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1.  Global atmospheric emissions of polycyclic aromatic hydrocarbons from 1960 to 2008 and future predictions 
Environmental science & technology  2013;47(12):6415-6424.
Global atmospheric emissions of 16 polycyclic aromatic hydrocarbons (PAHs) from 69 major sources were estimated for a period from 1960 to 2030. Regression models and a technology split method were used to estimate country and time specific emission factors, resulting in a new estimate of PAH emission factor variation among different countries and over time. PAH emissions in 2007 were spatially resolved to 0.1°× 0.1° grids based on a newly developed global high-resolution fuel combustion inventory (PKU-FUEL-2007). The global total annual atmospheric emission of 16 PAHs in 2007 was 504 Gg (331-818 Gg, as interquartile range), with residential/commercial biomass burning (60.5%), open-field biomass burning (agricultural waste burning, deforestation, and wildfire, 13.6%), and petroleum consumption by on-road motor vehicles (12.8%) as the major sources. South (87 Gg), East (111 Gg), and Southeast Asia (52 Gg) were the regions with the highest PAH emission densities, contributing half of the global total PAH emissions. Among the global total PAH emissions, 6.19% of the emissions were in the form of high molecular weight carcinogenic compounds and the percentage of the carcinogenic PAHs was higher in developing countries (6.22%) than in developed countries (5.73%), due to the differences in energy structures and the disparities of technology. The potential health impact of the PAH emissions was greatest in the parts of the world with high anthropogenic PAH emissions, because of the overlap of the high emissions and high population densities. Global total PAH emissions peaked at 592 Gg in 1995 and declined gradually to 499 Gg in 2008. Total PAH emissions from developed countries peaked at 122 Gg in the early 1970s and decreased to 38 Gg in 2008. Simulation of PAH emissions from 2009 to 2030 revealed that PAH emissions in developed and developing countries would decrease by 46-71% and 48-64%, respectively, based on the six IPCC SRES scenarios.
PMCID: PMC3753807  PMID: 23659377
Polycyclic aromatic hydrocarbons; global emission; source profile; time trend
2.  Long Term Effect of Land Reclamation from Lake on Chemical Composition of Soil Organic Matter and Its Mineralization 
PLoS ONE  2014;9(6):e99251.
Since the late 1950s, land reclamation from lakes has been a common human disturbance to ecosystems in China. It has greatly diminished the lake area, and altered natural ecological succession. However, little is known about its impact on the carbon (C) cycle. We conducted an experiment to examine the variations of chemical properties of dissolved organic matter (DOM) and C mineralization under four land uses, i.e. coniferous forest (CF), evergreen broadleaf forest (EBF), bamboo forest (BF) and cropland (CL) in a reclaimed land area from Taihu Lake. Soils and lake sediments (LS) were incubated for 360 days in the laboratory and the CO2 evolution from each soil during the incubation was fit to a double exponential model. The DOM was analyzed at the beginning and end of the incubation using UV and fluorescence spectroscopy to understand the relationships between DOM chemistry and C mineralization. The C mineralization in our study was influenced by the land use with different vegetation and management. The greatest cumulative CO2-C emission was observed in BF soil at 0–10 cm depth. The active C pool in EBF at 10–25 cm had longer (62 days) mean residence time (MRT). LS showed the highest cumulative CO2-C and shortest MRT comparing with the terrestrial soils. The carbohydrates in DOM were positively correlated with CO2-C evolution and negatively correlated to phenols in the forest soils. Cropland was consistently an outlier in relationships between DOM chemistry and CO2-evolution, highlighting the unique effects that this land use on soil C cycling, which may be attributed the tillage practices. Our results suggest that C mineralization is closely related to the chemical composition of DOM and sensitive to its variation. Conversion of an aquatic ecosystem into a terrestrial ecosystem may alter the chemical structure of DOM, and then influences soil C mineralization.
PMCID: PMC4048317  PMID: 24905998
3.  A Method of Moments Estimator for Random Effect Multivariate Meta-Analysis 
Biometrics  2012;68(4):1278-1284.
