Range-body mass interactions of a northern ungulate – a test of hypothesis

Summer diet, summer temperature, length of the growth season and animal density appeared to best explain annual and regional differences in calf and yearling body mass in moose from southeastern Norway. In general animals inhabiting steep, alpine landscapes had less body mass than animals using flat, low-altitude habitats. Autumn body mass of calves and yearlings decreased with increasing snow depth during the preceding winter and spring. However, calf body mass was more influenced by the summer range and less by the winter range than was body mass of yearlings. There was no indication that the effect of snow depth on autumn body mass was greater in moose living on poor than on good summer ranges. Body mass decreased with increasing competition for summer forage, while the winter range mainly had an density-independent effect. Habitat quality, expressed as regression lines between calf and yearling body mass and animal density (hunting yield), differed between regions. On ranges of medium and high altitude where birch (Betula spp.) rowan (Sorbus aucuparia) and bilberry (Vaccinium myrtillus) dominated moose summer diet, body mass decreased at a rapid rate with increasing animal density. Body mass decreased at a slower rate at low-altitude ranges and at high-altitude ranges where willow (Salix spp.) and forbs dominated the diet. Body mass of lactating cows decreased with increasing animal density, but animal density did not affect body mass of non-lactating cows. There was no indication that the decrease in autumn body mass with increasing moose density over the last 25 years has caused a decrease in animal condition (ability to survive the winter). The results are discussed in relation to the effect of summer and winter range on population regulation in moose. It is concluded that a density-dependent effect is apparent on the summer range even at low and intermediate population densities. On the winter range, on the other hand, density-dependence is likely to occur only at high levels of population density. Received: 4 February 1997 / Accepted: 1 February 1999     

Temporal relationships of a pulse of prolactin (PRL) to a pulse of a metabolite of PGF2α in mares

Hourly blood samples were collected from 10 mares during 24 h of each of the preluteolytic, luteolytic, and postluteolytic periods. The autocorrelation function of the R program was used to detect pulse rhythmicity, and the intra-assay CV was used to locate and characterize pulses of prolactin (PRL) and a metabolite of prostaglandin F2α (PGFM). Rhythmicity of PRL and PGFM concentrations was detected in 67% and 89% of mares, respectively. Combined for the three periods (no difference among periods), the PRL pulses were 5.2 ± 0.4 h (mean ± SEM) at the base, 7.5 ± 1.5 h between nadirs of adjacent pulses, and 12.3 ± 1.5 h from peak to peak. The peaks of PRL pulses were greater (P < 0.05) during the luteolytic period (46 ± 14 ng/mL) and postluteolytic period (52 ± 15 ng/mL) than during the preluteolytic period (17 ± 3 ng/mL). Concentrations of PRL during hours of a PGFM pulse were different (P < 0.003) within the luteolytic period and postluteolytic period and were greatest at the PGFM peak; PRL concentrations during a PGFM pulse were not different during the preluteolytic period. The frequency of the peak of PRL and PGFM pulses occurring at the same hour (synchrony) was greater for the luteolytic period (65%, P < 0.01) and postluteolytic period (50%, P < 0.001) than for the preluteolytic period (17%). This is the first report in mares on characterization and rhythmicity of PRL pulses, synchrony between PRL and PGFM pulses, and greater PRL activity during the luteolytic and postluteolytic periods than during the preluteolytic period.     

Synthesis of a cyclic isostere of α-methyl homoserine by a stereoselective acylation–alkylation sequence of a chiral γ-lactam

Starting from a chiral 4-hydroxymethyl pyrrolidin-2-one, an isostere of α-methyl homoserine tethered on a γ-lactam ring was prepared exploiting a stereoselective acylation–methylation sequence, followed by Curtius rearrangement, and structural assignment was confirmed by n.O.e. experiments. By reverting the sequence, the 3-carboxy-3-methyl derivative having the opposite configuration at C-3 was obtained with total stereoselection, but Curtius rearrangement invariably afforded only inseparable mixtures of decomposition products.     

