Rhamnose lipids – biosynthesis, microbial production and application potential

Biosurfactants containing rhamnose and β-hydroxydecanoic acid and called rhamnolipids are reviewed with respect to microbial producers, their physiological role, biosynthesis and genetics, and especially their microbial overproduction, physicochemical properties and potential applications. With Pseudomonas species, more than 100 g l⁻¹ rhamnolipids were produced from 160 g l⁻¹ soybean oil at a volumetric productivity of 0.4 g l⁻¹h⁻¹. The individual rhamnolipids are able to lower the surface tension of water from 72 mN m⁻¹ to 25–30 mN m⁻¹ at concentrations of 10–200 mg l⁻¹. After initial testing, rhamnolipids seem to have potential applications in combating marine oil pollution, removing oil from sand and in combating zoosporic phytopathogens. Rhamnolipids are also a source of l-rhamnose, which is already used for the industrial production of high-quality flavor components. Received: 1 July 1998 / Received revision: 11 September 1998 / Accepted: 13 September 1998     

Ethylbutyrate,a valproate-like compound,exhibits inositol-depleting effects — A potential mood-stabilizing drug

AimsTo screen for inositol-depleting valproate-like compounds as potential mood stabilizing drugs.Main methodsWe exploited the yeast Saccharomyces cerevisiae, as a model in which inositol de novo synthesis has been extensively characterized, to test the effects of ethyl butyrate (EB), 2-ethyl-butyric acid, sodium butyrate, and n-propyl hexanoate on inositol biosynthesis. Cell growth was followed by measuring the optical density of the cultures (spectrophotometrically), RNA abundance was determined by Northern blot analysis, intracellular inositol was measured by a fluorometric assay, and 1-d-myo-inositol-3-phosphate synthase activity was examined using a chromatographic method.Key findingsOf the tested compounds, only EB exhibited an inositol-depleting effect. The inositol-depleting effect of EB was achieved without significant adverse effect on cell growth, pointing to lesser toxicity compared to valproate.SignificanceThese results indicate that EB is a potential candidate for mood-stabilizing therapy.     

Helix induction potential of N-terminal α-methyl, α-amino acids

Summary A series of longer analogues of the C-peptide of RNAse A has been synthesized with the aim of assessing the helix induction potential in water of α-methyl, α-amino acids at the N-terminus of the chain. The circular dichroism data indicate that one isovaline residue is effective in increasing the helix content of the 13-residue peptide by about 7%.     

Design,synthesis, and structure–activity relationships of pyrazole derivatives as potential FabH inhibitors

Fatty acid biosynthesis is essential for bacterial survival. FabH, β-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and -negative bacteria. Fifty-six 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives were synthesized and developed as potent inhibitors of FabH. This inhibitor class demonstrates strong antibacterial activity. Escherichia coli FabH inhibitory assay and docking simulation indicated that the compounds 1-(5-(4-fluorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (12) and 1-(5-(4-chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (13) were potent inhibitors of E. coli FabH.     

WNK1： analysis of protein kinase structure, downstream targets, and potential roles in hypertension

The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis, lntronic deletions in the WNK1 gene resuk in its overexpression and lead to pseudohypoaldosteronism type Ⅱ, a disease with salt-sensitive hypertension and hyperkalemia. This review focuses on the recent evidence elucidating the structure of the kinase domain of WNK1 and functions of these kinases in normal and disease physiology. Their functions have implications for understanding the biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. The WNK kinases may be able to influence ion homeostasis through its effects on synaptotagmin function.     

N-α-PGP and PGP,potential biomarkers and therapeutic targets for COPD

Background

Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder for which new diagnostic and therapeutic approaches are required. Hallmarks of COPD are matrix destruction and neutrophilic airway inflammation in the lung. We have previously described two tri-peptides, N-α-PGP and PGP, which are collagen fragments and neutrophil chemoattractants. In this study, we investigate if N-α-PGP and PGP are biomarkers and potential therapeutic targets for COPD.

Methods

Induced sputum samples from COPD patients, healthy controls and asthmatics were examined for levels of N-α-PGP and PGP using mass spectrometry and for the ability to generate PGP de novo from collagen. Proteases important in PGP generation in the lung were identified by the use of specific inhibitors in the PGP generation assay and by instillation of proteases into mouse lungs. Serum levels of PGP were compared between COPD patients and controls.

