Chromosomal abnormalities in starved and marginally malnourished rats and in utero upon rehabilitation

The effects of starvation and marginal malnutrition (MN) on the lymphocytes of rats were evaluated by chromosomal analysis before and after rehabilitation. The effect of parental starvation or malnutrition on chromosomal aberrations in the foetus was also studied. Wistar rats, 30–35 days old, were starved for 5 days or fed a minimally restricted or a severely restricted diet for three weeks. At the end of the period of starvation or malnutrition, lymphocytes were isolated and chromosomal analysis was performed. Starved and severely restricted rats showed significantly higher mean chromosomal aberrations than the controls. These aberrations returned to a normal level when the experimental groups were rehabilitated for a month, indicating that the damage was transient. A chromosomal aberration study done on foetal cells from rehabilitated rats which had previously been starved or fed a severely restricted diet showed significantly increased values, indicating that some damage was permanent. A low number of implantations was also recorded in these experimental groups. These observations clearly indicate that young animals exposed to conditions like starvation or chronic malnutrition are prone to permanent damage of the genetic system.     

Testing hypotheses in macroevolution

Experimental manipulation of microevolution (changes in frequency of heritable traits in populations) has shed much light on evolutionary processes. But many evolutionary processes occur on scales that are not amenable to experimental manipulation. Indeed, one of the reasons that macroevolution (changes in biodiversity over time, space and lineages) has sometimes been a controversial topic is that processes underlying the generation of biological diversity generally operate at scales that are not open to direct observation or manipulation. Macroevolutionary hypotheses can be tested by using them to generate predictions then asking whether observations from the biological world match those predictions. Each study that identifies significant correlations between evolutionary events, processes or outcomes can generate new predictions that can be further tested with different datasets, allowing a cumulative process that may narrow down on plausible explanations, or lead to rejection of other explanations as inconsistent or unsupported. A similar approach can be taken even for unique events, for example by comparing patterns in different regions, lineages, or time periods. I will illustrate the promise and pitfalls of these approaches using a range of examples, and discuss the problems of inferring causality from significant evolutionary associations.     

Odor maps in the brain: Spatial aspects of odor representation in sensory surface and olfactory bulb

The olfactory sense detects and distinguishes a multitude of different odors. Recent progress in molecular as well as physiological approaches has elucidated basic principles of neuronal encoding of odorants, common to insects and vertebrates. The construction of neuronal representations for odors begins with the task of mapping the multidimensional odor space onto the two-dimensional sensory surface, and subsequently onto the olfactory bulb or antennal lobe. A distributed expression of odorant receptors, albeit restricted to subregions of the sensory surface (large, intermediate or small for zebrafish, mouse or drosophila, respectively), ensures a robust representation, insensitive to mechanical insult. Olfactory receptor neurons expressing the same odorant receptors converge to form a receptotopic map in the olfactory bulb or antennal lobe. The emerging coding principle is a chemotopic representation of odorants at the first brain level, realized either as combinatorial or as monospecific representation, depending on the odorant.     

Lipoperoxide formation in the retina in ocular siderosis

Summary Insertion of iron nail into the vitreous cavity provoked the formation of lipoperoxide in the retina. In accord with the increase in lipoperoxide in the retina, ERG began to decrease. In vitro experiment using isolated retina, lipoperoxide was found to be increased in the presence of ferric or ferrous ions, while it was inhibited by adding antioxidants or ethylenediamine tetraacetate. From these results, direct cause of retinal degeneration in siderosis could be ascribed to the formation of lipoperoxide by iron-ions liberated from the piece of iron, resulting into the degeneration of the visual cell layers of the retina.     

Proteases in apoptosis

The interleukin-1 β-converting enzyme (ICE)-like family proteases have recently been identified as key enzymes in apoptotic cell death. Among these proteases one can identify specific activities which may be involved in cytokine production or in resident protein cleavage. Several factors influence the constitutive apoptotic mechanism and may provide insight into the role of protease(s) in apoptosis. Although it appears that ICE family members play a most important role in promoting apoptotic cell death, evidence has been advanced that other proteases are also involved in sequential or parallel steps of apoptosis. Activation of a particular protease can lead to processing molecules either of the same or different proteases, leading to an activation of a protease cascade. Here we attempt to summarize the current thinking concerning these proteases and their involvement in apoptosis.     

