Genetic maps of the proximal half of chromosome arm 2L of Drosophila melanogaster

Drosophila mutants have played an important role in elucidating the physiologic function of genes. Large-scale projects have succeeded in producing mutations in a large proportion of Drosophila genes. Many mutant fly lines have also been produced through the efforts of individual laboratories over the past century. In an effort to make some of these mutants more useful to the research community, we systematically mapped a large number of mutations affecting genes in the proximal half of chromosome arm 2L to more precisely defined regions, defined by deficiency intervals, and, when possible, by individual complementation groups. To further analyze regions 36 and 39-40, we produced 11 new deficiencies with gamma irradiation, and we constructed 6 new deficiencies in region 30-33, using the DrosDel system. trans-heterozygous combinations of deficiencies revealed 5 additional functions, essential for viability or fertility.

UPLC-ESI-TOFMS-based metabolomics and gene expression dynamics inspector self-organizing metabolomic maps as tools for understanding the cellular response to ionizing radiation

Global transcriptomic and proteomic profiling platforms have yielded important insights into the complex response to ionizing radiation (IR). Nonetheless, little is known about the ways in which small cellular metabolite concentrations change in response to IR. Here, a metabolomics approach using ultraperformance liquid chromatography coupled with electrospray time-of-flight mass spectrometry was used to profile, over time, the hydrophilic metabolome of TK6 cells exposed to IR doses ranging from 0.5 to 8.0 Gy. Multivariate data analysis of the positive ions revealed dose- and time-dependent clustering of the irradiated cells and identified certain constituents of the water-soluble metabolome as being significantly depleted as early as 1 h after IR. Tandem mass spectrometry was used to confirm metabolite identity. Many of the depleted metabolites are associated with oxidative stress and DNA repair pathways. Included are reduced glutathione, adenosine monophosphate, nicotinamide adenine dinucleotide, and spermine. Similar measurements were performed with a transformed fibroblast cell line, BJ, and it was found that a subset of the identified TK6 metabolites were effective in IR dose discrimination. The GEDI (Gene Expression Dynamics Inspector) algorithm, which is based on self-organizing maps, was used to visualize dynamic global changes in the TK6 metabolome that resulted from IR. It revealed dose-dependent clustering of ions sharing the same trends in concentration change across radiation doses. "Radiation metabolomics," the application of metabolomic analysis to the field of radiobiology, promises to increase our understanding of cellular responses to stressors such as radiation.

Scalp field maps and their characterization

The present chapter gives a comprehensive introduction into the display and quantitative characterization of scalp field data. After introducing the construction of scalp field maps, different interpolation methods, the effect of the recording reference and the computation of spatial derivatives are discussed. The arguments raised in this first part have important implications for resolving a potential ambiguity in the interpretation of differences of scalp field data. In the second part of the chapter different approaches for comparing scalp field data are described. All of these comparisons can be interpreted in terms of differences of intracerebral sources either in strength, or in location and orientation in a nonambiguous way. In the present chapter we only refer to scalp field potentials, but mapping also can be used to display other features, such as power or statistical values. However, the rules for comparing and interpreting scalp field potentials might not apply to such data. Generic form of scalp field data Electroencephalogram (EEG) and event-related potential (ERP) recordings consist of one value for each sample in time and for each electrode. The recorded EEG and ERP data thus represent a two-dimensional array, with one dimension corresponding to the variable “time” and the other dimension corresponding to the variable “space” or electrode. Table 2.1 shows ERP measurements over a brief time period. The ERP data (averaged over a group of healthy subjects) were recorded with 19 electrodes during a visual paradigm. The parietal midline Pz electrode has been used as the reference electrode.

Consistent Layout for Thematic Software Maps

Software visualizations can provide a concise overview of a complex software system. Unfortunately, since software has no physical shape, there is no “natural“ mapping of software to a two-dimensional space. As a consequence most visualizations tend to use a layout in which position and distance have no meaning, and consequently layout typical diverges from one visualization to another. We propose a consistent layout for software maps in which the position of a software artifact reflects its \emph{vocabulary}, and distance corresponds to similarity of vocabulary. We use Latent Semantic Indexing (LSI) to map software artifacts to a vector space, and then use Multidimensional Scaling (MDS) to map this vector space down to two dimensions. The resulting consistent layout allows us to develop a variety of thematic software maps that express very different aspects of software while making it easy to compare them. The approach is especially suitable for comparing views of evolving software, since the vocabulary of software artifacts tends to be stable over time.

The bovine dilated cardiomyopathy locus maps to a 1.0-Mb interval on chromosome 18

Cardiomyopathies are myocardial diseases that lead to cardiac dysfunction, heart failure, arrhythmia, and sudden death. In human medicine, cardiomyopathies frequently warrant heart transplantation in children and adults. Bovine dilated cardiomyopathy (BDCMP) is a heart muscle disorder that has been observed during the last 30 years in cattle of Holstein-Friesian origin. In Switzerland BDCMP affects Swiss Fleckvieh and Red Holstein breeds. BDCMP is characterized by a cardiac enlargement with ventricular remodeling and chamber dilatation. The common symptoms in affected animals are subacute subcutaneous edema, congestion of the jugular veins, and tachycardia with gallop rhythm. A cardiomegaly with dilatation and hypertrophy of all heart chambers, myocardial degeneration, and fibrosis are typical postmortem findings. It was shown that all BDCMP cases reported worldwide traced back to a red factor-carrying Holstein-Friesian bull, ABC Reflection Sovereign. An autosomal recessive mode of inheritance was proposed for BDCMP. Recently, the disease locus was mapped to a 6.7-Mb interval MSBDCMP06-BMS2785 on bovine Chr 18 (BTA18). In the present study the BDCMP locus was fine mapped by using a combined strategy of homozygosity mapping and association study. A BAC contig of 2.9 Mb encompassing the crucial interval was constructed to establish the correct marker order on BTA18. We show that the disease locus is located in a gene-rich interval of 1.0 Mb and is flanked by the microsatellite markers DIK3006 and MSBDCMP51.