Meta-analysis is a powerful approach to combine evidence from multiple studies to make inference about one or more parameters of interest, such as regression coefficients. The validity of the fixed effect model meta-analysis depends on the underlying assumption that all studies in the meta-analysis share the same effect size. In the presence of heterogeneity, the fixed effect model incorrectly ignores the between-study variance and may yield false positive results. The random effect model takes into account both within-study and between-study variances. It is more conservative than the fixed effect model and should be favored in the presence of heterogeneity. In this paper, we develop a noniterative method of moments estimator for the between-study covariance matrix in the random effect model multivariate meta-analysis. To our knowledge, it is the first such method of moments estimator in the matrix form. We show that our estimator is a multivariate extension of DerSimonian and Laird’s univariate method of moments estimator, and it is invariant to linear transformations. In the simulation study, our method performs well when compared to existing random effect model multivariate meta-analysis approaches. We also apply our method in the analysis of a real data example.
PMCID: PMC4030295  PMID: 22551393
Between-study covariance matrix; Heterogeneity; Method of moments estimator; Multivariate meta-analysis; Random effect model
4.  Bryophyte-Cyanobacteria Associations during Primary Succession in Recently Deglaciated Areas of Tierra del Fuego (Chile) 
PLoS ONE  2014;9(5):e96081.
Bryophyte establishment represents a positive feedback process that enhances soil development in newly exposed terrain. Further, biological nitrogen (N) fixation by cyanobacteria in association with mosses can be an important supply of N to terrestrial ecosystems, however the role of these associations during post-glacial primary succession is not yet fully understood. Here, we analyzed chronosequences in front of two receding glaciers with contrasting climatic conditions (wetter vs drier) at Cordillera Darwin (Tierra del Fuego) and found that most mosses had the capacity to support an epiphytic flora of cyanobacteria and exhibited high rates of N2 fixation. Pioneer moss-cyanobacteria associations showed the highest N2 fixation rates (4.60 and 4.96 µg N g−1 bryo. d−1) very early after glacier retreat (4 and 7 years) which may help accelerate soil development under wetter conditions. In drier climate, N2 fixation on bryophyte-cyanobacteria associations was also high (0.94 and 1.42 µg N g−1 bryo. d−1) but peaked at intermediate-aged sites (26 and 66 years). N2 fixation capacity on bryophytes was primarily driven by epiphytic cyanobacteria abundance rather than community composition. Most liverworts showed low colonization and N2 fixation rates, and mosses did not exhibit consistent differences across life forms and habitat (saxicolous vs terricolous). We also found a clear relationship between cyanobacteria genera and the stages of ecological succession, but no relationship was found with host species identity. Glacier forelands in Tierra del Fuego show fast rates of soil transformation which imply large quantities of N inputs. Our results highlight the potential contribution of bryophyte-cyanobacteria associations to N accumulation during post-glacial primary succession and further describe the factors that drive N2-fixation rates in post-glacial areas with very low N deposition.
PMCID: PMC4018330  PMID: 24819926
5.  Effect of whole-body vibration for 3 months on arterial stiffness in the middle-aged and elderly 
Cardiovascular disease (CVD) is a common problem of middle-aged and older adults. Increased arterial stiffness is a CVD risk factor. Whole-body vibration (WBV) is a simple and convenient exercise for middle-aged and older adults; however, there have been few studies investigating the effect of WBV on arterial stiffness. This study mainly investigated the effect of WBV on arterial stiffness in middle-aged and older adults.
A total of 38 (21 women and 17 men) middle-aged and elderly subjects (average age, 61.9 years) were randomly divided into the WBV group and the control group for a 3-month trial. The WBV group received an intervention of 30 Hz and 3.2 g WBV in a natural full standing posture at a sports center. The brachial–ankle pulse wave velocity (baPWV), a marker of systemic arterial stiffness, and blood pressure and heart rate were measured before and after the intervention.
After 3 months, there were no significant changes in blood pressure or heart rate in both groups. However, the bilateral baPWV was significantly reduced in the WBV group (decreased by 0.65 m/second [P=0.014]; 0.63 m/second [P=0.041] in either side), but not in the control group. The comparison between the two groups was not statistically significant.
This study found that 3 months of WBV had a positive effect on arterial stiffness in middle-aged and older adults and could therefore be regarded as a supplementary exercise. Larger-scale studies are needed to confirm the effects of WBV in the future.
PMCID: PMC4026558  PMID: 24872684
whole-body vibration; arterial stiffness; middle-aged; elderly
6.  Brief Report: Concurrent cervical giant perimedullary arteriovenous fistula, aneurysm on a feeding artery of fistula and unilateral congenital carotid aplasia 
Giant perimedullary arteriovenous fistulae (GPAVFs) are extremely rare, particularly cervical GPAVFs whose incidence has not been tabulated. The occurrence of aneurysm on an artery feeding a GPAVF has previously not been described. Internal carotid artery aplasia is also very rare (0.01%). The concurrence of these disorders has previously not been recorded. We report a case of a 5-year-old female with increasing headaches, who was found to have intraventricular hemorrhage and above anomalies. Coil embolization of GPAVF and the adjacent aneurysm was attempted. Treatment was complicated by stroke and death. Embryological and anatomical factors underlying these anomalies as well as, management options are discussed.
