Machine-learning approaches for classifying haplogroup from Y chromosome STR data

Genetic variation on the non-recombining portion of the Y chromosome contains information about the ancestry of male lineages. Because of their low rate of mutation, single nucleotide polymorphisms (SNPs) are the markers of choice for unambiguously classifying Y chromosomes into related sets of lineages known as haplogroups, which tend to show geographic structure in many parts of the world. However, performing the large number of SNP genotyping tests needed to properly infer haplogroup status is expensive and time consuming. A novel alternative for assigning a sampled Y chromosome to a haplogroup is presented here. We show that by applying modern machine-learning algorithms we can infer with high accuracy the proper Y chromosome haplogroup of a sample by scoring a relatively small number of Y-linked short tandem repeats (STRs). Learning is based on a diverse ground-truth data set comprising pairs of SNP test results (haplogroup) and corresponding STR scores. We apply several independent machine-learning methods in tandem to learn formal classification functions. The result is an integrated high-throughput analysis system that automatically classifies large numbers of samples into haplogroups in a cost-effective and accurate manner.     

Expression of antimicrobial peptides and proteins in etanercept-treated psoriasis patients

Recent papers highlight the role of dysregulated expression of antimicrobial peptides and proteins (AMPs) in the pathogenesis of psoriasis. Etanercept, a blocker of the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α), is effective in the treatment of psoriasis. We aimed to evaluate the expression profiles of AMPs in psoriatic skin before and after a 6-week course of etanercept therapy. We included 12 psoriasis patients who underwent medium-dose etanercept treatment for 6weeks. At baseline and at the end of therapy immunohistochemistry from lesional skin was performed for psoriasin, LL-37, and human ?-defensin 2 (hBD-2). After 6-week treatment, the modified psoriasis area and severity index significantly decreased from 37.5±5.9 to 14±13.4. Lesional immunoreactivity scores of psoriasin, LL-37, and hBD-2 also significantly decreased after a 6-week course of etanercept. We have demonstrated that etanercept-induced improvement of psoriasic lesions is associated with a significant decline of AMP protein expression.     

The physiology of life-history trade-offs: experimental analysis of a hormonally induced life-history trade-off in Gryllus assimilis

Abstract Adult Gryllus assimilis given an analog of juvenile hormone exhibited reduced flight muscles and enlarged ovaries similar to those found in naturally occurring flightless individuals of species that are polymorphic for dispersal capability. Control and hormone-treated (flightless) G. assimilis did not differ in the amount of food consumed or assimilated on any of three diets that differed in nutrient quantity. Thus, enhanced ovarian growth of flightless individuals resulted from increased allocation of internal nutrients to reproduction (i.e., a trade-off) rather than from increased acquisition of nutrients. Compared with flight-capable controls, flightless G. assimilis also had reduced whole-organism respiration, reduced respiration of flight muscles, and reduced lipid and triglyceride (flight fuel) reserves. These differences are remarkably similar to those between naturally occurring flightless and flight-capable morphs of other Gryllus species. Results collectively suggest that the increased allocation of nutrients to ovarian growth in flightless G. assimilis and other Gryllus species results from reduced energetic costs of flight muscle maintenance and/or the biosynthesis or acquisition of lipids. Reduction in these energetic costs appears to be an important driving force in the evolution of flightlessness in insects. Respiratory metabolism associated with flight capability utilizes an increasing proportion of the energy budget of crickets as the quantity of nutrients in the diet is decreased. This leads to a magnification of greater ovarian growth of flightless versus flight-capable individuals on nutrient-poor diets.     

Sequence context modulates the stability of a GxxxG-mediated transmembrane helix-helix dimer

To quantify the relationship between sequence and transmembrane dimer stability, a systematic mutagenesis and thermodynamic study of the protein-protein interaction residues in the glycophorin A transmembrane helix-helix dimer was carried out. The results demonstrate that the glycophorin A transmembrane sequence dimerizes when its GxxxG motif is abolished by mutation to large aliphatic residues, suggesting that the sequence encodes an intrinsic propensity to self-associate independent of a GxxxG motif. In the presence of an intact GxxxG motif, the glycophorin A dimer stability can be modulated over a span of -0.5 kcal mol(-1) to +3.2 kcal mol(-1) by mutating the surrounding sequence context. Thus, these flanking residues play an active role in determining the transmembrane dimer stability. To assess the structural consequences of the thermodynamic effects of mutations, molecular models of mutant transmembrane domains were constructed, and a structure-based parameterization of the free energy change due to mutation was carried out. The changes in association free energy for glycophorin A mutants can be explained primarily by changes in packing interactions at the protein-protein interface. The energy cost of removing favorable van der Waals interactions was found to be 0.039 kcal mol(-1) per A2 of favorable occluded surface area. The value corresponds well with estimates for mutations in bacteriorhodopsin as well as for those mutations in the interiors of soluble proteins that create packing defects.     