Arachnomelia in Brown Swiss cattle maps to chromosome 5

Arachnomelia in Brown Swiss cattle is a monogenic autosomal recessive inherited congenital disorder of the skeletal system giving affected calves a spidery look (OMIA ID 000059). Over a period of 20 years 15 cases were sampled in the Swiss and Italian Brown cattle population. Pedigree data revealed that all affected individuals trace back to a single acknowledged carrier founder sire. A genome scan using 240 microsatellites spanning the 29 bovine autosomes showed homozygosity at three adjacent microsatellite markers on bovine Chr 5 in all cases. Linkage analysis confirmed the localization of the arachnomelia mutation in the region of the marker ETH10. Fine-mapping and haplotype analysis using a total of 34 markers in this region refined the critical region of the arachnomelia locus to a 7.19-Mb interval on bovine Chr 5. The disease-associated IBD haplotype was shared by 36 proven carrier animals and allows marker-assisted selection. As the corresponding human and mouse chromosome segments do not contain any clear functional candidate genes for this disorder, the mutation causing arachnomelia in the Brown Swiss cattle might help to identify an unknown gene in bone development.

Microstates in language-related brain potential maps show noun-verb differences

Brain processing of grammatical word class was studied analyzing event-related potential (ERP) brain fields. Normal subjects observed a randomized sequence of single German nouns and verbs on a computer screen, while 20-channel ERP field map series were recorded separately for both word classes. Spatial microstate analysis was applied, based on the observation that series of ERP maps consist of epochs of quasi-stable map landscapes and based on the rationale that different map landscapes must have been generated by different neural generators and thus suggest different brain functions. Space-oriented segmentation of the mean map series identified nine successive, different functional microstates, i.e., steps of brain information processing characterized by quasi-stable map landscapes. In the microstate from 116 to 172 msec, noun-related maps differed significantly from verb-related maps along the left–right axis. The results indicate that different neural populations represent different grammatical word classes in language processing, in agreement with clinical observations. This word class differentiation as revealed by the spatial–temporal organization of neural activity occurred at a time after word input compatible with speed of reading.

Prestimulus EEG microstates influence visual event-related potential microstates in field maps with 47 channels

The influence of the immediate prestimulus EEG microstate (sub-second epoch of stable topography/map landscape) on the map landscape of visually evoked 47-channel event-related potential (ERP) microstates was examined using the frequent, non-target stimuli of a cognitive paradigm (12 volunteers). For the two most frequent prestimulus microstate classes (oriented left anterior-right posterior and right anterior-left posterior), ERP map series were selectively averaged. The post-stimulus ERP grand average map series was segmented into microstates; 10 were found. The centroid locations of positive and negative map areas were extracted as landscape descriptors. Significant differences (MANOVAs and t-tests) between the two prestimulus classes were found in four of the ten ERP microstates. The relative orientation of the two ERP microstate classes was the same as prestimulus in some ERP microstates, but reversed in others. — Thus, brain electric microstates at stimulus arrival influence the landscapes of the post-stimulus ERP maps and therefore, information processing; prestimulus microstate effects differed for different post-stimulus ERP microstates.

Space–oriented EEG segmentation reveals changes in brain electric–field maps under the influence of a nootropic drug

Map landscape-based segmentation of the sequences of momentary potential distribution maps (42-channel recordings) into brain microstates during spontaneous brain activity was used to study brain electric field spatial effects of single doses of piracetam (2.9, 4.8, and 9.6 g Nootropil® UCB and placebo) in a double-blind study of five normal young volunteers. Four 15-second epochs were analyzed from each subject and drug condition. The most prominent class of microstates (covering 49% of the time) consisted of potential maps with a generally anterior-posterior field orientation. The map orientation of this microstate class showed an increasing clockwise deviation from the placebo condition with increasing drug doses (Fisher's probability product, p < 0.014). The results of this study suggest the use of microstate segmentation analysis for the assessment of central effects of medication in spontaneous multichannel electroencephalographic data, as a complementary approach to frequency-domain analysis.

MQN-Mapplet: Visualization of Chemical Space with Interactive Maps of DrugBank, ChEMBL, PubChem, GDB-11, and GDB-13

The MQN-mapplet is a Java application giving access to the structure of small molecules in large databases via color-coded maps of their chemical space. These maps are projections from a 42-dimensional property space defined by 42 integer value descriptors called molecular quantum numbers (MQN), which count different categories of atoms, bonds, polar groups, and topological features and categorize molecules by size, rigidity, and polarity. Despite its simplicity, MQN-space is relevant to biological activities. The MQN-mapplet allows localization of any molecule on the color-coded images, visualization of the molecules, and identification of analogs as neighbors on the MQN-map or in the original 42-dimensional MQN-space. No query molecule is necessary to start the exploration, which may be particularly attractive for nonchemists. To our knowledge, this type of interactive exploration tool is unprecedented for very large databases such as PubChem and GDB-13 (almost one billion molecules). The application is freely available for download at www.gdb.unibe.ch.