Results

N-α-PGP was detected in most COPD sputum samples but in no asthmatics or controls. PGP was detected in a few controls and in all COPD sputum samples, where it correlated with levels of myeloperoxidase. COPD sputum samples had the ability to generate N-α-PGP and PGP de novo from collagen. PGP generation by COPD sputum was blocked by inhibitors of matrix metalloproteases (MMP''s) 1 and 9 and prolyl endopeptidase. MMP''s 1 and 9 and prolyl endopeptidase acted synergistically to generate PGP in vivo when instilled into mouse lungs. Serum levels of PGP were also significantly higher in COPD patients than in controls

Conclusion

N-α-PGP and PGP may represent novel diagnostic tests and biomarkers for COPD. Inhibition of this pathway may provide novel therapies for COPD directed at the chronic, neutrophilic, airway inflammation which underlies disease progression.     

Polycomplexes – potential for bioseparation

This review discusses the properties of complexes formed by proteins with polyelectrolytes (PPC) and two polyelectrolyte molecules of opposite charge (PEC). The most highly charged polymers with ionic groups in each monomer unit are considered in this paper. There are all reasons to regard PEC as macromolecular compounds produced as a result of equilibrium reactions with inherent permanent exchange of polyions in water-salt solutions. They combine two properties that might appear at first sight to be mutually exclusive, i.e. rather high stability and lability. Introduction of bioaffinity ligands endows PEC with the recognition capacity sufficient for the purposes of bioseparation and bioanalysis. Antibody-PEC conjugates were successfully used in the immunoassay combining the advantages of both homogeneous and heterogeneous assays and for modeling of chaperone action. The unique properties of polyelectrolyte complexes in combination with bioaffinity ligands makes them promising for the development of highly efficient means of protein isolation, new immunoassay procedures and creation of reversibly soluble biocatalysts. This revised version was published online in July 2006 with corrections to the Cover Date.     

Are patients with potential celiac disease really potential? The answer of metabonomics

Celiac disease (CD) is an autoimmune disorder caused by a permanent sensitivity to gluten in genetically susceptible individuals. Accurate diagnosis of CD at an early stage and its treatment with a gluten-free diet (GFD) are important for optimum treatment and prognosis. Recently, by employing a noninvasive metabonomic approach, we have shown that CD has a well-defined metabonomic signature. Here we address potential CD patients, defined as subjects who do not have, and have never had, a jejunal biopsy consistent with clear CD, and yet have immunological abnormalities similar to those found in celiac patients. Sixty-one overt CD patients at diagnosis, 29 patients with potential CD, and 51 control subjects were examined by (1)H NMR of their serum and urine: out of 29 potential CD patients, 24 were classified as CD and 5 as control subjects. Potential CD largely shares the metabonomic signature of overt CD. Most metabolites found to be significantly different between control and CD subjects were also altered in potential CD. Our results demonstrate that metabolic alterations may precede the development of small intestinal villous atrophy and provide a further rationale for early institution of GFD in patients with potential CD, as recently suggested by prospective clinical studies.     

Design,synthesis, cytotoxicity,HuTopoIIα inhibitory activity and molecular docking studies of pyrazole derivatives as potential anticancer agents

In an attempt to find potential anticancer agents, a series of novel ethyl 4-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-2-oxo-6-(pyridin-3-yl)cyclohex-3-enecarboxylates 5a-i and 5-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-3-(pyridin-3-yl)-4,5-dihydropyrazole-1-carbothioamides 6a-i were designed, synthesized and evaluated for their topoisomerase IIα inhibitory activity and in vitro cytotoxicity against a panel of cancerous cell lines (MCF-7, NCI-H460, HeLa) and a normal cell line (HEK-293T). Molecular docking studies of all the synthesized compounds into the binding site of topoisomerase IIα protein (PDB ID: 1ZXM) were performed to gain a comprehensive understanding into plausible binding modes. These compounds were also screened for in silico drug-likeliness properties on the basis of the absorption, distribution, metabolism and excretion (ADME) prediction. Among all the synthesized compounds, analogue 5d showed superior cytotoxicity with an IC₅₀ value of 7.01 ± 0.60 μM for HeLa, 8.55 ± 0.35 μM for NCI-H460 and 14.31 ± 0.90 for MCF-7 cancer cell lines. Further, compound 5d showed 70.82% inhibition of topoisomerase IIα at a concentration of 100 μM with maximum docking score of −8.24. Results of ADME prediction revealed that most of these compounds showed in silico drug-likeliness properties within the ideal range.     

