Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern

Dysmorphic features, multisystem disease, and central nervous system involvement are common symptoms in congenital disorders of glycosylation, including several recently discovered Golgi-related glycosylation defects. In search for discriminative features, we assessed eleven children suspected with a Golgi-related inborn error of glycosylation. We evaluated all genetically unsolved patients, diagnosed with a type 2 transferrin isofocusing pattern in the period of 1999-2009. By combining biochemical results with characteristic clinical symptoms, we used a diagnostic flow chart to approach the underlying defect in patients with congenital disorders of glycosylation-IIx. According to specific symptoms and laboratory results, we initiated additional, targeted biochemical and genetic studies. We found a distinctive spectrum of congenital disorders of glycosylation type 2-associated anomalies including sudden hearing loss, brain malformations, wrinkled skin, and epilepsy in combination with skeletal dysplasia, dilated cardiomyopathy, sudden cardiac arrest, abnormal copper and iron metabolism, and endocrine abnormalities in our patients. One patient with severe cortical malformations and mild skin abnormalities was diagnosed with a known genetic syndrome, due to an ATP6V0A2 defect. Here, we present unique congenital disorders of glycosylation type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa and sensorineural hearing loss, a recently recognized symptom of congenital disorders of glycosylation. Based on our findings, we recommend clinicians to consider congenital disorders of glycosylation in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability.     

Achieving conservation when opportunity costs are high: optimizing reserve design in Alberta's oil sands region

Recent studies have shown that conservation gains can be achieved when the spatial distributions of biological benefits and economic costs are incorporated in the conservation planning process. Using Alberta, Canada, as a case study we apply these techniques in the context of coarse-filter reserve design. Because targets for ecosystem representation and other coarse-filter design elements are difficult to define objectively we use a trade-off analysis to systematically explore the relationship between conservation targets and economic opportunity costs. We use the Marxan conservation planning software to generate reserve designs at each level of conservation target to ensure that our quantification of conservation and economic outcomes represents the optimal allocation of resources in each case. Opportunity cost is most affected by the ecological representation target and this relationship is nonlinear. Although petroleum resources are present throughout most of Alberta, and include highly valuable oil sands deposits, our analysis indicates that over 30% of public lands could be protected while maintaining access to more than 97% of the value of the region's resources. Our case study demonstrates that optimal resource allocation can be usefully employed to support strategic decision making in the context of land-use planning, even when conservation targets are not well defined.     

Porphyromonas gingivalis Facilitates the Development and Progression of Destructive Arthritis through Its Unique Bacterial Peptidylarginine Deiminase (PAD)

Rheumatoid arthritis and periodontitis are two prevalent chronic inflammatory diseases in humans and are associated with each other both clinically and epidemiologically. Recent findings suggest a causative link between periodontal infection and rheumatoid arthritis via bacteria-dependent induction of a pathogenic autoimmune response to citrullinated epitopes. Here we showed that infection with viable periodontal pathogen Porphyromonas gingivalis strain W83 exacerbated collagen-induced arthritis (CIA) in a mouse model, as manifested by earlier onset, accelerated progression and enhanced severity of the disease, including significantly increased bone and cartilage destruction. The ability of P. gingivalis to augment CIA was dependent on the expression of a unique P. gingivalis peptidylarginine deiminase (PPAD), which converts arginine residues in proteins to citrulline. Infection with wild type P. gingivalis was responsible for significantly increased levels of autoantibodies to collagen type II and citrullinated epitopes as a PPAD-null mutant did not elicit similar host response. High level of citrullinated proteins was also detected at the site of infection with wild-type P. gingivalis. Together, these results suggest bacterial PAD as the mechanistic link between P. gingivalis periodontal infection and rheumatoid arthritis.     

Variation of the electronic dipole polarizability on the reaction path

The reaction force and the electronic flux, first proposed by Toro-Labbé et al. (J Phys Chem A 103:4398, 1999) have been expressed by the existing conceptual DFT apparatus. The critical points (extremes) of the chemical potential, global hardness and softness have been identified by means of the existing and computable energy derivatives: the Hellman-Feynman force, nuclear reactivity and nuclear stiffness. Specific role of atoms at the reaction center has been unveiled by indicating an alternative method of calculation of the reaction force and the reaction electronic flux. The electron dipole polarizability on the IRC has been analyzed for the model reaction HF + CO→HCOF. The electron polarizability determined on the IRC α _e (ξ) was found to be reasonably parallel to the global softness curve S(ξ). The softest state on the IRC (not TS) coincides with zero electronic flux.

