Biodegradation of triiodophenol by cell-free extracts of a pentachlorophenol-degrading Flavobacterium sp

Pentachlorophenol (PCP) degrading Flavobacterium sp. ATCC 39723 was found to degrade other polyhalogenated phenolic compounds, including triiodophenol, tribromophenol, and trichlorophenol. Each compound was able to induce the degradation of the other compounds. A PCP Flavobacterium sp. mutant, F-2, was unable to degrade any of the halogenated compounds. The results suggest that all of the polyhalogenated phenols were degraded by the same enzyme system. This observation led us to exploit the sensitive leuco crystal violet assay, which measures the iodide released from triiodophenol. Cell free extracts from PCP-induced cells were able to release iodide from triiodophenol. The reaction required NADPH and oxygen.     

Estimation of melting points of large set of persistent organic pollutants utilizing QSPR approach

The presence of polyhalogenated persistent organic pollutants (POPs), such as Cl/Br-substituted benzenes, biphenyls, diphenyl ethers, and naphthalenes has been identified in all environmental compartments. The exposure to these compounds can pose potential risk not only for ecological systems, but also for human health. Therefore, efficient tools for comprehensive environmental risk assessment for POPs are required. Among the factors vital for environmental transport and fate processes is melting point of a compound. In this study, we estimated the melting points of a large group (1419 compounds) of chloro- and bromo- derivatives of dibenzo-p-dioxins, dibenzofurans, biphenyls, naphthalenes, diphenylethers, and benzenes by utilizing quantitative structure—property relationship (QSPR) techniques. The compounds were classified by applying structure-based clustering methods followed by GA-PLS modeling. In addition, random forest method has been applied to develop more general models. Factors responsible for melting point behavior and predictive ability of each method were discussed.     

Discriminant functions

Discriminant Functions (DFs), first described by Fisher in 1936, have been applied to the classification of microcytic disorders such as iron deficiency and heterozygous thalassemia. Mathematically DFs are weighted linear combinations of variables. If the underlying assumption of multivariate normality is valid DFs provide the best possible classification. Variables may need to be transformed before the DF is derived. When two groups have to be classified it is easy to visualise the DF. With one variable the DF is represented by the point which provides the best separation. In the bivariate situation the two groups form ellipses and the DF is the best line of separation whilst in the trivariate case the two groups are ellipsoids and a plane forms the best separation. Ratios and power functions are equivalent to DFs but they are less efficient and less rigorously derived. To apply DFs in hematological practice it is necessary to carefully select the measurements to be included and to define the case selection criteria. Once the DF has been derived it should be tested on a new data set and its transferability assessed. Like any single test the DF will have sensitivity and specificity which may need to be adjusted by changing the "cut-off" if the DF is used for screening rather than for differential diagnosis.     

Are cockroaches reliable bioindicators of persistent organic pollutant contamination of indoor environments?

We measured the concentrations of selected persistent organic pollutants (POPs) such as parent and halogenated polycyclic aromatic hydrocarbons (PAHs and HPAHs) and polybrominated diphenyl ethers (PBDEs) in indoor dust (ID) and indoor cockroach samples collected from Shenzhen, South China. Biota-dust accumulation factors (BDAFs) were computed and utilized to quantify targeted pollutant bioaccumulation in ID and cockroaches. Generally, halogenated compounds have higher BDAFs when compared to non-halogenated compounds. There are significant differences (p < 0.05) between the BDAFs of non-halogenated POPs (PAHs) and halogenated POPs (HPAHs and PBDEs). Correlation analysis of target pollutants’ levels in ID and cockroaches were also conducted. The correlation coefficients for PAHs are less than 0.2 (p > 0.5) suggesting no significant relationship exists for PAHs between ID and cockroaches. In contrast, significant correlations exist for halogenated POPs (HPAH and PBDE) between ID and cockroaches (correlation coefficients >0.94, p < 0.0001). Based on this, the potential of cockroaches to be used as reliable bioindicators of POPs contamination of indoor environments was preliminarily evaluated. Our results indicate that indoor cockroaches may be useful bioindicator of indoor pollution for HPAHs and PBDEs contaminations.     

