A C?As lyase for degradation of environmental organoarsenical herbicides and animal husbandry growth promoters

Arsenic is the most widespread environmental toxin. Substantial amounts of pentavalent organoarsenicals have been used as herbicides, such as monosodium methylarsonic acid (MSMA), and as growth enhancers for animal husbandry, such as roxarsone (4-hydroxy-3-nitrophenylarsonic acid) [Rox(V)]. These undergo environmental degradation to more toxic inorganic arsenite [As(III)]. We previously demonstrated a two-step pathway of degradation of MSMA to As(III) by microbial communities involving sequential reduction to methylarsonous acid [MAs(III)] by one bacterial species and demethylation from MAs(III) to As(III) by another. In this study, the gene responsible for MAs(III) demethylation was identified from an environmental MAs(III)-demethylating isolate, Bacillus sp. MD1. This gene, termed arsenic inducible gene (arsI), is in an arsenic resistance (ars) operon and encodes a nonheme iron-dependent dioxygenase with C⋅As lyase activity. Heterologous expression of ArsI conferred MAs(III)-demethylating activity and MAs(III) resistance to an arsenic-hypersensitive strain of Escherichia coli, demonstrating that MAs(III) demethylation is a detoxification process. Purified ArsI catalyzes Fe²⁺-dependent MAs(III) demethylation. In addition, ArsI cleaves the C⋅As bond in trivalent roxarsone and other aromatic arsenicals. ArsI homologs are widely distributed in prokaryotes, and we propose that ArsI-catalyzed organoarsenical degradation has a significant impact on the arsenic biogeocycle. To our knowledge, this is the first report of a molecular mechanism for organoarsenic degradation by a C⋅As lyase.The metalloid arsenic is the most common environmental toxic substance, entering the biosphere primarily from geochemical sources, but also through anthropogenic activities (1). Arsenic is a group 1 human carcinogen that ranks first on the Agency for Toxic Substances and Disease Registry Priority List of Hazardous Substances (www.atsdr.cdc.gov/SPL/index.html). Microbial arsenic transformations create a global arsenic biogeocycle (1). These biotransformations include redox cycles between the relatively innocuous pentavalent arsenate and the considerably more toxic and carcinogenic trivalent arsenite (2, 3). In addition, many microbes, both prokaryotic and eukaryotic, have arsM genes for inorganic arsenite [As(III)] S-adenosylmethionine methyltransferases that methylate inorganic As(III) to mono-, di-, and tri-methylated species (4, 5). The genes encoding arsenic transforming enzymes are widely distributed, and these arsenic biotransformations have been proposed to play significant roles in the arsenic biogeocycle and in remodeling the terrain in volcanic areas such as Yellowstone National Park and regions of the world with high amounts of arsenic in soil and water such as West Bengal and Bangladesh (3, 6).Arsenicals, both inorganic and organic, have been used in agriculture in the United States for more than a century (7). Historically, the use of inorganic arsenical pesticides/herbicides has been largely replaced by methylated arsenicals such as monosodium methylarsonic acid (MSMA), which is still in use as an herbicide for turf maintenance on golf courses, sod farms, and highway rights of way, and for weed control on cotton fields (7). More complex pentavalent aromatic arsenicals such as roxarsone [4-hydroxy-3-nitrophenylarsonic acid, Rox(V)] have been largely used since the middle of the 1940s as antimicrobial growth promoters for poultry and swine to control Coccidioides infections and improve weight gain, feed efficiency, and meat pigmentation (8, 9). These aromatic arsenicals are largely excreted unchanged and introduced into the environment when chicken litter is applied to farmland as fertilizer (8). Pentavalent organoarsenicals are relatively benign and less toxic than inorganic arsenicals; however, aromatic (8–10) and methyl (11, 12) arsenicals are degraded into more toxic inorganic forms in the environment, which may contaminate the foods and water supplies. Although microbial degradation of environmental organoarsenicals has been documented (8, 9, 11, 13), no molecular details of the reaction have been reported. We recently demonstrated that a microbial community in Florida golf course soil carries out a two-step pathway of MSMA reduction and demethylation (14). Here we report the isolation of an environmental methylarsonous acid [MAs(III)]-demethylating bacterium Bacillus sp. MD1 (for “MAs(III) demethylating”) from Florida golf course soil and the cloning of the gene, termed arsenic inducible gene (arsI), responsible for MAs(III) demethylation. The gene product, ArsI, is nonheme iron-dependent dioxygenase with C⋅As lyase activity. ArsI cleaves the C⋅As bond in a wide range of trivalent organoarsenicals, including the trivalent roxarsone [Rox(III)], into As(III), which strongly suggests that the environmental pentavalent phenylarsenicals such as Rox(V) also undergo a two-step pathway of sequential reduction and ArsI-catalyzed dearylation, in analogy with the demethylation of MSMA by a microbial community. Thus, ArsI-catalyzed C⋅As bond cleavage is a newly identified mechanism for degradation of organoarsenical herbicides and antimicrobial growth promoters.     