TGFBR3, a potential negative regulator of TGF-β signaling, protects cardiac fibroblasts from hypoxia-induced apoptosis

A lot of evidence indicates that cardiac fibroblasts are essential for maintaining the structure and function of heart. The present study examined whether TGFBR3 (transforming growth factor type III receptor, also known as betaglycan) could prevent hypoxia-induced injury in neonatal mice cardiac fibroblasts, if so, its possible molecular targets. MTT, electron microscopy and TUNEL assay were used to identify cell viability and apoptosis in neonatal mice cardiac fibroblasts. Results showed that hypoxia for 24 h markedly reduce cell viability by 49.8 ± 8.9%, largely via apoptosis. However, hypoxia-induced apoptosis in cardiac fibroblasts were almost completely prevented by overexpression of TGFBR3. In the present study, hypoxia also induced TGF-β1, p-Smad2/3 expression, TGFBR1-TGFBR2 complex formation and collagen production in cardiac fibroblasts, which were attenuated substantially by TGFBR3 overexpression. TGFBR3 also reversed Bax up-regulation, Bcl-2 down-regulation and Caspase-3 activation induced by hypoxia in cardiac fibroblasts. Hypoxia or TGF-β1 itself triggered an increase of [Ca(2+) ](i) in cardiac fibroblasts, which were both inhibited by TGFBR3 overexpression. Taken together, our results indicate that TGFBR3 may act as a protective factor in apoptotic process of cardiac fibroblasts by negative regulation of TGF-β signaling and represent a potential therapeutic target for heart remodeling after hypoxia injury.     

Identifying potential evolutionary relationships within a facultative lycaenid-ant system： Ant association, oviposition, and butterfly-ant conflict

Facultative associations are commonly encountered between ants and lycaenids, although the nature and patterns of associations are typically unclear. This study investigated a facultative symbiosis involving the lycaenid Theclinesthes albocincta （Lycaenidae）, its host plant Adriana quadripartita and Australian native ants. Ants in the genera Ochetellus and Iridomyrmex were most frequently found in association with T. albocincta larvae, although Iridomyrmex ants were found in much lower abundance than were ants in Ochetellus. The abundances of Ochetellus and Iridomyrmex were highly correlated with larval abundance, but not egg abundance. Observations and experiments recorded oviposi- tion on male inflorescences on more than 95% of occasions, but oviposition was not greater on inflorescences with ants present. Behavioral assays showed that Iridomyrmex ants were aggressive towards female butterflies on significantly more occasions than were Ochetellus ants. These findings indicate potential evolutionary relationships between T. albocincta and two genera of ants that were abundant within the habitat.     

Physical examination of the potential tissue donor, what does literature tell us?

European Tissue Banks should carry out a physical examination as a part of the donor selection procedure. This is one of the obligations concerning donation and procurement mentioned in the European Commission directives on tissue banking. As the directives do not give any further specification on the content or on the procedure of the physical examination, a search of literature was done in order to find more information. Although data in literature generally remain quite vague, it was possible to set up a list of items which should be looked at during physical examination. This list can be used temporarily until further information is gathered from an international survey and from a risk assessment analysis.     

Photosynthesis and stomatal conductance of potato leaves—effects of leaf age,irradiance, and leaf water potential

Potatoes (Solanum tuberosum L., cv. Bintje) were grown in a naturally lit glasshouse. Laboratory measurements on leaves at three insertion levels showed a decline with leaf age in photosynthetic capacity and in stomatal conductance at near saturating irradiance. Conductance declined somewhat more with age than photosynthesis, resulting in a smaller internal CO₂ concentration in older relative to younger leaves. Leaves with different insertion number behaved similarly. The changes in photosynthesis rate and in nitrogen content with leaf age were closely correlated. When PAR exceeded circa 100 W m^–2 the rate of photosynthesis and stomatal conductance changed proportionally as indicated by a constant internal CO₂ concentration. The photosynthesis-irradiance data were fitted to an asymptotic exponential model. The parameters of the model are AMAX, the rate of photosynthesis at infinite irradiance, and EFF, the slope at low light levels. AMAX declined strongly with leaf age, as did EFF, but to a smaller extent. During drought stress photosynthetic capacity declined directly with decreasing water potential (range –0.6 to –1.1 MPa). Initially, stomatal conductance declined faster than photosynthetic capacity.Abbreviations LNx leaf number x, counted in acropetal direction - DAP days after planting - DALA days after leaf appearance - C_i CO₂ concentration in the leaf - C_a CO₂ concentration in ambient air - LWP leaf water potential - OP osmotic potential - PAR photosynthetically active radiation     

Tricin—a potential multifunctional nutraceutical

This review throws light on the natural occurrence and distribution of tricin (5,7,4′-trihydroxy-3′,5′-dimethoxyflavone) and its conjugated forms, as more common natural plant constituents than previously known. It examines the current literature dealing with its biosynthesis, regulation, biological significance, pharmacological effects, and potential role as a chemopreventive and anticancer agent. Because of its common occurrence in cereal grain plants and the wide spectrum of its health promoting effects, a metabolic engineering strategy is proposed to produce tricin in sufficient amounts for further experimentation, and increase its accumulation in wheat grain endosperm as a nutraceutical.     

