Occurrence of 4-tert-butylphenol (4-t-BP) biodegradation in an aquatic sample caused by the presence of Spirodela polyrrhiza and isolation of a 4-t-BP-utilizing bacterium

Although 4-tert-butylphenol (4-t-BP) is a serious aquatic pollutant, its biodegradation in aquatic environments has not been well documented. In this study, 4-t-BP was obviously and repeatedly removed from water from four different environments in the presence of Spirodela polyrrhiza, giant duckweed, but 4-t-BP persisted in the environmental waters in the absence of S. polyrrhiza. Also, 4-t-BP was not removed from autoclaved pond water with sterilized S. polyrrhiza. These results suggest that the 4-t-BP removal from the environmental waters was caused by biodegradation stimulated by the presence of S. polyrrhiza rather than by uptake by the plant. Moreover, Sphingobium fuliginis OMI capable of utilizing 4-t-BP as a sole carbon and energy source was isolated from the S. polyrrhiza rhizosphere. Strain OMI degraded 4-t-BP via a meta-cleavage pathway, and also degraded a broad range of alkylphenols with linear or branched alkyl side chains containing two to nine carbon atoms. Root exudates of S. polyrrhiza stimulated 4-t-BP degradation and cell growth of strain OMI. Thus, the stimulating effects of S. polyrrhiza root exudates on 4-t-BP-degrading bacteria might have contributed to 4-t-BP removal in the environmental waters with S. polyrrhiza. These results demonstrate that the S. polyrrhiza–bacteria association may be applicable to the removal of highly persistent 4-t-BP from wastewaters or polluted aquatic environments.     

RhoGAPs Attenuate Cell Proliferation by Direct Interaction with p53 Tetramerization Domain

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The effects of Eculizumab on the pathology of malignant atrophic papulosis

Background

Degos disease is a frequently fatal and incurable occlusive vasculopathy most commonly affecting the skin, gastrointestinal tract and brain. Vascular C5b-9 deposition and a type I interferon (IFN) rich microenvironment are held to be pathogenetically important in the evolution of the vascular changes. We recently discovered the use of eculizumab as a salvage drug in the treatment of near fatal Malignant atrophic papulosis (MAP). The effects of eculizumab on the pathology of MAP are explored.

Methods

Archival skin and gastrointestinal biopsy material was procured over a 2.5-year period before and after eculizumab therapy in our index case. Routine light microscopy and immunohistochemical assessment for C3d, C4d, C5b-9, MxA and caspase 3 were examined. Direct immunofluorescent studies were also conducted on select biopsy material.

Results

The patient had received eculizumab as a emergent life saving measure and following rapid improvement he continued with biweekly infusions for 4 years. Although improved he continues to have signs and symptoms of persistent abdominal disease. Pre-Eculizumab biopsies showed an active thrombotic microangiopathy associated with a high type I interferon signature and extensive vascular deposits of C5b-9 in skin and gastrointestinal biopsies. Endothelial cell apoptosis as revealed by Caspase 3 expression was noted. Inflammation comprising lymphocytes and macrophages along with mesenchymal mucin was observed as well. Post-eculizumab biopsies did not show active luminal thrombosis but only chronic sequelae of prior episodes of vascular injury. There was no discernible caspase 3 expression. After 12 months of therapy, C5b-9 was no longer detectable in tissue. The high type I IFN signature and inflammation along with mucin deposition was not altered by the drug. In addition, there was little effect of the drug on the occlusive fibrointimal arteriopathy which appears to be one characterized by extensive myofibroblastic expansion of the intima potentially as revealed by staining for smooth muscle actin without immunoreactivity for desmin and myogenin.

Conclusions

Complement activation and enhanced endothelial cell apoptosis play an important role in the thrombotic complications of MAP. However, the larger vessel proliferative intimal changes appear to be independent of complement activation and may be on the basis of other upstream mechanisms. Monitoring C5b-9 deposition in tissue is likely not of great value in assessing treatment response to eculizumab given the persistence of C5b-9 in tissue for several months despite clinically effective C5 blocking therapy. A more integrated approach addressing upstream and downstream pathways in addition to those attributable to complement activation are critical for the successful treatment of MAP. Eculizumab may be used as salvage therapy in critically ill patients with thrombotic microangiopathy.

     

Synthetic molecules: helping to unravel plant signal transduction

The application of small molecules has played a crucial role in identifying novel components involved in plant signalling. Compared to classic genetic approaches, small molecule screens offer notable advantages in dissecting plant biological processes, such as technical simplicity, low start-up costs, and most importantly, bypassing the problems of lethality and redundancy. To identify small molecules that target a biological process or protein of interest, robust and well-reasoned high-throughput screening approaches are essential. In this review, we present a series of principles and valuable approaches in small molecule screening in the plant model system Arabidopsis thaliana. We also provide an overview of small molecules that led to breakthroughs in uncovering phytohormone signalling pathways, endomembrane signalling cascades, novel growth regulators, and plant defence mechanisms. Meanwhile, the strategies to deciphering the mechanisms of these small molecules on Arabidopsis are highlighted. Moreover, the opportunities and challenges of small molecule applications in translational biology are discussed.     

Passive Smoking and Risk of Type 2 Diabetes: A Meta-Analysis of Prospective Cohort Studies

Backgrounds/Objective

The prevalence of diabetes is increasing rapidly all over the world. However, studies on passive smoking and type 2 diabetes have not been systematically assessed. Therefore, we conducted a meta-analysis to explore whether an association exists between passive smoking and risk of type 2 diabetes.