Comparative secretome analysis of human follicular dermal papilla cells and fibroblasts using shotgun proteomics

The dermal papilla cells (DPCs) of hair follicles are known to secrete paracrine factors for follicular cells. Shotgun proteomic analysis was performed to compare the expression profiles of the secretomes of human DPCs and dermal fibroblasts (DFs). In this study, the proteins secreted by DPCs and matched DFs were analyzed by 1DE/LTQ FTICR MS/MS, semi-quantitatively determined using emPAI mole percent values and then characterized using protein interaction network analysis. Among the 1,271 and 1,188 proteins identified in DFs and DPCs, respectively, 1,529 were further analyzed using the Ingenuity Pathway Analysis tool. We identified 28 DPC-specific extracellular matrix proteins including transporters (ECM1, A2M), enzymes (LOX, PON2), and peptidases (C3, C1R). The biochemically- validated DPC-specific proteins included thrombospondin 1 (THBS1), an insulin-like growth factor binding protein3 (IGFBP3), and, of particular interest, an integrin beta1 subunit (ITGB1) as a key network core protein. Using the shotgun proteomic technique and network analysis, we selected ITGB1, IGFBP3, and THBS1 as being possible hair-growth modulating protein biomarkers.     

Comparative mutagenicity of aliphatic epoxides in Salmonella

37 aliphatic epoxides comprising 6 subclasses (unsubstituted aliphatic epoxides, halogenated aliphatic epoxides, glycidyl esters, glycidates, glycidyl ethers and diglycidyl ethers) were tested, under code, for mutagenicity in Salmonella strains TA98, TA100, TA1535 and TA1537 and/or TA97 with and without metabolic activation using a standardized protocol. The 4 halogenated aliphatic epoxides and the 4 diglycidyl ethers were all mutagenic. The 2 glycidates were negative in all strain/activation systems used while all 5 glycidyl esters were mutagenic. 3 of the 8 unsubstituted aliphatic epoxides and 11 of the 12 glycidyl ethers were mutagenic. Glycidol also was mutagenic whereas 9,10-epoxyoctadecanoic acid, 2-ethylhexyl ester was not mutagenic. Of the 28 mutagenic compounds, all but neodecanoic acid, 2,3-epoxypropyl ester and 2-ethylhexyl glycidyl ether were detected in TA100 without activation. The latter two were detected only with activation in TA100 and TA1535. The majority of the other 26 chemicals were also mutagenic in TA1535 without activation. Good intra- and interlaboratory reproducibility was seen in the results of each of the 4 chemicals tested in more than one set of experiments. The current results confirm and extend the observations of other investigators regarding structural effects on the mutagenicity of members of the aliphatic epoxide class of chemicals.     

Synthesis and analysis of stabilizing ligands for FKBP-derived destabilizing domains

We recently identified mutants of the human FKBP12 protein that are unstable and rapidly degraded when expressed in mammalian cells. We call these FKBP mutants destabilizing domains (DDs), because their instability is conferred to any protein fused to the DDs. A cell-permeable ligand binds tightly to the DDs and prevents their degradation, thus providing small molecule control over intracellular protein levels. We now report the synthesis and functional characterization of a stabilizing ligand called Shield-2. The synthesis of Shield-2 is efficient, and this ligand binds to the FKBP(F36V) protein with a dissociation constant of 29 nM.     

Development of human health damage factors for tropospheric ozone considering transboundary transport on a global scale

Purpose

Air pollutants such as tropospheric ozone and PM_2.5 travel through large areas. The damage factors (DFs) presented by existing researches in life cycle impact assessment do not take into consideration transboundary movement. A previous study used a global chemistry transport model (CTM), to develop health damage factors for ten different regions around the world by considering the transboundary movement of PM_2.5. Under the same assessment procedure, this research is designed to calculate the ozone DFs by region and to find the effects of wide range movement on the DFs.