DNA barcode analysis of butterfly species from Pakistan points towards regional endemism

DNA barcodes were obtained for 81 butterfly species belonging to 52 genera from sites in north‐central Pakistan to test the utility of barcoding for their identification and to gain a better understanding of regional barcode variation. These species represent 25% of the butterfly fauna of Pakistan and belong to five families, although the Nymphalidae were dominant, comprising 38% of the total specimens. Barcode analysis showed that maximum conspecific divergence was 1.6%, while there was 1.7–14.3% divergence from the nearest neighbour species. Barcode records for 55 species showed <2% sequence divergence to records in the Barcode of Life Data Systems (BOLD), but only 26 of these cases involved specimens from neighbouring India and Central Asia. Analysis revealed that most species showed little incremental sequence variation when specimens from other regions were considered, but a threefold increase was noted in a few cases. There was a clear gap between maximum intraspecific and minimum nearest neighbour distance for all 81 species. Neighbour‐joining cluster analysis showed that members of each species formed a monophyletic cluster with strong bootstrap support. The barcode results revealed two provisional species that could not be clearly linked to known taxa, while 24 other species gained their first coverage. Future work should extend the barcode reference library to include all butterfly species from Pakistan as well as neighbouring countries to gain a better understanding of regional variation in barcode sequences in this topographically and climatically complex region.     

Nucleotide Sequence and Variation of IGF2 Gene Exon 6 in Bos Taurus and Bos Indicus Cattle

The major assumption of this study is that polymorphism of a gene could be used to investigate its allele-specific expression as well as its methylation and imprinting status. Therefore, the aim of this study was to analyze the polymorphism of the coding region of the bovine IGF2 gene and to determine the sequence of its gene exon 6 in Bos taurus and Bos indicus cattle. A single nucleotide “C” deletion/insertion polymorphism was found in both cattle subspecies and a G/T transversion (RFLP-MboII) in the Bos indicus IGF2 gene. A 407-bp fragment of bovine IGF2 exon 6 was sequenced and the sequences (including variable nucleotides) were deposited in the GenBank database. A comparative analysis was performed for this fragment from different species; 99.5% identity was found between Bos taurus and Bos indicus cattle.     

Computing fullerene encapsulation of non-metallic molecules: N2@C60 and NH3@C60

Some endohedral fullerenes have been considered as possible candidate species for molecular memories. Recently, the encapsulation inside the fullerene cages has been extended from atoms to small molecules, for example the nitrogen molecule was placed inside the fullerene cage. The observed N₂@C₆₀ endohedral is computed in the paper together with NH₃@C₆₀, which was not yet observed. The computations are based on structural optimizations using density-functional theory (DFT) methods. In the optimized structures, the analytical harmonic vibrational analysis was carried out and the encapsulation energetics were evaluated using the second order Møller-Plesset (MP2) perturbation treatment. The lowest-energy structure has the N₂ unit oriented towards a pair of parallel pentagons so that the complex exhibits D _5d symmetry. At the MP2 level, the encapsulation of N₂ into C₆₀ brings a potential energy gain of ? 9.3 kcal/mol while that for NH₃ is ? 5.2 kcal/mol. The entropy term is also evaluated, yielding the standard Gibbs-energy change at room temperature for the encapsulation of N₂ and NH₃ of ? 2.6 and 1.5 kcal/mol, respectively. Some computed structural and vibrational characteristics are also reported. Emerging broader landscape of future applications of such encapsulates in nanoscience and nantechnology is discussed.     

FROM MORE TO FEWER? TESTING AN ALLEGEDLY PERVASIVE TREND IN THE EVOLUTION OF MORPHOLOGICAL STRUCTURE

While evolutionary trends have long received much attention and have been widely disputed, new methods are now allowing the testing of directional hypotheses with increased rigor. Here, we test a general hypothesis about the way many kinds of discrete characters are thought to evolve, termed oligomerization. This is the tendency for serial structures (such as arthropod body and appendage segments) or armature (such as spines) to evolve primarily through loss and fusion. Focusing on the Crustacea, we use maximum likelihood methods to test for directional evolution in a large sample (> 500) of discrete traits, analyzed against molecular-based phylogenies. We find evidence for a significant trend toward trait loss, in accordance with the reduction principle. However, this trend is far from ubiquitous, with many characters exhibiting a reconstructed bias toward gains. These results suggest that caution must be used before drawing conclusions about which taxa are "primitive" or about the directionality of morphological shifts in the absence of phylogenetic analysis. Nevertheless, oligomerization-as a trend rather than a law-may be an important process that influences evolutionary trajectories from both morphological and functional perspectives.