Impact of conflict on demographic factors and their importance in negotiated settlement in southern Africa

"Though the concept of negotiated settlements gained its momentum in southern Africa--Angola, Mozambique, Namibia and South Africa--the full success of negotiations is yet to be seen in most of these countries.... Demographic consequences of conflicts are explained through a systemic model. The importance of demographic variables on negotiated settlement has also been explained the same way. There is no easy way out to overcome conflicts...but it is suggested that mutual consultation with opposition parties or minorities, or the suppressed people, would help ease many situations in Africa or elsewhere."     

Mastocytosis in suckling mice

Summary In suckling mice injected intraperitoneally with mitomycin C on the 1st to 5th day after birth and sacrificed in the course of 24 or 48 h after injection, mastocytosis occurred in the oral mucosa membrane, skin of the trunk or extremities and bone marrow of extremities.     

Differential signaling in presynaptic neurotransmitter release

Neuronal communication is tightly regulated by presynaptic signaling, thereby temporarily and locally secreting one or more transmitters in order to exert propagation or modulation of network activity. In the last 2 decades our insight into the molecular regulation of presynaptic transmitter vesicle traffic and fusion has exponentionally grown due to the identification of specific functional interactions between presynaptic proteins involved in these processes. In addition, a plethora of extracellular and intracellular messengers regulate neurotransmitter release, occasionally leading to short- or long-term adaptations of the synapse to altered environmental signals. Important in this respect is the ability of various nerve terminals to diverge their output by differentiation in secretion of co-localized transmitters. This divergence in presynaptic signaling may converge in the postsynaptic target neuron or spread to neighbouring cells. In this review differential presynaptic signaling mechanisms will be related to their potential divergent roles in transmitter release.Received 25 November 2004; received after revision 23 December 2004; accepted 28 December 2004 Available online 09 March 2005     

Cadmium-induced changes in renal hemodynamics in the domestic fowl

Low i.v. doses of cadmium chloride (15 micrograms Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed. It is suggested that the renal changes following the i.v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.     

Renin in mouse but not in rat submandibular glands

Summary Renin was found in the submandibular glands of male Quackenbush mice in concentrations higher than has been reported for any tissue of any strain or species. However, no renin-like activity could be detected in glands from male and female Wistar rats using either pH 5.8 or 7.4 for assay and a radioimmunoassay specific for renin's reaction product, angiotensin I. Rabbit submandibular glands contained renin.We wish to express our sincere thanks to Dr E. Hackenthal for his suggestions. This study was supported by the National Heath and Medical Research Council of Australia.     

The use of significance limits in graphical data representations

Summary Significance limits are proposed as an alternative to the use of standard deviation, standard error, or confidence or tolerance limits when experimental data are presented in a graphical form. This measurement of uncertainty allows graphical t-tests to be used both for the estimation of data variance and for an approximate statistical comparison between two or more data sets.     

Mastocytosis in suckling mice.

In suckling mice injected intraperitoneally with mitomycin C on the 1st to 5th day after birth and sacrificed in the course of 24 or 48 h after injection, mastocytosis occurred in the oral mucosa membrane, skin of the trunk or extremities and bone marrow of extremities.     

Periostin in inflammation and allergy

We found for the first time that IL-4 and IL-13, signature type 2 cytokines, are able to induce periostin expression. We and others have subsequently shown that periostin is highly expressed in chronic inflammatory diseases―asthma, atopic dermatitis, eosinophilc chronic sinusitis/chronic rhinosinusitis with nasal polyp, and allergic conjunctivitis—and that periostin plays important roles in the pathogenesis of these diseases. The epithelial/mesenchymal interaction via periostin is important for the onset of allergic inflammation, in which periostin derived from fibroblasts acts on epithelial cells or fibroblasts, activating their NF-κB. Moreover, the immune cell/non-immune cell interaction via periostin may be also involved. Now the significance of periostin has been expanded into other inflammatory or fibrotic diseases such as scleroderma and pulmonary fibrosis. The cross-talk of periostin with TGF-β or pro-inflammatory cytokines is important for the underlying mechanism of these diseases. Because of its pathogenic importance and broad expression, diagnostics or therapeutic drugs can be potentially developed to target periostin as a means of treating these diseases.     

Presence of NAD pyrophosphorylase in skeletal muscle in dystrophic mice

Summary NAD pyrophosphorylase (ATP:NMN adenylyltransferase) activity has been measured in the skeletal muscle of dystrophic mice. The amount of this enzyme in the dystrophic mice, as determined by three different methods, was about one half of that in the controls. In addition, the concentration of ATP was too low to be detected in crude extracts of dystrophic mouse skeletal muscle, which were prepared using Tris buffer alone or Tris buffer containing either 3 M KCl, or 1 mM PMSF.     