PMCID: PMC4051907  PMID: 24920990
8.  Association between Autoimmune Rheumatic Diseases and the Risk of Dementia 
BioMed Research International  2014;2014:861812.
Aim. Autoimmune rheumatic diseases (ARD) are characterized by systemic inflammation and may affect multiple organs and cause vascular events such as ischemic stroke and acute myocardial infarction. However, the association between ARD and increased risk of dementia is uncertain. This is a retrospective cohort study to investigate and compare the risk of dementia between patients clinically diagnosed with ARD and non-ARD patients during a 5-year follow-up period. Methods. Data were obtained from the Longitudinal Health Insurance Database 2000 (LHID2000). We included 1221 patients receiving ambulatory or hospitalization care and 6105 non-ARD patients; patients were matched by sex, age, and the year of index use of health care. Each patient was studied for 5 years to identify the subsequent manifestation of dementia. The data obtained were analyzed by Cox proportional hazard regression. Results. During the 5-year follow-up period, 30 ARD (2.48%) and 141 non-ARD patients (2.31%) developed dementia. During the 5-year follow-up period, there were no significant differences in the risks of any type of dementia (adjusted hazard ratio (HR), 1.18; 95% CI, 0.79–1.76) in the ARD group after adjusting for demographics and comorbidities. Conclusions. Within the 5-year period, patients with and without ARD were found to have similar risks of developing dementia.
PMCID: PMC4022061  PMID: 24877143
9.  Projected Range Contractions of European Protected Oceanic Montane Plant Communities: Focus on Climate Change Impacts Is Essential for Their Future Conservation 
PLoS ONE  2014;9(4):e95147.
Global climate is rapidly changing and while many studies have investigated the potential impacts of this on the distribution of montane plant species and communities, few have focused on those with oceanic montane affinities. In Europe, highly sensitive bryophyte species reach their optimum occurrence, highest diversity and abundance in the north-west hyperoceanic regions, while a number of montane vascular plant species occur here at the edge of their range. This study evaluates the potential impact of climate change on the distribution of these species and assesses the implications for EU Habitats Directive-protected oceanic montane plant communities. We applied an ensemble of species distribution modelling techniques, using atlas data of 30 vascular plant and bryophyte species, to calculate range changes under projected future climate change. The future effectiveness of the protected area network to conserve these species was evaluated using gap analysis. We found that the majority of these montane species are projected to lose suitable climate space, primarily at lower altitudes, or that areas of suitable climate will principally shift northwards. In particular, rare oceanic montane bryophytes have poor dispersal capacity and are likely to be especially vulnerable to contractions in their current climate space. Significantly different projected range change responses were found between 1) oceanic montane bryophytes and vascular plants; 2) species belonging to different montane plant communities; 3) species categorised according to different biomes and eastern limit classifications. The inclusion of topographical variables in addition to climate, significantly improved the statistical and spatial performance of models. The current protected area network is projected to become less effective, especially for specialised arctic-montane species, posing a challenge to conserving oceanic montane plant communities. Conservation management plans need significantly greater focus on potential climate change impacts, including models with higher-resolution species distribution and environmental data, to aid these communities' long-term survival.
PMCID: PMC3994024  PMID: 24752011
10.  Designing Mixed Species Tree Plantations for the Tropics: Balancing Ecological Attributes of Species with Landholder Preferences in the Philippines 
PLoS ONE  2014;9(4):e95267.
A mixed species reforestation program known as the Rainforestation Farming system was undertaken in the Philippines to develop forms of farm forestry more suitable for smallholders than the simple monocultural plantations commonly used then. In this study, we describe the subsequent changes in stand structure and floristic composition of these plantations in order to learn from the experience and develop improved prescriptions for reforestation systems likely to be attractive to smallholders. We investigated stands aged from 6 to 11 years old on three successive occasions over a 6 year period. We found the number of species originally present in the plots as trees >5 cm dbh decreased from an initial total of 76 species to 65 species at the end of study period. But, at the same time, some new species reached the size class threshold and were recruited into the canopy layer. There was a substantial decline in tree density from an estimated stocking of about 5000 trees per ha at the time of planting to 1380 trees per ha at the time of the first measurement; the density declined by a further 4.9% per year. Changes in composition and stand structure were indicated by a marked shift in the Importance Value Index of species. Over six years, shade-intolerant species became less important and the native shade-tolerant species (often Dipterocarps) increased in importance. Based on how the Rainforestation Farming plantations developed in these early years, we suggest that mixed-species plantations elsewhere in the humid tropics should be around 1000 trees per ha or less, that the proportion of fast growing (and hence early maturing) trees should be about 30–40% of this initial density and that any fruit tree component should only be planted on the plantation margin where more light and space are available for crowns to develop.