Structural characterization of a carbon monoxide adduct of a heme–DNA complex

Abstract  

The structure of a carbon monoxide (CO) adduct of a complex between heme and a parallel G-quadruplex DNA formed from a single repeat sequence of the human telomere, d(TTAGGG), has been characterized using ¹H and ¹³C NMR spectroscopy and density function theory calculations. The study revealed that the heme binds to the 3′-terminal G-quartet of the DNA though a π–π stacking interaction between the porphyrin moiety of the heme and the G-quartet. The π–π stacking interaction between the pseudo-C ₂-symmetric heme and the C ₄-symmetric G-quartet in the complex resulted in the formation of two isomers possessing heme orientations differing by 180° rotation about the pseudo-C ₂ axis with respect to the DNA. These two slowly interconverting heme orientational isomers were formed in a ratio of approximately 1:1, reflecting that their thermodynamic stabilities are identical. Exogenous CO is coordinated to heme Fe on the side of the heme opposite the G-quartet in the complex, and the nature of the Fe–CO bond in the complex is similar to that of the Fe–CO bonds in hemoproteins. These findings provide novel insights for the design of novel DNA enzymes possessing metalloporphyrins as prosthetic groups.     

Is aggregation of beta-amyloid peptides a mis-functioning of a current interaction process?

In a previous study, Hughes et al. [Proc. Natl. Acad. Sci. USA 93 (1996) 2065-2070] demonstrated that the amyloid peptide is able to interact with itself in a two-hybrid system and that interaction is specific. They further supported that the method could be used to define the sequences that might be important in nucleation-dependent aggregation. The sequence of the amyloid peptide can be split into four clusters, two hydrophilic (1-16 and 22-28) and two hydrophobic (17-21 and 29-42). We designed by molecular modeling and tested by the two-hybrid approach, series of mutations spread all over the sequence and changing the distribution of hydrophobicity and/or the spatial hindrance. In the two-hybrid assay, interaction of native Abeta is reproduced. Screening of mutations demonstrates that the C-domain (residues 29-40 (42)), the median domain (residues 17-22) and the N-domain (1-16) are all crucial for interaction. This demonstrates that almost all fragments of the amyloid peptide but a loop (residues 23-28) and the C-term amino acid are important for the native interaction. We support that the folded three-dimensional (3D) structure is the Abeta-Abeta interacting species, that the whole sequence is involved in that 3D fold which has a low secondary structure propensity and a high susceptibility to mutations and thus should have a low stability. The native fold of Abeta could be stabilized in Abeta-Abeta complexes which could in other circumstances facilitate the nucleation event of aggregation that leads to the formation of stable senile plaques.     

Characterization of a transient unfolding intermediate in a core mutant of γS-crystallin

In many age-related and neurological diseases, formerly native proteins aggregate via formation of a partially unfolded intermediate. γS-Crystallin is a highly stable structural protein of the eye lens. In the mouse Opj cataract, a non-conservative F9S mutation in the N-terminal domain core of γS allows the adoption of a native fold but renders the protein susceptible to temperature- and concentration-dependent aggregation, including fibril formation. Hydrogen/deuterium exchange and denaturant unfolding studies of this mutant protein (Opj) have suggested the existence of a partially unfolded intermediate in its aggregation pathway. Here, we used NMR and fluorescence spectroscopy to obtain evidence for this intermediate. In 3.5 M urea, Opj forms a stable and partially unfolded entity that is characterized by an unstructured N-terminal domain and a largely intact C-terminal domain. Under physiologically relevant conditions, Carr-Purcell-Meiboom-Gill T₂-relaxation dispersion experiments showed that the N-terminal domain residues were in conformational exchange with a loosely structured intermediate with a population of 1-2%, which increased with temperature. This provides direct evidence for a model in which proteins of native fold can explore an intermediate state with an increased propensity for formation of aggregates, such as fibrils. For the crystallins, this shows how inherited sequence variants or environmentally induced modifications can destabilize a well-folded protein, allowing the formation of intermediates able to act as nucleation sites for aggregation and the accumulation of light-scattering centers in the cataractous lens.     

“Pollination” of a fungus by a fly

Summary The mechanism resulting in fertilization of Epichloë typhina, a heterothallic ascomycete that is an endophytic pathogen of grasses, has now been discovered. Conidia of one mating type are produced in stromata and are then transferred by insects to individuals of the opposite mating type. One insect, Phorbia phrenione, is a particularly important vector of conidia. Once conidia of the opposite mating type have been transferred to a stroma, the life cycle continues with the formation of perithecia.     

Stereoselective formation of a 2′(3′)-aminoacyl ester of a nucleotide

Summary Reaction ofDl-serine and adenosine-5-phosphorimidazolide in the presence of adenosine-5-(O-methylphosphate) and imidazole resulted in the stereoselective synthesis of the aminoacyl nucleotide ester 2(3)-O-seryl-adenosine-5-(O-methylphosphate). The enantiomeric excess ofd-serine incorporated into 2(3)-O-seryl-adenosine-5-(O-methylphosphate) was about 9%. Adenylyl-(5N)-serine and an unknown product also incorporated an excess ofd-serine; however, serylserine showed an excess ofl-serine. The relationship of these results to the origin of the biological pairing ofl-amino acids and nucleotides containingd-ribose is discussed.     

