Leptin Response to Glucocorticoid Occurs at Physiological Doses and Is Abolished by Fasting

Objective: To examine the effects of graded doses of hydrocortisone (HC) on leptin secretion, and determine the effect of fasting. Research Methods and Procedures: This was a randomized, placebo‐controlled, crossover study, with a 1‐week “washout” period between interventions. Eight healthy subjects [age = 36 ± 2.3 years (±SE), body mass index = 31.5 ± 1.6 kg/m²] completed the dose‐response study in which an intravenous infusion of saline (placebo) or HC (30 or 100 mg) was administered for 24 hours. Four healthy subjects (age = 35.2 ± 3.0 years, body mass index = 27.1 ± 2.1 kg/m²) completed the fasting study, which entailed continuous infusion of saline, HC (300 mg/24 hours) in the fed state, or HC (300 mg/24 hours) with total caloric deprivation for 24 hours. Blood sampling was performed every 1 to 2 hours for measurement of leptin, cortisol, insulin, and glucose levels. Results: Peak hyperleptinemia occurred after 16 hours of HC infusion; peak/baseline leptin levels were 129% (placebo), 140% (30 mg of HC for 24 hours, p = 0.05), and 185% (100 mg of HC for 24 hours, p < 0.01). During infusion of HC (300 mg/24 hours or placebo), the peak/baseline plasma leptin levels were 16.1 ± 5.8/12.8 ± 5.9 ng/mL (placebo with food, 126%), 14.6 ± 6.0/12.5 ± 6.5 ng/mL (HC fasting, 117%), and 32.5 ± 12.5/12.0 ± 8.4 ng/mL (HC with food, 271%, p < 0.001). Discussion: Leptin secretory responses occur at physiological doses of HC, are obliterated by fasting, and thus may be of metabolic significance.     

A new photobioreactor for continuous microalgal production in hatcheries based on external-loop airlift and swirling flow

This study deals with the scale of a new photobioreactor for continuous microalgal production in hatcheries. The combination of the state-of-art with the constraints inherent to hatcheries has turned the design into a closed, artificially illuminated and external-loop airlift configuration based on a succession of elementary modules, each one being composed of two transparent vertical interconnected columns. The liquid circulation is ensured pneumatically (air injections) with respect to a swirling motion (tangential inlets). A single module of the whole photobioreactor was built-up to scale its geometry (diameter and length) and to optimize its design (air sparger, tangential inlets). The volumetric productivities were predicted by modeling radiative transfer and growth of Isochrysis affinis galbana (clone Tahiti). The hydrodynamics of the liquid phase was modeled in terms of global flow behavior (circulation and mixing times, Péclet number) and of swirling motion decay along the column (Particle Image Velocimetry). The aeration performances were determined by overall volumetric mass transfer measurements. Continuous cultures of Isochrysis affinis galbana (clone Tahiti) were run in two geometrical configurations, generating either an axial or a swirling flow. Lastly, the definitive options of design are presented as well as a 120-L prototype, currently implemented in a French mollusk hatchery and commercialized.     

Kinetic modeling of light limitation and sulfur deprivation effects in the induction of hydrogen production with Chlamydomonas reinhardtii: Part I. Model development and parameter identification

Chlamydomonas reinhardtii is a green microalga capable of turning its metabolism towards H2 production under specific conditions. However this H2 production, narrowly linked to the photosynthetic process, results from complex metabolic reactions highly dependent on the environmental conditions of the cells. A kinetic model has been developed to relate culture evolution from standard photosynthetic growth to H2 producing cells. It represents transition in sulfur-deprived conditions, known to lead to H2 production in Chlamydomonas reinhardtii, and the two main processes then induced which are an over-accumulation of intracellular starch and a progressive reduction of PSII activity for anoxia achievement. Because these phenomena are directly linked to the photosynthetic growth, two kinetic models were associated, the first (one) introducing light dependency (Haldane type model associated to a radiative light transfer model), the second (one) making growth a function of available sulfur amount under extracellular and intracellular forms (Droop formulation). The model parameters identification was realized from experimental data obtained with especially designed experiments and a sensitivity analysis of the model to its parameters was also conducted. Model behavior was finally studied showing interdependency between light transfer conditions, photosynthetic growth, sulfate uptake, photosynthetic activity and O2 release, during transition from oxygenic growth to anoxic H2 production conditions.     

A nonlinear model of ionic wave propagation along microtubules

Microtubules (MTs) are important cytoskeletal polymers engaged in a number of specific cellular activities including the traffic of organelles using motor proteins, cellular architecture and motility, cell division and a possible participation in information processing within neuronal functioning. How MTs operate and process electrical information is still largely unknown. In this paper we investigate the conditions enabling MTs to act as electrical transmission lines for ion flows along their lengths. We introduce a model in which each tubulin dimer is viewed as an electric element with a capacitive, inductive and resistive characteristics arising due to polyelectrolyte nature of MTs. Based on Kirchhoff’s laws taken in the continuum limit, a nonlinear partial differential equation is derived and analyzed. We demonstrate that it can be used to describe the electrostatic potential coupled to the propagating localized ionic waves. An erratum to this article can be found at     

Species identity, diversity and microbial carbon flow in reassembling macrobenthic communities

Intense disturbance may locally destroy patches of habitat and shape the landscape into a mosaic of reassembling communities. The development of ecosystem properties during such community reassembly is poorly understood. In intertidal bare sediments, trophic relations between microphytobenthos or heterotrophic bacteria and macrofauna invertebrates may guarantee fundamental ecosystem properties such as carbon flow through the food web. We studied the dynamic relation between reassembling macrofauna communities and such microbial carbon flow during recovery after severe disturbance. We deliberately induced prolonged hypoxia in winter and early summer and allowed recolonisation for periods of two and five months. Carbon flow was quantified from basal resources (microphytobenthos and bacteria) to intermediate consumers using ¹³C as a tracer. Within the period of study (5 months), microbial carbon flow fully recovered, although macrofauna diversity was still very low compared to the natural communities (ranging from 6 to 17 species). More than 90% of microbial carbon flow to macrofauna was due to the consumers that recolonised within two months. Two of these species were dominant contributors to microphytobenthos carbon transfer to fauna. Furthermore, at an early stage of reassembly, this ecosystem property was remarkably similar when disturbance took place at different times of the year (winter or early summer), although there were differences in assemblage composition and functional diversity. We conclude that species assemblages and ecosystem function developed relatively independently in this benthic system. We discuss which ecological factors may have caused such non-parallel development of macrofaunal communities and carbon flow.     

Dipeptidyl nitrile inhibitors of Cathepsin L

A series of potent Cathepsin L inhibitors with good selectivity with respect to other cysteine Cathepsins is described and SAR is discussed with reference to the crystal structure of a protein-ligand complex.     

C-5 substituted heteroaryl-3-pyridinecarbonitriles as PKCθ inhibitors: Part II

We previously reported that a 3-pyridinecarbonitrile analog with a furan substituent at C-5 and a 4-methylindol-5-ylamino substituent at C-4, 1, was a potent inhibitor of PKCθ (IC₅₀ = 4.5 nM). Replacement of the C-5 furan ring of 1 with bicyclic heteroaryl rings, led to compounds with significantly improved potency against PKCθ. Analog 6b with a 4-methylindol-5-ylamino group at C-4 and a 5-[(4-methylpiperazin-1-yl)methyl]-1-benzofuran-2-yl group at C-5 had an IC₅₀ value of 0.28 nM for the inhibition of PKCθ.