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1.  Population Explosion in the Yellow-Spined Bamboo Locust Ceracris kiangsu and Inferences for the Impact of Human Activity 
PLoS ONE  2014;9(3):e89873.
Geographic distance and geographical barriers likely play a considerable role in structuring genetic variation in species, although some migratory species may have less phylogeographic structure on a smaller spatial scale. Here, genetic diversity and the phylogenetic structure among geographical populations of the yellow-spined bamboo locust, Ceracris kiangsu, were examined with 16S rDNA and amplified fragment length polymorphisms (AFLPs). In this study, no conspicuous phylogeographical structure was discovered from either Maximum parsimony (MP) and Neighbor-joining (NJ) phylogenetic analyses. The effect of geographical isolation was not conspicuous on a large spatial scale.At smaller spatial scales local diversity of some populations within mountainous areas were detected using Nei's genetic distance and AMOVA. There is a high level of genetic diversity and a low genetic differentiation among populations in the C. kiangsu of South and Southeast China. Our analyses indicate that C. kiangsu is a monophyletic group. Our results also support the hypothesis that the C. kiangsu population is in a primary differentiation stage. Given the mismatch distribution, it is likely that a population expansion in C. kiangsu occurred about 0.242 Ma during the Quaternary interglaciation. Based on historical reports, we conjecture that human activities had significant impacts on the C. kiangsu gene flow.
doi:10.1371/journal.pone.0089873
PMCID: PMC3946154  PMID: 24603526
2.  Sparse principal component analysis by choice of norm 
Recent years have seen the developments of several methods for sparse principal component analysis due to its importance in the analysis of high dimensional data. Despite the demonstration of their usefulness in practical applications, they are limited in terms of lack of orthogonality in the loadings (coefficients) of different principal components, the existence of correlation in the principal components, the expensive computation needed, and the lack of theoretical results such as consistency in high-dimensional situations. In this paper, we propose a new sparse principal component analysis method by introducing a new norm to replace the usual norm in traditional eigenvalue problems, and propose an efficient iterative algorithm to solve the optimization problems. With this method, we can efficiently obtain uncorrelated principal components or orthogonal loadings, and achieve the goal of explaining a high percentage of variations with sparse linear combinations. Due to the strict convexity of the new norm, we can prove the convergence of the iterative method and provide the detailed characterization of the limits. We also prove that the obtained principal component is consistent for a single component model in high dimensional situations. As illustration, we apply this method to real gene expression data with competitive results.
doi:10.1016/j.jmva.2012.07.004
PMCID: PMC3601508  PMID: 23524453
sparse principal component analysis; high-dimensional data; uncorrelated or orthogonal principal components; iterative algorithm; consistency in high-dimensional
3.  Genome-wide characterization of microRNA in foxtail millet (Setaria italica) 
BMC Plant Biology  2013;13:212.
Background
MicroRNAs (miRNAs) are a class of short non-coding, endogenous RNAs that play key roles in many biological processes in both animals and plants. Although many miRNAs have been identified in a large number of organisms, the miRNAs in foxtail millet (Setaria italica) have, until now, been poorly understood.
Results
In this study, two replicate small RNA libraries from foxtail millet shoots were sequenced, and 40 million reads representing over 10 million unique sequences were generated. We identified 43 known miRNAs, 172 novel miRNAs and 2 mirtron precursor candidates in foxtail millet. Some miRNA*s of the known and novel miRNAs were detected as well. Further, eight novel miRNAs were validated by stem-loop RT-PCR. Potential targets of the foxtail millet miRNAs were predicted based on our strict criteria. Of the predicted target genes, 79% (351) had functional annotations in InterPro and GO analyses, indicating the targets of the miRNAs were involved in a wide range of regulatory functions and some specific biological processes. A total of 69 pairs of syntenic miRNA precursors that were conserved between foxtail millet and sorghum were found. Additionally, stem-loop RT-PCR was conducted to confirm the tissue-specific expression of some miRNAs in the four tissues identified by deep-sequencing.
Conclusions
We predicted, for the first time, 215 miRNAs and 447 miRNA targets in foxtail millet at a genome-wide level. The precursors, expression levels, miRNA* sequences, target functions, conservation, and evolution of miRNAs we identified were investigated. Some of the novel foxtail millet miRNAs and miRNA targets were validated experimentally.
doi:10.1186/1471-2229-13-212
PMCID: PMC3878754  PMID: 24330712
miRNA; Foxtail millet; Expression pattern; Mirtron; miRNA*; Targets; Synteny
4.  An Alternative Model for the Role of RP2 Protein in Flagellum Assembly in the African Trypanosome* 
The Journal of Biological Chemistry  2013;289(1):464-475.