PMCID: PMC3994060  PMID: 24751720
11.  The Altitudinal Patterns of Leaf C∶N∶P Stoichiometry Are Regulated by Plant Growth Form, Climate and Soil on Changbai Mountain, China 
PLoS ONE  2014;9(4):e95196.
Understanding the geographic patterns and potential drivers of leaf stoichiometry is critical for modelling the nutrient fluxes of ecosystems and to predict the responses of ecosystems to global changes. This study aimed to explore the altitudinal patterns and potential drivers of leaf C∶N∶P stoichiometry. We measured the concentrations of leaf C, N and P in 175 plant species as well as soil nutrient concentrations along an altitudinal transect (500–2300 m) on the northern slope of Changbai Mountain, China to explore the response of leaf C∶N∶P stoichiometry to plant growth form (PGF), climate and soil. Leaf C, N, P and C∶N∶P ratios showed significant altitudinal trends. In general, leaf C and C∶N∶P ratios increased while leaf N and P decreased with elevation. Woody and herbaceous species showed different responses to altitudinal gradients. Trees had the largest variation in leaf C, C∶N and C∶P ratios, while herbs showed the largest variation in leaf N, P and N∶P ratio. PGF, climate and soil jointly regulated leaf stoichiometry, explaining 17.6% to 52.1% of the variation in the six leaf stoichiometric traits. PGF was more important in explaining leaf stoichiometry variation than soil and climate. Our findings will help to elucidate the altitudinal patterns of leaf stoichiometry and to model ecosystem nutrient cycling.
PMCID: PMC3990608  PMID: 24743878
12.  Effects of Local Tree Diversity on Herbivore Communities Diminish with Increasing Forest Fragmentation on the Landscape Scale 
PLoS ONE  2014;9(4):e95551.
Forest fragmentation and plant diversity have been shown to play a crucial role for herbivorous insects (herbivores, hereafter). In turn, herbivory-induced leaf area loss is known to have direct implications for plant growth and reproduction as well as long-term consequences for ecosystem functioning and forest regeneration. So far, previous studies determined diverging responses of herbivores to forest fragmentation and plant diversity. Those inconsistent results may be owed to complex interactive effects of both co-occurring environmental factors albeit they act on different spatial scales. In this study, we investigated whether forest fragmentation on the landscape scale and tree diversity on the local habitat scale show interactive effects on the herbivore community and leaf area loss in subtropical forests in South Africa. We applied standardized beating samples and a community-based approach to estimate changes in herbivore community composition, herbivore abundance, and the effective number of herbivore species on the tree species-level. We further monitored leaf area loss to link changes in the herbivore community to the associated process of herbivory. Forest fragmentation and tree diversity interactively affected the herbivore community composition, mainly by a species turnover within the family of Curculionidae. Furthermore, herbivore abundance increased and the number of herbivore species decreased with increasing tree diversity in slightly fragmented forests whereas the effects diminished with increasing forest fragmentation. Surprisingly, leaf area loss was neither affected by forest fragmentation or tree diversity, nor by changes in the herbivore community. Our study highlights the need to consider interactive effects of environmental changes across spatial scales in order to draw reliable conclusions for community and interaction patterns. Moreover, forest fragmentation seems to alter the effect of tree diversity on the herbivore community, and thus, has the potential to jeopardize ecosystem functioning and forest regeneration.
