Sudden blindness due to bilateral optic neuropathy associated with cryptococcal meningitis in an AIDS patient

BackgroundCryptococcosis is one of the most frequent and severe AIDS defining illnesses.AimsWe present a patient with advanced HIV/AIDS disease and a diffuse meningoencephalitis due to Cryptococcus neoformans. The patient developed an acute and bilateral blindness associated with high cerebrospinal fluid pressure and optic neuropathy.MethodsPost-mortem anatomopathologic study revealed a high number of Cryptococcus in the central nervous system, including the optic nerves and the optic chiasm.ConclusionThe patient's sudden visual loss appeared to be related to the perineuritic arachnoiditis and the massive invasion of the optic nerves by the fungus.     

Novel mouse model reveals distinct activity-dependent and -independent contributions to synapse development

The balanced action of both pre- and postsynaptic organizers regulates the formation of neuromuscular junctions (NMJ). The precise mechanisms that control the regional specialization of acetylcholine receptor (AChR) aggregation, guide ingrowing axons and contribute to correct synaptic patterning are unknown. Synaptic activity is of central importance and to understand synaptogenesis, it is necessary to distinguish between activity-dependent and activity-independent processes. By engineering a mutated fetal AChR subunit, we used homologous recombination to develop a mouse line that expresses AChR with massively reduced open probability during embryonic development. Through histological and immunochemical methods as well as electrophysiological techniques, we observed that endplate anatomy and distribution are severely aberrant and innervation patterns are completely disrupted. Nonetheless, in the absence of activity AChRs form postsynaptic specializations attracting motor axons and permitting generation of multiple nerve/muscle contacts on individual fibers. This process is not restricted to a specialized central zone of the diaphragm and proceeds throughout embryonic development. Phenotypes can be attributed to separate activity-dependent and -independent pathways. The correct patterning of synaptic connections, prevention of multiple contacts and control of nerve growth require AChR-mediated activity. In contrast, myotube survival and acetylcholine-mediated dispersal of AChRs are maintained even in the absence of AChR-mediated activity. Because mouse models in which acetylcholine is entirely absent do not display similar effects, we conclude that acetylcholine binding to the AChR initiates activity-dependent and activity-independent pathways whereby the AChR modulates formation of the NMJ.     

Molecular and morphological evolution of the amphipod radiation of Lake Baikal

Lake Baikal, in Siberia, Russia, contains the highest biodiversity of any extant lake, including an impressive radiation of gammaroidean amphipods that are often cited as a classic case of adaptive radiation. However, relationships among Baikal's amphipods remain poorly understood. The phylogenetic history of 32 Lake Baikal amphipod species, representing most major lineages of the endemic fauna, was examined using three genes (COI, 16S rRNA, and 18S rRNA), and 152 morphological characters. Results support monophyly of the largest and most diverse of the Baikalian families, the Acanthogammaridae. Analyses suggest that a second Baikalian family, the fossorial Micruropodidae, is paraphyletic and composed of two divergent clades, one of which includes Macrohectopus branickii, a morphologically specialized pelagic planktivore traditionally assigned its own family. The extreme morphological and ecological divergence of Macrohectopus from its close genetic relatives, and conversely, the large genetic distances among other morphologically similar micruropodids, suggest that morphological and molecular evolution have often been uncoupled during the radiation of Baikal's amphipods. This study suggests that the amphipod fauna of Lake Baikal is polyphyletic; originating from two independent invasions of the lake.     

Persistence time of loss-of-function mutations at nonessential loci affecting eye color in Drosophila melanogaster

Persistence time of a mutant allele, the expected number of generations before its elimination from the population, can be estimated as the ratio of the number of segregating mutations per individual over the mutation rate per generation. We screened two natural populations of Drosophila melanogaster for mutations causing clear-cut eye phenotypes and detected 25 mutant alleles, falling into 19 complementation groups, in 1164 haploid genomes, which implies 0.021 eye mutations/genome. The de novo haploid mutation rate for the same set of loci was estimated as 2 x 10(-4) in a 10-generation mutation-accumulation experiment. Thus, the average persistence time of all mutations causing clear-cut eye phenotypes is approximately 100 generations (95% confidence interval: 61-219). This estimate shows that the strength of selection against phenotypically drastic alleles of nonessential loci is close to that against recessive lethals. In both cases, deleterious alleles are apparently eliminated by selection against heterozygous individuals, which show no visible phenotypic differences from wild type.     

Time Lapse in Vivo Visualization of Developmental Stabilization of Synaptic Receptors at Neuromuscular Junctions

The lifetime of nicotinic acetylcholine receptors (AChRs) in neuromuscular junctions (NMJs) is increased from <1 day to >1 week during early postnatal development. However, the exact timing of AChR stabilization is not known, and its correlation to the concurrent embryonic to adult AChR channel conversion, NMJ remodeling, and neuromuscular diseases is unclear. Using a novel time lapse in vivo imaging technology we show that replacement of the entire receptor population of an individual NMJ occurs end plate-specifically within hours. This makes it possible to follow directly in live animals changing stabilities of end plate receptors. In three different, genetically modified mouse models we demonstrate that the metabolic half-life values of synaptic AChRs increase from a few hours to several days after postnatal day 6. Developmental stabilization is independent of receptor subtype and apparently regulated by an intrinsic muscle-specific maturation program. Myosin Va, an F-actin-dependent motor protein, is also accumulated synaptically during postnatal development and thus could mediate the stabilization of end plate AChR.     

Heat tolerance,temperature acclimation,acute oxidative damage and canalization of haemoglobin expression in <Emphasis Type="Italic">Daphnia</Emphasis>

Daphnia is a widespread freshwater zooplankton species, which is both a classic and emerging new model for research in ecological physiology, ecotoxicology and evolutionary biology of adaptation to novel environments. Heat tolerance in Daphnia is known to depend both upon evolutionary history of a genotype and on individuals’ acclimation to elevated temperature and to correlate with the level of haemoglobin expression. We demonstrate the existence of north–south gradient of heat tolerance in North American D. pulex, which is not associated with any parallel changes in haemoglobin expression. Geographically distinct clones differ in the way their haemoglobin expression changes due to acclimation to a sub-stressful (28°C) temperature, but these changes are not correlated with the latitude of clones’ origin. Likewise, the effect of acclimation to sub-stressful temperature is independent from, and cannot be fully explained by, haemoglobin expression changes during acclimation. The degree of oxidative damage to haemoglobin, measured as the ratio of absorbance at 540:576 nm at the acclimation temperature, is a strong predictor of 28°C-acclimated Daphnia survival during an acute heat exposure. The comparison of haemoglobin expression in resistant and tolerant clones acclimated to different temperatures indicates that tolerant clones exhibit canalization of haemoglobin expression, possessing a high level of haemoglobin even at non-stressful temperatures. We discuss the evolutionary biology of adaptation and acclimation to elevated temperatures in an ecologically important component of freshwater ecosystems in the context of global climate change.     

Isolation and Purification of Fungal Luciferase from <Emphasis Type="Italic">Neonothopanus nimbi</Emphasis>

This is the first study to obtain a high-purity luciferase from the fungus Neonothopanus nambi biomass that is suitable for subsequent sequencing.     

Structure of fungal oxyluciferin,the product of the bioluminescence reaction

The structure of fungal oxyluciferin was determined, the enzymatic bioluminescence reaction under substrate saturation conditions with discrete monitoring of formed products was conducted, and the structures of the end products of the reaction were established. On the basis of these studies, the scheme of oxyluciferin degradation to the end products was developed. The structure of fungal oxyluciferin was confirmed by counter synthesis.