Background: RP2 function in ciliogenesis is enigmatic.
Results: Basal body tethering of TbRP2 depends only on N-terminal TOF-LisH motifs, TbRP2 depletion affects recruitment of transition zone proteins, and TbRP2 encodes the epitope recognized by YL1/2, a monoclonal antibody classically used to detect tyrosinated α-tubulin.
Conclusion: The previous model for RP2 function in trypanosomatids is questioned.
Significance: We give new insight into the assembly of the ciliary transition zone.
The tubulin cofactor C domain-containing protein TbRP2 is a basal body (centriolar) protein essential for axoneme formation in the flagellate protist Trypanosoma brucei, the causal agent of African sleeping sickness. Here, we show how TbRP2 is targeted and tethered at mature basal bodies and provide novel insight into TbRP2 function. Regarding targeting, understanding how several hundred proteins combine to build a microtubule axoneme is a fundamental challenge in eukaryotic cell biology. We show that basal body localization of TbRP2 is mediated by twinned, N-terminal TOF (TON1, OFD1, and FOP) and LisH motifs, motifs that otherwise facilitate localization of only a few conserved proteins at microtubule-organizing centers in animals, plants, and flagellate protists. Regarding TbRP2 function, there is a debate as to whether the flagellar assembly function of specialized, centriolar tubulin cofactor C domain-containing proteins is processing tubulin, the major component of axonemes, or general vesicular trafficking in a flagellum assembly context. Here we report that TbRP2 is required for the recruitment of T. brucei orthologs of MKS1 and MKS6, proteins that, in animal cells, are part of a complex that assembles at the base of the flagellum to regulate protein composition and cilium function. We also identify that TbRP2 is detected by YL1/2, an antibody classically used to detect α-tubulin. Together, these data suggest a general processing role for TbRP2 in trypanosome flagellum assembly and challenge the notion that TbRP2 functions solely in assessing tubulin “quality” prior to tubulin incorporation into the elongating axoneme.
doi:10.1074/jbc.M113.509521
PMCID: PMC3879569  PMID: 24257747
Centriole; Cilia; Protein Targeting; Trypanosoma Brucei; Tubulin; GTPase-activating Protein; Axoneme
5.  Inhibition of mitochondrial fragmentation diminishes Huntington’s disease–associated neurodegeneration 
The Journal of Clinical Investigation  2013;123(12):5371-5388.
Huntington’s disease (HD) is the result of expression of a mutated Huntingtin protein (mtHtt), and is associated with a variety of cellular dysfunctions including excessive mitochondrial fission. Here, we tested whether inhibition of excessive mitochondrial fission prevents mtHtt-induced pathology. We developed a selective inhibitor (P110-TAT) of the mitochondrial fission protein dynamin-related protein 1 (DRP1). We found that P110-TAT inhibited mtHtt-induced excessive mitochondrial fragmentation, improved mitochondrial function, and increased cell viability in HD cell culture models. P110-TAT treatment of fibroblasts from patients with HD and patients with HD with iPS cell–derived neurons reduced mitochondrial fragmentation and corrected mitochondrial dysfunction. P110-TAT treatment also reduced the extent of neurite shortening and cell death in iPS cell–derived neurons in patients with HD. Moreover, treatment of HD transgenic mice with P110-TAT reduced mitochondrial dysfunction, motor deficits, neuropathology, and mortality. We found that p53, a stress gene involved in HD pathogenesis, binds to DRP1 and mediates DRP1-induced mitochondrial and neuronal damage. Furthermore, P110-TAT treatment suppressed mtHtt-induced association of p53 with mitochondria in multiple HD models. These data indicate that inhibition of DRP1-dependent excessive mitochondrial fission with a P110-TAT–like inhibitor may prevent or slow the progression of HD.
doi:10.1172/JCI70911
PMCID: PMC3859413  PMID: 24231356
6.  Acute Inhibition of Excessive Mitochondrial Fission After Myocardial Infarction Prevents Long‐term Cardiac Dysfunction 
Background
Ischemia and reperfusion (IR) injury remains a major cause of morbidity and mortality and multiple molecular and cellular pathways have been implicated in this injury. We determined whether acute inhibition of excessive mitochondrial fission at the onset of reperfusion improves mitochondrial dysfunction and cardiac contractility postmyocardial infarction in rats.
