The Hylemon-Björkhem pathway of bile acid 7-dehydroxylation: history,biochemistry, and microbiology

Bile acids are detergents derived from cholesterol that function to solubilize dietary lipids, remove cholesterol from the body, and act as nutrient signaling molecules in numerous tissues with functions in the liver and gut being the best understood. Studies in the early 20th century established the structures of bile acids, and by mid-century, the application of gnotobiology to bile acids allowed differentiation of host-derived “primary” bile acids from “secondary” bile acids generated by host-associated microbiota. In 1960, radiolabeling studies in rodent models led to determination of the stereochemistry of the bile acid 7-dehydration reaction. A two-step mechanism was proposed, which we have termed the Samuelsson-Bergström model, to explain the formation of deoxycholic acid. Subsequent studies with humans, rodents, and cell extracts of Clostridium scindens VPI 12708 led to the realization that bile acid 7-dehydroxylation is a result of a multi-step, bifurcating pathway that we have named the Hylemon-Björkhem pathway. Due to the importance of hydrophobic secondary bile acids and the increasing measurement of microbial bai genes encoding the enzymes that produce them in stool metagenome studies, it is important to understand their origin.     

Physical limnological processes under ice

Penetration of solar radiation through ice and snow covering northern lakes produces a gravity current between regions with varying depths. This baroclinic current is a dominant physical process in winter because ice cover insulates lakes from the usual turbulence sources such as breaking surface waves and near-surface shear produced by the wind. The current forms a directed circulation from the littoral zone to the centre of the lake that is an important distribution mechanism for nutrients and other chemical and biological constituents. Heat transported by the current degrades the ice cover and makes surface travel hazardous. The thinning of the ice cover is most severe at the inlet to isolated bays with mean depths that differ significantly from the lake. At the mouth of a bay, the gravity current takes the form of a two-layer flow with inflow to the bay occurring near the surface. The lower layer has the largest temperature gradients and is dominated by a succession of progressive internal bores which decrease in amplitude overnight and with increasing cloud cover. The repetition of the bores occurs very close to the period of the uninodal barotropic seiche which suggests that the internal bores are forced by the surface seiche.     

Modified (−)-gallocatechin gallate-enriched green tea extract rescues age-related cognitive deficits by restoring hippocampal synaptic plasticity

Aging leads to cognitive impairments characterized by reduced hippocampal functions that are associated with impairment of long-term potentiation of CA1 synapses. Here, we assessed the safety and efficacy of modified (?)-gallocatechin gallate (GCG)-enriched green tea extract (HTP-GTE) in ameliorating the cognitive dysfunctions in late middle-aged murine model. We developed a novel HTP-GTE that was enriched with GCG via epimerization that involved heating. We compared the effects of oral administrations of conventional green tea and HTP-GTE in young and aged male C57/BL6 mice, and examined the changes in the hippocampal functions related to aging process. The functional outcome was assessed by the electrophysiological experiments to measure the long-term potentiation (LTP). HTP-GTE improved the age-related cognitive impairments via restoring long-term synaptic plasticity. We also identified that GCG was the main active component responsible for the HTP-GTE effect. The main molecular pathway in ameliorating the age-related cognitive dysfunctions involved protein kinase A (PKA) which was shown to be modulated by HTP-GTE. Thus, HTP-GTE has a therapeutic potential as a dietary supplement which may aid to rescue the impaired cognitive functions at the early phase of aging process through the modulation of LTP threshold.     

Influence of ventilation of the face on thermoregulation in Man during hyper- and hypothermia

It has been suggested that a thermal countercurrent exchange may occur in the cerebral vascular bed of humans, thereby creating for the brain a state of relative thermal independence with regard to the rest of the body. However, worrying questions have arisen concerning this suggestion. Experiments were carried out on seven young male volunteers. Hyper- and hypothermic conditions were produced by immersion in water at 38.5 degrees C and 25 degrees C, respectively. During the last few minutes of immersion, the face was cooled or warmed by ventilation with a 200 l.min-1 air flow at 5 degrees C or 40 degrees C, respectively. Internal and peripheral temperatures were recorded. Blood flow in the anastomotic vessels between face and brain was measured by Doppler techniques associated with computerized frequency analysis. The general responses were as classically described, i.e. an increase in peripheral and central temperatures during immersion in the warm bath and a decrease in these variables in the cold bath. The reactions produced by cooling or warming the face were small and easily explained by the direct changes of the heat load they induced. Whatever the thermal conditions, the blood flow in the anastomotic vessels between the vascular bed of the face and that of the brain was never reversed. It was concluded that there was no experimental evidence for an efficient thermal counter-current exchange in the vascular bed of the human head.     

Estimation des paramètres fondamentaux de la dynamique d'un estuaire à marées. On the Dynamics of a Tidal Estuary: Estimation of the Principal Factors

In order to obtain a better understanding on the relationship between salt and fresh-water masses in an estuary on the Northern Brittany coast, a study on the tidal dynamics has been carried out. A simple model for the calculation of the mean current velocities is proposed taking into account the estuarine topography, tidal parameters and river discharge. The model also estimates the Richardson, Froude and Reynolds estuarine numbers. These can be used in further studies on the particle transport in this estuary.     

