Chromatin ionic atmosphere analyzed by a mesoscale electrostatic approach

Characterizing the ionic distribution around chromatin is important for understanding the electrostatic forces governing chromatin structure and function. Here we develop an electrostatic model to handle multivalent ions and compute the ionic distribution around a mesoscale chromatin model as a function of conformation, number of nucleosome cores, and ionic strength and species using Poisson-Boltzmann theory. This approach enables us to visualize and measure the complex patterns of counterion condensation around chromatin by examining ionic densities, free energies, shielding charges, and correlations of shielding charges around the nucleosome core and various oligonucleosome conformations. We show that: counterions, especially divalent cations, predominantly condense around the nucleosomal and linker DNA, unburied regions of histone tails, and exposed chromatin surfaces; ionic screening is sensitively influenced by local and global conformations, with a wide ranging net nucleosome core screening charge (56-100e); and screening charge correlations reveal conformational flexibility and interactions among chromatin subunits, especially between the histone tails and parental nucleosome cores. These results provide complementary and detailed views of ionic effects on chromatin structure for modest computational resources. The electrostatic model developed here is applicable to other coarse-grained macromolecular complexes.     

Effects of Adaptive Support Ventilation and Synchronized Intermittent Mandatory Ventilation on Peripheral Circulation and Blood Gas Markers of COPD Patients with Respiratory Failure

The objective of the study was to investigate the effects of adaptive support ventilation (ASV) and synchronized intermittent mandatory ventilation (SIMV) on peripheral circulation of chronic obstructive pulmonary disease (COPD) patients with respiratory failure. 86 COPD patients with respiratory failure were recruited in this study. Self-control method was used to compare the effect of ASV and SIMV on the parameters of ventilation machine, heart rate, blood pressure, central venous pressure (CVP), and blood gas markers. When the patients in ASV and SIMV groups were compared, respiratory rate, tidal volume, and peak airway pressure (PIP) showed significant difference. When minute ventilation (MV) was compared, no significant difference was shown. When peripheral circulation parameters were compared, peripheral circulation heart rate, SBP, DBP, and CVP showed significant difference. Compared with SIMV group, PaO₂, pH, and SaO₂ values were remarkably increased (P < 0.01) while no significant difference was found for partial pressure of carbon dioxide (pCO₂) when two groups were compared. In conclusion, when mechanical ventilation was used in COPD patients with respiratory failure, ASV can significantly improve clinical outcomes.     

Classification of motor imagery tasks for BCI with multiresolution analysis and multiobjective feature selection

Background

Brain-computer interfacing (BCI) applications based on the classification of electroencephalographic (EEG) signals require solving high-dimensional pattern classification problems with such a relatively small number of training patterns that curse of dimensionality problems usually arise. Multiresolution analysis (MRA) has useful properties for signal analysis in both temporal and spectral analysis, and has been broadly used in the BCI field. However, MRA usually increases the dimensionality of the input data. Therefore, some approaches to feature selection or feature dimensionality reduction should be considered for improving the performance of the MRA based BCI.

Methods

This paper investigates feature selection in the MRA-based frameworks for BCI. Several wrapper approaches to evolutionary multiobjective feature selection are proposed with different structures of classifiers. They are evaluated by comparing with baseline methods using sparse representation of features or without feature selection.

Results and conclusion

The statistical analysis, by applying the Kolmogorov-Smirnoff and Kruskal–Wallis tests to the means of the Kappa values evaluated by using the test patterns in each approach, has demonstrated some advantages of the proposed approaches. In comparison with the baseline MRA approach used in previous studies, the proposed evolutionary multiobjective feature selection approaches provide similar or even better classification performances, with significant reduction in the number of features that need to be computed.

     

不同盐胁迫对柳枝稷生物量、品质和光合生理的影响

为明确不同盐胁迫对柳枝稷生物量、品质及光合生理的影响,以无盐胁迫作为对照(CK),选取0.40%Na Cl、0.80%Na2SO4和0.80%Na HCO3进行了土柱试验。结果表明:(1)与CK相比,Na Cl、Na2SO4、Na HCO3胁迫下柳枝稷地上生物量、地下生物量、总生物量、籽粒产量及根冠比均显著降低(P0.05),总生物量分别降低49.39%、60.52%、76.45%,Na HCO3对柳枝稷的生长抑制作用最强,Na Cl最弱;(2)Na Cl胁迫下柳枝稷地上生物质灰分含量显著增高14.89%,Na2SO4胁迫下硫(S)含量显著增高262.32%,纤维素含量显著降低13.71%,Na HCO3胁迫下钾(K)含量显著增高54.95%,半纤维素含量显著增高10.87%,灰分和S含量的增高不利于柳枝稷地上生物质的燃烧利用,纤维素含量的降低和半纤维素含量的增高不利于其转化利用;(3)Na Cl、Na2SO4、Na HCO3胁迫下柳枝稷叶片净光合速率(Pn)分别显著降低21.89%、29.54%和24.59%,气孔限制因素可能是其光合作用受到抑制、生物量下降的关键因素。     

Hydrogen Peroxide Is a Second Messenger in the Salicylic Acid-Triggered Adventitious Rooting Process in Mung Bean Seedlings