Methods and Results
We used a selective inhibitor of the fission machinery, P110, which we have recently designed. P110 treatment inhibited the interaction of fission proteins Fis1/Drp1, decreased mitochondrial fission, and improved bioenergetics in three different rat models of IR, including primary cardiomyocytes, ex vivo heart model, and an in vivo myocardial infarction model. Drp1 transiently bound to the mitochondria following IR injury and P110 treatment blocked this Drp1 mitochondrial association. Compared with control treatment, P110 (1 μmol/L) decreased infarct size by 28±2% and increased adenosine triphosphate levels by 70+1% after IR relative to control IR in the ex vivo model. Intraperitoneal injection of P110 (0.5 mg/kg) at the onset of reperfusion in an in vivo model resulted in improved mitochondrial oxygen consumption by 68% when measured 3 weeks after ischemic injury, improved cardiac fractional shortening by 35%, reduced mitochondrial H2O2 uncoupling state by 70%, and improved overall mitochondrial functions.
Conclusions
Together, we show that excessive mitochondrial fission at reperfusion contributes to long‐term cardiac dysfunction in rats and that acute inhibition of excessive mitochondrial fission at the onset of reperfusion is sufficient to result in long‐term benefits as evidenced by inhibiting cardiac dysfunction 3 weeks after acute myocardial infarction.
doi:10.1161/JAHA.113.000461
PMCID: PMC3835263  PMID: 24103571
cardiac myocytes; Drp1; heart; mitochondria; protein‐protein interaction inhibitor
7.  A new species of Polypedilum (Uresipedilum) Oyewo & Sæther, 1998 from Zhejiang Province of Oriental China (Diptera, Chironomidae) 
ZooKeys  2013;43-49.
A new species of Polypedilum (Uresipedilum) Oyewo & Sæther, 1998, Polypedilum (Uresipedilum) minimum sp. n. is described as male. A key to adult males of the subgenus from China is presented.
doi:10.3897/zookeys.320.5147
PMCID: PMC3744150  PMID: 23950682
Chironomidae; Polypedilum (Uresipedilum); key; new species; China
8.  The effect of Chinese Jinzhida recipe on the hippocampus in a rat model of diabetes-associated cognitive decline 
Background
To investigate the effects of treatment with Multi component Chinese Medicine Jinzhida (JZD) on behavioral deficits in diabetes-associated cognitive decline (DACD) rats and verify our hypothesis that JZD treatment improves cognitive function by suppressing the endoplasmic reticulum stress (ERS) and improving insulin signaling transduction in the rats’ hippocampus.
Methods
A rat model of type 2 diabetes mellitus (T2DM) was established using high fat diet and streptozotocin (30 mg/kg, ip). Insulin sensitivity was evaluated by the oral glucose tolerance test and the insulin tolerance test. After 7 weeks, the T2DM rats were treated with JZD. The step-down test and Morris water maze were used to evaluate behavior in T2DM rats after 5 weeks of treatment with JZD. Levels of phosphorylated proteins involved in the ERS and in insulin signaling transduction pathways were assessed by Western blot for T2DM rats’ hippocampus.
Results
Compared to healthy control rats, T2DM rats initially showed insulin resistance and had declines in acquisition and retrieval processes in the step-down test and in spatial memory in the Morris water maze after 12 weeks. Performance on both the step-down test and Morris water maze tasks improved after JZD treatment. In T2DM rats, the ERS was activated, and then inhibited the insulin signal transduction pathways through the Jun NH2-terminal kinases (JNK) mediated. JZD treatment suppressed the ERS, increased insulin signal transduction, and improved insulin resistance in the rats’ hippocampus.
Conclusions
Treatment with JZD improved cognitive function in the T2DM rat model. The possible mechanism for DACD was related with ERS inducing the insulin signal transduction dysfunction in T2DM rats’ hippocampus. The JZD could reduce ERS and improve insulin signal transduction and insulin resistance in T2DM rats’ hippocampus and as a result improved the cognitive function.
doi:10.1186/1472-6882-13-161
PMCID: PMC3735391  PMID: 23829668
Diabetes; Cognitive decline; Step down test; Morris water; Immunobloting analysis; Hippocampus
9.  Regulatory Role of Hypoxia Inducible Factor in the Biological Behavior of Nucleus Pulposus Cells 
Yonsei Medical Journal  2013;54(4):807-812.
