Molecular chaperones cooperate with PIM1 protease in the degradation of misfolded proteins in mitochondria.

ATP dependent proteolytic degradation of misfolded proteins in the mitochondrial matrix is mediated by the PIM1 protease and depends on the molecular chaperone proteins mt-hsp70 and Mdj1p. Chaperone function is essential to maintain misfolded proteins in a soluble state, a prerequisite for their degradation by PIM1 protease. In the absence of functional mt-hsp70 or Mdj1p misfolded proteins either remain associated with mt-hsp70 or form aggregates and thereby are no longer substrates for PIM1 protease. Mdj1p is shown to regulate the ATP dependent association of an unfolded polypeptide chain with mt-hsp70 affecting binding to as well as release from mt-hsp70. These findings establish a central role of molecular chaperone proteins in the degradation of misfolded proteins by PIM1 protease and thereby demonstrate a functional interrelation between components of the folding machinery and the proteolytic system within mitochondria.     

Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): six unique arylsulfatase B gene alleles causing variable disease phenotypes.

Mucopolysaccharidosis type VI, or Maroteaux-Lamy syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme arylsulfatase B (ASB), also known as N-acetylgalactosamine-4-sulfatase. Multiple clinical phenotypes of this autosomal recessively inherited disease have been described. Recent isolation and characterization of the human ASB gene facilitated the analysis of molecular defects underlying the different phenotypes. Conditions for PCR amplification of the entire open reading frame from genomic DNA and for subsequent direct automated DNA sequencing of the resulting DNA fragments were established. Besides two polymorphisms described elsewhere that cause methionine-for-valine substitutions in the arylsulfatase B gene, six new mutations in six patients were detected: four point mutations resulting in amino acid substitutions, a 1-bp deletion, and a 1-bp insertion. The point mutations were two G-to-A and two T-to-C transitions. The G-to-A transitions cause an arginine-for-glycine substitution at residue 144 in a homoallelic patient with a severe disease phenotype and a tyrosine-for-cysteine substitution at residue 521 in a potentially heteroallelic patient with the severe form of the disease. The T-to-C transitions cause an arginine-for-cysteine substitution at amino acid residue 192 in a homoallelic patient with mild symptoms and a proline-for-leucine substitution at amino acid 321 in a homoallelic patient with the intermediate form. The insertion between nucleotides T1284 and G1285 resulted in a loss of the 100 C-terminal amino acids of the wild-type protein and in the deletion of nucleotide C1577 in a 39-amino-acid C-terminal extension of the ASB polypeptide. Both mutations were detected in homoallelic patients with the severe form of the disease. Expression of mutant cDNAs encoding the four amino acid substitutions and the deletion resulted in severe reduction of both ASB protein levels and arylsulfatase enzyme activity in comparison with a wild-type control. The six mutations described in the present study were unique among 25 unrelated mucopolysaccharidosis VI patients, suggesting a broad molecular heterogeneity of the Maroteaux-Lamy syndrome.     

Relationships among the herbicide and functional sites of acetohydroxy acid synthase from Chlorella emersonii

The properties of acetohydroxy acid synthase (AHAS, EC 4.1.3.18) from wild-type Chlorella emersonii (var. Emersonii, CCAP-211/11n) and two spontaneous sulfometuron methyl (SMM)-resistant mutants were examined. The AHAS from both mutants was resistant to SMM and cross-resistant to imazapyr (IM) and the triazolopyrimidine sulfonanilide herbicide XRD-498 (TP). The more-SMM-resistant mutant had AHAS with altered catalytic parameters (K _m, specificity), but unchanged sensitivity to the feedback inhibitors valine and leucine. The second mutant enzyme was less sensitive to the feedback inhibitors, but had otherwise unchanged kinetic parameters. Inhibition-competition experiments indicated that the three herbicides (SMM, IM, TP) bind in a mutually exclusive manner, but that valine can bind simultaneously with SMM or TP. The three herbicide classes apparently bind to closely overlapping sites. We suggest that the results with C. emersonii and other organisms can all be explained if there are separate binding sites for herbicides, feedback inhibitors and substrates.Abbreviations AHAS acetohydroxy acid synthase - AL acetolactate - AHB acetohydroxybutyrate - IM imazapyr - TP triazolopyrimidine sulfonanilide herbicide XRD-498 - R enzyme specificity - SMM sulfometuron methyl This research was supported in part by the United States — Israel Binational Science Foundation (BSF), Jerusalem, Israel (Grant 86-00205) and the Fund for Basic Research, Israel Academy of Sciences.     