In plants, salicylic acid (SA) is a signaling molecule that regulates disease resistance responses, such as systemic acquired resistance (SAR) and hypertensive response (HR). SA has been implicated as participating in various biotic and abiotic stresses. This study was conducted to investigate the role of SA in adventitious root formation (ARF) in mung bean (Phaseolus radiatus L) hypocotyl cuttings. We observed that hypocotyl treatment with SA could significantly promote the adventitious root formation, and its effects were dose and time dependent. Explants treated with SA displayed a 130% increase in adventitious root number compared with control seedlings. The role of SA in mung bean hypocotyl ARF as well as its interaction with hydrogen peroxide (H₂O₂) were also elucidated. Pretreatment of mung bean explants with N, N’-dimethylthiourea (DMTU), a scavenger for H₂O₂, resulted in a significant reduction of SA-induced ARF. Diphenyleneiodonium (DPI), a specific inhibitor of membrane-linked NADPH oxidase, also inhibited the effect of adventitious rooting triggered by SA treatment. The determination of the endogenous H₂O₂ level indicated that the seedlings treated with SA could induce H₂O₂ accumulation compared with the control treatment. Our results revealed a distinctive role of SA in the promotion of adventitious rooting via the process of H₂O₂ accumulation. This conclusion was further supported by antioxidant enzyme activity assays. Based on these results, we conclude that the accumulation of free H₂O₂ might be a downstream event in response to SA-triggered adventitious root formation in mung bean seedlings.     

The initiative role of XPC protein in cisplatin DNA damaging treatment-mediated cell cycle regulation

XPC is an important DNA damage recognition protein involved in DNA nucleotide excision repair. We have studied the role of the XPC protein in cisplatin treatment-mediated cell cycle regulation. Through the comparison of microarray data obtained from human normal fibroblasts and two individual XPC-defective cell lines, 486 genes were identified as XPC-responsive genes in the cisplatin treatment (with a minimal 1.5-fold change) and 297 of these genes were further mapped to biological pathways and gene ontologies. The cell cycle and cell proliferation-related genes were the most affected genes by the XPC defect in the cisplatin treatment. Many other cellular function genes were also affected by the XPC defect in the treatment. Western blot hybridization results revealed that the XPC defect reduced the p53 responses to the cisplatin treatment. The ability to activate caspase-3 was also attenuated in the XPC cells with the treatment. These results suggest that the XPC protein plays a critical role in initiating the cisplatin DNA damaging treatment-mediated signal transduction process, resulting in activation of the p53 pathway and cell cycle arrest that allow DNA repair and apoptosis to take place. These results reveal an important role of the XPC protein in the cancer prevention.     

Adiponectin Alleviates Genioglossal Mitochondrial Dysfunction in Rats Exposed to Intermittent Hypoxia

Background

Genioglossal dysfunction is involved in the pathophysiology of obstructive sleep apnea hypoxia syndrome (OSAHS) characterized by nocturnal chronic intermittent hypoxia (CIH). The pathophysiology of genioglossal dysfunction and possible targeted pharmacotherapy for alleviation of genioglossal injury in CIH require further investigation.

Methodology/Principal Findings

Rats in the control group were exposed to normal air, while rats in the CIH group and CIH+adiponectin (AD) group were exposed to the same CIH condition (CIH 8 hr/day for 5 successive weeks). Furthermore, rats in CIH+AD group were administrated intravenous AD supplementation at the dosage of 10 µg, twice a week for 5 consecutive weeks. We found that CIH-induced genioglossus (GG) injury was correlated with mitochondrial dysfunction, reduction in the numbers of mitochondrias, impaired mitochondrial ultrastructure, and a reduction in type I fibers. Compared with the CIH group, impaired mitochondrial structure and function was significantly improved and a percentage of type I fiber was elevated in the CIH+AD group. Moreover, compared with the control group, the rats’ GG in the CIH group showed a significant decrease in phosphorylation of LKB1, AMPK, and PGC1-α, whereas there was significant rescue of such reduction in phosphorylation within the CIH+AD group.

Conclusions

CIH exposure reduces mitochondrial biogenesis and impairs mitochondrial function in GG, while AD supplementation increases mitochondrial contents and alleviates CIH-induced mitochondrial dysfunction possibly through the AMPK pathway.     

Low-dose endotoxin induces inflammation by selectively removing nuclear receptors and activating CCAAT/enhancer-binding protein δ

Subclinical levels of circulating endotoxin are associated with the pathogenesis of diverse human inflammatory diseases, by mildly inducing the expression of proinflammatory mediators. In this study, we examined the molecular mechanism responsible for the effect of low-dose LPS in macrophages. In contrast to high-dose LPS, which activates NF-κB and induces the robust expression of proinflammatory mediators, we observed that low-dose LPS failed to activate NF-κB. Instead, it selectively activated C/EBPδ and removed nuclear repressors, including peroxisome proliferator-activated receptor α and retinoic acid receptor α, enabling a mild and leaky expression of proinflammatory mediators. The effect of low-dose LPS required IRAK-1, which interacts with and acts upstream of IκB kinase ε to contribute to LPS-mediated induction of C/EBPδ and proinflammatory mediators. Additionally, mice fed a high-fat diet acquired elevated levels of endotoxin and proinflammatory mediators in an IRAK-1-dependent fashion. Taken together, these data reveal a distinct pathway preferentially used by low-dose endotoxin in initiating low-grade inflammation.     

Intermediate states of ribonuclease III in complex with double-stranded RNA

Bacterial ribonuclease III (RNase III) can affect RNA structure and gene expression in either of two ways: as a processing enzyme that cleaves double-stranded (ds) RNA, or as a binding protein that binds but does not cleave dsRNA. We previously proposed a model of the catalytic complex of RNase III with dsRNA based on three crystal structures, including the endonuclease domain of RNase III with and without bound metal ions and a dsRNA binding protein complexed with dsRNA. We also reported a noncatalytic assembly observed in the crystal structure of an RNase III mutant, which binds but does not cleave dsRNA, complexed with dsRNA. We hypothesize that the RNase III*dsRNA complex can exist in two functional forms, a catalytic complex and a noncatalytic assembly, and that in between the two forms there may be intermediate states. Here, we present four crystal structures of RNase III complexed with dsRNA, representing possible intermediates.