Interactions between Light Situation,Depth of Mixing and Phytoplankton Growth during the Spring Period of Full Circulation

Investigations lasting several years at the artificial Lake Saidenbach have shown that, due to the poor light situation expressed in terms of average daily radiation (Riley 1957), mean daily exposure (Reynolds 1973), extinction depth and the ratio ^zmis/^zeu, no mass development of the phytoplankton should actually occur during the spring complete circulation. In practice, however, the period of complete circulation of the water in spring is not only a prerequisite for, but often also the factor causing, the mass development (usually Asterionella formosa). The poor light situation and the fact that the vertical phytoplankton profile shows significant differences between the plankton concentrations at different depths indicate that the spring complete circulation does not represent a complete recirculation, and thus mixing, of the water down to the bottom but involves only episodic and local partial recirculations interspersed with periods of relatively slight turbulence. The actual mixing depth during this period of complete circulation is therefore obviously less than the mean depth of the water concerned, which is commonly assumed to equal. This permits the algae in the upper layers to grow. Respiratory losses of the phytoplankton at greater depths probably remain slight due to their adaptation to low light intensities in winter.     

Induction of purple sulfur bacterial growth in dairy wastewater lagoons by circulation

Aims:  To determine whether circulation of dairy wastewater induces the growth of phototrophic purple sulfur bacteria (PSB).
Methods and Results:  Two dairy wastewater lagoons that were similar in size, geographic location, number and type of cattle loading the lagoons were chosen. The only obvious visual difference between them was that one was stagnant and the water was brown in colour (Farm 1), and the other was circulated and the water was red in colour because of the presence of PSB that contained carotenoid pigments (Farm 2). Both wastewaters were sampled monthly for 3 months and assayed for PSB and extractable carotenoid pigments (ECP). After this point, circulators were placed in the wastewater lagoon on Farm 1, and samples were taken monthly for 9 months and assayed for PSB and ECP. Before the installation of circulators, no PSB-like 16S rRNA sequences or ECP were observed in the wastewater from Farm 1; however, both were observed in the wastewater from Farm 2. After the installation of circulators, statistically greater levels of PSB and extractable carotenoid pigments were observed in the wastewater from Farm 1.
Conclusions:  Circulation enhances the growth of PSB in dairy wastewater.
Significance and Impact of this Study:  Because PSB utilize H₂S and volatile organic acids (VOA) as an electron source for photosynthesis, and VOA and alcohols as a carbon source for growth, the increase in these bacteria should reduce H₂S, volatile organic compounds and alcohol emissions from the lagoons, enhancing the air quality in dairy farming areas.     

The secondary vascular system of Actinopterygii: interspecific variation in origins and investment

Vascular casts of 3 species of Chondrichthyes, 1 of Dipnoi, 1 of Chondrostei and 14 species of the Teleostei were examined by light and scanning electron microscopy in order to give a qualitative and quantitative analysis of interarterial anastomoses (iaas) that indicate the presence (or absence) of a secondary vascular system (SVS). Anastomoses were found to originate from a variety of different primary blood vessels, many of which have not been previously identified as giving rise to secondary vessels. Segmental arteries derived from the dorsal aorta and supplying body musculature were major sites of origin of the SVS, although there was considerable variation in where, in the hierarchy of arterial branching, the anastomoses occurred. The degree of investment in a SVS was species specific, with more active species having a higher degree of secondary vascularisation. This difference was quantified using an absolute count of iaas between Anguilla reinhardtii and Trachinotus baillonii. A range of general features of the SVS is also described. No evidence of iaas was found on the coeliac, mesenteric or renal circulation in any species. Evidence of iaas was lacking in the dipnoan and chondrichthyan species examined, suggesting that a SVS is restricted to Actinopterygii. The presence and distribution of a SVS does not appear to be exclusively linked to phylogenetic position, but rather to the physiological adaptation of the species.The online version of the original article can be found at     

Fast scan magnetic resonance imaging and Doppler ultrasonography of uteroplacental hemodynamics in the rhesus monkey (Macaca mulatta)

Fast scan magnetic resonance imaging, color Doppler ultrasonography, and magnetic resonance angiography were used to demonstrate the uteroplacental hemodynamics in rhesus monkeys. “Jets” of maternal blood spurting into the placenta were observed with, or without, the use of a contrast medium from 114 days to the term of pregnancy. Cumulative intravenous doses of cocaine hydrochloride brought about changes in the sequences of imaging of the maternal blood inflow to the placenta. These methods appear suitable for non-invasive monitoring of the effects of drugs on placental function.     

Optimization of extracorporeal membrane oxygenation therapy using near‐infrared spectroscopy to assess changes in peripheral circulation: A pilot study

Near‐infrared spectroscopy (NIRS) has been proposed as a noninvasive modality for detecting complications in patients undergoing extracorporeal membrane oxygenation (ECMO), and it can simultaneously reveal the global circulatory status of these patients. We optimized ECMO therapy on the basis of real‐time peripheral NIRS probing. Three patients underwent venoarterial (VA) ECMO and one patient underwent venovenous (VV) ECMO. All patients received peripheral ECMO cannulation with routine distal perfusion catheter placement. We designed an experimental protocol to adjust ECMO blood flow over 1 hour. Hemodynamic responses were measured using NIRS devices attached to the calf at approximately 60% of the distance from the ankle to the knee. HbO₂ levels change substantially with adjustments in ECMO flow, and they are more sensitive than HHb levels and the tissue saturation index (TSI) are. NIRS for optimizing ECMO therapy may be reliable for monitoring global circulatory status.