Aloe Emodin Reduces Phthiodiolone Dimycocerosate Potentiating Vancomycin Susceptibility on Mycobacteria

Treatment of tuberculosis still represent a major public health issue. The emergence of multi-and extensively-drug resistant (MDR and XDR) Mycobacterium tuberculosis clinical strains further pinpoint the urgent need for new anti-tuberculous drugs. We previously showed that vancomycin can target mycobacteria lacking cell wall integrity, especially those lacking related phthiocerol and phthiodolone dimycocerosates, PDIM A and PDIM B, respectively. As aloe emodin was previously hypothesized to be able to target the synthesis of mycobacterial cell wall lipids, we tested its ability to potentiate glycopeptides antimycobacterial activity. The aloe emodin with the vancomycin induced a combination effect beyond simple addition, close to synergism, at a concentration lower to reported IC₅₀ cytotoxic value, on M. bovis BCG and on H37Rv M. tuberculosis. Interestingly, out of six MDR and pre-XDR clinical strains, one showed a strong synergic susceptibility to the drug combination. Mycobacterial cell wall lipid analyses highlighted a selective reduction of PDIM B by aloe emodin.     

Presence of bark influences the succession of cryptogamic wood-inhabiting communities on conifer fallen logs

Predictors of cryptogamic wood-inhabiting communities need to be examined to understand the drivers of forest biodiversity. We estimated the influence of bark cover on the wood-inhabiting vegetation on conifer logs in early stages of epixylic succession in mature European boreal and hemi-boreal forests. Abundance of substrate groups with respect to log attributes was estimated with generalized linear and generalized linear mixed models. The structure and composition of epixylic communities was analysed using non-metric multidimensional scaling with subsequent environmental fitting. The abundance of true epixylics was inversely related to bark cover. In the first stage, bark cover did not influence the abundance of epiphytes and epigeous species; positively influenced the abundance of facultative epixylics on spruce logs and negatively influenced it on pine logs. In the second stage, the effect of bark cover was positive for epiphytes and epigeous species on spruce logs and for facultative epixylics independent of log species identity and negative for epigeous species on pine logs. Generalist species did not depend on bark cover. Total cover of wood-inhabiting vegetation was marginally influenced by bark cover. The effect of bark cover on epixylic vegetation at community level was negligible. In general, bark cover favours the establishment and growth of species with low substrate specificity. This preference may lead to either burial of logs by epigeous bryophytes, or facilitation of succession towards the dominance of ground vegetation.     

Uncovering the regeneration strategies of zebrafish organs: a comprehensive systems biology study on heart,cerebellum, fin,and retina regeneration

Background

Regeneration is an important biological process for the restoration of organ mass, structure, and function after damage, and involves complex bio-physiological mechanisms including cell differentiation and immune responses. We constructed four regenerative protein-protein interaction (PPI) networks using dynamic models and AIC (Akaike’s Information Criterion), based on time-course microarray data from the regeneration of four zebrafish organs: heart, cerebellum, fin, and retina. We extracted core and organ-specific proteins, and proposed a recalled-blastema-like formation model to uncover regeneration strategies in zebrafish.

Results

It was observed that the core proteins were involved in TGF-β signaling for each step in the recalled-blastema-like formation model and TGF-β signaling may be vital for regeneration. Integrins, FGF, and PDGF accelerate hemostasis during heart injury, while Bdnf shields retinal neurons from secondary damage and augments survival during the injury response. Wnt signaling mediates the growth and differentiation of cerebellum and fin neural stem cells, potentially providing a signal to trigger differentiation.

Conclusion

Through our analysis of all four zebrafish regenerative PPI networks, we provide insights that uncover the underlying strategies of zebrafish organ regeneration.

     

A refined method of quantifying deceleration capacity index for heart rate variability analysis

Background

Phase-rectified signal averaging (PRSA) was often applied to assess the cardiac vagal modulation. Despite its broad use, this method suffers from the confounding effects of anomalous variants of sinus rhythm. This study aimed to improve the original PRSA method in deceleration capacity (DC) quantification.

Methods

The refined deceleration capacity (DC_ref) was calculated by excluding from non-vagally mediated abnormal variants of sinus rhythms. Holter recordings from 202 healthy subjects and 51 patients with end-stage renal disease (ESRD) have been used for validity. The DC_ref was compared to original DC (DC_org) by the area under receiver operating characteristic curve.

Results

Experimental results demonstrate that the original and refined DCs calculated from 24-h, 2-h, and 30-min Holter recordings are significantly lower in patients with ESRD than those in the healthy group. In receiver operating characteristic curve analysis, the DC_ref provides better performance than the DC_org in distinguishing between the patients with ESRD and healthy control subjects. Furthermore, the refined PRSA technique enhances the low frequency and attenuates high frequency components for spectral analysis in ESRD patients.

Conclusions

The DC_ref appears to reduce the influence of non-vagally mediated abnormal variants of sinus rhythm and highlighting the pathological influence. DC_ref, especially assessed from short-term electrocardiography recordings, may be complementary to existing autonomic function assessment, risk stratification, and efficacy prediction strategies.