Intervertebral disc (IVD) degeneration is implicated as a major cause of low back pain. The alternated phenotypes, reduced cell survival, decreased metabolic activity, loss of matrix production and dystrophic mineralization of nucleus pulposus (NP) cells may be key contributors to progressive IVD degeneration. IVD is the largest avascular structure in the body, characterized by low oxygen tension in vivo. Hypoxia-inducible factor (HIF) is a master transcription factor that is induced upon hypoxia and directs coordinated cellular responses to hypoxic environments. This review summarizes relevant studies concerning the involvement of HIF in the regulation of biological behaviors of NP cells. We describe current data on the expression of HIF in NP cells and further discuss the various roles that HIF plays in the regulation of the phenotype, survival, metabolism, matrix production and dystrophic mineralization of NP cells. Here, we conclude that HIF may be a promising target for the prevention and treatment of IVD degeneration.
doi:10.3349/ymj.2013.54.4.807
PMCID: PMC3663214  PMID: 23709411
Hypoxia inducible factor; intervertebral disc degeneration; nucleus pulposus
10.  Undecylprodigiosin Induced Apoptosis in P388 Cancer Cells Is Associated with Its Binding to Ribosome 
PLoS ONE  2013;8(6):e65381.
Prodigiosins (PGs) are a family of natural red pigments with anticancer activity, and one member of the family has entered clinical phase II trials. However, the anticancer mechanisms of PGs remain largely unclear. This study was designed to investigate the molecular basis of anticancer activity of UP, a derivative of PGs, in P388 cells. By introducing pharmacological inhibitors and utilizing a variety of analytical approaches including western blotting, flow cytometry and confocal laser microscopy, we found that UP inhibited proliferation of P388 via arresting cells at G2/M phase and inducing cells apoptosis, which was related to the activation of P38, JNK rather than ERK1/2 signaling. ROS regeneration and acidification in cells appear not involved in UP induced apoptosis. Furthermore, utilizing mass spectrometry, sucrose density gradient fractionation and immunofluorescence staining, we discovered that UP was apparently located at ribosome. These results together indicate that ribosome may be the potential target of UP in cancer cells, which opened a new avenue in delineating the anticancer mechanism of PGs.
doi:10.1371/journal.pone.0065381
PMCID: PMC3682955  PMID: 23799011
11.  Effects of rosuvastatin on expression of angiotensin-converting enzyme 2 after vascular balloon injury in rats 
Objective
To investigate the effects and mechanisms of rosuvastatin on angiotensin -converting enzyme 2 (ACE2) in the process of neointimal formation after vascular balloon injury in rats, and to explore the effects of ACE2 and rosuvastatin in restenosis.
Methods
Thirty-six Wistar rats were randomly allocated into three groups: control group (n = 12), surgery group (n = 12), and statin group (n = 12). Aortic endothelial denudation of rats was performed using 2F balloon catheters. At days 14 and 28 after injury, aortic arteries were harvested to examine the following. Intimal thickening was examined by hematoxylin and eosin staining. We measured angiotensin II (Ang II) and angiotensin 1-7 (Ang-[1–7]) levels by a radioimmunological method or enzyme-linked immunosorbent assay. Protein and mRNA expression of ACE2 and Ang II type 1 receptor (AT1) were investigated by immunohistochemistry, Western blots, and Reverse transcriptase-polymerase chain reaction (RT-PCR). We measured changes in proliferating cell nuclear antigen (PCNA) by immunohistochemistry. The level of phosphorylated extracellular signal regulated kinase 1/2 (P-ERK1/2) was evaluated by Western blotting.
Results
Proliferation of vascular smooth muscle cells (VSMC) and intimal thickening were higher at day 14 after vascular balloon injury in the surgery group compared with the control group. Proliferation of VSMC was decreased by day 28 after injury, while intimal thickening continued. With rosuvastatin treatment, the extent of VSMC proliferation and intimal thickening was reduced at day 14 and 28 after injury. Ang II and P-ERK levels were significantly increased, Ang-(1–7) levels were significantly decreased, mRNA and protein expressions of ACE2 were significantly decreased, and AT1 expression was significantly increased at days 14 and 28 after vascular balloon injury in the surgery group compared with the control group. PCNA expression was higher in the surgery group than in the control group, and it was significantly decreased after being given rosuvastatin. Expression of ACE2 mRNA and protein, and Ang-(1–7) levels were significantly increased, while AT1 expression and levels of Ang II and P-ERK were significantly decreased in the statin group compared with the surgery group.
