Cell proliferation and polyamine metabolism in 9L cells treated with (2R,5R)-6-heptyne-2,5-diamine or alpha-difluoromethylornithine

We studied the effects of the ornithine decarboxylase inhibitors (2R,5R)-6-heptyne-2,5-diamine (R,R,-MAP) and alpha-difluoromethylornithine (DFMO) on cell proliferation and polyamine metabolism in 9L rat brain tumour cells. Treatment with 5 microM R,R-MAP inhibited cell proliferation to the same extent as did treatment with 1 mM DFMO. Both inhibitors depleted putrescine and spermidine concentrations to less than detectable levels within 24 h and 48 h of drug treatment, respectively; spermine levels were not affected significantly by either inhibitor. The effects of DFMO on 9L cell cycle kinetics were similar to those of R,R-MAP. During the first 3 days of treatment, both drugs caused an accumulation of cells in G1 and a reduction of cells in S phase, as compared with control cells with a slowing in the rate of cell cycle traverse. In cultures seeded at low (1 x 10(5)), medium (5 x 10(5)), or high (2 x 10(6)) cell densities in a 25 cm2 flask, inhibition of cell proliferation and polyamine depletion by both R,R-MAP and DFMO was more pronounced at the lower densities relative to the density-matched control cells. Thus, R,R-MAP was a more potent inhibitor of ornithine decarboxylase than was DFMO in 9L cells, and the inhibitory effects of both compounds on cell proliferation and polyamine biosynthesis were greater in actively proliferating cells.     

Brain potentials associated with pattern displacement and saccadic eye movements in humans and rhesus monkeys

Visual evoked potentials (VEPs) to the onset of motion of visual patterns and brain responses associated with saccadic eye movements (SRPs) were compared in human subjects and in rhesus monkeys. Three different velocities of pattern motion were employed. In humans, brain responses were recorded from six scalp areas. In monkeys, transcortical recordings were obtained from chronically implanted electrodes in the occipital, temporo-parietal, and frontal areas. In humans there was a clear difference in VEPs to the pattern motion between the anterior (Fz, Cz) and posterior (Pz, Oz) scalp regions. The earliest component was a positive peak at 85 ms at Oz followed by a negativity around 110 ms. In the fronto-central leads the VEP was characterized by a negativity at 145 ms and a subsequent broad positive component around 250 ms. SRP responses differed in the early components from the VEPs to pattern motion but a good correspondence was found in the morphology of the late components of the two types of brain potentials. Furthermore, flashed-on VEPs and SRPs elicited a late positivity of more pronounced amplitude than VEPs to pattern displacement. In monkeys similar findings were found: an early negative component of the pattern-displacement VEP could not be observed in the SRP responses over the visual cortex while the late portion of the SRP waveform was greater than the late positivity of the VEP to motion-onset.     

Further data on the origin of gonadotropin releasing hormone in the median eminence of the rat hypothalamus

Gonadotropin releasing hormone (GnRH) content of the two halves of the median eminence of the rat hypothalamus was determined by radioimmunoassay three weeks after three different unilateral knife cuts around the preoptic area. A unilateral cut in front or above the area caused a more than 25% decrease in the GnRH content of the two halves of the median eminence. A cut lateral to the preoptic region had only a slight effect similar to that observed after sham operations. The data suggest that probably more than 50% of the rat median eminence GnRH derives from outside the preoptic-suprachiasmatic region. The GnRH fibres projecting to the median eminence but arising from outside the preoptic region, probably mainly from GnRH perikarya in the limbs of the diagonal band of Broca and septum, enter this area partly from rostral and partly from above, but not from lateral direction. partly from rostral and partly from above, but not from lateral direction. Several of these fibres probably cross before terminating in the median eminence.     

Binding of hexabrachions to heparin and DNA

Hexabrachions are extracellular proteins expressed in certain tissues and at specific points in development. cDNA sequencing has revealed that they contain a region of repeats that are similar to the type III homology units of fibronectin. The corresponding region of fibronectin contains heparin- and DNA-binding domains. We have compared the heparin and DNA binding of hexabrachion secreted by the human glioblastoma cell line U87MG to that of fibronectin. Both proteins bound to heparin-agarose in low salt (0.05 M NaCl) buffers. Using linear salt gradients, hexabrachion was eluted from heparin prior to fibronectin. The addition of 5 mM CaCl2 decreased the affinity of both proteins for heparin, but it had a greater effect upon the binding of fibronectin. Free heparin but not chondroitin sulfate inhibited the binding of both proteins to heparin-agarose. In addition, hexabrachion bound to DNA as fibronectin does, and this binding could be inhibited by heparin but not by chondroitin sulfate. Unlike fibronectin, hexabrachion did not bind to gelatin when samples containing both proteins were passed over gelatin-agarose, also indicating that there was no interaction between hexabrachion and fibronectin. In contrast to hexabrachion isolated from brain, the protein secreted by the human glioblastoma cell line U87MG does not bear the HNK-1 epitope which is on a carbohydrate that can mediate interactions between cells.     