Methods

The DFs by regions are defined as changes in disability-adjusted life years (DALYs) derived from changes in tropospheric ozone concentration around the world which is induced by an increase in emissions of the unit amount of nitrogen oxides (NO_x) and non-methane volatile organic compounds (NMVOC). DFs for ten regions are calculated as follows. Firstly, the concentration change of worldwide ozone caused by a change in emission of a substance from one region is estimated with a global scale CTM for both NO_x and NMVOC. Secondly, DALY changes on the world due to a change in concentration of ozone are estimated by using population data and epidemiological concentration-response functions for mortality and morbidity. Finally, the above calculations are done for all targeted ten regions.

Results and discussion

DFs of NO_x and NMVOC for ten regions were calculated as 0.3–4.2?×?10^?5 DALY/kg and 0.2–5.6?×?10^?6 DALY/kg, respectively. It was found DFs might be underestimated around 10 to 70 % by region if the transboundary movement is not taken into consideration. In many regions in the northern hemisphere, about 60 % of damage occurs outside the emission area, which is larger than that of southern hemispheric regions due to a larger population exposed to downwind places. In regions of China and India, however, the influence on other regions accounted for only 10 % because these regions involve larger influences in the source region. The impact of NO titration effect can be seen in cold seasons in many regions, but it was found that the effect is remarkable on an annual average only in Europe, a cold region with large emissions.

Conclusions

The human health DFs of NO_x and NMVOC considering effects of transboundary movement of tropospheric ozone are estimated for ten regions by using a global CTM. As a future work, it is important to show the interannual sensitivity of the DFs through chronological assessments.

     

Pathogenic KDM5B variants in the context of developmental disorders

Histone modifying enzymes are involved in the posttranslational modification of histones and the epigenetic control of gene expression. They play a critical role in normal development, and there is increasing evidence of their role in developmental disorders (DDs). DDs are a group of chronic, severe conditions that impact the physical, intellectual, language and/or behavioral development of an individual. There are very few treatment options available for DDs such that these are conditions with significant unmet clinical need. Recessive variants in the gene encoding histone modifying enzyme KDM5B are associated with a DD characterized by developmental delay, facial dysmorphism and camptodactyly. KDM5B is responsible for the demethylation of lysine 4 on the amino tail of histone 3 and plays a vital role in normal development and regulating cell differentiation. This review explores the literature on KDM5B and what is currently known about its roles in development and developmental disorders.     

Intraspecies diversity of dormant forms of <Emphasis Type="Italic">Mycobacterium smegmatis</Emphasis>

The non-spore-forming gram-positive bacterium Mycobacterium smegmatis mc² 155, related to M. tuberculosis, was revealed to be capable of forming different types of dormant forms (DFs) during the life cycle of its cultures. The relationship between the intraspecies diversity of DFs and the cultivation conditions of the mycobacterium was established. The DFs possessed the following common properties: (i) maintenance of viability for a long period of time (5 months), (ii) resistance to deleterious factors such as heat treatment, and (iii) morphological and ultrastructural peculiarities that distinguish DFs from vegetative cells. The diversity of M. smegmatis DFs manifested itself in differences in terms of structural organization, conditions required for growth renewal, and capacity to produce antibiotic-resistant variants upon germination on selective media. Well-differentiated cystlike dormant cells (CDCs) were formed in the cultures grown in synthetic SR1 medium with fivefold-decreased nitrogen content. The structural organization of CDCs differed from that of other DF types mainly in the presence of club-shaped cells, thickened lamellar cell walls, coarse cytoplasm texture, and large electron-transparent triacylglyceride inclusion bodies. It was possible to use mycobacterial CDCs as a source of PCR-competent DNA. CDC populations were heterogeneous in cell buoyant density, and the individual fractions, which we isolated, were found to differ in thermal stability and the ability to revert to growth under standard conditions. Coccoid DFs, which retained their colony-forming capacity for a long time but were less heat-resistant than the CDCs, were formed by mycobacteria grown in standard Sauton’s medium with initial pH value decreased to 6.2. Poorly differentiated DFs resulted from growing mycobacterial cultures in Sauton’s medium with a fivefold-decreased phosphorus content. Upon germination of various DF types, the variants resistant to kanamycin (200 μg/ml) and tetracycline (20 μg/ml) were obtained. CDC suspensions incubated for 5 months demonstrated the highest percentage (1.5%) of antibiotic-resistant clones. The data obtained on the DF diversity of M. smegmatis, a fast-growing relative of M. tuberculosis, contribute to our understanding of the flexibility of the survival strategy of this bacterium in nature and in the host organism.     

