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Mapping the gene for sex-linked anemia: an inherited defect of intestinal iron absorption in the mouse.

The sex-linked anemic (sla) mouse carries an anemia that results from an inherited defect of intestinal iron absorption and provides an ideal model with which to investigate this poorly understood yet clinically important process. We have precisely mapped the sla locus within the central region of the X chromosome in relation to a panel of microsatellite markers. Analysis of over 500 progeny from an intraspecific intercross and a smaller intraspecific backcross segregating sla established the following locus order in the sla region: DXMit45-sla- (DXMit16, DXMit96)-DXMit41-DXMit169-DXMit170- DXMit148-(DXMit18, DXMit171)-DXMit84-DXMit64. The two microsatellites DXMit16 and DXMit96 are located 0.60 +/- 0.35cM from sla and form the telomeric limit of the sla region. The mapping of the sla locus is an important first step to identifying the gene itself.

Anemia, Iron-Deficiency↗

Transcriptional analysis of Bacillus subtilis rRNA-tRNA operons. I. The tRNA gene cluster of rrnB has an internal promoter.

Although the sequence and organization of many Bacillus subtilis tRNA genes are known, primary transcripts from these regions have not been previously analyzed. In this paper, S1 nuclease mapping, S1-type mapping, and Northern analyses were applied to the end of the 23 S rRNA, the 5 S rRNA, and the 21 tRNA genes of B. subtilis operon rrnB. Primary transcripts from the 5 S rRNA and tRNA genes up to approximately 600-800 nucleotides long were observed with S1-type mapping. The presence of discrete bands of processing intermediates indicated preferred processing points within the initial transcript. S1 nuclease mapping delineated a start point for transcription between the second and third tRNA genes. The -10 sequence was within the 37-base pair spacer region between tRNA genes, and the -35 sequence was within the structural gene for the upstream tRNA. Precursors from this region were evident during midexponential growth and two sporulation stages. Thus, in addition to promotion from the rRNA promoters, 19 of the 21 downstream tRNA genes are also under the control of an internal tRNA gene promoter. The accompanying paper (Vold, B. S., Green, C. J., Narasimhan, N., Strem, M., and Hansen, J. N. (1988) J. Biol. Chem. 263, 14485-14490) investigates the minor 5 S rRNA and 16 tRNA genes of another rRNA-tRNA gene set and emphasizes unique promoter elements in that system as well as a potentially unique rRNA processing scheme.

Base Sequence↗

Reorganization of microtubular cytoskeleton and formation of cellular processes during post-telophase in haemanthus endosperm.

We followed time-dependent post-telophase reorganization of the microtubule cytoskeleton on immunostained preparations of endosperm of the higher plant Haemanthus. After completion of mitosis, the phragmoplast continued to reorganize for several hours. This prompted the formation of phragmoplast-like derivatives (secondary and accessory phragmoplasts and peripheral microtubular ring). Next, elongated cellular protrusions (processes) appeared at the cell periphery. These processes contained long microtubule bundles and disorderly arranged actin filaments. Microtubule converging centers or accessory phragmoplasts were often present at the tips of the processes. Observation in vivo demonstrated that processes were formed at the cell periphery as extensions of lammelipodia or filopodia-type protrusions that commonly terminated with cytoplasmic blobs. We suggest that processes are derivatives of a peripheral microtubular ring that reorganizes gradually into cellular protrusions. Endosperm processes have several features of neuronal cells, or animal somatic cells with overexpressed MAPs. Since microtubule-containing processes were never detected shortly after extrusion of the cells from the embryo sac, this course of events might be restricted specifically to extruded endosperm and triggered either by removal of cells, their placement in monolayer on agar substrate, or both. Thus, post telophase behavior of endosperm cells offers a novel experimental system for studies of cytoskeleton in higher plants.

Actin Cytoskeleton↗

A proposed hierarchical fuzzy inference system for the diagnosis of arthritic diseases.

Development of computer-based medical inference systems is always confronted with some difficulties. In this paper, difficulties of designing an inference system for the diagnosis of arthritic diseases are described, including variations of disease manifestations under various situations and conditions. Furthermore, the need for a huge knowledge base would result in low efficiency of the inference system. We proposed a hierarchical model of the fuzzy inference system as a possible solution. With such a model, the diagnostic process is divided into two levels. The first level of the diagnosis reduces the scope of diagnosis to be processed by the second level. This will reduce the amount of input and mapping for the whole diagnostic process. Fuzzy relational theory is the core of this system and it is used in both levels to improve the accuracy.