Drought,heat and salt stress induce the expression of a citrus homologue of an atypical late-embryogenesis Lea5 gene

In a search for genes that are induced in citrus cell suspension in response to salt stress, a cDNA clone with high homology to cotton Lea5 gene was isolated. Data base analysis of the protein deduced from the nucleotide sequence indicates that, like in cotton, the protein from citrus contains regions with significant hydropathic character. The gene, designated C-Lea5, is expressed in citrus leaves as well as cell suspension. The steady-state level of C-Lea5 is increased in cell suspension that is grown in the presence of 0.2 M NaCl. This phenomenon is also observed in leaves of citrus plants irrigated with NaCl and in citrus seedlings which are exposed to drought and heat stress. We suggest that the osmotic stress resulted from elevated level of salt is responsible for the increase in the level of C-Lea5.     

Cannot see the diversity for all the species: Evaluating inclusion criteria for local species lists when using abundant citizen science data

Abundant citizen science data on species occurrences are becoming increasingly available and enable identifying composition of communities occurring at multiple sites with high temporal resolution. However, for species displaying temporary patterns of local occurrences that are transient to some sites, biodiversity measures are clearly dependent on the criteria used to include species into local species lists. Using abundant opportunistic citizen science data from frequently visited wetlands, we investigated the sensitivity of α‐ and β‐diversity estimates to the use raw versus detection‐corrected data and to the use of inclusion criteria for species presence reflecting alternative site use. We tested seven inclusion criteria (with varying number of days required to be present) on time series of daily occurrence status during a breeding season of 90 days for 77 wetland bird species. We show that even when opportunistic presence‐only observation data are abundant, raw data may not produce reliable local species richness estimates and rank sites very differently in terms of species richness. Furthermore, occupancy model based α‐ and β‐diversity estimates were sensitive to the inclusion criteria used. Total species lists (all species observed at least once during a season) may therefore mask diversity differences among sites in local communities of species, by including vagrant species on potentially breeding communities and change the relative rank order of sites in terms of species richness. Very high sampling effort does not necessarily free opportunistic data from its inherent bias and can produce a pattern in which many species are observed at least once almost everywhere, thus leading to a possible paradox: The large amount of biological information may hinder its usefulness. Therefore, when prioritizing among sites to manage or preserve species diversity estimates need to be carefully related to relevant inclusion criteria depending on the diversity estimate in focus.     

Introgressive hybridization of Senecio hercynicus and S. ovatus (Compositae,Senecioneae) along an altitudinal gradient in Harz National Park (Germany)

Introgressive hybridization of Senecio hercynicus and S. ovatus (Compositae, Senecioneae) was studied in a hybrid zone on the southern slopes of Mt Brocken (Harz Mountains, Germany). A total of 415 plants representing 10 stands along an altitudinal gradient were investigated using multivariate statistical analyses of morphological characters and molecular markers (random amplified polymorphic DNA[RAPD]). Both types of traits detected pure S. hercynicus stands on the summit plateau, pure S. ovatus stands at the lowest elevations, and hybrid swarms at intermediate elevations. While morphological and molecular patterns coincided, some individuals in hybrid stands combined morphological patterns typical of S. ovatus with RAPD patterns typical of S. hercynicus, and vice versa. In general, introgression was symmetrical within stands, though one stand combined S. ovatus characters with the glandular hair typical for S. hercynicus, and two stands combined a S. hercynicus typical RAPD genotype with morphological characters shifted towards S. ovatus. Because pure stands of S. hercynicus occurred only on the summit plateau of Mt Brocken, and markers typical for S. ovatus were detectable in stands up to 1040 m a.s.l., future fusion or assimilation of the rare form, S. hercynicus, by the more widespread S. ovatus appears possible at Mt Brocken.     

