Global lung function initiative 2012 reference values for spirometry in Asian Americans

Background Spirometry reference values specifically designed for Asian Americans are currently unavailable. The performance of Global Lung Function Initiative 2012 (GLI-2012) equations on assessing spirometry in Asian Americans has not been evaluated. This study aimed to assess the fitness of relevant GLI-2012 equations for spirometry in Asian Americans. Methods Asian subjects who never smoked and had qualified spirometry data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Z-scores of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were separately constructed with GLI-2012 equations for North East (NE) Asians, South East (SE) Asians, and individuals of mixed ethnic origin (Mixed). In addition, Proportions of subjects with observed spirometry data below the lower limit of normal (LLN) were also evaluated on each GLI-2012 equation of interest. Results This study included 567 subjects (250 men and 317 women) aged 6–79 years. Spirometry z-scores (z-FEV1, z-FVC, and z-FEV1/FVC) based on GLI-2012 Mixed equations had mean values close to zero (− 0.278 to − 0.057) and standard deviations close to one (1.001 to 1.128); additionally, 6.0% (95% confidence interval (CI) 3.1–8.9%) and 6.4% (95% CI 3.7–9.1%) of subjects were with observed data below LLN for FEV1/FVC in men and women, respectively. In contrast, for NE Asian equations, all mean values of z-FEV1 and z-FVC were smaller than − 0.5; for SE Asian equations, mean values of z-FEV1/FVC were significantly smaller than zero in men (− 0.333) and women (− 0.440). Conclusions GLI-2012 equations for individuals of mixed ethnic origin adequately fitted spirometry data in this sample of Asian Americans. Future studies with larger sample sizes are needed to confirm these findings

A Putative Transcription Factor MYT2 Regulates Perithecium Size in the Ascomycete Gibberella zeae

The homothallic ascomycete fungus Gibberella zeae is a plant pathogen that is found worldwide, causing Fusarium head blight (FHB) in cereal crops and ear rot of maize. Ascospores formed in fruiting bodies (i.e., perithecia) are hypothesized to be the primary inocula for FHB disease. Perithecium development is a complex cellular differentiation process controlled by many developmentally regulated genes. In this study, we selected a previously reported putative transcription factor containing the Myb DNA-binding domain MYT2 for an in-depth study on sexual development. The deletion of MYT2 resulted in a larger perithecium, while its overexpression resulted in a smaller perithecium when compared to the wild-type strain. These data suggest that MYT2 regulates perithecium size differentiation. MYT2 overexpression affected pleiotropic phenotypes including vegetative growth, conidia production, virulence, and mycotoxin production. Nuclear localization of the MYT2 protein supports its role as a transcriptional regulator. Transcriptional analyses of trichothecene synthetic genes suggest that MYT2 additionally functions as a suppressor for trichothecene production. This is the first study characterizing a transcription factor required for perithecium size differentiation in G. zeae, and it provides a novel angle for understanding sexual development in filamentous fungi

Curcumin-Loaded Apotransferrin Nanoparticles Provide Efficient Cellular Uptake and Effectively Inhibit HIV-1 Replication In Vitro

Curcumin (diferuloylmethane) shows significant activity across a wide spectrum of conditions, but its usefulness is rather limited because of its low bioavailability. Use of nanoparticle formulations to enhance curcumin bioavailability is an emerging area of research.In the present study, curcumin-loaded apotransferrin nanoparticles (nano-curcumin) prepared by sol-oil chemistry and were characterized by electron and atomic force microscopy. Confocal studies and fluorimetric analysis revealed that these particles enter T cells through transferrin-mediated endocytosis. Nano-curcumin releases significant quantities of drug gradually over a fairly long period, ∼50% of curcumin still remaining at 6 h of time. In contrast, intracellular soluble curcumin (sol-curcumin) reaches a maximum at 2 h followed by its complete elimination by 4 h. While sol-curcumin (GI(50) = 15.6 µM) is twice more toxic than nano-curcumin (GI(50) = 32.5 µM), nano-curcumin (IC(50)<1.75 µM) shows a higher anti-HIV activity compared to sol-curcumin (IC(50) = 5.1 µM). Studies in vitro showed that nano-curcumin prominently inhibited the HIV-1 induced expression of Topo II α, IL-1β and COX-2, an effect not seen with sol-curcumin. Nano-curcumin did not affect the expression of Topoisomerase II β and TNF α. This point out that nano-curcumin affects the HIV-1 induced inflammatory responses through pathways downstream or independent of TNF α. Furthermore, nano-curcumin completely blocks the synthesis of viral cDNA in the gag region suggesting that the nano-curcumin mediated inhibition of HIV-1 replication is targeted to viral cDNA synthesis.Curcumin-loaded apotransferrin nanoparticles are highly efficacious inhibitors of HIV-1 replication in vitro and promise a high potential for clinical usefulness

A Putative Transcription Factor MYT1 Is Required for Female Fertility in the Ascomycete Gibberella zeae

