Crown size and hypodontia in the permanent dentition of moderl Skolt Lapps

The teeth of modern Skolt Lapps from northern Finland are considerably larger than those of their ancestors of the Eighteenth Century. The increase is probably attributable to improved nutrition. One or more teeth, excluding the third molars, were congenitally missing in 18.8% of the population aged 5 to 20 years. Relative to a standard the anterior teeth are larger than the posterior teeth, particularly the premolars. This accords well with the hypodontia pattern which is dominated by premolar agenesis.     

Constituents of human muscle in isometric fatigue.

Three subjects performed five successive isometric contractions to fatigue; the tension in any one experiment was constant at tensions varying from 20 to 80% of the maximal voluntary contraction (MVC). The interval between contractions was held constant at 11 min. Muscle biopsy specimens were obtained at the start of the experiment, after the first, fourth, and fifth, and before the second and fifth of the successive contractions. The concentrations of ATP, CP, glycogen, and lactate were measured in each sample of muscle. Changes in ATP and glycogen were insufficient to be held accountable for the development of isometric fatigue. Changes in CP and lactate were large after fatigue at intermediate tensions, but those of CP were considered unlikely to be responsible for the fatigue. At tensions of 30-50% MVC the increase in lactate could be responsible for fatigue either directly or by indirect changes in pH; at higher and lower tensions the possibility that lactate is directly implicated in the development of fatigue seems remote.     

Proton nuclear magnetic resonance analysis of anomeric structure of glycosphingolipids. The globo-series (one to five sugars).

Proton nuclear magnetic resonance spectroscopy has been reevaluated concerning the assignment of anomeric structure of glycosphingolipids. Solubility problems due to a varying number of sugars are avoided by permethylation, allowing a wide range of glycolipids to be compared. High resolution spectra were recorded in chloroform solution for the following substances with known structure, most of them representing a successive building up of members of the globo-series: ceramide, Galβ1 → 1Cer, a mixture of Glcα1 → 1Cer and Glcβ1 → 1Cer, lactosylceramide, globotriaosylceramide, globotetraosylceramide (globoside), and GalNAcα1 → 3globotetraosylceramide (Forssman hapten). Resonances originating in anomeric protons were identified and possible interference from other signals was defined. A complex set of resonances from H-1 of hexosamines was probably due to two separate conformers of the acetamido group caused by N-methylation. The complexity disappeared upon reduction with LiAlH₄. The chemical shifts and coupling constants were characteristic for the configuration of the glycosidic bond, the type of monomer, and in part for its location in the chain. At present, spectra may be recorded from 200-μg samples. It is concluded that the good quality and resolution obtained make this technique an alternative method to the presently used enzymatic degradation for establishing anomeric structure of glycosphingolipids.     

Reconstitution of the Anti-Apoptotic Bcl-2 Protein into Lipid Membranes and Biophysical Evidence for Its Detergent-Driven Association with the Pro-Apoptotic Bax Protein

The anti-apoptotic B-cell CLL/lymphoma-2 (Bcl-2) protein and its counterpart, the pro-apoptotic Bcl-2-associated X protein (Bax), are key players in the regulation of the mitochondrial pathway of apoptosis. However, how they interact at the mitochondrial outer membrane (MOM) and there determine whether the cell will live or be sentenced to death remains unknown. Competing models have been presented that describe how Bcl-2 inhibits the cell-killing activity of Bax, which is common in treatment-resistant tumors where Bcl-2 is overexpressed. Some studies suggest that Bcl-2 binds directly to and sequesters Bax, while others suggest an indirect process whereby Bcl-2 blocks BH3-only proteins and prevents them from activating Bax. Here we present the results of a biophysical study in which we investigated the putative interaction of solubilized full-length human Bcl-2 with Bax and the scope for incorporating the former into a native-like lipid environment. Far-UV circular dichroism (CD) spectroscopy was used to detect direct Bcl-2-Bax-interactions in the presence of polyoxyethylene-(23)-lauryl-ether (Brij-35) detergent at a level below its critical micelle concentration (CMC). Additional surface plasmon resonance (SPR) measurements confirmed this observation and revealed a high affinity between the Bax and Bcl-2 proteins. Upon formation of this protein-protein complex, Bax also prevented the binding of antimycin A₂ (a known inhibitory ligand of Bcl-2) to the Bcl-2 protein, as fluorescence spectroscopy experiments showed. In addition, Bcl-2 was able to form mixed micelles with Triton X-100 solubilized neutral phospholipids in the presence of high concentrations of Brij-35 (above its CMC). Following detergent removal, the integral membrane protein was found to have been fully reconstituted into a native-like membrane environment, as confirmed by ultracentrifugation and subsequent SDS-PAGE experiments.     