内质网相关性降解与呼吸系统疾病

内质网相关性降解（ERAD）通过清除内质网腔内的错误折叠蛋白质,从而预防和缓解内质网应激,是真核生物蛋白质质量控制和维持细胞正常功能状态的重要机制。ERAD包含底物（即错误折叠蛋白）识别、底物泛素化与逆转运、底物降解三个基本环节,其中任何一个环节失调都会导致细胞功能障碍,并可能进一步导致疾病的发生与发展。近几年研究发现,ERAD参与了COPD、肺癌、肺囊性纤维化等疾病发生过程。本文就参与ERAD的相关因子的研究进展进行综述。     

Functional diversity within the simple gut microbiota of the honey bee

Animals living in social communities typically harbor a characteristic gut microbiota important for nutrition and pathogen defense. Accordingly, in the gut of the honey bee, Apis mellifera, a distinctive microbial community, composed of a taxonomically restricted set of species specific to social bees, has been identified. Despite the ecological and economical importance of honey bees and the increasing concern about population declines, the role of their gut symbionts for colony health and nutrition is unknown. Here, we sequenced the metagenome of the gut microbiota of honey bees. Unexpectedly, we found a remarkable degree of genetic diversity within the few bacterial species colonizing the bee gut. Comparative analysis of gene contents suggests that different species harbor distinct functional capabilities linked to host interaction, biofilm formation, and carbohydrate breakdown. Whereas the former two functions could be critical for pathogen defense and immunity, the latter one might assist nutrient utilization. In a γ-proteobacterial species, we identified genes encoding pectin-degrading enzymes likely involved in the breakdown of pollen walls. Experimental investigation showed that this activity is restricted to a subset of strains of this species providing evidence for niche specialization. Long-standing association of these gut symbionts with their hosts, favored by the eusocial lifestyle of honey bees, might have promoted the genetic and functional diversification of these bee-specific bacteria. Besides revealing insights into mutualistic functions governed by the microbiota of this important pollinator, our findings indicate that the honey bee can serve as a model for understanding more complex gut-associated microbial communities.     

Calcium phosphate/poly(D,L-lactic-co-glycolic acid) composite bone substitute materials: evaluation of temporal degradation and bone ingrowth in a rat critical-sized cranial defect

Objectives: The present study aimed to provide temporal information on material degradation and bone formation using composite (C) bone defect filler materials consisting of calcium phosphate cement (CaP) and poly(d ,l ‐lactic‐co‐glycolic acid) (PLGA) microparticles (20 or 30 wt%) in rat critical‐sized cranial defects. Materials and methods: Critical‐sized bicortical cranial defects were created in 48 rats and CaP/PLGA cement composites were implanted for 4, 8 and 12 weeks (n=8). Results: Histological analysis of the retrieved specimens revealed that implant degradation was significantly faster for C30% (remaining implant up to 89.4 ± 4.4% at 12 weeks) compared with C20% (remaining implant upto 94.8 ± 2.1% at 12 weeks), albeit that overall degradation was limited. Although bone formation was limited in both experimental groups (upto 685765.9 μm² for C20% vs. 917603.3 μm² for C30%), C30% showed a significant temporal increase of total bone formation. The percentage of defect bridging was comparable for C20% and C30% at all implantation periods (range 40 ± 25.5% at week 4 to 65 ± 20% at week 12 for C20%; range 51.8 ± 7.8% at week 4 to 70.5 ± 16.2% at week 12 for C30%). Conclusion: The amount of PLGA‐microparticles in the CaP/PLGA cement composites demonstrated acceleration of material degradation, while bone formation was found not to be influenced. Further optimization of the composite material is necessary to increase control over degradation and tissue ingrowth. To cite this article :
van de Watering FCJ, van den Beucken JJJP, Walboomers XF, Jansen JA. Calcium phosphate/poly(d ,l ‐lactic‐co‐glycolic acid) composite bone substitute materials: evaluation of temporal degradation and bone ingrowth in a rat critical‐sized cranial defect.
Clin. Oral Impl. Res. 23 , 2012; 151–159.
doi: 10.1111/j.1600‐0501.2011.02218.x     

Preparation and Evaluation at the Delta Opioid Receptor of a Series of Linear Leu-Enkephalin Analogues Obtained by Systematic Replacement of the Amides

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Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s Disease: In Vitro and in Vivo Studies

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Cancer‐associated ischemic stroke is associated with elevated d‐dimer and fibrin degradation product levels in acute ischemic stroke with advanced cancer

Aim: Although several studies have reported various causes of ischemic stroke in patients with cancer, only a few have evaluated the clinical relevance of ischemic stroke pathogenesis to cancer. The aim of the present study was to elucidate the clinical characteristics of cancer‐associated ischemic stroke. Methods: We evaluated 154 ischemic stroke patients without cancer and 57 ischemic stroke patients with cancer who had either received continuous treatment for cancer within 5 years before to the onset of ischemic stroke, or who had been diagnosed with cancer within 1 year after the onset of ischemic stroke. Cancer patients were grouped into “cancer‐associated ischemic stroke,” the “conventional ischemic stroke,” or “other.” Results: A total of 15 patients (26%) were classified into the cancer‐associated ischemic stroke in cancer patients. In univariate analysis of the cancer‐associated ischemic stroke and the others, there were significant differences in the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of d ‐dimer, fibrin degradation product and hemoglobin. With multivariate regression analysis of those factors, the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of d ‐dimer and fibrin degradation product remained as statistically independent factors, which were associated with cancer‐associated ischemic stroke (n = 111, χ² = 67.21, P < 0.0001). Conclusion: In acute ischemic stroke, the cancer‐associated ischemic stroke is associated with elevated d ‐dimer and fibrin degradation products, even after controlling hypertension, hyperlipidemia and advanced cancer (clinical stage IV). Geriatr Gerontol Int 2012; 12: 468–474.