Algorithms↗

Overexpression of the 77-kD echinoderm microtubule-associated protein (EMAP), a WD-40 repeat protein, in baculovirus-infected Sf9 cells.

The purpose of this study was to test whether any assembly-promoting microtubule-associated protein (MAP) would bundle microtubules and induce process formation in recombinant baculovirus-infected Sf9 cells, in particular, whether a non-neural MAP from a normally rounded cell would produce cellular asymmetries. To carry out these experiments, we constructed a recombinant baculovirus that expressed the full-length 77-kD EMAP, an abundant MAP that localizes to the mitotic spindle of cleavage-stage sea urchin embryos and to the interphase array of microtubules in adult coelomocytes. Expression of EMAP in Sf9 cells had no detectable effect on cellular morphology, microtubule organization, or stability. These results indicate that process formation in Sf9 cells is MAP specific.

Animals↗

Molecular characterization of the Anopheles gambiae 2L telomeric region via an integrated transgene.

A Drosophila P-element derivative (pUChsneo) integrated into the telomeric region of the left arm of the second chromosome of Anopheles gambiae was used to clone the proximally flanking An. gambiae sequences. Molecular analyses revealed that the pUChsneo construct was partially duplicated and had integrated into a subterminal minisatellite. This satellite has a repeat unit of 820 bp and is located exclusively at the tip of 2L. No sequence similarity to subterminal minisatellites from other dipterans was detected, but some structural features such as tandem subrepeats are shared. The end of the chromosome was mapped with respect to restriction sites in pUChsneo at approximately generation 100 after the integration event. Considering inevitable terminal nucleotide loss due to incomplete DNA replication, we conclude that the chromosome end must have undergone a dramatic elongation process since it was mapped in generation 23.

Animals↗

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 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 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.

Adult↗

Fast Fourier transform-based correlation of DNA sequences using complex plane encoding.

The detection of similarities between DNA sequences can be accomplished using the signal-processing technique of cross-correlation. An early method used the fast Fourier transform (FFT) to perform correlations on DNA sequences in O(n log n) time for any length sequence. However, this method requires many FFTs (nine), runs no faster if one sequence is much shorter than the other, and measures only global similarity, so that significant short local matches may be missed. We report that, through the use of alternative encodings of the DNA sequence in the complex plane, the number of FFTs performed can be traded off against (i) signal-to-noise ratio, and (ii) a certain degree of filtering for local similarity via k-tuple correlation. Also, when comparing probe sequences against much longer targets, the algorithm can be sped up by decomposing the target and performing multiple small FFTs in an overlap-save arrangement. Finally, by decomposing the probe sequence as well, the detection of local similarities can be further enhanced. With current advances in extremely fast hardware implementations of signal-processing operations, this approach may prove more practical than heretofore.

Algorithms↗

[Evaluation of hemodynamic changes in inflammatory hyperplastic processes in the thyroid gland with the aid of ultrasound color mapping].

Ultrasound dopplerography techniques constitute an investigation of highly informative value, designed to study vascularization of pathological states of the thyroid gland. It permits the most effective and comprehensive evaluation of the organ circulation along the periphery of the capsule, in the parenchyma, in all pathological formations. This warrants the use of the method in diagnosing, in identification of the process dissemination beyond the organ into the surrounding tissues or regional lymph nodes. Colour Doppler-mapping of the thyroid gland is a highly sensitive method of investigation of neovascularization of the organ which comes to be changed in cancer depending on the stage of the process.

Adolescent↗

Growing applications and advancements in microarray technology and analysis tools.

In today's field of genomics, traditional gene-by-gene approach is not adequate to meet the demand of processing information generated from mapping the complex biology of the human genome. More global views of analyzing the magnitude of information are necessary, such as with microarrays. Microarray technology today is rapidly uncovering broad patterns of genetic activity and showing insight into gene functions, processes, and pathways. With the growing technology, imminent knowledge is being generated looking into transcriptional processes and biological mechanisms from many different organisms and phylogeny. Many tools are being developed to assist with the analysis of such high-throughput data, many applications are being utilized by this technology, and the field is growing and expanding rapidly to accommodate the expanding genomics era.

