Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder resulting from motor neuron death. Approximately 10% of cases are familial (FALS), typically with a dominant inheritance mode. Despite numerous advances in recent years, nearly 50% of FALS cases have unknown genetic aetiology. Here we show that mutations within the profilin 1 (PFN1) gene can cause FALS. PFN1 is crucial for the conversion of monomeric (G)-actin to filamentous (F)-actin. Exome sequencing of two large ALS families showed different mutations within the PFN1 gene. Further sequence analysis identified 4 mutations in 7 out of 274 FALS cases. Cells expressing PFN1 mutants contain ubiquitinated, insoluble aggregates that in many cases contain the ALS-associated protein TDP-43. PFN1 mutants also display decreased bound actin levels and can inhibit axon outgrowth. Furthermore, primary motor neurons expressing mutant PFN1 display smaller growth cones with a reduced F/G-actin ratio. These observations further document that cytoskeletal pathway alterations contribute to ALS pathogenesis.     

Towards an Understanding of Rich Picture Interpretation

Systemic Practice and Action Research - This paper considers the value of the Rich Picture (RP) as a means to capture data from multiple groups exploring a question, problem or issue. RPs emerge...     

The genome sequence of Atlantic cod reveals a unique immune system

Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC)?II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC?II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC?I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC?II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.     

Perception: Embodiment and Beyond

In this commentary on Don Ihde’s paper “Stretching the in-between: embodiment and beyond” I argue that perceptions and observations are based on tacit frames and these frames are expressed through pre-reflexive intuitions thus giving meaning to the perceived content of observations. However, if the objective or given information in perception is incomplete or missing our brain and nervous system will intuitively and unconsciously fill in the missing information in order to act—these particular pieces of added information may not be relevant to the decoding of the given content of perception at all.     

Observations on Double-crested Cormorants ( Phalacrocorax auritus ) at sportfishing waters in southwestern Utah

Counts of Double-crested Cormorants ( Phalacrocorax auritus ) were made at 13 reservoirs and lakes in southwestern Utah during 1989-91 to determine current abundance of that species. Food habits of cormorants were studied at three of the reservoirs in 1989. Data were also collected on trout abundance during standardized gill-netting to make comparisons between cormorant numbers and trout abundance. Cormorants were observed at all waters studied except one and were generally most numerous during the spring as they migrated through the area. Estimated cormorant abundance ranged from 0 to 34 bird-days per ha and was highest at the larger, lower-elevation reservoirs. Cormorants were summer residents at several of the larger reservoirs and nested successfully at Piute Reservoir. Trout accounted for 24-81% of the diet of cormorants, with Utah chubs constituting most of the remainder of the diet. Estimates of the annual consumption of fish by cormorants ranged from 0 to 15.8 kg per ha. The index of trout abundance was inversely related to cormorant abundance ( P < .01) at the waters studied. Cormorants apparently have increased in numbers and extended their range in southwestern Utah during the past decade. This change may be the result of factors that have led to similar changes throughout North America as well as some factors unique to Utah. Methods to mitigate the impact of predation by piscivorous birds of sportfisheries are discussed. The Utah Division of Wildlife Resources has initiated a new management plan at Minersville Reservoir that incorporates piscivorous birds into sportfish management at that reservoir.     

Distribution and abundance of native Bonneville cutthroat trout ( Oncorhynchus clarki utah ) in southwestern Utah

The Bonneville cutthroat trout ( Oncorhynchus clarki utah ; BCT) was once abundant throughout the Bonneville Basin. In southwestern Utah, however, only 3 local populations of the subspecies were known to exist in 1977, when conservation efforts to protect and replicate them began. By 1995 remnant populations were known in 6 streams, and replicate populations had been established in an additional 16. Populations of BCT in southwestern Utah streams were survey by electrofishing in 1994 and 1995 to describe the subspecies' status. Estimated densities of age-1 and older BCT ranged from 118 to 546 fish per km. Biomass estimates ranged from 8 to 64 kg per ha. Several age groups of BCT were collected at most locations. Six populations were classified as self-sustaining, 9 as expanding through natural recruitment, 6 as new, and 1 as hybridized. Overall status of BCT in southwestern Utah has improved since 1977, but conservation measures must continue to maintain a positive trend.     

Cystinurie undl -cystinsteinbildung beim hund

Summary Cystinuria andl-Cystine lithiasis, is a rather rare hereditary metabolic disease in human beings. Due to the high purity ofl-Cystine stones formed in the urinary tract, they can serve as ideal models for studies on the chemical dissolution of kidney stones in general. By systematic examinations, it is possible to find for these purposes, dogs in which a cystinuria is present.

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Herrn Prof.Forenbacher, Vet. Med. Fakultät der Universität Zagreb, danken wir für die Übersendung von Steinen, und FrauM. Stoffers für die technische Mitarbeit.