Conclusions
Expression of ACE2 mRNA and protein is decreased in the process of intimal thickening after balloon injury. The inhibitory effect of rosuvastatin on intimal thickening is related to upregulation of ACE2, an increase in Ang-(1–7), downregulation of AT1, and activation of the P-ERK pathway.
doi:10.3969/j.issn.1671-5411.2013.02.009
PMCID: PMC3708055  PMID: 23888175
Balloon injury; Angiotensin converting enzyme 2; Extracellular signal regulated kinase; Rosuvastatin
12.  Robust Segmentation of Overlapping Cells in Histopathology Specimens Using Parallel Seed Detection and Repulsive Level Set 
IEEE transactions on bio-medical engineering  2011;59(3):10.1109/TBME.2011.2179298.
Automated image analysis of histopathology specimens could potentially provide support for early detection and improved characterization of breast cancer. Automated segmentation of the cells comprising imaged tissue microarrays (TMA) is a prerequisite for any subsequent quantitative analysis. Unfortunately, crowding and overlapping of cells present significant challenges for most traditional segmentation algorithms. In this paper, we propose a novel algorithm which can reliably separate touching cells in hematoxylin stained breast TMA specimens which have been acquired using a standard RGB camera. The algorithm is composed of two steps. It begins with a fast, reliable object center localization approach which utilizes single-path voting followed by mean-shift clustering. Next, the contour of each cell is obtained using a level set algorithm based on an interactive model. We compared the experimental results with those reported in the most current literature. Finally, performance was evaluated by comparing the pixel-wise accuracy provided by human experts with that produced by the new automated segmentation algorithm. The method was systematically tested on 234 image patches exhibiting dense overlap and containing more than 2200 cells. It was also tested on whole slide images including blood smears and tissue microarrays containing thousands of cells. Since the voting step of the seed detection algorithm is well suited for parallelization, a parallel version of the algorithm was implemented using graphic processing units (GPU) which resulted in significant speed-up over the C/C++ implementation.
doi:10.1109/TBME.2011.2179298
PMCID: PMC3655778  PMID: 22167559
Mean Shift; Level Set; Segmentation; Seed Detection; Parallel Computing
13.  A Fast, Automatic Segmentation Algorithm for Locating and Delineating Touching Cell Boundaries in Imaged Histopathology 
Methods of information in medicine  2012;51(3):10.3414/ME11-02-0015.
Summary
Background
Automated analysis of imaged histopathology specimens could potentially provide support for improved reliability in detection and classification in a range of investigative and clinical cancer applications. Automated segmentation of cells in the digitized tissue microarray (TMA) is often the prerequisite for quantitative analysis. However overlapping cells usually bring significant challenges for traditional segmentation algorithms.
Objectives
In this paper, we propose a novel, automatic algorithm to separate overlapping cells in stained histology specimens acquired using bright-field RGB imaging.
Methods
It starts by systematically identifying salient regions of interest throughout the image based upon their underlying visual content. The segmentation algorithm subsequently performs a quick, voting based seed detection. Finally, the contour of each cell is obtained using a repulsive level set deformable model using the seeds generated in the previous step. We compared the experimental results with the most current literature, and the pixel wise accuracy between human experts' annotation and those generated using the automatic segmentation algorithm.
Results
The method is tested with 100 image patches which contain more than 1000 overlapping cells. The overall precision and recall of the developed algorithm is 90% and 78%, respectively. We also implement the algorithm on GPU. The parallel implementation is 22 times faster than its C/C++ sequential implementation.
Conclusion
The proposed overlapping cell segmentation algorithm can accurately detect the center of each overlapping cell and effectively separate each of the overlapping cells. GPU is proven to be an efficient parallel platform for overlapping cell segmentation.
doi:10.3414/ME11-02-0015
PMCID: PMC3650677  PMID: 22526139
Parallel Computing; Segmentation; Seed detection; Pathology images
14.  Characterization and Functional Analysis of the Potato Pollen-Specific Microtubule-Associated Protein SBgLR in Tobacco 
PLoS ONE  2013;8(3):e60543.