Gibberella zeae is an important pathogen of major cereal crops. The fungus produces ascospores that forcibly discharge from mature fruiting bodies, which serve as the primary inocula for disease epidemics. In this study, we characterized an insertional mutant Z39P105 with a defect in sexual development and identified a gene encoding a putative transcription factor designated as MYT1. This gene contains a Myb DNA-binding domain and is conserved in the subphylum Pezizomycotina of Ascomycota. The MYT1 protein fused with green fluorescence protein localized in nuclei, which supports its role as a transcriptional regulator. The MYT1 deletion mutant showed similar phenotypes to the wild-type strain in vegetative growth, conidia production and germination, virulence, and mycotoxin production, but had defect in female fertility. A mutant overexpressing MYT1 showed earlier germination, faster mycelia growth, and reduced mycotoxin production compared to the wild-type strain, suggesting that improper MYT1 expression affects the expression of genes involved in the cell cycle and secondary metabolite production. This study is the first to characterize a transcription factor containing a Myb DNA-binding domain that is specific to sexual development in G. zeae

OBILJEŽJA POČINITELJA NASILNIČKIH DELIKATA NA PODRUČJU PRIMORSKO-GORANSKE ŽUPANIJE OBZIROM NA POVRAT

Availability of sophisticated statistical modelling for developing robust reference equations has improved interpretation of lung function results. In 2012, the Global Lung function Initiative(GLI) published the first global all-age, multi-ethnic reference equations for spirometry but these lacked equations for those originating from the Indian subcontinent (South-Asians). The aims of this study were to assess the extent to which existing GLI-ethnic adjustments might fit South-Asian paediatric spirometry data, assess any similarities and discrepancies between South-Asian datasets and explore the feasibility of deriving a suitable South-Asian GLI-adjustment. Methods: Spirometry datasets from South-Asian children were collated from four centres in India and five within the UK. Records with transcription errors, missing values for height or spirometry, and implausible values were excluded(n=110). Results: Following exclusions, cross-sectional data were available from 8,124 children (56.3% male; 5-17 years). When compared with GLI-predicted values from White Europeans, forced expired volume in 1s (FEV1) and forced vital capacity (FVC) in South-Asian children were on average 15% lower, ranging from 4-19% between centres. By contrast, proportional reductions in FEV1 and FVC within all but two datasets meant that the FEV1/FVC ratio remained independent of ethnicity. The ‘GLI-Other’ equation fitted data from North India reasonably well while ‘GLI-Black’ equations provided a better approximation for South-Asian data than the ‘GLI-White’ equation. However, marked discrepancies in the mean lung function z-scores between centres especially when examined according to socio-economic conditions precluded derivation of a single South-Asian GLI-adjustment. Conclusion: Until improved and more robust prediction equations can be derived, we recommend the use of ‘GLI-Black’ equations for interpreting most South-Asian data, although ‘GLI-Other’ may be more appropriate for North Indian data. Prospective data collection using standardised protocols to explore potential sources of variation due to socio-economic circumstances, secular changes in growth/predictors of lung function and ethnicities within the South-Asian classification are urgently required

Calpain Cleavage of Brain Glutamic Acid Decarboxylase 65 Is Pathological and Impairs GABA Neurotransmission

Previously, we have shown that the GABA synthesizing enzyme, L-glutamic acid decarboxylase 65 (GAD65) is cleaved to form its truncated form (tGAD65) which is 2–3 times more active than the full length form (fGAD65). The enzyme responsible for cleavage was later identified as calpain. Calpain is known to cleave its substrates either under a transient physiological stimulus or upon a sustained pathological insult. However, the precise role of calpain cleavage of fGAD65 is poorly understood. In this communication, we examined the cleavage of fGAD65 under diverse pathological conditions including rats under ischemia/reperfusion insult as well as rat brain synaptosomes and primary neuronal cultures subjected to excessive stimulation with high concentration of KCl. We have shown that the formation of tGAD65 progressively increases with increasing stimulus concentration both in rat brain synaptosomes and primary rat embryo cultures. More importantly, direct cleavage of synaptic vesicle - associated fGAD65 by calpain was demonstrated and the resulting tGAD65 bearing the active site of the enzyme was detached from the synaptic vesicles. Vesicular GABA transport of the newly synthesized GABA was found to be reduced in calpain treated SVs. Furthermore, we also observed that the levels of tGAD65 in the focal cerebral ischemic rat brain tissue increased corresponding to the elevation of local glutamate as indicated by microdialysis. Moreover, the levels of tGAD65 was also proportional to the degree of cell death when the primary neuronal cultures were exposed to high KCl. Based on these observations, we conclude that calpain-mediated cleavage of fGAD65 is pathological, presumably due to decrease in the activity of synaptic vesicle - associated fGAD65 resulting in a decrease in the GABA synthesis - packaging coupling process leading to reduced GABA neurotransmission