Selective enrichment of Pseudomonas spp. defective in catabolism after exposure to halogenated substrates.

Significant selective enrichments of mutants defective in catabolic pathways can be achieved by exposure of pseudomonad cells to halogenated analogs of growth substrates. Between 3 and 95% of viable clones rescued from such enrichments have been defective in specific catabolic pathways. This has been demonstrated for eight different catabolic pathways for aromatic compounds in pseudomonads, in which the genes are located on plasmids or on the chromosome. The plasmid-encoded pathways studied include those for the catabolism of p-cymene (CYM), m- and p-xylenes (TOL), naphthalene (NAH), salicylate (SAL), and 4-methylphthalate (MOP), and the chromosome-encoded pathways include those for p-hydroxybenzoate, monohydric phenols, and p-anisate utilization. The recalcitrance of halogenated compounds may, in part, be explained by these observations, which introduce an as yet not widely recognized factor in assessment of biodegradability of halogenated compounds and their effects on the transformation of the natural substrates.     

Compounds from the sea with actions on the cardiovascular and central nervous systems

Recent efforts at probing into the oceans have produced evidence that marine invertebrates such as gorgonians and sponges offer a rich reserve of pharmacologically interesting molecules. Our investigations indicate that it is possible to obtain novel compounds both structurally and pharmacologically. For example, autonomium from a sponge is a dual adrenergic combined with cholinergic molecule, with a structure that may be considered a hybrid between a catecholamine and choline. Various terpenoids and indole derivatives from marine organisms have been found to possess activities on the central nervous system. Several peptides from sea anemones are cardiotonic and have initiated a new concept of chemical structure believed to be associated with cardiac activity. A number of closely related halogenated cyclic ethers are good inhibitors of drug metabolism. Thus, there seems little doubt that the sea warrants an extensive chemical and pharmacological examination.     

Helical assembly in the death domain (DD) superfamily

Death domain (DD) superfamily members play a central role in apoptotic and inflammatory signaling through formation of oligomeric molecular scaffolds. These scaffolds promote the activation of proinflammatory and apoptotic initiator caspases, as well as Ser/Thr kinases. Interactions between DDs are facilitated by a conserved set of interaction surfaces, type I, type II, and type III. Recently structural information on a ternary complex containing the DDs of MyD88, IRAK4, and IRAK2 and a binary complex containing Fas and FADD DDs has become available. This review will focus on how the three DD interaction surfaces cooperate to facilitate the assembly of these oligomeric signaling complexes.     

Do polybrominated diphenyl ethers (PBDE) increase the risk of thyroid cancer?

An increased incidence of thyroid cancer has been reported in many parts of the world including the United States during the past several decades. Recently emerging evidence has demonstrated that polyhalogenated aromatic hydrocarbons (PHAH), particularly polybrominated diphenyl ethers (PBDE), alter thyroid hormone homeostasis and cause thyroid dysfunction. However, few studies have been conducted to test whether exposure to PBDE and other PHAH increases the risk of thyroid cancer. Here, we hypothesize that elevated exposure to PHAH, particularly PBDE, increases the risk of thyroid cancer and may explain part of the increase in incidence of thyroid cancer during the past several decades. In addition, genetic and epigenetic variations in metabolic pathway genes may alter the expression and function of metabolic enzymes which are involved in the metabolism of endogenous thyroid hormones and the detoxification of PBDE and other PHAH. Such variation may result in different individual susceptibilities to PBDE and other PHAH and the subsequent development of thyroid cancer. The investigation of this hypothesis will lead to an improved understanding of the role of PBDE and other PHAH in thyroid tumorigenesis and may provide a real means to prevent this deadly disease.     

