Metabolic regulation in Streptomyces parvulus during actinomycin D synthesis, studied with 13C- and 15N-labeled precursors by 13C and 15N nuclear magnetic resonance spectroscopy and by gas chromatography-mass spectrometry.

Recent studies have suggested that the onset of synthesis of actinomycin D in Streptomyces parvulus is due to a release from L-glutamate catabolic repression. In the present investigation we showed that S. parvulus has the capacity to maintain high levels of intracellular glutamate during the synthesis of actinomycin D. The results seem contradictory, since actinomycin D synthesis cannot start before a release from L-glutamate catabolic repression, but a relatively high intracellular pool of glutamate is needed for the synthesis of actinomycin D. Utilizing different labeled precursors, D-[U-13C]fructose and 13C- and 15N-labeled L-glutamate, and nuclear magnetic resonance techniques, we showed that carbon atoms of an intracellular glutamate pool of S. parvulus were not derived biosynthetically from the culture medium glutamate source but rather from D-fructose catabolism. A new intracellular pyrimidine derivative whose nitrogen and carbon skeletons were derived from exogenous L-glutamate was obtained as the main glutamate metabolite. Another new pyrimidine derivative that had a significantly reduced intracellular mobility and that was derived from D-fructose catabolism was identified in the cell extracts of S. parvulus during actinomycin D synthesis. These pyrimidine derivatives may serve as a nitrogen store for actinomycin D synthesis. In the present study, the N-trimethyl group of a choline derivative was observed by 13C nuclear magnetic resonance spectroscopy in growing S. parvulus cells. The choline group, as well as the N-methyl groups of sarcosine, N-methyl-valine, and the methyl groups of an actinomycin D chromophore, arose from D-fructose catabolism. The 13C enrichments found in the peptide moieties of actinomycin D were in accordance with a mechanism of actinomycin D synthesis from L-glutamate and D-fructose.     

Pathogenesis-related proteins are developmentally regulated in tobacco flowers

The accumulation of pathogenesis-related proteins (PR) in tobacco leaves has been casually related to pathogen and specific physiological stresses. The known enzymatic function of some of these proteins is potentially antimicrobial. By using antibodies specific to three classes of pathogenesis-related proteins, we examined tobacco plants during their normal growth. The pathogenesis-related proteins accumulated during the normal development of the tobacco flower. The PR-1 class of proteins (biological function unknown) is located in sepal tissue. PR-P, Q polypeptides are endochitinases and are present in pedicels, sepals, anthers, and ovaries. A glycoprotein serologically related to the PR-2,N,O class is a (1,3)-beta-glucanase and is present in pistils. Differential appearance during flower development, in situ localization, and post-translational processing of floral pathogenesis-related proteins point to a hitherto unsuspected function these classes of pathogenesis-related proteins play in the normal process of flowering and reproductive physiology.     

Metastases to skeletal muscles and interferon treatment.

Blood-borne metastases to a skeletal muscle are rare and may originate in various primary tumors. Recurrent solitary metastasis of renal cell carcinoma, and metastatic lesion as part of disseminated malignant melanoma in skeletal muscles are reported in two patients. In both cases interferon treatment with or without chemotherapy failed in arresting the disease.     

The Response to High CO2 Levels Requires the Neuropeptide Secretion Component HID-1 to Promote Pumping Inhibition

Carbon dioxide (CO₂) is a key molecule in many biological processes; however, mechanisms by which organisms sense and respond to high CO₂ levels remain largely unknown. Here we report that acute CO₂ exposure leads to a rapid cessation in the contraction of the pharynx muscles in Caenorhabditis elegans. To uncover the molecular mechanisms underlying this response, we performed a forward genetic screen and found that hid-1, a key component in neuropeptide signaling, regulates this inhibition in muscle contraction. Surprisingly, we found that this hid-1-mediated pathway is independent of any previously known pathways controlling CO₂ avoidance and oxygen sensing. In addition, animals with mutations in unc-31 and egl-21 (neuropeptide secretion and maturation components) show impaired inhibition of muscle contraction following acute exposure to high CO₂ levels, in further support of our findings. Interestingly, the observed response in the pharynx muscle requires the BAG neurons, which also mediate CO₂ avoidance. This novel hid-1-mediated pathway sheds new light on the physiological effects of high CO₂ levels on animals at the organism-wide level.     

Effects of positive reinforcement training techniques on the psychological welfare of zoo‐housed chimpanzees (Pan troglodytes)

Captive environments encompass various factors that can elevate stress levels and jeopardize the wellbeing of the captive animals. The use of positive reinforcement training (PRT) techniques enables researchers and caretakers to reduce tension directly associated with potentially stressful procedures and states. The current study tested the general effect of PRT on the wellbeing of zoo‐housed chimpanzees (Pan troglodytes) by measuring behaviors that reflect poor and good welfare and that were not directly connected to the specific aim of the training session. The behavior of a group of twelve chimpanzees was measured throughout the day from the exhibition yard, at baseline (12 weeks) and during the PRT period (10 weeks). The results show a significant decrease in abnormal and stress‐related behaviors and a significant rise in prosocial affiliative behaviors following implementation of the training program. The training was shown to have a greater positive effect on low‐ranking individuals compared with high‐ranking ones. This research shows for the first time that PRT offers an enrichment effect whose general influence lasts throughout the day, irrespective of any direct link to a specific trained behavior. Consequently, it can be claimed that PRT presents an effective enrichment tool that can be implemented with captive animals. Because of the above‐noted differential effect between high‐ and low‐ranking chimpanzees, however, this should be taken into consideration when combining PRT with the non‐human primates' daily routine. Am. J. Primatol. 71:687–695, 2009. © 2009 Wiley‐Liss, Inc.     

Glial epigenetics in neuroinflammation and neurodegeneration

Epigenetic regulation shapes the differentiation and response to stimuli of all tissues and cells beyond what genetics would dictate. Epigenetic regulation acts through covalent modifications of DNA and histones while leaving the nucleotide code intact. However, these chromatin modifications are known to be vital components of the regulation of cell fate and response. With regards to the central nervous system (CNS), little is known about how epigenetic regulation shapes the function of neural cell types. The focus of research so far has been on epigenetic regulation of neuronal function and the role of epigenetics in tumorigenesis. However, the glial cell compartment, which makes up 90 % of all CNS cells, has so far received scant attention as to how epigenetics shape their differentiation and function. Here, we highlight current knowledge about epigenetic changes in glial cells occurring during CNS injury, neuroinflammatory conditions and neurodegenerative disease. This review offers an overview of the current understanding of epigenetic regulation in glial cells in CNS disease.