Genome assembly comparison identifies structural variants in the human genome

Numerous types of DNA variation exist, ranging from SNPs to larger structural alterations such as copy number variants (CNVs) and inversions. Alignment of DNA sequence from different sources has been used to identify SNPs and intermediate-sized variants (ISVs). However, only a small proportion of total heterogeneity is characterized, and little is known of the characteristics of most smaller-sized (<50 kb) variants. Here we show that genome assembly comparison is a robust approach for identification of all classes of genetic variation. Through comparison of two human assemblies (Celera's R27c compilation and the Build 35 reference sequence), we identified megabases of sequence (in the form of 13,534 putative non-SNP events) that were absent, inverted or polymorphic in one assembly. Database comparison and laboratory experimentation further demonstrated overlap or validation for 240 variable regions and confirmed >1.5 million SNPs. Some differences were simple insertions and deletions, but in regions containing CNVs, segmental duplication and repetitive DNA, they were more complex. Our results uncover substantial undescribed variation in humans, highlighting the need for comprehensive annotation strategies to fully interpret genome scanning and personalized sequencing projects.     

Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma

We performed exome sequencing to detect somatic mutations in protein-coding regions in seven melanoma cell lines and donor-matched germline cells. All melanoma samples had high numbers of somatic mutations, which showed the hallmark of UV-induced DNA repair. Such a hallmark was absent in tumor sample-specific mutations in two metastases derived from the same individual. Two melanomas with non-canonical BRAF mutations harbored gain-of-function MAP2K1 and MAP2K2 (MEK1 and MEK2, respectively) mutations, resulting in constitutive ERK phosphorylation and higher resistance to MEK inhibitors. Screening a larger cohort of individuals with melanoma revealed the presence of recurring somatic MAP2K1 and MAP2K2 mutations, which occurred at an overall frequency of 8%. Furthermore, missense and nonsense somatic mutations were frequently found in three candidate melanoma genes, FAT4, LRP1B and DSC1.     

Hindia sphaeroidalis Duncan from the Devonian of Nevada (Porifera)

The small, spherical, lithistid sponge, Hindia sphaeroidalis Duncan, 1879, is reported from the Devonian and Silurian of the Great Basin for the first time. Devonian specimens came from the Emsian Bartine Member of the McColley Formation from near Roberts Creek, Roberts Mountains, and from the Eifelian part of the Nevada Group near Bishops Creek, north of Wells, Nevada. The Silurian occurrence, questioned because of poor preservation, is from the Laketown Dolomite, on Tunnel Spring Mountain in western Millard County, Utah.     

Ultraconservation identifies a small subset of extremely constrained developmental enhancers

Extended perfect human-rodent sequence identity of at least 200 base pairs (ultraconservation) is potentially indicative of evolutionary or functional uniqueness. We used a transgenic mouse assay to compare the embryonic enhancer activity of 231 noncoding ultraconserved human genome regions with that of 206 extremely conserved regions lacking ultraconservation. Developmental enhancers were equally prevalent in both populations, suggesting instead that ultraconservation identifies a small, functionally indistinct subset of similarly constrained cis-regulatory elements.     

Dominating attitudes in the graph model for conflict resolution

A formal methodology for analyzing the importance of weighing a decision maker’s attitudes in a conflict is introduced and applied to the problem of negotiating a fair transfer of a brownfield property. A decision maker’s attitudes are expressed in his consideration of his own preferences,as well as those of his opponents.Dominating attitudes are used to suggest that in a circumstance in which a decision maker takes into account multiple perspectives due to his attitudes,he may favor one perspective more heavily.The analysis of a brownfield acquisition conflict illustrates the types of insights that this methodology reveals.     

Electrochemical characterization of the Pt /PEDOT electrode in DMFC

Poly-(3, 4-ethylenedioxythiophene) (PEDOT) was applied in making electrodes and gas diffusion layer for direct methanol fuel cells (DMFC). Electrochemical characterizations of Pt/PEDOT electrodes, made by two different methods, were investigated by cyclic voltammetry, methanol oxidation tests and DMFC performance. The platinum particle structure in PEDOT/PSS (poly?styrene sulfonic acid) films was investigated by SEM and TEM. Our research work showed that PEDOT influenced the catalytic activity behavior in three different ways when it was applied to the anode, cathode and the gas diffusion layer. The DMFC performance agreed with the cyclic voltammetry and methanol oxidation test results.     

Helminths of the southwestern toad, Bufo Microscaphus , Woodhouse's toad, Bufo woodhousii (Bufonidae), and their hybrids from central Arizona

The gastrointestinal tracts, lungs and urinary bladders from 77 Bufo microscaphus , 61 Bufo woodhousii , and 8 of their hybrids were examined for helminthes. One species of trematode ( Glypthelmins quieta ), 1 species of cestode ( Distoichometra bufonis ), and 5 species of nematodes ( Aplectana incerta, A. itzocanensis, Rhabdias americanus, Physaloptera sp., and Physocephalus sp.) were found. The greatest prevalence (41%) and mean intensity (231.7) were recorded for Aplectana incerta in Bufo woodhousii . It appears hybrids harbor fewer parasites than either parent species.     

Quantum encounters of the cold kind

Since the introduction of laser-cooling techniques for neutral atoms in the early 1980s, the study of collisional interactions between atoms and molecules has been extended to the regime of ultracold temperatures. With nanokelvin temperatures now attainable, our ability to probe the interactions, both experimentally and theoretically, has also progressed. Understanding of the subtle and often highly quantum-mechanical effects that are manifest at such low energies has advanced to the point where new precision measurements are matched by highly accurate theoretical calculations. Low-energy phenomena such as Bose-Einstein condensation and the photoassociation of atoms into bound molecules are now accurately described with no free parameters.     

Golgi biogenesis in Toxoplasma gondii

Two models have been put forward to explain the growth of new Golgi during the cell cycle. The first suggests that a new Golgi grows out of the endoplasmic reticulum by de novo synthesis. The second suggests that a pre-existing Golgi is needed for the growth of a new one, that is, the Golgi is an autonomously replicating organelle. To resolve this issue, we have exploited the simplicity of the apicomplexan parasite Toxoplasma gondii, which has only a single Golgi stack. Here we show, by using video fluorescence microscopy and three-dimensional reconstructions of serial thin sections, that the Golgi grows by a process of lateral extension followed by medial fission. Further fission leads to the inheritance by each daughter of a pair of Golgi structures, which then coalesce to re-form a single Golgi. Our results indicate that new Golgi grow by autonomous duplication and raise the possibility that the Golgi is a paired structure that is analogous to centrioles.