On the biology and thermal developmental requirements of the cotton mealybug,Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae) in Egypt

This study evaluated the thermal requirements for development of the cotton mealybug Phenacoccus solenopsis depending on different biological parameters on Okra leaves Abelmoschus esculentusat under two constant temperatures (20 and 30 °C) at (RH 65%, 12:12 h. light/dark). The effect of temperature on eggs was ineffective since it hatched shortly to first nymphal instars after deposition. While the tested temperature caused significant effects on nymphal durations, pupation rate (pre-male stage), females emergence %, pre-oviposition, longevity, post-oviposition periods and fecundity in females (egg deposition, ovisacs numbers and hatchability %). The thermal constant and developmental zero were calculated to be 7.29 °C and 79.9 degree-days (DDs) for eggs, 11.67 °C and 272.9 DDs for nymphal stages, 11.06 °C and 46.4 DDs for males and then 3.31 °C and 554.1 DDs for females, respectively. The duration of the life cycle was 65.6 ± 10.36 days at 20 °C; this was shortened to 35.51 ± 1.12 days at 30 °C. The thermal requirements to complete the insect development for one generation was 8.2 °C for the developmental zero and 774.1 DDs for the thermal constant. Based on the thermal requirements values, the average life cycle duration from January to December 2016 was 61.78 days and the number of annual generations was 7.143 when the average annual temperature was 23.29 °C.     

Purification and characterization of a bacterial dehalogenase with activity toward halogenated alkanes, alcohols and ethers

An enzyme that is capable of hydrolytic conversion of halogenated aliphatic hydrocarbons to their corresponding alcohols was purified from a 1,6-dichlorohexane-degrading bacterium. The dehalogenase was found to be a monomeric protein of relative molecular mass 28,000. The affinity for its substrates was relatively low with Km values for short-chain haloalkanes in the range 0.1-0.9 mM. The aliphatic dehalogenase showed a much broader substrate range than has been reported for halidohydrolases so far. Novel classes of substrates include dihalomethanes, C5-C9 1-halo-n-alkanes, secondary alkylhalides, halogenated alcohols and chlorinated ethers. Several of these compounds are important environmental pollutants, e.g. methylbromide, dibromomethane, 1,2-dibromoethane, 1,3-dichloropropene, and bis(2-chloroethyl)ether. The degradation of chiral 2-bromoalkanes appeared to proceed without stereochemical preference. Optically active 2-bromobutane was converted with inversion of configuration at the chiral carbon atom, suggesting that the dehalogenase reaction proceeds by a nucleophilic substitution involving a carboxyl group or base catalysis.     

Halogenated diterpenoids from the red alga Laurencia nipponica

Chemical compositions of three collections of the red alga Laurencia nipponica from the western part of the Sea of Japan were studied. One of them contained a series of the previously known sesquiterpenoids. Another one gave C15 bromoallene ethers, predominantly. Finally, two new halogenated diterpenes, 15-bromoparguer-9(11)-ene-16-ol and 15-bromoparguer-7-ene-16-ol, were isolated from the third collection of the same species. Structures of these diterpenoids were established by 1D and 2D NMR (1H-1H COSY, DEPT, HMQC, HMBC and NOESY) along with molecular calculations for conformations having lowest energies and mass spectroscopy. Diversity and variability of halogenated secondary metabolites in L. nipponica were discussed.     