Microtubule-associated proteins play a crucial role in the regulation of microtubule dynamics, and are very important for plant cell and organ development. SBgLR is a potato pollen-specific protein, with five imperfect V-V-E-K-K-N/E-E repetitive motifs that are responsible for microtubule binding activity. In present study, SBgLR showed typical microtubule-associated protein characteristics; it bound tubulin and microtubules, and colocalized with microtubules in vitro. We also found that SBgLR could form oligomers, and that both the SBgLR monomers and oligomers bundle microtubules in vitro. Constitutive expression of SBgLR in tobacco caused curving and right-handed twisting root growth, abnormal directional cell expansion and cell layer arrangement, and pollen abortion. Immunofluorescence staining assays revealed that microtubule organization is altered in root epidermal cells in SBgLR-overexpressing lines. These suggest that SBgLR functions as a microtubule-associated protein in pollen development. Our results indicate that normal organization of MTs may be crucial for pollen development.
doi:10.1371/journal.pone.0060543
PMCID: PMC3607588  PMID: 23536914
15.  The relationship between low pH in intervertebral discs and low back pain: a systematic review 
Introduction
To systematically review the relationship between low pH in intervertebral discs and low back pain.
Material and methods
Electronic database (PubMed, ISI Web of Science, Cochrane Library, CINAHL, AMED, and China National Knowledge Infrastructure) searches and hand searching of conference proceedings were conducted. Two authors independently evaluated the methodological quality and abstracted relevant data according to standard criteria. Then the experimental methods and samples employed in the finally retrieved articles were assessed.
Results
We first retrieved 136 articles regarding pain and pH, and only 16 of them were mainly about low back pain and pH. Finally, 7 articles met our expectation to focus on the pathogenesis of low back pain caused by pH. In these 7 studies the authors held three opinions to explain the pathogenesis of low back pain in relation to low pH. First, low pH caused by lactate stimulates the muscle and increases the muscle tension, which causes low back pain. Second, low pH stimulates the nerve roots and produces the feeling of pain. Third, low pH changes the matrix metabolism, leading to neuronal death and low back pain.
Conclusions
In this systematic review we propose a new hypothesis that low back pain may be caused by low pH based on the previous literature. Further experimental studies are necessary to verify our hypothesis. This hypothesis will promote our understanding of the pathogenesis of low back pain and the development of novel diagnostic and therapeutic approaches for low back pain.
doi:10.5114/aoms.2012.32401
PMCID: PMC3542485  PMID: 23319966
low back pain; pH; acidity; intervertebral disc; systematic review
16.  DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7 
Vanadium compounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal anticancer agents in combination to its low toxicity. Here, we found a vanadium compound Van-7 as an inhibitor of Topo I other than Topo II using topoisomerase-mediated supercoiled DNA relaxation assay. Agarose gel electrophoresis and comet assay showed that Van-7 treatment did not produce cleavable complexes like HCPT, thereby suggesting that Topo I inhibition occurred upstream of the relegation step. Further studies revealed that Van-7 inhibited Topo I DNA binding involved in its intercalating DNA. Van-7 did not affect the catalytic activity of DNase I even up to100 μM. Van-7 significantly suppressed the growth of cancer cell lines with IC50 at nanomolar concentrations and arrested cell cycle of A549 cells at G2/M phase. All these results indicate that Van-7 is a potential selective Topo I inhibitor with anticancer activities as a kind of Topo I suppressor, not Topo I poison.
doi:10.1155/2012/756374
PMCID: PMC3465879  PMID: 23055949
17.  Climate Change and Children’s Health—A Call for Research on What Works to Protect Children 
Climate change is affecting and will increasingly influence human health and wellbeing. Children are particularly vulnerable to the impact of climate change. An extensive literature review regarding the impact of climate change on children’s health was conducted in April 2012 by searching electronic databases PubMed, Scopus, ProQuest, ScienceDirect, and Web of Science, as well as relevant websites, such as IPCC and WHO. Climate change affects children’s health through increased air pollution, more weather-related disasters, more frequent and intense heat waves, decreased water quality and quantity, food shortage and greater exposure to toxicants. As a result, children experience greater risk of mental disorders, malnutrition, infectious diseases, allergic diseases and respiratory diseases. Mitigation measures like reducing carbon pollution emissions, and adaptation measures such as early warning systems and post-disaster counseling are strongly needed. Future health research directions should focus on: (1) identifying whether climate change impacts on children will be modified by gender, age and socioeconomic status; (2) refining outcome measures of children’s vulnerability to climate change; (3) projecting children’s disease burden under climate change scenarios; (4) exploring children’s disease burden related to climate change in low-income countries; and (5) identifying the most cost-effective mitigation and adaptation actions from a children’s health perspective.
