Noninvasive detection of endotoxin-induced mucus hypersecretion in rat lung by MRI

Using magnetic resonance imaging (MRI), we detected a signal in the lungs of Brown Norway rats after intratracheal administration of endotoxin [lipopolysaccharide (LPS)]. The signal had two components: one, of diffuse appearance and higher intensity, was particularly prominent up to 48 h after LPS; the second, showing an irregular appearance and weaker intensity, was predominant later. Bronchoalveolar lavage fluid analysis indicated that generalized granulocytic (especially neutrophilic) inflammation was a major contributor to the signal at the early time points, with mucus being a major factor contributing at the later time points. The facts that animals can breathe freely during data acquisition and that neither respiration nor cardiac triggering is applied render this MRI approach attractive for the routine testing of anti-inflammatory drugs. In particular, the prospect of noninvasively detecting a sustained mucus hypersecretory phenotype in the lung brings an important new perspective to models of chronic obstructive pulmonary diseases in animals.     

Molecular population genetics of inducible antibacterial peptide genes in Drosophila melanogaster

Insects respond to septic infection in part by producing a suite of antimicrobial peptides that may be subject to host-pathogen coevolutionary dynamics. In order to infer population genetic forces acting on Drosophila antibacterial peptide genes, we examine global properties of polymorphism and divergence in the Drosophila melanogaster defensin, drosocin, metchnikowin, attacin C, diptericin A, and cecropin A, B, and C genes. As a functional class, antibacterial peptides exhibit low levels of interspecific amino acid divergence. There are multiple amino acid polymorphisms segregating within D. melanogaster, however, a high proportion of which change the charge or polarity of the variable residue. These polymorphisms are particularly prevalent in processed signal and propeptide domains. We find that models of coevolutionary "arms races" and selectively maintained hypervariability do not adequately describe the population dynamics of mature antibacterial peptides in D. melanogaster, but that a highly significant excess of high-frequency derived polymorphisms coupled with substantial intralocus linkage disequilibrium suggests that positive selection may act on antibacterial peptide genes. Some attributes of the data may be consistent with a simple demographic model of population founding followed by expansion, but departures from the equilibrium null tend to be more pronounced in the peptide genes than at other loci around the genome.     

Microtubule organization in the differentiating transfer cells of the placenta inLilium spp.

Summary Placental cells in the ovarian transmitting tissue ofLilium spp. are organized as transfer cells with inbuddings facing the ovarian locule. A detailed analysis of microtubule (MT) organization during development of these polarized cells is reported here. Formation of wall projections occurs at the apical part of the cell starting on the day of anthesis, and a fully mature secretion zone is found four days after anthesis. MTs are organized into distinct cortical and central arrays. The cortical array undergoes a unique transition at anthesis. MTs in the basal half of the cell remain in longitudinal bundles while in the apical half of the cell their longitudinal orientation is replaced by a transverse alignment. One day after anthesis, these transverse bundles become a meshwork of short, randomly organized MTs, while MTs in the basal half of the cell retain their longitudinal alignment. The realignment of MTs in the apical half of the cell coincides with the deposition of the secondary cell wall. The central array is composed of short, randomly arranged strands of MTs in the cytoplasm between the nucleus and the apical and basal periclinal walls of the cell. This array first appears as solitary strands in the apical part of the cell one day before anthesis. The central array extends during development and is eventually seen in the basal half of the cell. We propose that MTs in the cortical region near the apical wall act as templates for the deposition of cellulose microfibrils in the secondary cell wall. MTs in the central array in these transfer cells may be involved in the trafficking of vesicles and/or positioning of organelles near the secretion zone.Abbreviations MT microtubule - daa day after anthesis - dba day before anthesis     

A review of planktivorous fishes: Their evolution,feeding behaviours,selectivities, and impacts