PMCID: PMC3990639  PMID: 24743315
13.  Antioxidative Potential of Duranta Repens (Linn.) Fruits Against H2O2 Induced Cell Death In Vitro 
The effects of Duranta repens fruits were investigated on H2O2 induced oxidative cell death to evaluate its antioxidative potential in vitro. HEK293T cells were treated with different concentrations [0–1000 µg/ ml] of ethanol extract (E-Ex) and methanol extract (M-Ex) of D. repens for 24h, and then treated with 100 µM H2O2 for 24h. Cell viability, antioxidant parameters of cells, and antioxidant constituents of the extracts were determined. Treatment with limited dose of E-Ex or M-Ex increased the survival rate of H2O2-treated HEK293T cells, however the extra-high dose showed growth inhibitory effect. Treatment with E-Ex or M-Ex protected cellular lipid per-oxidation. In vitro analyses showed the 2,2-diphenyl-1-picrylhydrazyl and H2O2 scavenging activities as well as reducing potential of the extracts. We report here that the limited dose of E-Ex and M-Ex possess antioxidative potential, which can protect H2O2-induced oxidative cell damage.
PMCID: PMC3777584  PMID: 24146472
Duranta repens (Linn.); Oxidative cell death; Lipid per-oxidation; Antioxidant; Phytochemicals
14.  Biomass Allocation Patterns across China’s Terrestrial Biomes 
PLoS ONE  2014;9(4):e93566.
Root to shoot ratio (RS) is commonly used to describe the biomass allocation between below- and aboveground parts of plants. Determining the key factors influencing RS and interpreting the relationship between RS and environmental factors is important for biological and ecological research. In this study, we compiled 2088 pairs of root and shoot biomass data across China’s terrestrial biomes to examine variations in the RS and its responses to biotic and abiotic factors including vegetation type, soil texture, climatic variables, and stand age. The median value of RS (RSm) for grasslands, shrublands, and forests was 6.0, 0.73, and 0.23, respectively. The range of RS was considerably wide for each vegetation type. RS values for all three major vegetation types were found to be significantly correlated to mean annual precipitation (MAP) and potential water deficit index (PWDI). Mean annual temperature (MAT) also significantly affect the RS for forests and grasslands. Soil texture and forest origin altered the response of RS to climatic factors as well. An allometric formula could be used to well quantify the relationship between aboveground and belowground biomass, although each vegetation type had its own inherent allometric relationship.
PMCID: PMC3977935  PMID: 24710503
15.  Regulatory Effects of Resveratrol on Antioxidant Enzymes: a Mechanism of Growth Inhibition and Apoptosis Induction in Cancer Cells 
Molecules and Cells  2013;35(3):219-225.
Resveratrol (RSV) is a natural polyphenol that is known as a powerful chemopreventive and chemotherapeutic anticancer molecule. This study focused on the effects of RSV on the activities and expression levels of antioxidant enzymes in the cancer cells. Prostate cancer PC-3 cells, hepatic cancer HepG2 cells, breast cancer MCF-7 cells and the non-cancerous HEK293T kidney epithelial cells were treated with a wide range of RSV concentrations (10–100 μM) for 24–72 h. Cell growth was estimated by trypan blue staining, activities of the antioxidant enzymes were measured spectrophotometrically, expression levels of the antioxidant enzymes were quantified by digitalizing the protein band intensities on Western blots, and the percentage of apoptotic cells was determined by flow cytometry. Treatment with a low concentration of RSV (25 μM) significantly increased superoxide dismutase (SOD) activity in PC-3, HepG2 and MCF-7 cells, but not in HEK293T cells. Catalase (CAT) activity was increased in HepG2 cells, but no effect was found on glutathione peroxidase (GPX) upon RSV treatment. RSV-induced SOD2 expression was observed in cancer cells, although the expression of SOD1, CAT and GPX1 was unaffected. Apoptosis increased upon RSV treatment of cancer cells, especially in PC-3 and HepG2 cells. Together, our data demonstrated that RSV inhibits cancer cell growth with minimal effects on non-cancerous cells. We postulate that the disproportional up-regulation of SOD, CAT and GPX expression and enzymatic activity in cancer cells results in the mitochondrial accumulation of H2O2, which in turn induces cancer cell apoptosis.
PMCID: PMC3887918  PMID: 23456297
Apoptosis; HepG2 cells; MCF-7 cells; PC-3 cells; resveratrol; superoxide dismutase
16.  Quantification of mitochondrial toxicity in HIV-infected individuals by quantitative PCR compared to flow cytometry 
Non-invasive diagnostic assays to evaluate mitochondrial toxicity could have significant clinical utility for HIV-infected individuals on antiretroviral therapy (ART).
This study compared the ratio of mitochondrial to nuclear DNA determined by quantitative PCR to the ratio of mitochondrial to nuclear-encoded proteins by flow cytometry, in peripheral blood mononuclear cells from 73 HIV-infected individuals with and without risk factors for mitochondrial toxicity.
