Psychosine-induced alterations in peroxisomes of twitcher mouse liver

Krabbe disease is a neuroinflammatory disorder in which galactosylsphingosine (psychosine) accumulates in nervous tissue. To gain insight into whether the psychosine-induced effects in nervous tissue extend to peripheral organs, we investigated the expression of cytokines and their effects on peroxisomal structure/functions in twitcher mouse liver (animal model of Krabbe disease). Immunofluorescence analysis demonstrated TNF-α and IL-6 expression, which was confirmed by mRNAs quantitation. Despite the presence of TNF-α, lipidomic analysis did not indicate a significant decrease in sphingomyelin or an increase in ceramide fractions. Ultrastructural analysis of catalase-dependent staining of liver sections showed reduced reactivity without significant changes in peroxisomal contents. This observation was confirmed by assaying catalase activity and quantitation of its mRNA, both of which were found significantly decreased in twitcher mouse liver. Western blot analysis demonstrated a generalized reduction of peroxisomal matrix and membrane proteins. These observations indicate that twitcher mouse pathobiology extends to the liver, where psychosine-induced TNF-α and IL-6 compromise peroxisomal structure and functions.     

Increased abundance of the non-indigenous zooplanktivore, <Emphasis Type=Italic>Bythotrephes longimanus</Emphasis>, is strongly correlated with greater spring prey availability in Canadian Shield lakes

The non-indigenous zooplanktivore, Bythotrephes longimanus, is a large Palaearctic cladoceran that is spreading rapidly in the Great Lakes watershed in North America. As a voracious predator, Bythotrephes can reduce herbivorous cladoceran abundance and diversity; however, the variables that affect its abundance are not well understood. To determine what bottom-up factors are associated with the abundance and seasonal dynamics of established Bythotrephes populations, two Bythotrephes datasets from lakes in south-central Ontario, Canada, were analysed using multiple regression and multivariate analyses: a multi-lake dataset of nine lakes sampled in 2003 and a multi-year dataset of one of these lakes, Harp Lake, sampled from 1994–1998 and 2001–2004. Bottom-up variables tested were Secchi disk depth, epilimnetic temperature, cladoceran (prey) density, total phosphorus, dissolved organic carbon and Chlorophyll a, as well as maximum depth for the multi-lake dataset. In both analyses and datasets, springtime abundance of herbivorous cladocerans was consistently found to be a significant factor associated with Bythotrephes (June–September) abundance; Bythotrephes annual abundance was significantly and positively associated with mean May and June prey abundance, along with mean Secchi disk depth for the multi-lake dataset, and groups of lakes or years with similar Bythotrephes seasonal abundance patterns were predicted by June prey abundance. Additionally, prey availability was the dominant contributor towards changes in weekly Bythotrephes birth rates calculated for two of the study lakes. Our study suggests that prey availability influences Bythotrephes abundance, which provides evidence that Bythotrephes establishment success is affected by the abundance of its prey.     

Anti-apoptotic therapeutic approaches in liver diseases: do they really make sense?

A variety of data suggesting apoptotic cell death as a key feature of liver injury stimulated researchers to investigate the therapeutic potential of anti-apoptotic strategies in experimental models. However, the overestimated role of apoptotic cell death in liver injury has tempered the clinical translation of the protection afforded by anti-apoptotic regimes in experimental models. Thus, the hope for apoptosis modulation as potential treatment strategy for injured liver in humans could not be confirmed. Herein, we evaluated the degree of apoptosis in different hepatic stress models which are relevant for the human pathophysiology. Using morphological criteria of apoptosis, caspase-3 activation as well as TUNEL assay in combination with a positive control of apoptosis in liver injury, we quantified apoptotic cell death discriminating between parenchymal and non-parenchymal cells and confirmed these results by cleaved caspase-3 and PARP-1 protein expression. Discussing our findings and relating them to the existing literature on the potential role of apoptotic cell death, we strongly recommend reconsidering anti-apoptotic strategies to ameliorate liver injury efficiently.     

Selectivity of Ferric Enterobactin Binding and Cooperativity of Transport in Gram-Negative Bacteria

The ligand-gated outer membrane porin FepA serves Escherichia coli as the receptor for the siderophore ferric enterobactin. We characterized the ability of seven analogs of enterobactin to supply iron via FepA by quantitatively measuring the binding and transport of their ⁵⁹Fe complexes. The experiments refuted the idea that chirality of the iron complex affects its recognition by FepA and demonstrated the necessity of an unsubstituted catecholate coordination center for binding to the outer membrane protein. Among the compounds we tested, only ferric enantioenterobactin, the synthetic, left-handed isomer of natural enterobactin, and ferric TRENCAM, which substitutes a tertiary amine for the macrocyclic lactone ring of ferric enterobactin but maintains an unsubstituted catecholate iron complex, were recognized by FepA (K_d ≈ 20 nM). Ferric complexes of other analogs (TRENCAM-3,2-HOPO; TREN-Me-3,2-HOPO; MeMEEtTAM; MeME-Me-3,2-HOPO; K₃MECAMS; agrobactin A) with alterations to the chelating groups and different net charge on the iron center neither adsorbed to nor transported through FepA. We also compared the binding and uptake of ferric enterobactin by homologs of FepA from Bordetella bronchisepticus, Pseudomonas aeruginosa, and Salmonella typhimurium in the native organisms and as plasmid-mediated clones expressed in E. coli. All the transport proteins bound ferric enterobactin with high affinity (K_d ≤ 100 nM) and transported it at comparable rates (≥50 pmol/min/10⁹ cells) in their own particular membrane environments. However, the FepA and IroN proteins of S. typhimurium failed to efficiently function in E. coli. For E. coli, S. typhimurium, and P. aeruginosa, the rate of ferric enterobactin uptake was a sigmoidal function of its concentration, indicating a cooperative transport reaction involving multiple interacting binding sites on FepA.     

Multiscale modelling of Potts shunt as a potential palliative treatment for suprasystemic idiopathic pulmonary artery hypertension: a paediatric case study

Biomechanics and Modeling in Mechanobiology - Potts shunt (PS) was suggested as palliation for patients with suprasystemic pulmonary arterial hypertension (PAH) and right ventricular (RV) failure....     

From dusk till dawn: camera traps reveal the diel patterns of flower feeding by hawkmoths

1. Diel rhythms of foraging activity by animal flower visitors can reflect niche partitioning and are considered an important component of selection on floral traits. However, it has been notoriously difficult to obtain objective information on the patterns of flower visitation by crepuscular and nocturnal insects. 2. Motion-activated cameras were used for field-based studies of hawkmoth foraging behaviour on six African plant species. 3. The results showed that short-tongued hawkmoth species forage mainly around dusk and then sporadically throughout the night, whereas long-tongued hawkmoth species feed consistently throughout the night, with a peak shortly before midnight. 4. These results provide the first quantitative estimates of diel patterns of interactions between multiple hawkmoth and plant species and, when combined with qualitative reports from other studies, suggest that differences in diel activity between the two main hawkmoth functional groups (short- and long-tongued) are consistent across the Old and New Worlds.     

Locus Heterogeneity for Waardenburg Syndrome is Predictive of Clinical Subtypes

Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I (WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between −2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3.