The classical approach of limnologists has been to consider the interactions between lake ecosystem components as an unidirectional flow of influence from nutrients to the phytoplankton, to the zooplankton, and finally to the fish, through successive controls by physical, chemical, and biological processes (Strakraba, 1967). The effect of planktivorous fishes on zooplankton and phytoplankton communities was not recognized until the studies of Hrbáek et al. (1961), Hrbáek (1962), Brooks & Dodson (1965) and Strakraba (1965). They showed that (1) in ponds and lakes in the presence of planktivorous fishes the zooplankton communities were composed of smaller bodied species than in those lacking planktivores, and (2) the resulting small-bodied zooplankton communities affected the phytoplankton communities. Although the variability of the phytoplankton response to fish predation showed the importance of other factors (such as nutrient limitation and interspecific competition of algae), these studies emphasized that zooplankton and phytoplankton communities can be affected by the feeding selectivity of planktivorous fishes. During the last two decades, many limnological studies have focused on this dramatic impact of fish on plankton communities. The direct response of zooplankton communities to visual fish predation (i.e. particulate feeding) has been of major interest, whereas the multilevel effects of filter-feeding fish (predation on zooplankton plus grazing on phytoplankton) have been neglected. The objectives of this review are to document fish-plankton interrelationships in order to (1) provide insights into the impact of fish on plankton communities, and (2) outline mechanistic models of planktivory according to the feeding repertory and the selectivity of the fish, the adaptive responses of the plankton, and the environmental conditions.The approach adopted here is based on field and laboratory experimental results derived from the literature on tropical and temperate freshwater (occasionally marine) systems. Four types of planktivorous fish are distinguished: the gape-limited larvae and small fish species, the particulate feeders, the pump filter feeders, and the tow-net filter feeders. For each type of planktivore, the mechanisms of prey selection are analyzed from the point of view of both the predator and the prey. To investigate the main determinants of the predator feeding selectivity, and to discuss its potential effects on prey communities, the predation-act is divided into a sequence of successive events (Holling, 1966): detection, pursuit, capture, retention, and digestion for particulate feeders; and capture, retention, and digestion for filter feeders. The strengths and weaknesses of various measures of selectivity (i.e. electivity indices), as well as their appropriate usages are considered. Available prey selection models and optimal foraging theories are analyzed for the different planktivore feeding modes. Mechanistic models based on Holling's (loc. cit.) approach are proposed for each feeding mode to determine differential prey vulnerabilities and optimal diet breadth.This review has application to several fields, including general ecology, limnology, fisheries management (for example, utilization of planktonic resources, stocking, introduction, or maintenance of natural fish populations), and biological control of the eutrophication processes (biomanipulation approaches). It emphasizes the real need for more knowledge of the feeding selectivity and food utilization of planktivores. It concludes that predator and prey are mutually adapted. Thus, in most cases, study of plankton dynamics and water quality should include the assessment of fish predation and grazing pressures.     

GALNT2 Expression Is Reduced in Patients with Type 2 Diabetes: Possible Role of Hyperglycemia

Impaired insulin action plays a major role in the pathogenesis of type 2 diabetes, a chronic metabolic disorder which imposes a tremendous burden to morbidity and mortality worldwide. Unraveling the molecular mechanisms underlying insulin resistance would improve setting up preventive and treatment strategies of type 2 diabetes. Down-regulation of GALNT2, an UDPN-acetyl-alpha-D-galactosamine polypeptideN-acetylgalactosaminyltransferase-2 (ppGalNAc-T2), causes impaired insulin signaling and action in cultured human liver cells. In addition, GALNT2 mRNA levels are down-regulated in liver of spontaneously insulin resistant, diabetic Goto-Kakizaki rats. To investigate the role of GALNT2 in human hyperglycemia, we measured GALNT2 mRNA expression levels in peripheral whole blood cells of 84 non-obese and 46 obese non-diabetic individuals as well as of 98 obese patients with type 2 diabetes. We also measured GALNT2 mRNA expression in human U937 cells cultured under different glucose concentrations. In vivo studies indicated that GALNT2 mRNA levels were significantly reduced from non obese control to obese non diabetic and to obese diabetic individuals (p<0.001). In vitro studies showed that GALNT2 mRNA levels was reduced in U937 cells exposed to high glucose concentrations (i.e. 25 mmol/l glucose) as compared to cells exposed to low glucose concentration (i.e. 5.5 mmol/l glucose +19.5 mmol/l mannitol). In conclusion, our data indicate that GALNT2 is down-regulated in patients with type 2 diabetes and suggest that this association is, at least partly, secondary to hyperglycemia. Further studies are needed to understand whether GALNT2 down-regulation plays a pathogenic role in maintaining and/or aggravating the metabolic abnormalities of diabetic milieu.     

Exo1 competes with repair synthesis, converts NER intermediates to long ssDNA gaps, and promotes checkpoint activation

Ultraviolet (UV) light induces DNA-damage checkpoints and mutagenesis, which are involved in cancer protection and tumorigenesis, respectively. How cells identify DNA lesions and convert them to checkpoint-activating structures is a major question. We show that during repair of UV lesions in noncycling cells, Exo1-mediated processing of nucleotide excision repair (NER) intermediates competes with repair DNA synthesis. Impediments of the refilling reaction allow Exo1 to generate extended ssDNA gaps, detectable by electron microscopy, which drive Mec1 kinase activation and will be refilled by long-patch repair synthesis, as shown by DNA combing. We provide evidence that this mechanism may?be stimulated by closely opposing UV lesions, represents a strategy to redirect problematic repair intermediates to alternative repair pathways, and may also be extended to physically different DNA damages. Our work has significant implications for understanding the coordination between repair of DNA lesions and checkpoint pathways to preserve genome stability.