The Microbiota Is Essential for the Generation of Black Tea Theaflavins-Derived Metabolites

Background

Theaflavins including theaflavin (TF), theaflavin-3-gallate (TF3G), theaflavin-3′-gallate (TF3′G), and theaflavin-3,3′-digallate (TFDG), are the most important bioactive polyphenols in black tea. Because of their poor systemic bioavailability, it is still unclear how these compounds can exert their biological functions. The objective of this study is to identify the microbial metabolites of theaflavins in mice and in humans.

Methods and Findings

In the present study, we gavaged specific pathogen free (SPF) mice and germ free (GF) mice with 200 mg/kg TFDG and identified TF, TF3G, TF3′G, and gallic acid as the major fecal metabolites of TFDG in SPF mice. These metabolites were absent in TFDG- gavaged GF mice. The microbial bioconversion of TFDG, TF3G, and TF3′G was also investigated in vitro using fecal slurries collected from three healthy human subjects. Our results indicate that TFDG is metabolized to TF, TF3G, TF3′G, gallic acid, and pyrogallol by human microbiota. Moreover, both TF3G and TF3′G are metabolized to TF, gallic acid, and pyrogallol by human microbiota. Importantly, we observed interindividual differences on the metabolism rate of gallic acid to pyrogallol among the three human subjects. In addition, we demonstrated that Lactobacillus plantarum 299v and Bacillus subtilis have the capacity to metabolize TFDG.

Conclusions

The microbiota is important for the metabolism of theaflavins in both mice and humans. The in vivo functional impact of microbiota-generated theaflavins-derived metabolites is worthwhile of further study.     

Immediate and one-year outcome of patients presenting with Acute Coronary Syndrome complicated by stroke: Findings from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2)

ABSTRACT: BACKGROUND: Stroke is a potential complication of acute coronary syndrome (ACS). The aim of this study was to identify the prevalence, risk factors predisposing to stroke, in-hospital and 1-year mortality among patients presenting with ACS in the Middle East. METHODS: For a period of 9 months in 2008 to 2009, 7,930 consecutive ACS patients were enrolled from 65 hospitals in 6 Middle East countries. RESULTS: The prevalence of in-hospital stroke following ACS was 0.70%. Most cases were ST segment elevation MI-related (STEMI) and ischemic stroke in nature. Patients with in-hospital stroke were 5 years older than patients without stroke and were more likely to have hypertension (66% vs. 47.6%, P = 0.001). There were no differences between the two groups in regards to gender, other cardiovascular risk factors, or prior cardiovascular disease. Patients with stroke were more likely to present with atypical symptoms, advanced Killip class and less likely to be treated with evidence-based therapies. Independent predictors of stroke were hypertension, advanced killip class, ACS type --STEMI and cardiogenic shock. Stroke was associated with increased risk of in-hospital (39.3% vs. 4.3%) and one-year mortality (52% vs. 12.3%). CONCLUSION: There is low incidence of in-hospital stroke in Middle-Eastern patients presenting with ACS but with very high in-hospital and one-year mortality rates. Stroke patients were less likely to be appropriately treated with evidence-based therapy. Future work should be focused on reducing the risk and improving the outcome of this devastating complication.     

Substrate-binding model of the chlorophyll biosynthetic magnesium chelatase BchH subunit

Photosynthetic organisms require chlorophyll and bacteriochlorophyll to harness light energy and to transform water and carbon dioxide into carbohydrates and oxygen. The biosynthesis of these pigments is initiated by magnesium chelatase, an enzyme composed of BchI, BchD, and BchH proteins, which catalyzes the insertion of Mg(2+) into protoporphyrin IX (Proto) to produce Mg-protoporphyrin IX. BchI and BchD form an ATP-dependent AAA(+) complex that transiently interacts with the Proto-binding BchH subunit, at which point Mg(2+) is chelated. In this study, controlled proteolysis, electron microscopy of negatively stained specimens, and single-particle three-dimensional reconstruction have been used to probe the structure and substrate-binding mechanism of the BchH subunit to a resolution of 25A(.) The apo structure contains three major lobe-shaped domains connected at a single point with additional densities at the tip of two lobes termed the "thumb" and "finger." With the independent reconstruction of a substrate-bound BchH complex (BchH.Proto), we observed a distinct conformational change in the thumb and finger subdomains. Prolonged proteolysis of native apo-BchH produced a stable C-terminal fragment of 45 kDa, and Proto was shown to protect the full-length polypeptide from degradation. Fitting of a truncated BchH polypeptide reconstruction identified the N- and C-terminal domains. Our results show that the N- and C-terminal domains play crucial roles in the substrate-binding mechanism.     

The Dynamics of Conjunctive and Disjunctive Boolean Network Models

For many biological networks, the topology of the network constrains its dynamics. In particular, feedback loops play a crucial role. The results in this paper quantify the constraints that (unsigned) feedback loops exert on the dynamics of a class of discrete models for gene regulatory networks. Conjunctive (resp. disjunctive) Boolean networks, obtained by using only the AND (resp. OR) operator, comprise a subclass of networks that consist of canalyzing functions, used to describe many published gene regulation mechanisms. For the study of feedback loops, it is common to decompose the wiring diagram into linked components each of which is strongly connected. It is shown that for conjunctive Boolean networks with strongly connected wiring diagram, the feedback loop structure completely determines the long-term dynamics of the network. A formula is established for the precise number of limit cycles of a given length, and it is determined which limit cycle lengths can appear. For general wiring diagrams, the situation is much more complicated, as feedback loops in one strongly connected component can influence the feedback loops in other components. This paper provides a sharp lower bound and an upper bound on the number of limit cycles of a given length, in terms of properties of the partially ordered set of strongly connected components.     