Algorithms↗

Computer verification of fluence map for intensity modulated radiation therapy.

In a treatment planning system for intensity modulated radiation therapy (IMRT), the time sequence of multileaf collimator (MLC) settings are derived from an optimal fluence map as a postoptimization process using a software module called a "leaf sequencer." The dosimetric accuracy of the dynamic delivery depends on the functionality of the module and it is important to verify independently the correctness of the leaf sequences for each field of a patient treatment. This verification is unique to the IMRT treatment and has been done using radiographic film, electronic portal imaging device (EPID) or electronic imaging system (BIS). The measurement tests both the leaf sequencer and the dynamic multileaf collimator (MLC) delivery system, providing a reliable assurance of clinical IMRT treatment. However, this process is labor intensive and time consuming. In this paper, we propose to separate quality assurance (QA) of the leaf sequencer from the dynamic MLC delivery system. We describe a simple computer algorithm for the verification of the leaf sequences. The software reads in the leaf sequences and simulates the motion of the MLC leaves. The generated fluence map is then compared quantitatively with the reference map from the treatment planning system. A set of pre-defined QA indices is introduced to measure the "closeness" between the computed and the reference maps. The approach has been used to validate the CORVUS (NOMOS Co., Sewickley, PA) treatment plans. The results indicate that the proposed approach is robust and suitable to support the complex IMRT QA process.

Algorithms↗

Mapping neural interactivity onto regional activity: an analysis of semantic processing and response mode interactions.

Neuroimaging studies of cognition have typically been designed to identify brain regions that are active during a cognitive process. However, identifying how brain regions interact may be equally important. In a recent study we found that the pattern of activation associated with a semantic task differed depending on how subjects made a response, suggesting that there was an interaction between the neural systems underlying response mode and semantic processing (J. M. Jennings et al., 1997, NeuroImage 5, 229-239). This result raises two important questions, which we examined here: (1) How did the regions underlying semantic performance influence one another, or interact, to produce a different pattern of activation in each case? (2) What can be learned about the neurobiology of semantic processing when different regions are identified as a function of response? We addressed these questions using structural equation modeling. This technique produced functional network models representing the effect of different regions on each other during the semantic task for each response. A common network of regions associated with semantic processing was observed and included the left inferior frontal and left superior temporal cortices, with other regions brought into that network depending on response (e.g., right middle frontal). Moreover, changes in the influences among these regions across response condition predicted the pattern of activation found previously. These results show how an arbitrary response can affect the neural pathways associated with a cognitive process, likely due to the parallel and reentrant organization of the brain, and emphasize the importance of examining functional connections when studying cognition.

Adult↗

Pragmatics in analogical mapping.

Theories of analogical reasoning differ in the roles they ascribe to pragmatic factors as a source of constraints on analogical mappings. The multiconstraint theory as instantiated in the ACME model (Holyoak & Thagard, 1989a) claims that pragmatic constraints interact with structural and semantic constraints within the mapping stage itself, in addition to influencing pre-mapping and post-mapping stages. Participants in three experiments were asked to generate mappings between non-isomorphic analogs for which mappings for some elements were ambiguous on structural grounds. In all experiments, manipulations of participants' processing goals influenced their preferred mappings. At the same time, goal-irrelevant information contributed to many-to-one mappings (Experiments 1 and 2) and to the resolution of mappings that were ambiguous on the basis of goal-relevant information alone (Experiment 3). The qualitative pattern of results was successfully simulated using the ACME model, implementing the impact of processing goals as an inhibitory process of selective attention.

Association↗

A 13-A map of the actin-scruin filament from the limulus acrosomal process.

We have determined the structure of the actin-scruin filament to 13-A resolution using a combination of low-dose EM and image analysis. The three-dimensional map reveals four actin-actin contacts: two within each strand and two between strands. The conformation of the actin subunit is different from that in the Holmes et al. (1990) model as refined by Lorenz et al. (1993). In particular, subdomain II is tilted in a similar way to that seen by Orlova and Egelman (1993) in F-Mg2(+)-ADP actin filaments in the absence of Ca2+. Scruin appears to consist of two domains of approximately equal volume. Each scruin subunit cross-links the two strands in the actin filament. Domain I of scruin contacts subdomain I of actin and makes a second contact at the junction of subdomains III and IV. Domain II of scruin contacts actin at subdomains I and II of a neighboring actin subunit. The two scruin domains thus bind differently to actin.