Nontraditional problems of antihypertensive management

Problems with patient screening, disease labeling, diagnosis confirmation, patient compliance and physician adherence continue to undermine efforts to control hypertension and prevent its complications.Simple screening involves patient selection bias, limited new diagnosis, arterial pressure lability, ambiguous disease definition, complex measurement imprecision and deficient patient follow-through. Case finding may improve some of these deficiencies. Recent data suggest that labeling a person as hypertensive may produce impaired self-concept, marital dissatisfaction and absence from work. Newer series confirm the low prevalence of curable, secondary hypertension among unselected patients and strongly argue for restricting extensive hypertensive evaluations to selected subpopulations. Patient noncompliance is highly prevalent, poorly predicted and imprecisely measured. Based on successful trials, specific suggestions can be made to achieve maximum patient compliance and physician adherence to diagnostic and therapeutic guidelines.     

Taxonomy of primycin producing actinomycetes. I. Description of the type strain of thermomonospora galeriensis.

Strain FBUA 1274 (=strain 28/650707, Hungarian National Collection of Medical Bacteria, National Institute of Public Health, Budapest) is designated the type strain of Thermonospora galeriensis (Vályi-Nagy et al.) comb. nov., and the morphological characteristics of this strain are described.     

Brain‐derived neurotrophic factor selectively regulates dendritogenesis of parvalbumin‐containing interneurons in the main olfactory bulb through the PLCγ pathway

Molecular mechanisms of neurotrophin signaling on dendrite development and dynamics are only partly understood. To address the role of brain‐derived neurotrophic factor (BDNF) in the morphogenesis of GABAergic neurons of the main olfactory bulb, we analyzed mice lacking BDNF, mice carrying neurotrophin‐3 (NT3) in the place of BDNF, and TrkB signaling mutant mice with a receptor that can activate phospholipase Cγ (PLCγ) but is unable to recruit the adaptors Shc/Frs2. BDNF deletion yielded a compressed olfactory bulb with a significant loss of parvalbumin (PV) immunoreactivity in GABAergic interneurons of the external plexiform layer. Dendrite development of PV‐positive interneurons was selectively attenuated by BDNF since other Ca²⁺‐binding protein‐containing neuron populations appeared unaffected. The deficit in PV‐positive neurons could be rescued by the NT3/NT3 alleles. The degree of PV immunoreactivity was dependent on BDNF and TrkB recruitment of the adaptor proteins Shc/Frs2. In contrast, PLCγ signaling from the TrkB receptor was sufficient for dendrite growth in vivo and consistently, blocking PLCγ prevented BDNF‐dependent dendrite development in vitro. Collectively, our results provide genetic evidence that BDNF and TrkB signaling selectively regulate PV expression and dendrite growth in a subset of neurochemically‐defined GABAergic interneurons via activation of the PLCγ pathway. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006     

Chronic coccidian infestation compromises flight feather quality in house sparrows Passer domesticus

Parasites usurp indispensable resources for birds during a moult, and this is particularly relevant for those parasites residing in host intestines. This might compromise the nutritionally demanding moult and, thus, feather functionality. Although lower feather quality has profound and multifaceted adverse effects on residual fitness, surprisingly, little is known about parasites' effect on feather traits, especially over the longer term. We conducted an aviary experiment by medicating half of a group of naturally infested house sparrows Passer domesticus against intestinal coccidians for 15 months, spanning two consecutive postnuptial moults, whereas the other half was kept infested (i.e. without medication). Coccidian infestation significantly and negatively affected the size of the uropygial gland during the second moulting period compared to the medicated group. Furthermore, wing length was significantly shorter after the second moulting in the non‐medicated compared to the medicated female birds, which indicates that the negative effects of coccidians emerge only after a prolonged exposure to parasite infestation. Non‐medicated birds grew poorer quality flight feathers detected in a large number of feather traits both after the first and second moults. In the case of non‐medicated birds, the primaries were lighter and shorter, and had a smaller vane area, thinner rachis and decreased stiffness, although a higher barb and barbule density, which may have various consequences for fitness through reducing flight performance. Our findings demonstrate that, besides the well‐known immediate consequences for host breeding success, parasites might also have serious, long‐lasting effects through influencing feather quality and, ultimately, fitness of the host. © 2013 The Linnean Society of London     

Large‐brained birds suffer less oxidative damage

Large brains (relative to body size) might confer fitness benefits to animals. Although the putative costs of well‐developed brains can constrain the majority of species to modest brain sizes, these costs are still poorly understood. Given that the neural tissue is energetically expensive and demands antioxidants, one potential cost of developing and maintaining large brains is increased oxidative stress (‘oxidation exposure’ hypothesis). Alternatively, because large‐brained species exhibit slow‐paced life histories, they are expected to invest more into self‐maintenance such as an efficacious antioxidative defence machinery (‘oxidation avoidance’ hypothesis). We predict decreased antioxidant levels and/or increased oxidative damage in large‐brained species in case of oxidation exposure, and the contrary in case of oxidation avoidance. We address these contrasting hypotheses for the first time by means of a phylogenetic comparative approach based on an unprecedented data set of four redox state markers from 85 European bird species. Large‐brained birds suffered less oxidative damage to lipids (measured as malondialdehyde levels) and exhibited higher total nonenzymatic antioxidant capacity than small‐brained birds, whereas uric acid and glutathione levels were independent of brain size. These results were not altered by potentially confounding variables and did not depend on how relative brain size was quantified. Our findings partially support the ‘oxidation avoidance’ hypothesis and provide a physiological explanation for the linkage of large brains with slow‐paced life histories: reduced oxidative stress of large‐brained birds can secure brain functionality and healthy life span, which are integral to their lifetime fitness and slow‐paced life history.