our recent study shows that Arabidopsis cyclic nucleotide gated channel2 (CNGC2) contributes to Ca2+ uptake and senescence signaling. The CNGC2 loss-of-function mutant dnd1 displays reduced Ca2+ accumulation in leaves and a series of early senescence phenotypes compared to wild type (WT). Notably, endogenous NO content in dnd1 leaves is lower than leaves of WT. Application of an NO donor can effectively rescue a number of early senescence phenotypes found in the dnd1 plants. Current evidence supports the notion that NO functions as a negative regulator in senescence signaling and our model supports this point. In this article, we expand our discussion of CNGC2 mediated Ca2+ uptake and other related signaling components involved in the plant senescence signaling cascade.
doi:10.4161/psb.6.3.14356
PMCID: PMC3142425
PMID: 21358265
Arabidopsis; calcium; cyclic nucleotide gated channel; nitric oxide; plant ion channel; senescence
Background
Spinocerebellar ataxia (SCA) refers to a disease entity in which polyglutamine aggregates are over-produced in Purkinje cells (PCs) of the cerebellum as well as other neurons in the central nervous system, and the formation of intracellular polyglutamine aggregates result in the loss of neurons as well as deterioration of motor functions. So far there is no effective neuroprotective treatment for this debilitating disease although numerous efforts have been made. Mesenchymal stem cells (MSCs) possess multi-lineage differentiation potentials as well as immuno-modulatory properties, and are theoretically good candidates for SCA treatment. The purpose of this study is to investigate whether transplantation of human MSCs (hMSCs) can rescue cerebellar PCs and ameliorate motor function deterioration in SCA in a pre-clinical animal model.
Method
Transgenic mice bearing poly-glutamine mutation in ataxin-2 gene (C57BL/6J SCA2 transgenic mice) were serially transplanted with hMSCs intravenously or intracranially before and after the onset of motor function loss. Motor function of mice was evaluated by an accelerating protocol of rotarod test every 8 weeks. Immunohistochemical stain of whole brain sections was adopted to demonstrate the neuroprotective effect of hMSC transplantation on cerebellar PCs and engraftment of hMSCs into mice brain.
Results
Intravenous transplantation of hMSCs effectively improved rotarod performance of SCA2 transgenic mice and delayed the onset of motor function deterioration; while intracranial transplantation failed to achieve such neuroprotective effect. Immunohistochemistry revealed that intravenous transplantation was more effective in the preservation of the survival of cerebellar PCs and engraftment of hMSCs than intracranial injection, which was compatible to rotarod performance of transplanted mice.
Conclusion
Intravenous transplantation of hMSCs can indeed delay the onset as well as improve the motor function of SCA2 transgenic mice. The results of this preclinical study strongly support further exploration of the feasibility to transplant hMSCs for SCA patients.
doi:10.1186/1423-0127-18-54
PMCID: PMC3174876
PMID: 21824437
In 1992, John Daly et al. reported the isolation and structure determination of epibatidine. Epibatidine’s unique structure and its potent nicotinic agonist activity have had a tremendous impact on nicotine receptor research. This research has led to a better understanding of the nicotinic acetylcholine receptor (nAChR) pharmacophore and to epibatidine analogues with potential as pharmacotherapies for treating various CNS disorders. In this study, we report the synthesis, receptor binding ([3H]epibatidine and [125I]iodoMLA), and in vivo pharmacological properties (mouse tail flick, hot plate, hypothermia, and spontaneous activity) of a series of 3′-(substituted phenyl)epibatidine analogues (5a–m). Results from these studies have added to the understanding of the nAChR pharmacophore and led to nicotinic partial agonists that may have potential for smoking cessation. All the analogues had affinities for the α4β2 nAChR similar to epibatidine (1). 3′-(3-Dimethylaminophenyl)epibatidine (5m) has a nicotinic partial agonist pharmacological profile similar to the smoking cessation drug varenicline. Other analogues are partial agonists with varying degrees of nicotinic functional agonist and antagonist activity. 3′-(3-Aminophenyl)epibatidine (5j) is a more potent functional agonist and antagonist in all tests than varenicline. 3′-(3-Fluorophenyl)epibatidine and 3′-(3-chlorophenyl)epibatidine (5c and 5e) are more potent than varenicline when tested as agonists in four pharmacological tests and antagonists when evaluated against nicotine in the analgesia hot-plate test.
doi:10.1021/np9006124
PMCID: PMC2846203
PMID: 20038125
Li, Tao | Hu, Andina | Li, Shiqing | Luo, Yan | Huang, Juan | Yu, Honghua | Ma, Wei | Pan, Jianying | Zhong, Qi | Yang, Jin | Wu, Jianming | Tang, Shibo
Purpose
The purpose of the current study was to investigate the effect of topical administration of KH906 on corneal neovascularization (NV).