doi:10.3390/ijerph9093298
PMCID: PMC3499869  PMID: 23202687
climate change; child health; mechanism; mitigation; adaptation
18.  A new species of the genus Microtendipes Kieffer, 1915 (Diptera, Chironomidae) from Oriental China  
ZooKeys  2012;80-89.
A new species of the genus Microtendipes Kieffer, 1915, Microtendipes zhejiangensis sp.n., is described, and its morphological description and illustrations are given. A catalogue of the genus in Oriental Region is provided and a key to the males of Microtendipes in the Oriental Region is given.
doi:10.3897/zookeys.212.3329
PMCID: PMC3428705  PMID: 22933851
Microtendipes; new species; key; catalogue; Oriental Region
19.  Spatial clusters of suicide in Australia 
BMC Psychiatry  2012;12:86.
Background
Understanding the spatial distribution of suicide can inform the planning, implementation and evaluation of suicide prevention activity. This study explored spatial clusters of suicide in Australia, and investigated likely socio-demographic determinants of these clusters.
Methods
National suicide and population data at a statistical local area (SLA) level were obtained from the Australian Bureau of Statistics for the period of 1999 to 2003. Standardised mortality ratios (SMR) were calculated at the SLA level, and Geographic Information System (GIS) techniques were applied to investigate the geographical distribution of suicides and detect clusters of high risk in Australia.
Results
Male suicide incidence was relatively high in the northeast of Australia, and parts of the east coast, central and southeast inland, compared with the national average. Among the total male population and males aged 15 to 34, Mornington Shire had the whole or a part of primary high risk cluster for suicide, followed by the Bathurst-Melville area, one of the secondary clusters in the north coastal area of the Northern Territory. Other secondary clusters changed with the selection of cluster radius and age group. For males aged 35 to 54 years, only one cluster in the east of the country was identified. There was only one significant female suicide cluster near Melbourne while other SLAs had very few female suicide cases and were not identified as clusters. Male suicide clusters had a higher proportion of Indigenous population and lower median socio-economic index for area (SEIFA) than the national average, but their shapes changed with selection of maximum cluster radii setting.
Conclusion
This study found high suicide risk clusters at the SLA level in Australia, which appeared to be associated with lower median socio-economic status and higher proportion of Indigenous population. Future suicide prevention programs should focus on these high risk areas.
doi:10.1186/1471-244X-12-86
PMCID: PMC3464902  PMID: 22824367
20.  Two new species of Bryophaenocladius Thienemann, 1934 (Diptera, Chironomidae) from China  
ZooKeys  2012;51-60.
Two new species of Bryophaenocladius Thienemann, 1934, Bryophaenocladius mucronatus sp. n. and Bryophaenocladius parictericus sp. n. are described and illustrated as males. A key to male imagines of the genus from China is presented.
doi:10.3897/zookeys.208.3378
PMCID: PMC3406447  PMID: 22859872
Chironomidae; Bryophaenocladius; new species; key; China
21.  Polyoxygenated Sterols from the South China Sea Soft Coral Sinularia sp 
Marine Drugs  2012;10(7):1422-1432.
Chemical investigation of the ethanol extract of soft coral Sinularia sp. collected from the South China Sea led to the isolation of three new polyoxygenated sterols, (3S,23R,24S)-ergost-5-ene-3β,23α,25-triol (1), (24S)-ergostane-6-acetate-3β,5α,6β,25-tetraol (2), (24S)-ergostane-6-acetate-3β,6β,12β,25-tetraol (3) together with three known ones (4–6). The structures, including relative configurations of the new compounds (1–3), were elucidated by detailed analysis of spectroscopic data (IR, UV, NMR, MS) and by comparison with related reported compounds. The absolute configuration of 1 was further determined by modified Mosher’s method. Compound 5 exhibited moderate cytotoxicity against K562 cell line with an IC50 value of 3.18 μM, but also displayed strong lethality toward the brine shrimp Artemia salina with a LC50 value of 0.96 μM.
doi:10.3390/md10071422
PMCID: PMC3407921  PMID: 22851916
soft coral; Sinularia sp.; polyoxygenated sterols; cytotoxicity
22.  Rapid Identification of Orexin Receptor Binding Ligands Using Cell-Based Screening Accelerated with Magnetic Beads 
Molecular Biosystems  2009;6(1):102-107.
