α-MSH Stimulates Glucose Uptake in Mouse Muscle and Phosphorylates Rab-GTPase-Activating Protein TBC1D1 Independently of AMPK

The melanocortin system includes five G-protein coupled receptors (family A) defined as MC1R-MC5R, which are stimulated by endogenous agonists derived from proopiomelanocortin (POMC). The melanocortin system has been intensely studied for its central actions in body weight and energy expenditure regulation, which are mainly mediated by MC4R. The pituitary gland is the source of various POMC-derived hormones released to the circulation, which raises the possibility that there may be actions of the melanocortins on peripheral energy homeostasis. In this study, we examined the molecular signaling pathway involved in α-MSH-stimulated glucose uptake in differentiated L6 myotubes and mouse muscle explants. In order to examine the involvement of AMPK, we investigate α-MSH stimulation in both wild type and AMPK deficient mice. We found that α-MSH significantly induces phosphorylation of TBC1 domain (TBC1D) family member 1 (S237 and T596), which is independent of upstream PKA and AMPK. We find no evidence to support that α-MSH-stimulated glucose uptake involves TBC1D4 phosphorylation (T642 and S704) or GLUT4 translocation.     

Septum volume and food‐storing behavior are related in parids

The hippocampal formation (HF) of food‐storing birds is larger than non‐storing species, and the size of the HF in food‐storing Black‐Capped Chickadees (Poecile atricapillus) varies seasonally. We examined whether the volume of the septum, a medial forebrain structure that shares reciprocal connections with the HF, demonstrates the same species and seasonal variation as has been shown in the HF. We compared septum volume in three parid species; non‐storing Blue Tits (Parus caeruleus) and Great Tits (Parus major), and food‐storing Black‐Capped Chickadees. We found the relative septum volume to be larger in chickadees than in the non‐storing species. We also compared septum and nucleus of the diagonal band (NDB) volume of Black‐Capped Chickadees at different times of the year. We found that the relative septum volume varies seasonally in food‐storing birds. The volume of the NDB does not vary seasonally. Due to the observed species and seasonal variation, the septum, like the hippocampal formation of food‐storing birds, may be specialized for some aspects of food‐storing and spatial memory. © 2002 Wiley Periodicals, Inc. J Neurobiol 51: 215–222, 2002     

Relationships Between Animal Health Monitoring and the Risk Assessment Process

Risk assessment is part of the risk analysis process as it is used in veterinary medicine to estimate risks related to international trade and food safety. Data from monitoring and surveillance systems (MO&SS) are used throughout the risk assessment process for hazard identification, release assessment, exposure assessment and consequence assessment. As the quality of risk assessments depends to a large extent on the availability and quality of input data, there is a close relationship between MO&SS and risk assessment. In order to improve the quality of risk assessments, MO&SS should be designed according to minimum quality standards. Second, recent scientific developments on state-of-the-art design and analysis of surveys need to be translated into field applications and legislation. Finally, knowledge about the risk assessment process among MO&SS planners and managers should be promoted in order to assure high-quality data.     

Galectin 9 is the sugar-regulated urate transporter/channel UAT

UAT, also designated galectin 9, is a multifunctional protein that can function as a urate channel/transporter, a regulator of thymocyte-epithelial cell interactions, a tumor antigen, an eosinophil chemotactic factor, and a mediator of apoptosis. We review the evidence that UAT is a transmembrane protein that transports urate, describe our molecular model for this protein, and discuss the evidence from epitope tag and lipid bilayer studies that support this model of the transporter. The properties of recombinant UAT are compared with those of urate transport into membrane vesicles derived from proximal tubule cells in rat kidney cortex. In addition, we review channel functions predicted by our molecular model that resulted in the novel finding that the urate channel activity is regulated by sugars and adenosine. Finally, the presence and possible functions of at least 4 isoforms of UAT and a closely related gene hUAT2 are discussed. Published in 2004.     

Scale down of recombinant protein production: a comparative study of scaling performance

A large bioreactor is heterogeneous with respect to concentration gradients of substrates fed to the reactor such as oxygen and growth limiting carbon source. Gradient formation will highly depend on the fluid dynamics and mass transfer capacity of the reactor, especially in the area in which the substrate is added. In this study, some production-scale (12 m³ bioreactor) conditions of a recombinant Escherichia coli process were imitated on a laboratory scale. From the large-scale cultivations, it was shown that locally high concentration of the limiting substrate fed to the process, in this case glucose, existed at the level of the feedpoint. The large-scale process was scaled down from: (i) mixing time experiments performed in the large-scale bioreactor in order to identify and describe the oscillating environment and (ii) identification of two distinct glucose concentration zones in the reactor. An important parameter obtained from mixing time experiments was the residence time in the feed zone of about 10 seconds. The size of the feed zone was estimated to 10%. Based on these observations the scale-down reactor with two compartments was designed. It was composed of one stirred tank reactor and an aerated plug flow reactor, in which the effect of oscillating glucose concentration on biomass yield and acetate formation was studied. Results from these experiments indicated that the lower biomass yield and higher acetate formation obtained on a large scale compared to homogeneous small-scale cultivations were not directly caused by the cell response to the glucose oscillation. This was concluded since no acetate was accumulated during scale-down experiments. An explanation for the differences in results between the two reactor scales may be a secondary effect of high glucose concentration resulting in an increased glucose metabolism causing an oxygen consumption rate locally exceeding the transfer rate. The results from pulse response experiments and glucose concentration measurements, at different locations in the reactor, showed a great consistency for the two feeding/pulse positions used in the large-scale bioreactor. Furthermore, measured periodicity from mixing data agrees well with expected circulation times for each impeller volume. Conclusions are drawn concerning the design of the scale-down reactor.     

Circadian clock adjustment to plant iron status depends on chloroplast and phytochrome function

Plant chloroplasts are not only the main cellular location for storage of elemental iron (Fe), but also the main site for Fe, which is incorporated into chlorophyll, haem and the photosynthetic machinery. How plants measure internal Fe levels is unknown. We describe here a new Fe‐dependent response, a change in the period of the circadian clock. In Arabidopsis, the period lengthens when Fe becomes limiting, and gradually shortens as external Fe levels increase. Etiolated seedlings or light‐grown plants treated with plastid translation inhibitors do not respond to changes in Fe supply, pointing to developed chloroplasts as central hubs for circadian Fe sensing. Phytochrome‐deficient mutants maintain a short period even under Fe deficiency, stressing the role of early light signalling in coupling the clock to Fe responses. Further mutant and pharmacological analyses suggest that known players in plastid‐to‐nucleus signalling do not directly participate in Fe sensing. We propose that the sensor governing circadian Fe responses defines a new retrograde pathway that involves a plastid‐encoded protein that depends on phytochromes and the functional state of chloroplasts.