The amino acid sequence of the agglutinin isolated from the red marine alga Bryothamnion triquetrum defines a novel lectin structure

The primary structure of a lectin isolated from the red alga Bryothamnion triquetrum was established by combination of Edman degradation of sets of overlapping peptides and mass spectrometry. It contains 91 amino acids and two disulphide bonds. The primary structure of the B. triquetrum lectin does not show amino acid sequence similarity with known plant and animal lectin structures. Hence, this protein may be the paradigm of a novel lectin family.     

Differential basal synthesis of Hsp70/Hsc70 contributes to interindividual variation in Hsp70/Hsc70 inducibility

The source of intraspecies variation in the expression of heat shock proteins (HSPs) remains unresolved but could shed light on differential stress tolerance and disease susceptibility. This study investigated the influence of variable basal HSP synthesis on differential inducibility of HSP synthesis. Basal and heat-induced synthesis of the major HSP families in peripheral blood monocytes from healthy donors (n=42) were analysed using biometabolic labelling and densitometry. Basal Hsp70/Hsc70 synthesis and percentage induction of Hsp70/Hsc70 synthesis were significantly correlated (r=−0.57, p<0.0001), and described most accurately by an exponential decay equation (R=0.68, R²=0.46). This regression equation suggests that increasing levels of basal Hsp70/Hsc70 synthesis are accompanied byan exponential decrease in the percentage induction of Hsp70/Hsc70 synthesis. The model fits data from European and non-European population groups independently, although both coefficients in the regression equation were larger for non-Europeans. This implies population group as an additional factor influencing differential HSP expression. The differential inducibility of Hsp70/Hsc70 due to variable basal synthesis of Hsp70/Hsc70 and based upon population group may contribute to differential stress tolerance or disease susceptibility. Received 27 March 2000; received after revision 19 June 2000; accepted 20 June 2000     

4-Hydroxynonenal-modified amyloid-beta peptide inhibits the proteasome: possible importance in Alzheimer's disease

The amyloid β-peptide (Aβ) is a 4-kDa species derived from the amyloid precursor protein, which accumulates in the brains of patients with Alzheimer’s disease. Although we lack full understanding of the etiology and pathogenesis of selective neuron death, considerable data do imply roles for both the toxic Aβ and increased oxidative stress. Another significant observation is the accumulation of abnormal, ubiquitin-conjugated proteins in affected neurons, suggesting dysfunction of the proteasome proteolytic system in these cells. Recent reports have indicated that Aβ can bind and inhibit the proteasome, the major cytoslic protease for degrading damaged and ubiquitin-conjugated proteins. Earlier results from our laboratory showed that moderately oxidized proteins are preferentially recognized and degraded by the proteasome; however, severely oxidized proteins cannot be easily degraded and, instead, inhibit the proteasome. We hypothesized that oxidatively modified Aβ might have a stronger (or weaker) inhibitory effect on the proteasome than does native Aβ. We therefore also investigated the proteasome inhibitory action of Aβ _1–40 (a peptide comprising the first 40 residues of Aβ) modified by the intracellular oxidant hydrogen peroxide, and by the lipid peroxidation product 4-hydroxynonenal (HNE). H₂O₂ modification of Aβ _1–40 generates a progressively poorer inhibitor of the purified human 20S proteasome. In contrast, HNE modification of Aβ _1–40 generates a progressively more selective and efficient inhibitor of the degradation of fluorogenic peptides and oxidized protein substrates by human 20S proteasome. This interaction may contribute to certain pathological manifestations of Alzheimer’s disease Received 26 September 2000; accepted 26 September 2000     

Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions

The activins (dimers of betaA or betaB subunits, encoded by the genes Inhba and Inhbb, respectively) are TGF-beta superfamily members that have roles in reproduction and development. Whereas mice homozygous for the Inhba-null allele demonstrate disruption of whisker, palate and tooth development, leading to neonatal lethality, homozygous Inhbb-null mice are viable, fertile and have eye defects. To determine if these phenotypes were due to spatiotemporal expression differences of the ligands or disruption of specific ligand-receptor interactions, we replaced the region of Inhba encoding the mature protein with Inhbb, creating the allele Inhbatm2Zuk (hereafter designated InhbaBK). Although the craniofacial phenotypes of the Inhba-null mutation were rescued by the InhbaBK allele, somatic, testicular, genital and hair growth were grossly affected and influenced by the dosage and bioactivity of the allele. Thus, functional compensation within the TGF-beta superfamily can occur if the replacement gene is expressed appropriately. The novel phenotypes in these mice further illustrate the usefulness of insertion strategies for defining protein function.     

A highly unsaturated fatty acid predicts carbon transfer between primary producers and consumers

The factors that regulate energy transfer between primary producers and consumers in aquatic ecosystems have been investigated for more than 50 years. Among all levels of the food web (plants, herbivores, carnivores), the plant-animal interface is the most variable and least predictable link. In hypereutrophic lakes, for example, biomass and energy transfer is often inhibited at the phytoplankton-zooplankton link, resulting in an accumulation of phytoplankton biomass instead of sustaining production at higher trophic levels, such as fish. Accumulation of phytoplankton (especially cyanobacteria) results in severe deterioration of water quality, with detrimental effects on the health of humans and domestic animals, and diminished recreational value of water bodies. We show here that low transfer efficiencies between primary producers and consumers during cyanobacteria bloom conditions are related to low relative eicosapentaenoic acid (20:5omega3) content of the primary producer community. Zooplankton growth and egg production were strongly related to the primary producer 20:5omega3 to carbon ratio. This indicates that limitation of zooplankton production by this essential fatty acid is of central importance at the pelagic producer-consumer interface.     

Human cerebellar activity reflecting an acquired internal model of a new tool

Theories of motor control postulate that the brain uses internal models of the body to control movements accurately. Internal models are neural representations of how, for instance, the arm would respond to a neural command, given its current position and velocity. Previous studies have shown that the cerebellar cortex can acquire internal models through motor learning. Because the human cerebellum is involved in higher cognitive function as well as in motor control, we propose a coherent computational theory in which the phylogenetically newer part of the cerebellum similarly acquires internal models of objects in the external world. While human subjects learned to use a new tool (a computer mouse with a novel rotational transformation), cerebellar activity was measured by functional magnetic resonance imaging. As predicted by our theory, two types of activity were observed. One was spread over wide areas of the cerebellum and was precisely proportional to the error signal that guides the acquisition of internal models during learning. The other was confined to the area near the posterior superior fissure and remained even after learning, when the error levels had been equalized, thus probably reflecting an acquired internal model of the new tool.