PCR detected similar mitochondrial/nuclear DNA in HIV-infected individuals without a history of ART, and those receiving ART with lipodystrophy, lipoatrophy or a history of suspected lactic acidosis. However, the ratio was significantly greater in ART-untreated compared to those receiving either stavudine or didanosine. In contrast, flow cytometry did not detect any differences in mitochondrial/nuclear protein (1). There was no correlation between the assays (rho = −0.05, p = 0.65).
Assessment of the mitochondrial/nuclear DNA ratio by quantitative PCR performed better than the mitochondrial/nuclear-encoded protein ratio by flow cytometry to detect adverse effects of nucleoside analogues on mitochondria.
PMCID: PMC3966180  PMID: 23044657
HIV; Antiretroviral Therapy; Mitochondrial Toxicity; Flow Cytometry; Quantitative PCR; Diagnostics
17.  Elevated Atmospheric CO2 Triggers Compensatory Feeding by Root Herbivores on a C3 but Not a C4 Grass 
PLoS ONE  2014;9(3):e90251.
Predicted increases in atmospheric carbon dioxide (CO2) concentrations often reduce nutritional quality for herbivores by increasing the C∶N ratio of plant tissue. This frequently triggers compensatory feeding by aboveground herbivores, whereby they consume more shoot material in an attempt to meet their nutritional needs. Little, however, is known about how root herbivores respond to such changes. Grasslands are particularly vulnerable to root herbivores, which can collectively exceed the mass of mammals grazing aboveground. Here we provide novel evidence for compensatory feeding by a grass root herbivore, Sericesthis nigrolineata, under elevated atmospheric CO2 (600 µmol mol−1) on a C3 (Microlaena stipoides) but not a C4 (Cymbopogon refractus) grass species. At ambient CO2 (400 µmol mol−1) M. stipoides roots were 44% higher in nitrogen (N) and 7% lower in carbon (C) concentrations than C. refractus, with insects performing better on M. stipoides. Elevated CO2 decreased N and increased C∶N in M. stipoides roots, but had no impact on C. refractus roots. Root-feeders displayed compensatory feeding on M. stipoides at elevated CO2, consuming 118% more tissue than at ambient atmospheric CO2. Despite this, root feeder biomass remained depressed by 24%. These results suggest that compensatory feeding under elevated atmospheric CO2 may make some grass species particularly vulnerable to attack, potentially leading to future shifts in the community composition of grasslands.
PMCID: PMC3961222  PMID: 24651855
18.  Allele-Specific Knockdown of ALS-Associated Mutant TDP-43 in Neural Stem Cells Derived from Induced Pluripotent Stem Cells 
PLoS ONE  2014;9(3):e91269.
TDP-43 is found in cytoplasmic inclusions in 95% of amyotrophic lateral sclerosis (ALS) and 60% of frontotemporal lobar degeneration (FTLD). Approximately 4% of familial ALS is caused by mutations in TDP-43. The majority of these mutations are found in the glycine-rich domain, including the variant M337V, which is one of the most common mutations in TDP-43. In order to investigate the use of allele-specific RNA interference (RNAi) as a potential therapeutic tool, we designed and screened a set of siRNAs that specifically target TDP-43M337V mutation. Two siRNA specifically silenced the M337V mutation in HEK293T cells transfected with GFP-TDP-43wt or GFP-TDP-43M337V or TDP-43 C-terminal fragments counterparts. C-terminal TDP-43 transfected cells show an increase of cytosolic inclusions, which are decreased after allele-specific siRNA in M337V cells. We then investigated the effects of one of these allele-specific siRNAs in induced pluripotent stem cells (iPSCs) derived from an ALS patient carrying the M337V mutation. These lines showed a two-fold increase in cytosolic TDP-43 compared to the control. Following transfection with the allele-specific siRNA, cytosolic TDP-43 was reduced by 30% compared to cells transfected with a scrambled siRNA. We conclude that RNA interference can be used to selectively target the TDP-43M337V allele in mammalian and patient cells, thus demonstrating the potential for using RNA interference as a therapeutic tool for ALS.
PMCID: PMC3961241  PMID: 24651281
19.  Secondary oligodendroglioma after postoperative irradiation for medulloblastoma: a case report and review of the literature 
Medulloblastoma, a malignant, invasive embryonal tumor of the cerebellum, occurs most often in children. It has high metastatic potential and is usually treated by aggressive multimodal therapy, including surgery, chemotherapy and craniospinal irradiation. Multiple secondary tumors have been reported following craniospinal irradiation. It is rare with the occurrence of oligodendroglioma after irradiation. In this report, we described a patient with secondary oligodendroglioma after postoperative craniospinal irradiation for medulloblastoma.