Acrosome↗

Significance probability mapping: the final touch in t-statistic mapping.

Significance Probability Mapping (SPM), based on Student's t-statistic, is widely used for comparing mean brain topography maps of two groups. The map resulting from this process represents the distribution of t-values over the entire scalp. However, t-values by themselves cannot reveal whether or not group differences are significant. Significance levels associated with a few t-values are therefore commonly indicated on map legends to give the reader an idea of the significance levels of t-values. Nevertheless, a precise significance level topography cannot be achieved with these few significance values. We introduce a new kind of map which directly displays significance level topography in order to relieve the reader from converting multiple t-values to their corresponding significance probabilities, and to obtain a good quantification and a better localization of regions with significant differences between groups. As an illustration of this type of map, we present a comparison of EEG activity in Alzheimer's patients and age-matched control subjects for both wakefulness and REM sleep.

Aged↗

The temporal dynamics of tics in Gilles de la Tourette syndrome.

BACKGROUND: Statistical characterization of tic behavior in Gilles de la Tourette syndrome (GTS) may provide insight into the dynamic functioning of the human central nervous system, as well as improve the quantitative assessment of tic symptom severity. METHODS: Twenty-two medication-free GTS subjects underwent videotaping of their tics. The intervals between temporally adjacent tics were measured, and the statistical properties of these intervals were assessed through graphical representation of frequency distributions, autoregressive integrated moving average (ARIMA) modeling, spectral analysis, and construction of first return maps. RESULTS: The frequency distribution of tic interval durations followed an inverse power law of temporal scaling. Spectral analyses similarly demonstrated that the spectral power density of tic interval duration scales inversely with frequency. ARIMA modeling suggested that the time series for tics are nonstationary as well as moving average processes. The first return maps demonstrated "burstlike" behavior and short-term periodicity in tics, and proved that successive tic intervals are not statistically independent. Graphic display of the time series confirmed shortterm periodicity, and in addition suggested the presence of period doubling. CONCLUSIONS: These findings are suggestive though not conclusive evidence for the presence of a fractal, deterministic, and possibly chaotic process in the tic time series. These analytic methods provide insight into the temporal features of tics that commonly are described clinically (such as short-term bouts or bursting, and longer term waxing and waning), and they reveal certain important temporal features of tics that have not been clinically described. The methods may also prove useful in the improved characterization of tic symptom severity.

Adolescent↗

Neural processing of illusory and real contours revealed by high-density ERP mapping.

Event-related potential (ERP) studies have shown that responses to illusory (IC), as compared to no contours (NC), may differ within 200 ms following stimulus presentation. However, whether these responses reflect the modulation of similar, or the activation of distinct brain regions has never been assessed. Using ERP map series and source localisation analyses, we compared early responses (0-200 ms) to IC and NC, as well as to real contours (RC). Although IC displayed higher field strength during the N1 component, topo-graphical analyses showed a similar sequence of stable field configurations in all conditions. Source localisation applied to the N1 map revealed bilateral activation of lateral-occipital regions. These results suggest that both IC and RC processing modulate a common network associated with filling-in processes and figure-ground segregation.

Adult↗

Human auditory event-related processes in the time-frequency plane.

Sensory stimuli produce phase-locked and non-phase-locked changes in brain activity as indexed by EEG and MEG. Time-frequency methods such as wavelets, when carefully applied, allow simultaneous analysis of both types of activity. Here we used wavelets of different time and frequency resolutions in combination with spatial mapping to identify these processes. We found that auditory stimulation leads to a pattern of large-magnitude power increases and small-magnitude power decreases. The power increases, ranging from the theta to the beta frequency band, were accounted for by the transient auditory responses P50m, N100m and P200m. Following these responses, we observed a power reduction of non-phase-locked activity which occurred 250-500 ms after stimulus onset in the 14-24 Hz frequency range and could be localized to the temporal and parietal brain areas. These results indicate that auditory event-related processes consist not only of the well-established transient responses but also of power reductions of ongoing, non-phase-locked brain processes.

Acoustic Stimulation↗