We report here a simple and rapid method by which to screen one bead one compound libraries for highly specific ligands to cell surface proteins such as G protein-coupled receptors. This protocol, which harvests “hits” in a cell-based binding screen magnetically, eliminates the most tedious aspects of previously published bead screening techniques and allows millions of different compounds to be screened rapidly and cheaply. The method is demonstrated using the Orexin Receptor 1, which resulted in the isolation of moderate potency antagonists.
doi:10.1039/b915611a
PMCID: PMC3379552  PMID: 20024071
Orexin receptor 1 peptoid magnetic screen
23.  Review of Dicrotendipes Kieffer from China (Diptera, Chironomidae)  
ZooKeys  2012;23-36.
The genus Dicrotendipes Kieffer from China, including 8 species, is reviewed. Two new species, Dicrotendipes nudus sp. n. and Dicrotendipes saetanumerosus sp. n. are described and the male imagines are illustrated; the record of Dicrotendipes fusconotatus (Kieffer) is the first for China. A key to the males of Dicrotendipes in China is given.
doi:10.3897/zookeys.183.2834
PMCID: PMC3332026  PMID: 22573947
Chironomidae; Dicrotendipes; new species; key; China
24.  Fstl1 Antagonizes BMP Signaling and Regulates Ureter Development 
PLoS ONE  2012;7(4):e32554.
Bone morphogenetic protein (BMP) signaling pathway plays important roles in urinary tract development although the detailed regulation of its activity in this process remains unclear. Here we report that follistatin-like 1 (Fstl1), encoding a secreted extracellular glycoprotein, is expressed in developing ureter and antagonizes BMP signaling activity. Mouse embryos carrying disrupted Fstl1 gene displayed prominent hydroureter arising from proximal segment and ureterovesical junction defects. These defects were associated with significant reduction in ureteric epithelial cell proliferation at E15.5 and E16.5 as well as absence of subepithelial ureteral mesenchymal cells in the urinary tract at E16.5 and E18.5. At the molecular level, increased BMP signaling was found in Fstl1 deficient ureters, indicated by elevated pSmad1/5/8 activity. In vitro study also indicated that Fstl1 can directly bind to ALK6 which is specifically expressed in ureteric epithelial cells in developing ureter. Furthermore, Sonic hedgehog (SHH) signaling, which is crucial for differentiation of ureteral subepithelial cell proliferation, was also impaired in Fstl1-/- ureter. Altogether, our data suggest that Fstl1 is essential in maintaining normal ureter development by antagonizing BMP signaling.
doi:10.1371/journal.pone.0032554
PMCID: PMC3317656  PMID: 22485132
25.  Some theoretical properties of Silverman's method for Smoothed functional principal component analysis 
Journal of multivariate analysis  2011;102(4):741-767.
Principal component analysis (PCA) is one of the key techniques in functional data analysis. One important feature of functional PCA is that there is a need for smoothing or regularizing of the estimated principal component curves. Silverman's method for smoothed functional principal component analysis is an important approach in situation where the sample curves are fully observed due to its theoretical and practical advantages. However, lack of knowledge about the theoretical properties of this method makes it difficult to generalize it to the situation where the sample curves are only observed at discrete time points. In this paper, we first establish the existence of the solutions of the successive optimization problems in this method. We then provide upper bounds for the bias parts of the estimation errors for both eigenvalues and eigenfunctions. We also prove functional central limit theorems for the variation parts of the estimation errors. As a corollary, we give the convergence rates of the estimations for eigenvalues and eigenfunctions, where these rates depend on both the sample size and the smoothing parameters. Under some conditions on the convergence rates of the smoothing parameters, we can prove the asymptotic normalities of the estimations.
doi:10.1016/j.jmva.2010.12.001
PMCID: PMC3079282  PMID: 21516205
Functional PCA; smoothing methods; roughness penalty; convergence rates; functional central limit theorem; asymptotic normality

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