Rapid acquisition of long spatial sequences in long-term memory

Learning complex movement sequences requires an active, attentional selection of the content that is learned. The selection mechanism can not be investigated in classical stimulus-guided sequence learning paradigms because it requires a movement sequence production that is not triggered by external stimuli. In deferred imitation learning the whole stimulus sequence is presented and reproduction is started only after the presentation has ended. In order to investigate how the selective control of the learning process proceeds in natural learning situations and to investigate all influencing parameters we developed a new paradigm in which long sequences were learned by deferred imitation learning. In this task a long sequence of stimuli was presented on a graphic tablet and reproduced by manual pointing after the stimulus presentation was finished. Since the sequence exceeded the capacity of working memory because of its length it had to be reproduced and learned in several trials. Therefore, an attentional selection was required during learning. In our first study a method for evaluating reproduction performance in the new learning paradigm was developed. The assignment of reproductions to target positions posed a major methodological difficulty. This problem was solved by introducing an assignment algorithm that takes the order of reproduction into account. The algorithm was explained, it was further compared to an algorithm that performs a nearest neighbor assignment and finally validated by a comparison to a human operator assignment. The results showed that the assignment algorithm is an appropriate method for analyzing long sequences of pointing movements and is suitable for evaluating reproduction performance and learning progress in deferred imitation learning of long sequences. In the second study we investigated further how long sequences of pointing movements are acquired. Long-term retention tests showed that the sequences were retained for at least two weeks in long-term memory. A transfer test showed that the sequences were represented in an effector independent representation. The distributions of pointing positions were analyzed in detail in order to characterize the control signal of the pointing movements. The analysis showed that position errors to successive target positions were not dependent on the movement direction and further, that directional error did not propagate to reproductions of successive target positions. These results suggest that end points rather than movement trajectories are memorized in this learning task. Our third study evaluated the organization and reorganization of the sequence representation in memory. The change in sequence reproduction without intermediate presentations showed that the remembered target positions drifted away from the initial representation, where the target drift saturated after about 5 trials. The analysis of the drift direction of representations of single target positions showed that there was no systematic drift direction for single subjects. Further it indicated that the representation did not drift to similar, but to different patterns across subjects. In order to investigate whether sequences are encoded in chunks or as single target positions we performed an experiment in which two target positions in a well learned sequence were exchanged. We analyzed the effect of the target exchange on target positions neighboring the exchanged target position. The target exchange effected neither the position nor the variance of neighboring memorized target positions. These results support the view that single target positions rather than chunks of target positions are memorized. Thus our study suggests that the sequence acquisition is guided by an active selection process which is able to quickly acquire abstract movement plans. Our findings further support the view that these movement plans are represented as strings of independent, absolute target positions

Aggregation of Single Nucleotide Polymorphisms in a Human H5N1 Clade 2.2 Hemagglutinin

The rapid evolution of the H5N1 serotype of avian influenza has been explained by a mechanism involving the selection of single nucleotide polymorphisms generated by copy errors. The recent emergence of H5N1 Clade 2.2 in fifty countries, offered a unique opportunity to view the acquisition of new polymorphism in these evolving genomes. We analyzed the H5N1 hemagglutinin gene from a fatal human case from Nigeria in 2007. The newly emerged polymorphisms were present in diverse H5N1 isolates from the previous year. The aggregation of these polymorphisms from clade 2.2 sub-clades was not supported by recent random mutations, and was most easily explained by recombination between closely related sequences

Metabolite Mapping with Extended Brain Coverage Using a Fast Multisection MRSI Pulse Sequence and a Multichannel Coil

Multisection magnetic resonance spectroscopic imaging is a widely used pulse sequence that has distinct advantages over other spectroscopic imaging sequences, such as dynamic shimming, large region-of-interest coverage within slices, and rapid data acquisition. It has limitations, however, in the number of slices that can be acquired in realistic scan times and information loss from spacing between slices. In this paper, we synergize the multi-section spectroscopic imaging pulse sequence with multichannel coil technology to overcome these limitations. These combined techniques now permit elimination of the gaps between slices and acquisition of a larger number of slices to realize the whole brain metabolite mapping without incurring the penalties of longer repetition times (and therefore longer acquisition times) or lower signal-to-noise ratios