Extended vomer flaps in cleft palate repair: a preliminary report

It is the author's belief that poor healing due to deficient mesenchyme at the junction of the hard and soft palates probably constitutes the essential reason for some failures of palatoplasty. In order to provide extra tissue to reinforce the above-mentioned region and to facilitate efficient velar lengthening, the use of an extension of the vomer flap detached from the roof of the pharynx is proposed. Such extended vomer flaps have been applied successfully both on the oral and nasal sides in 50 patients. The necessity of further and longer observations is obvious.     

Short-term storage and cryopreservation of black grouse Tetrao tetrix and capercaillie T. urogallus semen

Assisted reproductive technologies can be an important part of programs directed for maintenance and protection of genetic variability. The objective of this study was to develop methods for liquid storage and cryopreservation of semen capercaillie and black grouse semen. Our results provide for the first time evidence for successful short-term storage and cryopreservation of capercaillie and black grouse semen using criteria of sperm motility characteristics as quality indices. Sperm motility could be protected up to 48 h liquid storage; however, 24-h storage should be preferable. Cryopreservation secured 40–60% post-thaw motility (as compared with control), both for freshly collected and 24-h-stored semen. In conclusion, a procedure for short-term and cryopreservation of capercaillie and black grouse semen are now available. These assisted reproductive technologies can be implemented into captive breeding programs for these species.     

Comparison of the transmembrane helices of bovine rhodopsin in the crystal structure and the C α template based on cryo-electron microscopy maps and sequence analysis of the G protein-coupled receptors

G protein-coupled receptors (GPCR) are activated by a diverse array of extracellular signals, ranging from light to polypeptide molecules. The receptors propagate these signals intracellularly using G protein secondary messenger pathways. A common feature in the architecture of these receptors is their seven transmembrane domains. The first crystal structure of a GPCR, bovine rhodopsin, has recently been solved at 2.8 Å. We compared the seven membrane-spanning helices (TMH) from the crystal structure of bovine rhodopsin with those from the low-resolution model of bovine rhodopsin based on the cryo-electron microscopy structure of frog rhodopsin developed by Dr Joyce Baldwin. The model developed by Baldwin used a consensus sequence approach to predict the rotational position of each helix with respect to the other six helices. Superposition of the entire helix bundle of the Baldwin model with the crystal structure gave a RMS difference (RMSD) of 3.2 Å for the 198 C f atoms which suggests a high level of similarity in the arrangement of the helices. Except for TMH IV (RMSD of 4.0 Å), the position of corresponding helices within the helix bundle overlapped well. The superposition of individual helices showed that the RMSD values over 3 Å in the global superposition were largely due to one or more of the following: (i) differences in the unraveling and kinks for these helices, (ii) translation of TMH perpendicular to the membrane and (iii) rotation of helices up to 31°, except for TMH IV in which an additional contribution to the RMSD came from the aforementioned observation. As other crystal structures of GPCRs become available, a comparison with the Baldwin consensus model may reveal larger differences than those observed here.     

Robust regression methods for real-time polymerase chain reaction

Current real-time polymerase chain reaction (PCR) data analysis methods implement linear least squares regression methods for primer efficiency estimation based on standard curve dilution series. This method is sensitive to outliers that distort the outcome and are often ignored or removed by the end user. Here, robust regression methods are shown to provide a reliable alternative because they are less affected by outliers and often result in more precise primer efficiency estimators than the linear least squares method.     

Reversing borealization as a means to restore biodiversity in Central-European mountainforests – an example from the Krkonoše Mountains, Czech Republic

Forestry in the Central-European mountains is confronted with a severe forest decline, which is attributed to the combined effects of 'borealization', brought about by large scale continued spruce (mainly Picea abies) monocultures, and atmospheric deposition. Borealization is defined as enhanced soil acidification and litter accumulation, retarded nutrient cycling and changed forest climate in such planted coniferous forest ecosystems. An additional effect of borealization is a major decline in biodiversity of the stands. Based on a comparative study of Norway spruce and European beech stands in the Krkonoe National Park (Czech Republic), it is concluded that traditional management should be abandoned and that management should instead focus on regeneration towards broad-leaved or mixed forest stands, to enhance the stability of forest ecosystems and their biodiversity, and to reverse borealization in lower montane zones. Available surveys of forest typology were evaluated for their suitability in regeneration management and were found to be unsuitable, since they reflect the effects of borealization rather than true site conditions. The two main pioneer tree species, birch (Betula pendula) and mountain ash (Sorbus aucuparia), were found to improve soil conditions and reverse borealization. Furthermore, trends in natural vegetation and soil development in declined forests and clear-cuts, and their relevance for forest restoration management were studied, focusing on borealization and plant species diversity. It is concluded that this natural development offers very good possibilities for a more passive, low-cost restoration management.