Methods
To induce corneal neovascularization, chemical cauterization of the corneas of the right eyes of forty-eight New Zealand white rabbits was performed by touching the central cornea with an 8-mm-diameter NaOH-soaked Whatman filter paper for 60 s. On the next day after modeling, the rabbits were randomly and equally divided into six groups: PBS control group, 0.1% dexamethasone group, 10 mg/ml Avastin group, 5 mg/ml KH906 group, 10 mg/ml KH906 group, and 20 mg/ml KH906 group. The rabbits in the six groups received topical administration of 50 μl of the different solutions on the cornea four times per day for 14 days. Corneal neovascularization was analyzed by slit-lamp biomicroscopy 10 and 14 days after chemical cauterization. Corneal fluorescein staining was performed to evaluate the extent of corneal epithelial defect on the 7th, 10th, and 14th days. The VEGF level of the cornea was evaluated by ELISA assay.
Results
On the 10th and 14th days after chemical cauterization, the length of the longest new vessel and the areas of corneal neovascularization in all KH906-treated groups were significantly reduced compared to those of the PBS-treated group (p<0.05). The VEGF level of the cornea in all KH906-treated groups was significantly decreased compared to that of the PBS-treated group (p<0.05). Corneal fluorescein staining showed that KH906 had no effect on corneal epithelial healing.
Conclusions
Topical administration of KH906 significantly inhibited alkali burn-induced corneal neovascularization in rabbits. The new eye drops of KH906 may have a broad application for human corneal neovascularization in the near future.
PMCID: PMC3081801
PMID: 21528000
Through the integrated approach of remote sensing and geographic information system (GIS) techniques, four Landsat TM/ETM+ imagery acquired during 1979 and 2008 were used to quantitatively characterize the patterns of land use and land cover change (LULC) and urban sprawl in the fast-growing Shanghai Metropolis, China. Results showed that, the urban/built-up area grew on average by 4,242.06 ha yr−1. Bare land grew by 1,594.66 ha yr−1 on average. In contrast, cropland decreased by 3,286.26 ha yr−1 on average, followed by forest and shrub, water, and tidal land, which decreased by 1,331.33 ha yr−1, 903.43 ha yr−1, and 315.72 ha yr−1 on average, respectively. As a result, during 1979 and 2008 approximately 83.83% of the newly urban/built-up land was converted from cropland (67.35%), forest and shrub (9.12%), water (4.80%), and tidal land (2.19%). Another significant change was the continuous increase in regular residents, which played a very important role in contributing to local population growth and increase in urban/built-up land. This can be explained with this city’s huge demand for investment and qualified labor since the latest industrial transformation. Moreover, with a decrease in cropland, the proportion of population engaged in farming decreased 13.84%. Therefore, significant socio-economic transformation occurred, and this would lead to new demand for land resources. However, due to very scarce land resources and overload of population in Shanghai, the drive to achieve economic goals at the loss of cropland, water, and the other lands is not sustainable. Future urban planning policy aiming at ensuring a win-win balance between sustainable land use and economic growth is urgently needed.
doi:10.3390/s110201794
PMCID: PMC3273998
PMID: 22319382
land use and land cover change (LULC); land use dynamics; remote sensing; GIS; Shanghai; China
Background In the past, many data collection systems were in operation for different HIV/AIDS projects in China. We describe the creation of a unified, web-based national HIV/AIDS information system designed to streamline data collection and facilitate data use.
Methods Integration of separate HIV/AIDS data systems was carried out in three phases. Phase 1, from January 2006 to December 2007, involved creating a set of unified data collection forms that took into account existing program needs and the reporting requirements of various international organizations. Phase 2, from January to October 2007, involved creating a web-based platform to host the integrated HIV/AIDS data collection system. Phase 3, from November to December 2007, involved pilot testing the new, integrated system prior to nationwide application.
Results Eight web-based data collection subsystems based on one platform began operation on 1 January 2008. These eight subsystems cover: (i) HIV/AIDS case reporting; (ii) HIV testing and counselling; (iii) antiretroviral treatment (ART) for adults; (iv) ART for children; (v) behavioural interventions for high-risk groups; (vi) methadone maintenance treatment; (vii) sentinel and behavioural surveillance; and (viii) local county background information. The system provides real-time data to monitor HIV testing, prevention and treatment programs across the country.