Hydroimidazolone Modification of the Conserved Arg12 in Small Heat Shock Proteins: Studies on the Structure and Chaperone Function Using Mutant Mimics

Methylglyoxal (MGO) is an α-dicarbonyl compound present ubiquitously in the human body. MGO reacts with arginine residues in proteins and forms adducts such as hydroimidazolone and argpyrimidine in vivo. Previously, we showed that MGO-mediated modification of αA-crystallin increased its chaperone function. We identified MGO-modified arginine residues in αA-crystallin and found that replacing such arginine residues with alanine residues mimicked the effects of MGO on the chaperone function. Arginine 12 (R12) is a conserved amino acid residue in Hsp27 as well as αA- and αB-crystallin. When treated with MGO at or near physiological concentrations (2–10 µM), R12 was modified to hydroimidazolone in all three small heat shock proteins. In this study, we determined the effect of arginine substitution with alanine at position 12 (R12A to mimic MGO modification) on the structure and chaperone function of these proteins. Among the three proteins, the R12A mutation improved the chaperone function of only αA-crystallin. This enhancement in the chaperone function was accompanied by subtle changes in the tertiary structure, which increased the thermodynamic stability of αA-crystallin. This mutation induced the exposure of additional client protein binding sites on αA-crystallin. Altogether, our data suggest that MGO-modification of the conserved R12 in αA-crystallin to hydroimidazolone may play an important role in reducing protein aggregation in the lens during aging and cataract formation

Fatty Acid Composition of Developing Sea Buckthorn (Hippophae rhamnoides L.) Berry and the Transcriptome of the Mature Seed

Background: Sea buckthorn (Hippophae rhamnoides L.) is a hardy, fruit-producing plant known historically for its medicinal and nutraceutical properties. The most recognized product of sea buckthorn is its fruit oil, composed of seed oil that is rich in essential fatty acids, linoleic (18:2\u3c9-6) and \u3b1-linolenic (18:3\u3c9-3) acids, and pulp oil that contains high levels of monounsaturated palmitoleic acid (16:1\u3c9-7). Sea buckthorn is fast gaining popularity as a source of functional food and nutraceuticals, but currently has few genomic resources; therefore, we explored the fatty acid composition of Canadian-grown cultivars (ssp. mongolica) and the sea buckthorn seed transcriptome using the 454 GS FLX sequencing technology. Results: GC-MS profiling of fatty acids in seeds and pulp of berries indicated that the seed oil contained linoleic and \u3b1-linolenic acids at 33-36% and 30-36%, respectively, while the pulp oil contained palmitoleic acid at 32-42%. 454 sequencing of sea buckthorn cDNA collections from mature seeds yielded 500,392 sequence reads, which identified 89,141 putative unigenes represented by 37,482 contigs and 51,659 singletons. Functional annotation by Gene Ontology and computational prediction of metabolic pathways indicated that primary metabolism (protein>nucleic acid>carbohydrate>lipid) and fatty acid and lipid biosynthesis pathways were highly represented categories. Sea buckthorn sequences related to fatty acid biosynthesis genes in Arabidopsis were identified, and a subset of these was examined for transcript expression at four developing stages of the berry. Conclusion: This study provides the first comprehensive genomic resources represented by expressed sequences for sea buckthorn, and demonstrates that the seed oil of Canadian-grown sea buckthorn cultivars contains high levels of linoleic acid and \u3b1-linolenic acid in a close to 1:1 ratio, which is beneficial for human health. These data provide the foundation for further studies on sea buckthorn oil, the enzymes involved in its biosynthesis, and the genes involved in the general hardiness of sea buckthorn against environmental conditions.Peer reviewed: YesNRC publication: Ye

Integrated Assessment of Heavy Metal Contamination in Sediments from a Coastal Industrial Basin, NE China

The purpose of this study is to investigate the current status of metal pollution of the sediments from urban-stream, estuary and Jinzhou Bay of the coastal industrial city, NE China. Forty surface sediment samples from river, estuary and bay and one sediment core from Jinzhou bay were collected and analyzed for heavy metal concentrations of Cu, Zn, Pb, Cd, Ni and Mn. The data reveals that there was a remarkable change in the contents of heavy metals among the sampling sediments, and all the mean values of heavy metal concentration were higher than the national guideline values of marine sediment quality of China (GB 18668-2002). This is one of the most polluted of the world’s impacted coastal systems. Both the correlation analyses and geostatistical analyses showed that Cu, Zn, Pb and Cd have a very similar spatial pattern and come from the industrial activities, and the concentration of Mn mainly caused by natural factors. The estuary is the most polluted area with extremely high potential ecological risk; however the contamination decreased with distance seaward of the river estuary. This study clearly highlights the urgent need to make great efforts to control the industrial emission and the exceptionally severe heavy metal pollution in the coastal area, and the immediate measures should be carried out to minimize the rate of contamination, and extent of future pollution problems