PMCID: PMC4014266  PMID: 24817982
Medulloblastoma; oligodendroglioma; radiation-induced glioma
20.  Differential roles of the ubiquitin proteasome system and autophagy in the clearance of soluble and aggregated TDP-43 species 
Journal of Cell Science  2014;127(6):1263-1278.
TAR DNA-binding protein (TDP-43, also known as TARDBP) is the major pathological protein in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Large TDP-43 aggregates that are decorated with degradation adaptor proteins are seen in the cytoplasm of remaining neurons in ALS and FTD patients post mortem. TDP-43 accumulation and ALS-linked mutations within degradation pathways implicate failed TDP-43 clearance as a primary disease mechanism. Here, we report the differing roles of the ubiquitin proteasome system (UPS) and autophagy in the clearance of TDP-43. We have investigated the effects of inhibitors of the UPS and autophagy on the degradation, localisation and mobility of soluble and insoluble TDP-43. We find that soluble TDP-43 is degraded primarily by the UPS, whereas the clearance of aggregated TDP-43 requires autophagy. Cellular macroaggregates, which recapitulate many of the pathological features of the aggregates in patients, are reversible when both the UPS and autophagy are functional. Their clearance involves the autophagic removal of oligomeric TDP-43. We speculate that, in addition to an age-related decline in pathway activity, a second hit in either the UPS or the autophagy pathway drives the accumulation of TDP-43 in ALS and FTD. Therapies for clearing excess TDP-43 should therefore target a combination of these pathways.
PMCID: PMC3953816  PMID: 24424030
TDP-43; ALS; Autophagy; Proteasome; Aggrephagy; UPS
21.  Encouraging Family Forest Owners to Create Early Successional Wildlife Habitat in Southern New England 
PLoS ONE  2014;9(2):e89972.
Encouraging family forest owners to create early successional habitat is a high priority for wildlife conservation agencies in the northeastern USA, where most forest land is privately owned. Many studies have linked regional declines in wildlife populations to the loss of early successional habitat. The government provides financial incentives to create early successional habitat, but the number of family forest owners who actively manage their forests remains low. Several studies have analyzed participation of family forest owners in federal forestry programs, but no study to date has focused specifically on creation of wildlife habitat. The objective of our study was to analyze the experience of a group of wildlife-oriented family forest owners who were trained to create early successional habitat. This type of family forest owners represents a small portion of the total population of family forest owners, but we believe they can play an important role in creating wildlife habitat, so it is important to understand how outreach programs can best reach them. The respondents shared some characteristics but differed in terms of forest holdings, forestry experience and interest in earning forestry income. Despite their strong interest in wildlife, awareness about the importance of early successional habitat was low. Financial support from the federal government appeared to be important in motivating respondents to follow up after the training with activities on their own properties: 84% of respondents who had implemented activities received federal financial support and 47% would not have implemented the activities without financial assistance. In order to mobilize greater numbers of wildlife-oriented family forest owners to create early successional habitat we recommend focusing outreach efforts on increasing awareness about the importance of early successional habitat and the availability of technical and financial assistance.
PMCID: PMC3935950  PMID: 24587160
22.  A Phenological Timetable of Oak Growth under Experimental Drought and Air Warming 
PLoS ONE  2014;9(2):e89724.
Climate change is expected to increase temperature and decrease summer precipitation in Central Europe. Little is known about how warming and drought will affect phenological patterns of oaks, which are considered to possess excellent adaptability to these climatic changes. Here, we investigated bud burst and intra-annual shoot growth of Quercus robur, Q. petraea and Q. pubescens grown on two different forest soils and exposed to air warming and drought. Phenological development was assessed over the course of three growing seasons. Warming advanced bud burst by 1–3 days °C−1 and led to an earlier start of intra-annual shoot growth. Despite this phenological shift, total time span of annual growth and shoot biomass were not affected. Drought changed the frequency and intensity of intra-annual shoot growth and advanced bud burst in the subsequent spring of a severe summer drought by 1–2 days. After re-wetting, shoot growth recovered within a few days, demonstrating the superior drought tolerance of this tree genus. Our findings show that phenological patterns of oaks are modified by warming and drought but also suggest that ontogenetic factors and/or limitations of water and nutrients counteract warming effects on the biomass and the entire span of annual shoot growth.