Crystallization and identification of a binary complex of a elastase-I and a Carboxypeptidase Aγ from porcine pancreas

A binary complex of elastase I and Carboxypeptidase Aγ has been isolated and crystallized from activated extracts of porcine pancreas. The purification procedure included ammonium sulfate fractionation and autolysis treatment followed by crystallization. The two components in the complex have been separated by DEAE-Sephadex A-50 column chromatography to homogeneity and their identification was demonstrated by NH₂-terminal sequence analysis. An analysis of the reconstitution crystal from the mixtures of both components showed that the complex consisted of a 1:1 molar ratio with elastase I and Carboxypeptidase Aγ, forming a binary complex in crystalline state.     

Structure and Properties of a Complex of α-Synuclein and a Single-Domain Camelid Antibody

The aggregation of the intrinsically disordered protein α-synuclein to form fibrillar amyloid structures is intimately associated with a variety of neurological disorders, most notably Parkinson's disease. The molecular mechanism of α-synuclein aggregation and toxicity is not yet understood in any detail, not least because of the paucity of structural probes through which to study the behavior of such a disordered system. Here, we describe an investigation involving a single-domain camelid antibody, NbSyn2, selected by phage display techniques to bind to α-synuclein, including the exploration of its effects on the in vitro aggregation of the protein under a variety of conditions. We show using isothermal calorimetric methods that NbSyn2 binds specifically to monomeric α-synuclein with nanomolar affinity and by means of NMR spectroscopy that it interacts with the four C-terminal residues of the protein. This latter finding is confirmed by the determination of a crystal structure of NbSyn2 bound to a peptide encompassing the nine C-terminal residues of α-synuclein. The NbSyn2:α-synuclein interaction is mediated mainly by side-chain interactions while water molecules cross-link the main-chain atoms of α-synuclein to atoms of NbSyn2, a feature we believe could be important in intrinsically disordered protein interactions more generally. The aggregation behavior of α-synuclein at physiological pH, including the morphology of the resulting fibrillar structures, is remarkably unaffected by the presence of NbSyn2 and indeed we show that NbSyn2 binds strongly to the aggregated as well as to the soluble forms of α-synuclein. These results give strong support to the conjecture that the C-terminal region of the protein is not directly involved in the mechanism of aggregation and suggest that binding of NbSyn2 could be a useful probe for the identification of α-synuclein aggregation in vitro and possibly in vivo.     

Effects of a half a millennium winter on a deep lake – a shape of things to come?

Analyses of the effects of extreme climate periods have been used as a tool to predict ecosystem functioning and processes in a warmer world. The winter half‐year 2006/2007 (w06/07) has been extremely warm and was estimated to be a half‐a‐millennium event in central Europe. Here we analyse the consequences of w06/07 for the temperatures, mixing dynamics, phenologies and population developments of algae and daphnids (thereafter w06/07 limnology) in a deep central European lake and investigate to what extent analysis of w06/07 limnology can really be used as a predictive tool regarding future warming. Different approaches were used to put the observations during w06/07 into context: (1) a comparison of w06/07 limnology with long‐term data, (2) a comparison of w06/07 limnology with that of the preceding year, and (3) modelling of temperature and mixing dynamics using numerical experiments. These analyses revealed that w06/07 limnology in Lake Constance was indeed very special as the lake did not mix below 60 m depth throughout winter. Because of this, anomalies of variables associated strongly with mixing behaviour, e.g., Schmidt stability and a measure for phosphorus upward mixing during winter exceeded several standard deviations the long‐term mean of these variables. However, our modelling results suggest that this extreme hydrodynamical behaviour was only partially due to w06/07 meteorology per se, but depended also strongly on the large difference in air temperature to the previous cold winter which resulted in complete mixing and considerable cooling of the water column. Furthermore, modelling results demonstrated that with respect to absolute water temperatures, the model ‘w06/07’ most likely underestimates the increase in water temperature in a warmer world as one warm winter is not sufficient to rise water temperatures in a deep lake up to those expected under a future climate.     

Growth of a Capsid Mutant of Bacteriophage φX174 in a Temperature-Sensitive Strain of Escherichia coli

A capsid mutant of X174 is capable of forming replicative form and synthesizing single strands at the restrictive temperature in a dnaB mutant of Escherichia coli. Under similar conditions, the wild-type bacteriophage is incapable of either step in viral synthesis.     