     

Protein phosphatases in higher plants: multiplicity of type 2A phosphatases in Arabidopsis thaliana

Two DNA fragments, AP-1 and AP-2, encoding amino acid sequences closely related to Ser/Thr protein phosphatases were amplified from Arabidopsis thaliana genomic DNA. Fragment AP-1 was used to screen. A. thaliana cDNA libraries and several positive clones were isolated. Clones EP8a and EP14a were sequenced and found to encode almost identical proteins (97% identity). Both proteins are 306 amino acids in length and are very similar (79–80% identity) to the mammalian isotypes of the catalytic subunit of protein phosphatase 2A. Therefore, they have been designated PP2A-1 and PP2A-2. A third cDNA clone, EP7, was isolated and sequenced. The polypeptide encoded (308 amino acids, lacking the initial Met codon) is 80% identical with human phosphatases 2A and was named PP2A-3. The PP2A-3 protein is extremely similar (95% identity) to the predicted protein from a cDNA clone previously found in Brassica napus. Southern blot analysis of genomic DNA using AP-1 and AP-2 probes, as well as probes derived from clones EP7, EP8a and EP14a strongly indicates that at least 6 genes closely related to type 2A phosphatases are present in the genome of A. thaliana. Northern blot analysis using the same set of probes demonstrates that, at the seedling stage, the mRNA levels for PP2A-1, PP2A-3 and the gene containing the AP-1 sequence are much higher than those of PP2A-2 and AP-2. These results demonstrate that a multiplicity of type 2A phosphatases might be differentially expressed in higher plants.     

Glutathione S-transferase M1 and T1 gene polymorphism and COPD risk in smokers: an updated analysis

We evaluated the association between GSTM1 and GSTT1 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease (COPD) in smokers. A meta-analysis of the published case–control studies was performed. Published literature was retrieved from PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI), with last update in February, 2011. Data were extracted and a fixed- or random-effects model was used to calculate pooled odds ratios with 95% confidence intervals depending on statistical heterogeneity. Fourteen eligible studies, comprising 1,665 COPD cases and 1,614 controls, were included in the meta-analysis. The combined analyses showed that there was a significant difference in GSTM1 genotype distribution between COPD cases and controls among Caucasians, but not among Asians. The combined GSTM1/GSTT1 null genotype conferred a 1.36-fold greater risk for COPD in Asian smokers. The GSTT1 null genotype alone was not associated with enhanced risk for COPD. The GSTM1 null genotype is significantly associated with an increasing susceptibility to COPD in Caucasian smokers, but not in Asian smokers. The GSTM1/GSTT1 null genotype is a significant risk factor for developing COPD in Asian smokers. The GSTT1 null genotype, however, was not associated with COPD.     

High-level production of 1,3-propanediol from crude glycerol by <Emphasis Type="Italic">Clostridium butyricum</Emphasis> AKR102a

The aim of this study was to optimize a biotechnological process for the production of 1,3-propanediol (1,3-PD) based on low-quality crude glycerol derived from biodiesel production. Clostridium butyricum AKR102a was used in fed-batch fermentations in 1-L and 200-L scale. The newly discovered strain is characterized by rapid growth, high product tolerance, and the ability to use crude glycerol at the lowest purity directly gained from a biodiesel plant side stream. Using pure glycerol, the strain AKR102 reached 93.7 g/L 1,3-PD with an overall productivity of 3.3 g/(L*h). With crude glycerol under the same conditions, 76.2 g/L 1,3-PD was produced with a productivity of 2.3 g/(L*h). These are among the best results published so far for natural producers. The scale up to 200 L was possible. Due to the simpler process design, only 61.5 g/L 1,3-PD could be reached with a productivity of 2.1 g/(L*h).     

Traveling EEG slow oscillation along the dorsal attention network initiates spontaneous perceptual switching

An ambiguous figure such as the Necker cube causes spontaneous perceptual switching (SPS). The mechanism of SPS in multistable perception has not yet been determined. Although early psychological studies suggested that SPS may be caused by fatigue or satiation of orientation, the neural mechanism of SPS is still unknown. Functional magnetic resonance imaging (fMRI) has shown that the dorsal attention network (DAN), which mainly controls voluntary attention, is involved in bistable perception of the Necker cube. To determine whether neural dynamics along the DAN cause SPS, we performed simultaneous electroencephalography (EEG) and fMRI during an SPS task with the Necker cube, with every SPS reported by pressing a button. This EEG–fMRI integrated analysis showed that (a) 3–4 Hz spectral EEG power modulation at fronto-central, parietal, and centro-parietal electrode sites sequentially appeared from 750 to 350 ms prior to the button press; and (b) activations correlating with the EEG modulation traveled along the DAN from the frontal to the parietal regions. These findings suggest that slow oscillation initiates SPS through global dynamics along the attentional system such as the DAN.     

The effects of riparian forest disturbance on stream temperature,sedimentation, and morphology

Forested headwater streams rely on their riparian areas for temperature regulation, woody debris inputs, and sediment retention. These products and services may be altered by disturbances such as timber harvest, windthrow, or development. This study investigated the effects of riparian forest disturbance by removing trees using 50 and 90% basal area harvests and by directly felling some trees into eight streams in eastern West Virginia. On summer afternoons, water temperature increased in the 50 and 90% BAH treatments at average rates of 0.18 and 0.79°C/100 m, respectively. The 90% BAH treatments had the potential to disrupt fish and invertebrate communities via increased water temperature. New roads and log landings associated with the riparian logging had no detectable effect on sedimentation or turbidity. Large woody debris (LWD) additions increased habitat complexity but no net increase in pool area was observed. Greater morphological instability was observed within the LWD addition sections as pools were both created and destroyed at significantly higher rates. Experimentally manipulating small riparian patches may be an analog for small-scale natural and anthropogenic disturbances. These common events are assumed to alter streams, but there are few experimental studies quantifying their effects.