Methods

We searched PubMed, EMBASE, Cochrane library and Web of Science up to April 9^th, 2013, to identify prospective cohort studies that assessed passive smoking and risk of type 2 diabetes. The fixed-effect model was used to calculate the overall relative risk (RR).

Result

4 prospective cohort studies were included for analysis, with a total of 112,351 participants involved. The pooled RR was 1.28 (95% confidence interval (CI) 1.14 to 1.44) comparing those who were exposed to passive smoking with those who were not. Subgroup, sensitivity analysis and publication bias test suggested the overall result of this analysis was robust.

Conclusions

Passive smoking is associated with a significantly increased risk of type 2 diabetes. Further well-designed studies are warranted to confirm this association.     

Human Vocal Attractiveness as Signaled by Body Size Projection

Voice, as a secondary sexual characteristic, is known to affect the perceived attractiveness of human individuals. But the underlying mechanism of vocal attractiveness has remained unclear. Here, we presented human listeners with acoustically altered natural sentences and fully synthetic sentences with systematically manipulated pitch, formants and voice quality based on a principle of body size projection reported for animal calls and emotional human vocal expressions. The results show that male listeners preferred a female voice that signals a small body size, with relatively high pitch, wide formant dispersion and breathy voice, while female listeners preferred a male voice that signals a large body size with low pitch and narrow formant dispersion. Interestingly, however, male vocal attractiveness was also enhanced by breathiness, which presumably softened the aggressiveness associated with a large body size. These results, together with the additional finding that the same vocal dimensions also affect emotion judgment, indicate that humans still employ a vocal interaction strategy used in animal calls despite the development of complex language.     

<Emphasis Type="Italic">Bruguiera hainesii</Emphasis>, a critically endangered mangrove species,is a hybrid between <Emphasis Type="Italic">B. cylindrica</Emphasis> and <Emphasis Type="Italic">B. gymnorhiza</Emphasis> (Rhizophoraceae)

Bruguiera hainesii (Rhizophoraceae) is one of the two Critically Endangered mangrove species listed in the IUCN Red List of Threatened Species. Although the species is vulnerable to extinction, its genetic diversity and the evolutionary relationships with other Bruguiera species are not well understood. Also, intermediate morphological characters imply that the species might be of hybrid origin. To clarify the genetic relationship between B. hainesii and other Bruguiera species, we conducted molecular analyses including all six Bruguiera species using DNA sequences of two nuclear genes (CesA and UNK) and three chloroplast regions (intergenic spacer regions of trnL-trnF, trnS-trnG and atpB-rbcL). For nuclear DNA markers, all nine B. hainesii samples from five populations were heterozygous at both loci, with one allele was shared with B. cylindrica, and the other with B. gymnorhiza. For chloroplast DNA markers, the two haplotypes found in B. hainesii were shared only by B. cylindrica. These results suggested that B. hainesii is a hybrid between B. cylindrica as the maternal parent and B. gymnorhiza as the paternal one. Furthermore, chloroplast DNA haplotypes found in B. hainesii suggest that hybridization has occurred independently in regions where the distribution ranges of the parental species meet. As the IUCN Red List of Threatened Species currently excludes hybrids (except for apomictic plant hybrids), the conservation status of B. hainesii should be reconsidered.     

Possible target‐related proteins and signal network of bufalin in A549 cells suggested by both iTRAQ‐based and label‐free proteomic analysis

Bufalin (BF) exhibited antiproliferation and antimigration effects on human A549 lung cancer cells. To search its target‐related proteins, protein expression profiles of BF‐treated and control cells were compared using two quantitative proteomic methods, iTRAQ‐based and label‐free proteomic analysis. A total of 5428 proteins were identified in iTRAQ‐based analysis while 6632 proteins were identified in label‐free analysis. The number of common identified proteins of both methods was 4799 proteins. By application of 1.20‐fold for upregulated and 0.83‐fold for downregulated cutoff values, 273 and 802 differentially expressed proteins were found in iTRAQ‐based and label‐free analysis, respectively. The number of common differentially expressed proteins of both methods was 45 proteins. Results of bioinformational analysis using Metacore^TM showed that the two proteomic methods were complementary and both suggested the involvement of oxidative stress and regulation of gene expression in the effects of BF, and fibronectin‐related pathway was suggested to be an important pathway affected by BF. Western blotting assay results confirmed BF‐induced change in levels of fibronectin and other related proteins. Overexpression of fibronectin by plasmid transfection ameliorated antimigration effects of BF. Results of the present study provided information about possible target‐related proteins and signal network of BF.     

MAP4K4: an emerging therapeutic target in cancer

The serine/threonine kinase MAP4K4 is a member of the Ste20p (sterile 20 protein) family. MAP4K4 was initially discovered in 1995 as a key kinase in the mating pathway in Saccharomyces cerevisiae and was later found to be involved in many aspects of cell functions and many biological and pathological processes. The role of MAP4K4 in immunity, inflammation, metabolic and cardiovascular disease has been recognized. Information regarding MAP4K4 in cancers is extremely limited, but increasing evidence suggests that MAP4K4 also plays an important role in cancer and MAP4K4 may represent a novel actionable cancer therapeutic target. This review summarizes our current understanding of MAP4K4 regulation and MAP4K4 in cancer. MAP4K4-specific inhibitors have been recently developed. We hope that this review article would advocate more basic and preclinical research on MAP4K4 in cancer, which could ultimately provide biological and mechanistic justifications for preclinical and clinical test of MAP4K4 inhibitor in cancer patients.