Characterization of a predominantly pistil-expressed gene encoding a γ-thionin-like protein of Petunia inflata

We isolated a cDNA clone from a pistil cDNA library of Petunia inflata which encodes a protein, PPT, with sequence similarity to -thionins. Characterization of a genomic clone containing a PPT gene revealed the presence of a single intron. Northern analysis revealed that the PPT gene was predominantly expressed in the pistil during all stages of flower development. Since thionins have been implicated in plant defense against pathogens, PPT may play a role similar to that of other defense-related proteins found in the pistil, defending the pistil against pathogen infection.     

Familial transmission of a dysmorphic syndrome: a variant example of Kabuki syndrome?

Familial transmission of a dysmorphic syndrome: a variant example of Kabuki syndrome?: We report a Romanian family with a dysmorphic syndrome in three generations: a boy, his mother and maternal grandfather, who all presented with the typical facial appearance, characteristic skeletal and dermatoglyphic findings of Kabuki syndrome, but no mental retardation, short stature and visceral abnormalities. The phenotype observed in this family may represent the mild end of a spectrum of clinical manifestations described in this condition. This report provides a further evidence for autosomal dominant transmission of the disorder.     

Who's afraid of a cognitive neuroscience of creativity?

This article has two goals. First, the ideas outlined here can be seen as a sustained and disciplined demolition project aimed at sanitizing our bad habits of thinking about creativity. Apart from the enormous amount of fluff out there, the study of creativity is, quite unfortunately, still dominated by a number of rather dated ideas that are either so simplistic that nothing good can possibly come out of them or, given what we know about the brain, factually mistaken. As cognitive neuroscience is making more serious contact with the knowledge base of creativity, we must, from the outset, clear the ground of these pernicious fossil traces from a bygone era. The best neuroimaging techniques help little if we don't know what to look for. Second, as an antidote to these theoretical duds, the article offers fresh ideas on possible mechanisms of creativity. Given that they are grounded in current understanding of cognitive and neural processes, it is hoped that these ideas represent steps broadly pointing in the right direction. In the end, the fundamental question we must ask ourselves is what, exactly, are the mental processes--or their critical elements--that yield creative thoughts.     

Generation and exploration of a dense genetic map in a region of a QTL affecting corpora lutea in a Meishan × Yorkshire cross

Previously genomic scans revealed quantitative trait loci (QTL) on porcine Chromosome 8 (SSC8) as significantly affecting the number of corpora lutea (CL) in swine. In one study, statistical evidence for the putative QTL was found in the chromosomal region defined by the microsatellites (MS) SW205, SW444, SW206, and SW29. A Yeast Artificial Chromosome library was screened by using the corresponding primers for clones containing these MS by PCR. From five positive YAC clones, 10 additional MS were isolated and mapped to SSC8 with the INRA-University of Minnesota porcine Radiation Hybrid (IMpRH) panel. The genetic map position of the QTL has been refined by addition of these 10 markers. The QTL evaluation included pedigrees of F₂-intercross Meishan × Yorkshire design, with phenotypic data of 108 F₂ female offspring and genotypic data for 29 MS markers on SSC8. The analysis was performed by using the least squares regression method. The calculated QTL effect for CL obtained by the multilocus least squares method showed a maximum test statistic (F value = 13.98) at position 99 cM between three MS derived from YACs containing SW205 and SW1843 spanning an interval of 7.1 cM. The point-wise (nominal) P-value was 5.21 × 10⁻⁶ corresponding to a genome-wide P-value of 0.009. The additive QTL effect explained 17.4% of the phenotypic variance. Received: 23 December 2000 / Accepted: 07 May 2001     

Is a genome a codeword of an error-correcting code?

Since a genome is a discrete sequence, the elements of which belong to a set of four letters, the question as to whether or not there is an error-correcting code underlying DNA sequences is unavoidable. The most common approach to answering this question is to propose a methodology to verify the existence of such a code. However, none of the methodologies proposed so far, although quite clever, has achieved that goal. In a recent work, we showed that DNA sequences can be identified as codewords in a class of cyclic error-correcting codes known as Hamming codes. In this paper, we show that a complete intron-exon gene, and even a plasmid genome, can be identified as a Hamming code codeword as well. Although this does not constitute a definitive proof that there is an error-correcting code underlying DNA sequences, it is the first evidence in this direction.