PMCID: PMC3933646  PMID: 24586988
23.  Meta-Analysis of Pollen Limitation Reveals the Relevance of Pollination Generalization in the Atlantic Forest of Brazil 
PLoS ONE  2014;9(2):e89498.
Despite the extensive knowledge of pollen limitation in angiosperms, its assessment within tropical forests is still limited. Especially lacking are large scale comparisons of species within this biome – one that is highly diverse but also becoming increasingly threatened. In fact, many tropical plant species depend upon pollinators for reproduction but evaluation of the impact of this dependence via different levels of pollination specialization has yet to be made at the biome scale. We assessed the occurrence and magnitude of pollen limitation for species in the Brazilian Atlantic forest and tested the association of pollination specialization, breeding system, and life habit with pollination efficiency. We compiled data from studies published between 1985 and 2012. We calculated species' effect size (d) from data on fruit set after hand cross-pollination and natural pollination and conducted standard and phylogenetically independent meta-analysis. Overall pollen limitation was moderate, with magnitude of 0.50, and 95% confidence interval [0.37, 0.62] for 126 species. Pollen limitation was observed in 39% of species. Pollination specialization was the factor that best explained the occurrence of pollen limitation. Specifically, phenotypic and ecological specialists (plants with zygomorphic flowers and pollinated by one species of pollinator, respectively) had higher pollen limitation than generalist plants (actinomorphic flowers and pollination by two or more species). Functional generalists (plants pollinated by three or more functional groups) were not pollen limited. On the other hand, breeding system and life habit were not associated to pollen limitation. Pollen limitation was observed in the Atlantic forest and its magnitude was comparable to that for angiosperms as a whole. The finding that pollination specialization was the strongest predictor of pollen limitation suggests that specialist plants in this biome may be most prone to the reproductive failure as a result of pollinator loss.
PMCID: PMC3931788  PMID: 24586827
24.  Probing substrate influence on graphene by analyzing Raman lineshapes 
We provide a new approach to identify the substrate influence on graphene surface. Distinguishing the substrate influences or the doping effects of charged impurities on graphene can be realized by optically probing the graphene surfaces, included the suspended and supported graphene. In this work, the line scan of Raman spectroscopy was performed across the graphene surface on the ordered square hole. Then, the bandwidths of G-band and 2D-band were fitted into the Voigt profile, a convolution of Gaussian and Lorentzian profiles. The bandwidths of Lorentzian parts were kept as constant whether it is the suspended and supported graphene. For the Gaussian part, the suspended graphene exhibits much greater Gaussian bandwidths than those of the supported graphene. It reveals that the doping effect on supported graphene is stronger than that of suspended graphene. Compared with the previous studies, we also used the peak positions of G bands, and I2D/IG ratios to confirm that our method really works. For the suspended graphene, the peak positions of G band are downshifted with respect to supported graphene, and the I2D/IG ratios of suspended graphene are larger than those of supported graphene. With data fitting into Voigt profile, one can find out the information behind the lineshapes.
PMCID: PMC3924919  PMID: 24506825
Substrate influence; Graphene; Raman lineshapes; Voigt fitting
25.  Sequence Kernel Association Test for Quantitative Traits in Family Samples 
Genetic epidemiology  2012;37(2):196-204.
A large number of rare genetic variants have been discovered with the development in sequencing technology and the lowering of sequencing costs. Rare variant analysis may help identify novel genes associated with diseases and quantitative traits, adding to our knowledge of explaining heritability of these phenotypes. Many statistical methods for rare variant analysis have been developed in recent years, but some of them require the strong assumption that all rare variants in the analysis share the same direction of effect, and others requiring permutation to calculate the p-values are computer intensive. Among these methods, the sequence kernel association test (SKAT) is a powerful method under many different scenarios. It does not require any assumption on the directionality of effects, and statistical significance is computed analytically. In this paper, we extend SKAT to be applicable to family data. The family-based SKAT (famSKAT) has a different test statistic and null distribution compared to SKAT, but is equivalent to SKAT when there is no familial correlation. Our simulation studies show that SKAT has inflated type I error if familial correlation is inappropriately ignored, but has appropriate type I error if applied to a single individual per family to obtain an unrelated subset. In the contrast, famSKAT has the correct type I error when analyzing correlated observations, and it has higher power than competing methods in many different scenarios. We illustrate our approach to analyze the association of rare genetic variants using glycemic traits from the Framingham Heart Study.
PMCID: PMC3642218  PMID: 23280576
rare variant analysis; quantitative traits; family samples; heritability; linear mixed effects model

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