有机卤呼吸微生物菌群营养交互的作用机制

有机卤呼吸细菌(organohalide-respiringbacteria,OHRB)是污染场地土壤与地下水中厌氧降解及生物修复有机卤代污染物的主力军。微生物种群间的资源竞争、生长抑制、代谢交叉喂养(crossfeeding,即营养的动态交换,包括碳源、氮源、氨基酸、维生素、核苷酸、电子供体、电子受体和其他生长因子等)、水平基因转移及其他交互作用机制是群落结构稳定平衡的基础,有利于促进有机卤代污染物消减效率的最大化。本文围绕OHRB种群及与其他微生物种群间的互作机制(如交叉喂养机制、竞争机制及抑制机制等)进行了概述,并对未来互作机制的研究进行了探讨与展望,旨在为有机卤代物污染场地生物修复效率的提高提供科学理论和技术参考依据。     

Spectrum of MHC class II variability in Darwin's finches and their close relatives

The study describes >400 major histocompatibility complex (MHC) class II B exon 2 and 114 intron 2 sequences of 36 passerine bird species, 13 of which belong to the group of Darwin's finches (DFs) and the remaining 23 to close or more distant relatives of DFs in Central and South America. The data set is analyzed by a combination of judiciously selected statistical methods. The analysis reveals that reliable information concerning MHC organization, including the assignment of sequences to loci, and evolution, as well as the process of species divergence, can be obtained in the absence of genomic sequence data, if the analysis is taken several steps beyond the standard phylogenetic tree construction approach. The main findings of the present study are these: The MHC class II B region of the passerine birds is as elaborate in its organization, divergence, and genetic diversity as the MHC of the eutherian mammals, specifically the primates. Hence, the reported simplicity of the fowl MHC is an oddity. With the help of appropriate markers, the divergence of the MHC genes can be traced deep in the phylogeny of the bird taxa. Transspecies polymorphism is rampant at many of the bird MHC loci. In this respect, the DFs behave as if they were a single, genetically undifferentiated population. There is thus far no indication of alleles that could be considered species, genus, or even DF group specific. The implication of these findings is that DFs are in the midst of adaptive radiations, in which morphological differentiation into species is running ahead of genetic differentiation in genetic systems such as the MHC or the mitochondrial DNA. The radiations are so young that there has not been enough time to sort out polymorphisms at most of the loci among the morphologically differentiating species. These findings parallel those on Lake Victoria haplochromine fishes. Several of the DF MHC allelic lineages can be traced back to the MHC genes of the species Tiaris obscura, which we identified previously as the closest extant relative of DFs in continental America.     

Metabolic profiling in validation of plasma biomarkers for green tea polyphenols

Green tea polyphenols (GTP) effectively protect against chronic diseases in various animal models but human studies have been inconclusive. GTP components and metabolites in body fluids have been suggested as potential biomarkers, but validation of these biomarkers has rarely been done in human populations. A randomized, double-blinded, and placebo-controlled phase IIa chemoprevention study with GTP was conducted in 120 human subjects for 3 months. To validate GTP biomarker profiles, plasma samples were collected at baseline, 1-month, and 3-month and were analyzed by HPLC-Coularray electrochemical detection (ECD) for specific GTP components as well as for non-targeted metabolites. The levels of 2 GTP components, epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG), were homogenous at baseline (p > 0.45) but were significantly elevated (p < 0.01) by GTP treatment. Metabolic profiling identified 106 metabolites, and 56 of them were chosen to construct discriminant functions (DFs) based on the data at 3 months. The DFs clearly separated the placebo, 500 mg GTP, and 1000 mg GTP groups with an accuracy rate of 97.3%. When the DFs were applied to the combined baseline and 1-month data, the accuracy rate was 62.9% in classifying subjects into the 3 intervention groups. DFs derived from 1-month data showed similar results. Overall, this study validated plasma EGCG and ECG as reliable biomarkers for GTP consumption, and found metabolic profiles effective in discriminating different GTP dosages.