Conclusion China’s new unified, web-based HIV/AIDS information system has improved the efficiency of data collection, reporting, analysis and use, as well as data quality and security. It is a powerful tool to support policy making, program evaluation and implementation of the national HIV/AIDS program and, thus, may serve a model for other countries.
doi:10.1093/ije/dyq213
PMCID: PMC2992618
PMID: 21113041
HIV/AIDS; information system; web-based; surveillance; monitoring and evaluation; unified; China
AIM: To investigate the clinical significance of C-reactive protein (CRP) values in determining the endpoint of antibiotic treatment for liver abscess after drainage.
METHODS: The endpoints of antibiotic treatment in 46 patients with pyogenic liver abscess after complete percutaneous drainage were assessed by performing a retrospective study. After complete percutaneous drainage, normal CRP values were considered as the endpoint in 18 patients (experimental group), and normal body temperature for at least 2 wk were considered as the endpoints in the other 28 patients (control group).
RESULTS: The duration of antibiotic treatment after complete percutaneous drainage was 15.83 ± 6.45 d and 24.25 ± 8.18 d for the experimental and the control groups, respectively (P = 0.001), being significantly shorter in the experimental group than in the control group. The recurrence rate was 0% for both groups. However, we could not obtain the follow-up data about 3 patients in the control group.
CONCLUSION: CRP values can be considered as an independent factor to determine the duration of the antibiotic treatment for pyogenic liver abscess after complete percutaneous drainage.
doi:10.3748/wjg.v16.i38.4871
PMCID: PMC2955259
PMID: 20939118
Liver abscess; C-reactive protein; Antibiotic treatment; Drainage; Retrospective studies
Ma, Wei | Detels, Roger | Feng, Yuji | Wu, Zunyou | Shen, Limei | Li, Yu | Li, Zezhen | Chen, Fang | Wang, Aimin | Liu, Taiming
Objectives
To find and compare the levels of acceptance of and barriers to voluntary counselling and testing (VCT) among adults in two different counties of Guizhou province, China, one in which the China CARES project was operating and the other in which it was not.
Design
A longitudinal design with two-stage cluster sampling was employed.
Methods
A total of 1012 participants were recruited in the two counties. All participants were interviewed, then given a coupon for free VCT after the interview. Participants were paid for returning the coupon within 2 months, whether tested or not. The uptake of VCT was measured within 2 months after the interview.
Results
The study found that the levels of HIV/AIDS knowledge and acceptability of VCT among the adults in both counties were low. Although 459 participants (43.5%) expressed an intent to use the VCT services, only 193 (16.5%) actually visited the VCT facilities, and only 42 (3.7%) actually took an HIV test within 2 months after the interview. The use of VCT was related to occupation, age, transportation difficulties, health status, ethnicity, and high-risk behaviors. The main barriers to HIV testing included perceiving oneself as low risk, fear of unsolicited disclosure, and fear of stigma and discrimination that would result from taking the test.
Conclusion
Education about HIV/AIDS and VCT needs to be improved, and levels of stigma and discrimination reduced, in order to enhance the uptake of VCT services, an essential step for the initiation of treatment.
doi:10.1097/01.aids.0000304708.64294.3f
PMCID: PMC2903547
PMID: 18172381
attitudes and practices; China; HIV; knowledge; voluntary counselling and HIV testing
As glucose is known to induce insulin secretion in pancreatic β cells, this study investigated the role of a phospholipase D (PLD)-related signaling pathway in insulin secretion caused by high glucose in the pancreatic β-cell line MIN6N8. It was found that the PLD activity and PLD1 expression were both increased by high glucose (33.3 mM) treatment. The dominant negative PLD1 inhibited glucose-induced Beta2 expression, and glucose-induced insulin secretion was blocked by treatment with 1-butanol or PLD1-siRNA. These results suggest that high glucose increased insulin secretion through a PLD1-related pathway. High glucose induced the binding of Arf6 to PLD1. Pretreatment with brefeldin A (BFA), an Arf inhibitor, decreased the PLD activity as well as the insulin secretion. Furthermore, BFA blocked the glucose-induced mTOR and p70S6K activation, while mTOR inhibition with rapamycin attenuated the glucose induced Beta2 expression and insulin secretion. Thus, when taken together, PLD1 would appear to be an important regulator of glucose-induced insulin secretion through an Arf6/PLD1/mTOR/p70S6K/Beta2 pathway in MIN6N8 cells.
doi:10.3858/emm.2010.42.6.047
PMCID: PMC2892599
PMID: 20448441
ADP-ribosylation factor 6; insulin; insulin-secreting cells; mTOR protein; phospholipase D1