The emergence and fate of horizontally acquired genes in Escherichia coli

Bacterial species, and even strains within species, can vary greatly in their gene contents and metabolic capabilities. We examine the evolution of this diversity by assessing the distribution and ancestry of each gene in 13 sequenced isolates of Escherichia coli and Shigella. We focus on the emergence and demise of two specific classes of genes, ORFans (genes with no homologs in present databases) and HOPs (genes with distant homologs), since these genes, in contrast to most conserved ancestral sequences, are known to be a major source of the novel features in each strain. We find that the rates of gain and loss of these genes vary greatly among strains as well as through time, and that ORFans and HOPs show very different behavior with respect to their emergence and demise. Although HOPs, which mostly represent gene acquisitions from other bacteria, originate more frequently, ORFans are much more likely to persist. This difference suggests that many adaptive traits are conferred by completely novel genes that do not originate in other bacterial genomes. With respect to the demise of these acquired genes, we find that strains of Shigella lose genes, both by disruption events and by complete removal, at accelerated rates

MRI-only based radiotherapy treatment planning for the rat brain on a Small Animal Radiation Research Platform (SARRP)

Computed tomography (CT) is the standard imaging modality in radiation therapy treatment planning (RTP). However, magnetic resonance (MR) imaging provides superior soft tissue contrast, increasing the precision of target volume selection. We present MR-only based RTP for a rat brain on a small animal radiation research platform (SARRP) using probabilistic voxel classification with multiple MR sequences. Six rat heads were imaged, each with one CT and five MR sequences. The MR sequences were: T1-weighted, T2-weighted, zero-echo time (ZTE), and two ultra-short echo time sequences with 20 mu s (UTE1) and 2 ms (UTE2) echo times. CT data were manually segmented into air, soft tissue, and bone to obtain the RTP reference. Bias field corrected MR images were automatically segmented into the same tissue classes using a fuzzy c-means segmentation algorithm with multiple images as input. Similarities between segmented CT and automatic segmented MR (ASMR) images were evaluated using Dice coefficient. Three ASMR images with high similarity index were used for further RTP. Three beam arrangements were investigated. Dose distributions were compared by analysing dose volume histograms. The highest Dice coefficients were obtained for the ZTE-UTE2 combination and for the T1-UTE1-T2 combination when ZTE was unavailable. Both combinations, along with UTE1-UTE2, often used to generate ASMR images, were used for further RTP. Using 1 beam, MR based RTP underestimated the dose to be delivered to the target (range: 1.4%-7.6%). When more complex beam configurations were used, the calculated dose using the ZTE-UTE2 combination was the most accurate, with 0.7% deviation from CT, compared to 0.8% for T1-UTE1-T2 and 1.7% for UTE1-UTE2. The presented MR-only based workflow for RTP on a SARRP enables both accurate organ delineation and dose calculations using multiple MR sequences. This method can be useful in longitudinal studies where CT's cumulative radiation dose might contribute to the total dose

How the other half lives: CRISPR-Cas's influence on bacteriophages

CRISPR-Cas is a genetic adaptive immune system unique to prokaryotic cells used to combat phage and plasmid threats. The host cell adapts by incorporating DNA sequences from invading phages or plasmids into its CRISPR locus as spacers. These spacers are expressed as mobile surveillance RNAs that direct CRISPR-associated (Cas) proteins to protect against subsequent attack by the same phages or plasmids. The threat from mobile genetic elements inevitably shapes the CRISPR loci of archaea and bacteria, and simultaneously the CRISPR-Cas immune system drives evolution of these invaders. Here we highlight our recent work, as well as that of others, that seeks to understand phage mechanisms of CRISPR-Cas evasion and conditions for population coexistence of phages with CRISPR-protected prokaryotes.Comment: 24 pages, 8 figure