Sperm PLCζ: From structure to Ca oscillations,egg activation and therapeutic potential

Significant evidence now supports the assertion that cytosolic calcium oscillations during fertilization in mammalian eggs are mediated by a testis-specific phospholipase C (PLC), termed PLC-zeta (PLCζ) that is released into the egg following gamete fusion. Herein, we describe the current paradigm of PLCζ in this fundamental biological process, summarizing recent important advances in our knowledge of the biochemical and physiological properties of this enzyme. We describe the data suggesting that PLCζ has distinct features amongst PLCs enabling the hydrolysis of its substrate, phosphatidylinositol 4,5-bisphosphate (PIP₂) at low Ca²⁺ levels. PLCζ appears to be unique in its ability to target PIP₂ that is present on intracellular vesicles. We also discuss evidence that PLCζ may be a significant factor in human fertility with potential therapeutic capacity.     

Modeling the potential suitable habitat of Impatiens hainanensis,a limestone-endemic plant北大核心CSCD

Aims Modelling potential distribution ranges of threatened species is of great significance for their conservation. In this paper, the distribution of potential suitable habitat of Impatiens hainanensis, a limestone-endemic and endangered plant in Hainan Island, was studied to provide scientific basis for their effective in situ conservation and re-introduction of I. hainanensis. Methods Based on eight occurrence sites and 12 environmental variables, the Maximum Entropy (MaxEnt) algorithm and GIS technology were used to create a model linking the distribution ranges of I. hainanensis with environments. With data on five actual distribution sites and five non-occurrence sites, four model evaluation metrics (area under the receiver operating characteristic curve (AUC), kappa coefficient, true skill statistic (TSS), overall accuracy) were used to evaluate the predictive performance and accuracy of this model. Important findings The results indicated that the indicative value of all four evaluation metrics were above 0.9, indicating that the MaxEnt model can effectively predict the potential suitable habitats of I. hainanensis. Slope, precipitation of the driest quarter and coefficients of precipitation variation were the three main environmental factors influencing the distribution of I. hainanensis. At present, the most suitable habitat includes western and southern parts of Baisha County, the central and southern parts of Changjiang County, the eastern part of the Dongfang City and northeastern Ledong County, accounting for 1.8% of land area on Hainan Island. Since the potential suitable habitat of I. hainanensis is rare and severely fragmented, the protection of this species is urgent. We suggest to collect the seeds of various geographic populations of I. hainanensis to establish a germplasm resource bank. The most suitable habitat of the species, including Tian’an Village and Jiangbian Village in Dongfang City, northeast of Ledong County (Jiaxi Reserve), should be selected as the priority places for future extensive field surveys and re-introduction. © Chinese Journal of Plant Ecology.     

Microbial diversity at Mitchell Peninsula,Eastern Antarctica: a potential biodiversity “hotspot”

Mitchell Peninsula is located towards the East of the Windmill Islands in eastern Antarctica. It is an ice-free polar desert, and knowledge of its soil microbial taxonomic composition is limited. In this study, we investigated the soil microbial taxonomic composition using multiplex 454 pyrosequencing targeting the bacterial 16S rRNA and the fungal ITS genes; and the bacterial and fungal abundances were estimated using quantitative PCR. In total, 40 bacterial and five fungal phyla were identified comprising 111 bacterial and 22 fungal classes, respectively. Mitchell Peninsula soil exhibited a unique bacterial taxonomic profile. In contrast to the usual dominance of Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes in polar and temperate soils, Mitchell Peninsula was rich in the poorly studied Chloroflexi (31.7 %), candidate divisions WPS-2 (8.1 %) and AD3 (5.1 %), while the commonly observed Bacteroidetes and Firmicutes were present in relative abundances below 1 %. The fungal community consisted of Ascomycota (77 %) and Basidiomycota (10 %), and was dominated by the lichenous fungal class Lecanoromycetes (46.4 %). Network analysis revealed the presence of several microbial clusters that each potentially occupied a different environmental niche, and fewer numbers of correlations were identified between bacteria within each cluster compared with the lichen community, where extensive community dynamics may be present. As Mitchell Peninsula exhibits a unique microbial taxonomic composition, not previously observed in any reported polar or temperate ecosystem, we believe it is a potential microbial biodiversity “hotspot”, which warrants further investigation to examine the role of the dominance of these uncharacterised candidate divisions in this extreme ecosystem.