Timing of propagule release significantly alters the deposition area of resulting aerial dispersal

Aim The aim of this study is to determine whether changes to the seasonal and circadian timing of propagule release can a have a significant effect on the area covered by resulting aerial dispersal. Location Western Australia. Methods Using the atmospheric pollution model (TAPM), an existing meso‐scale dispersal model, a range of release patterns was simulated and the resulting deposition compared. Comparisons were based on observations of deposition patterns and the calculated area of deposition. Results Small changes to the timing of propagule release were shown to significantly impact on the area experiencing deposition from the resulting aerial dispersal. Main conclusions Simulations performed in this study show that, for small propagules, changes to the timing of release can lead to alternate, clearly differentiable dispersal events. Small changes in both the seasonal and circadian patterns of release can have significant effects on the area that experiences deposition during the resulting dispersal event. This effect is particularly important at the landscape scale and when there is a need to quantify individual dispersal events. Predictive modelling of aerial dispersal needs to be undertaken with an understanding of the manner in which biological and environmental factors that affect the timing of propagule release can influence results. Results presented highlight the need to characterize the epidemiology of pathogenic organisms of importance to biosecurity as much as possible before they arrive.     

Identifying the functional groups and the influence of synthetic chelators on Cd availability and microbial biomass carbon in Cd-contaminated soil

Synthetic chelators play an important role in boosting the microbial biomass carbon (MBC), dissolved organic carbon (DOC), and heavy metal solubility in a contaminated soil toward a sustainability of environment for agricultural crops. Castor plant was grown under different levels of Cd contaminated soil (?Cd and +Cd) following adding three chelating agents, ethylenediaminetetraacetic acid (H₄EDTA), nitriloacetic acid (H₃ NTA), and NH₄ citrate (ammonium citrate) to the soil at rates of 10, 15, and 25 mmol in 5 kg of soil per pot. The highest bioavailable Cd concentrations in soil and castor plant were obtained from NH₄ citrate and H₄EDTA treatments in the contaminated soil. Fourier transform infrared (FTIR) analysis showed that NH₄ citrate was the most effective chelator in Cd-contaminated soil. MBC and DOC contents were significantly increased and reached at 81.98–80.37 and 1.96–1.90 mg kg^?1 respectively, in the (H₃ NTA) and NH₄ citrate treatments in Cd-contaminated soil. Further research is needed to investigate the use of chelators in the phytoextraction of Cd-contaminated soils under field conditions and whether it may be beneficial in accelerating the phytoextraction of Cd through hyperaccumulating plants.     

Bioaccessibility-Based Risk Assessment of PAHs in Soils from Sites of Different Anthropogenic Activities in Lagos,Nigeria Using the Fed Organic Estimation Human Simulation Test Method

The aim of this study was to carry out a bioaccessibility-based risk assessment of polycyclic aromatic hydrocarbons (PAHs) in soils from sites of different anthropogenic activities in Lagos, Nigeria. Using an in vitro gastrointestinal model—Fed Organic Estimation Human Simulation Test method (FOREShT), the concentration of bioaccessible 16 priority US Environmental Protection Agency (USEPA) PAHs in soils were determined. Total concentration of 16 priority USEPA PAHs was also determined. The concentration range was 702–253,922 ng g^?1 and 92–760 ng g^?1 for total and bioaccessible PAHs, respectively. For persons involved with activities at these sites no health risks were observed, based on bioaccessibility values of PAHs. Mean daily intake of PAHs from these soils were below the oral mean daily intake threshold for PAHs in food. Also, overall estimated theoretical cancer risk (2.5 × 10^?09, 6.5 × 10^?07, 5.5 × 10^?10, 2.7 × 10^?09, 6.5 × 10^?10, 9.5 × 10^?10, 2.0 × 10^?09, and 4.1 × 10^?07 for the eight sites based on their bioaccessible concentration) for exposure to PAHs in surface soils were below the health guidelines for extreme (1 × 10^?04) and normal (1 × 10^?06) exposures.     

The potency of lemon (Citrus limon L.) essential oil to control some fungal diseases of grapevine wood

This study aimed to evaluate the in vitro antifungal activity (AA) of the essential oil (EO) of lemon (Citrus limon L.) against three pathogenic fungi attacking grapevine wood. The composition of the EO was also studied. Ten volatile components were identified by gas chromatography–mass spectrometry. The results showed that the EO consists of volatile components where monoterpene hydrocarbons are the most abundant ones. Four major components were identified, which represent 99.9% of the total EO (limonene, neral, ß-pinene, and ?-terpinene). The AA of the EO was evaluated against three pathogenic fungi attacking grapevine wood (Eutypa sp., Botryosphaeria dothidea, and Fomitiporia mediterranea). The results showed that the EO exerts AA against all tested fungi and significantly inhibits their growth. Eutypa sp. is the most sensitive fungus. These results show, for the first time, a new use for the EO of lemon (C. limon L.) to control fungal diseases of grapevine wood.