How to Make a Rodent Giant: Genomic Basis and Tradeoffs of Gigantism in the Capybara,the World’s Largest Rodent

Gigantism results when one lineage within a clade evolves extremely large body size relative to its small-bodied ancestors, a common phenomenon in animals. Theory predicts that the evolution of giants should be constrained by two tradeoffs. First, because body size is negatively correlated with population size, purifying selection is expected to be less efficient in species of large body size, leading to increased mutational load. Second, gigantism is achieved through generating a higher number of cells along with higher rates of cell proliferation, thus increasing the likelihood of cancer. To explore the genetic basis of gigantism in rodents and uncover genomic signatures of gigantism-related tradeoffs, we assembled a draft genome of the capybara (Hydrochoerus hydrochaeris), the world’s largest living rodent. We found that the genome-wide ratio of nonsynonymous to synonymous mutations (ω) is elevated in the capybara relative to other rodents, likely caused by a generation-time effect and consistent with a nearly neutral model of molecular evolution. A genome-wide scan for adaptive protein evolution in the capybara highlighted several genes controlling postnatal bone growth regulation and musculoskeletal development, which are relevant to anatomical and developmental modifications for an increase in overall body size. Capybara-specific gene-family expansions included a putative novel anticancer adaptation that involves T-cell-mediated tumor suppression, offering a potential resolution to the increased cancer risk in this lineage. Our comparative genomic results uncovered the signature of an intragenomic conflict where the evolution of gigantism in the capybara involved selection on genes and pathways that are directly linked to cancer.     

Molecular engineering of a thermostable carbohydrate-binding module

Structure–function studies are frequently practiced on the very diverse group of natural carbohydrate-binding modules in order to understand the target recognition of these proteins. We have taken a step further in the study of carbohydrate-binding modules and created variants with novel binding properties by molecular engineering of one such molecule of known 3D-structure. A combinatorial library was created from the sequence encoding a thermostable carbohydrate-binding module, CBM4-2 from a Rhodothermus marinus xylanase, and the phage-display technology was successfully used for selection of variants with specificity towards different carbohydrate polymers (birchwood xylan, Avicel?, ivory nut mannan and recently also xyloglucan), as well as towards a glycoprotein (human IgG4). Our work not only generated a number of binders with properties that would suite a range of biotechnological applications, but analysis the selected binders also helped us to identify residues important for their specificities.     

Effect of decimation on the classification rate of non-linear analysis methods applied to uterine EMG signals

Recently, much attention has been paid to the use of non-linear analysis techniques for the characterization of biological signals. Several measures have been proposed to detect non-linear characteristics in time series. The effect of sampling frequency on the performance of these non-linear methods has rarely been evaluated. In this paper, we present a preliminary study of this effect for four methods that are widely used in non-linearity detection: Time reversibility, Sample Entropy, Lyapunov Exponents and Delay Vector Variance. These methods have been applied to real uterine EMG signals with the aim of distinguishing between pregnancy and labor contractions. The signals were used to classify contractions before and after decimating them by a factor 10. The results show that decimation improves the performance for sample entropy. It reduces it considerably for Delay Vector Variance and only slightly for Time reversibility and Lyapunov exponents. Time reversibility still gives the highest classification rate. The methods were much less computationally expensive after down sampling.