The short‐ and long‐term fitness consequences of natal dispersal in a wild bird population

Dispersal is a key process in population and evolutionary ecology. Individual decisions are affected by fitness consequences of dispersal, but these are difficult to measure in wild populations. A long‐term dataset on a geographically closed bird population, the Mauritius kestrel, offers a rare opportunity to explore fitness consequences. Females dispersed further when the availability of local breeding sites was limited, whereas male dispersal correlated with phenotypic traits. Female but not male fitness was lower when they dispersed longer distances compared to settling close to home. These results suggest a cost of dispersal in females. We found evidence of both short‐ and long‐term fitness consequences of natal dispersal in females, including reduced fecundity in early life and more rapid aging in later life. Taken together, our results indicate that dispersal in early life might shape life history strategies in wild populations.     

Metabolically Protective Cytokines Adiponectin and Fibroblast Growth Factor-21 Are Increased by Acute Overfeeding in Healthy Humans

Context

Circulating levels of metabolically protective and adverse cytokines are altered in obese humans and rodent models. However, it is not clear whether these cytokines are altered rapidly in response to over-nutrition, or as a later consequence of the obese state.

Methods

Forty sedentary healthy individuals were examined prior to and at 3 and 28 days of high fat overfeeding (+1250 kCal/day, 45% fat). Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), adiposity, serum levels of adiponectin and fibroblast growth factor-21 (FGF21), fatty acid binding protein-4 (FABP4), lipocalin-2 and plasminogen activator factor-1 (PAI1) were assessed. Statistics were performed by repeated measures ANOVA.

Results

Overfeeding increased weight, body fat and liver fat, fasting glucose, insulin and reduced insulin sensitivity by clamp (all P <0.05). Metabolically protective cytokines, adiponectin and FGF21 were increased at day 3 of overfeeding (P ≤0.001) and adiponectin was also elevated at day 28 (P=0.001). FABP4, lipocalin-2 and PAI-1 were not changed by overfeeding at either time point.

Conclusion

Metabolically protective cytokines, adiponectin and FGF-21, were increased by over nutrition and weight gain in healthy humans, despite increases in insulin resistance. We speculate that this was in attempt to maintain glucose homeostasis in a state of nutritional excess. PAI-I, FABP4 and lipocalin 2 were not altered by overfeeding suggesting that changes in these cytokines may be a later consequence of the obese state. Clinical trial registration: www.clinicaltrials.gov (NCT00562393)     

Description of intertidal macro- and meiobenthic assemblages in Maxwell Bay, King George Island, South Shetland Islands, Southern Ocean

The intertidal benthic fauna of the Antarctic coastal areas is largely unknown and has long been thought to be absent or, at most, to be scarce. Since climate changes cause a progressive expansion of ice-free intertidal soft-bottom areas, the fauna of these areas could serve as essential criterion to evaluate the kind and dimension of such changes. We therefore investigated the faunal composition of the intertidal soft-bottom area of Maxwell Bay (King George Island, South Shetlands) in December 2006. Samples for quantitative analyses were taken from the soft-bottom during low tide using a plastic corer. We performed detailed analyses of the soft-bottom beneath a cobble layer, while hard-bottom and macrophytes were only sporadically investigated. Approximately 5,000 specimens were collected of which polychaetes (37.3 ± 7.6 (max. 44.7) ind. × 100 cm^?³) and harpacticoids (28.9 ± 28.5 (max. 104.0) ind. × 10 cm^?³) were the most abundant macro- and meiofauna taxa of the soft-bottom, followed by oligochaetes, nematodes, mollusks, and amphipods. A total of 58 macrofauna species were registered, of which 27 were identified only to a supraspecific level. The most species-rich macrofauna taxon was polychaetes with at least 24 species, followed by amphipods, gastropods, and oligochaetes with 6 species each. The harpacticoid copepods were represented by 15 families with more than 30 species. In summary, we show that the Antarctic intertidal soft-bottom is densely populated by macro- and meiofauna and that it deserves closer attention in the future to determine whether it can indeed serve as an indicator of the effect of climate changes on the Antarctic coastal areas.