Membrane trafficking in neuronal maintenance and degeneration

Defects in membrane trafficking and degradation are hallmarks of most, and maybe all, neurodegenerative disorders. Such defects typically result in the accumulation of undegraded proteins due to aberrant endosomal sorting, lysosomal degradation, or autophagy. The genetic or environmental cause of a specific disease may directly affect these membrane trafficking processes. Alternatively, changes in intracellular sorting and degradation can occur as cellular responses of degenerating neurons to unrelated primary defects such as insoluble protein aggregates or other neurotoxic insults. Importantly, altered membrane trafficking may contribute to the pathogenesis or indeed protect the neuron. The observation of dramatic changes to membrane trafficking thus comes with the challenging need to distinguish pathological from protective alterations. Here, we will review our current knowledge about the protective and destructive roles of membrane trafficking in neuronal maintenance and degeneration. In particular, we will first focus on the question of what type of membrane trafficking keeps healthy neurons alive in the first place. Next, we will discuss what alterations of membrane trafficking are known to occur in Alzheimer’s disease and other tauopathies, Parkinson’s disease, polyQ diseases, peripheral neuropathies, and lysosomal storage disorders. Combining the maintenance and degeneration viewpoints may yield insight into how to distinguish when membrane trafficking functions protectively or contributes to degeneration.     

The role of glycosylation in protein antigenic properties

Glycosylation of proteins is a common event and contributes to protein antigenic properties. Most data have been obtained from model studies on glycoprotens with well-defined structure or synthetic glycopeptides and their respective monoclonal antibodies. Antibodies raised against glycoprotein antigens may be specific for their carbohydrate units which are recognized irrespective of the protein carrier (carbohydrate epitopes), or in the context of the adjacent amino acid residues (glycopeptidic epitopes). Conformation or proper exposure of peptidic epitopes of glycoproteins is also frequently modulated by glycosylation due to intramolecular carbohydrate-protein interactions. The effects of glycosylation are broad: glycosylation may 'inactivate' the peptidic epitope or may be required for its reactivity with the antibody, depending on the structure of the antigenic site and antibody fine specificity. Evidence is increasing that similar effects of glycosylation pertain to T cell-dependent cellular immune responses. Glycosylated peptides can be bound and presented by MHC class I or II molecules and elicit glycopeptide-specific T cell clones. Received 5 July 2001; received after revision 9 October 2001; accepted 11 October 2001     

Aptamer and its applications in neurodegenerative diseases

Aptamers are small single-stranded DNA or RNA oligonucleotide fragments or small peptides, which can bind to targets by high affinity and specificity. Because aptamers are specific, non-immunogenic and non-toxic, they are ideal materials for clinical applications. Neurodegenerative disorders are ravaging the lives of patients. Even though the mechanism of these diseases is still elusive, they are mainly characterized by the accumulation of misfolded proteins in the central nervous system. So it is essential to develop potential measures to slow down or prevent the onset of these diseases. With the advancements of the technologies, aptamers have opened up new areas in this research field. Aptamers could bind with these related target proteins to interrupt their accumulation, subsequently blocking or preventing the process of neurodegenerative diseases. This review presents recent advances in the aptamer generation and its merits and limitations, with emphasis on its applications in neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, transmissible spongiform encephalopathy, Huntington’s disease and multiple sclerosis.     

Presence of NAD pyrophosphorylase in skeletal muscle in dystrophic mice

NAD pyrophosphorylase (ATP:NMN adenylyltransferase) activity has been measured in the skeletal muscle of dystrophic mice. The amount of this enzyme in the dystrophic mice, as determined by three different methods, was about one half of that in the controls. In addition, the concentration of ATP was too low to be detected in crude extracts of dystrophic mouse skeletal muscle, which were prepared using Tris buffer alone or Tris buffer containing either 3 M KCl, or 1 mM PMSF.     

Involvement of the circadian system in photoperiodic control of pubertal development in female deer mice, Peromyscus maniculatus

Pubertal development in female deer mice, Peromyscus maniculatus, was stimulated by exposure to light cycles of LD 16:8, LD 6:30 or LD 6:54, but not by exposure to cycles of LD 6:18 or LD 6:42. These results support the hypothesis that female deer mice use a circadian rhythm of responsiveness to light to measure photoperiodic time.