Biology subjects

Kaplan, A.

Publications and source records attributed to Kaplan, A..

26 records · Page 2Linked to original sources

bioRxiv2020

Difference in somatosensory event-related potentials in the blind subjects leads to better performance in tactile P300 BCI

In this study, we have created an 8-command P300 tactile BCI with two stimuli types, running on a minimally modified consumer Braille display and tested it on 10 blind subjects and 10 sighted controls. Blind subjects have demonstrated 27% higher median accuracy than sighted controls (p < 0.05), proving that the blind subjects are not only able to use tactile BCI but also can achieve superior results in comparison with sighted subjects. Median accuracy in the blind group with the best stimuli type has reached 95%. The difference in event-related potentials between groups is located in frontocentral sites before 300 ms post-stimulus and corresponds with early cognitive ERP components. The blind subjects have higher amplitude and lower latency of ERPs. This result is consistent through experimental conditions with different tactile stimuli. The classification performance for the blind subjects is correlated with Braille reading speed. This enables a discussion about mechanisms of plastic changes during sensory compensation after vision loss and its dependence on personal perceptual experience. Author summarySensory compensation following vision loss can be recognized as a unique model for neural plasticity. However, the magnitude of the effect and the specific tasks where its manifested is still a subject for debate. In this study, we have created a tactile brain-computer interface game to study how somatosensory processing is different between the blind and the sighted people. The participants were required to attend to tactile stimuli, and the correct stimulus was selected using realtime EEG classification. We have shown, for the first time, that the blind subjects are significantly better than the sighted in tactile brain-computer interface tasks. We have also found, that individual performance is correlated with Braille proficiency. This result links personal perceptual abilities in two different sensory tasks. EEG analysis revealed that differences in performance can be attributed to early cognitive processing steps. Along with practical considerations in brain-computer interface development, the results also add to the data on cognitive processing in the blind and enable the discussion on the importance of Braille education.

neuroscience↗

bioRxiv2018

White matter microstructure in women with acute and remitted anorexia nervosa: an exploratory neuroimaging study

Anorexia nervosa (AN) is a highly heritable psychiatric disorder characterized by starvation and emaciation and associated with changes in brain structure. The precise nature of these changes remains unclear, as does their developmental time course and capacity for reversal with weight restoration. In this exploratory neuroimaging study, we sought to characterize changes in white matter microstructure in women with acute and remitted AN. Diffusion-weighted MRI data was collected from underweight women with a current diagnosis of AN (acAN: n=23), weight-recovered women with a past diagnosis of AN (recAN: n=23), and age-matched healthy control women (HC: n=24). Image processing and analysis were performed with Tract-Based Spatial Statistics, part of FSL, and group differences in voxel-wise, brain-wide fractional anisotropy (FA) and mean diffusivity (MD), indices of white matter microstructure, were tested with nonparametric permutation and threshold free cluster enhancement. No significant main effect of group on FA was identified. A significant main effect of group on MD was observed in a large cluster covering 9.2% of white matter and including substantial portions of the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus, and post hoc analyses revealed similar effects of group on axial diffusivity (AD) and radial diffusivity (RD). Cluster-wise MD was significantly higher in acAN participants (+3.8%) and recAN participants (+2.9%) than healthy controls, and the same was true for cluster-wise AD and RD. Trait-based increases in diffusivity, consistent with atypical myelination and impaired axon integrity, suggest a link between altered white matter microstructure and vulnerability to AN, and evidence of reduced oligodendrocyte density in AN provides further support for this hypothesis. Potential mechanisms of action include atypical neurodevelopment and systemic inflammation.

neuroscience↗

bioRxiv2018

Neuroanatomical correlates of temperament and cognitive function in women with and without anorexia nervosa

Brain-behavior relationships that could provide insight into risk-associated pathophysiology have not been thoroughly assessed in anorexia nervosa (AN). Therefore, we sought to identify grey and white matter signatures of AN symptoms and risk factors (trait anxiety, set-shifting impairment) in a sample enriched for AN vulnerability, including acute and remitted AN patients and their unaffected sisters (n = 72, aged 18 - 48 years). MRI/DTI data were acquired on a 3T scanner and processed with Freesurfer and FSL TBSS. Relationships between clinical variables of interest and regional subcortical volume, vertex-wise cortical surface architecture (thickness, surface area, local gyrification), and voxel-wise white matter microstructure (FA, MD) were tested with separate linear regressions, including age, BMI, lifetime AN diagnosis, and intracranial volume as covariates, where appropriate. Significance was determined using a Bonferroni-corrected threshold, p(t) [≤] 0.001. We detected distinct associations linking AN symptoms to lateral occipital cortical thickness and insular/cingulate gyrification and trait anxiety to lingual cortical thickness and superior parietal gyrification, and we detected overlapping associations linking AN symptoms and set-shifting impairment to frontoparietal gyrification. No other brain-behavior relationships emerged. Our findings suggest that variations in site-specific cortical morphology could give rise to core features of AN and shared temperamental and cognitive-behavioral risk factors for AN.

neuroscience↗

bioRxiv2017

Auxiliary ATP binding sites power rapid unwinding by RecBCD

RecBCD, responsible for the initiation of double stranded break repair in bacteria, is a processive DNA helicase with an unwinding rate approaching [~]1,600 bp{middle dot}s-1. The mechanism enabling RecBCD to achieve such fast unwinding rate is not known. We employed a combination of equilibrium and time-resolved binding experiments, and ensemble and single molecule activity assays to uncover the molecular mechanism underlying RecBCDs rapid catalysis. We report the existence of auxiliary binding sites, where ATP binds with lower affinity and with distinct chemical interactions as compared to the known catalytic sites. The catalytic rate of RecBCD is reduced both by preventing and by strengthening ATP binding to these sites, suggesting that the dynamics of ATP at these sites modulates the enzymes rate. We propose a model by which RecBCD achieves its fast unwinding rate by utilizing the weaker binding sites to increase the flux of ATP to its catalytic sites.

biophysics↗

bioRxiv2017

The mechano-chemistry of reverse transcriptase

Retroviral reverse transcriptase catalyses the synthesis of an integration-competent dsDNA molecule, using as a substrate the viral RNA. Using optical tweezers, we follow the Murine Leukemia Virus reverse transcriptase as it performs strand-displacement polymerization on a template under mechanical force. Our results indicate that reverse transcriptase functions as a Brownian ratchet, with dNTP binding as the rectifying reaction of the ratchet. We also found that reverse transcriptase is a relatively passive enzyme, able to polymerize on structured templates by exploiting their thermal breathing. Finally, our results indicate that the enzyme enters the recently characterized backtracking state from the pre-translocation complex.

biophysics↗

bioRxiv2017

RecBCD possesses strong coupling between DNA and nucleotides binding that may propel stepping mechanism during translocation

Double-strand DNA breaks are the severest type of genomic damage, requiring rapid response to ensure survival. RecBCD helicase in prokaryotes initiates processive and rapid DNA unzipping essential for break repair. Yet, the energetics of RecBCD during translocation along the DNA track needs to be quantitatively clarified. Specifically, its essential to understand how RecBCD switches between its binding states to enable its translocation. Here we determine, by systematic affinity measurements, the degree of coupling between DNA and nucleotide binding to RecBCD. We show that, in the presence of ADP, RecBCD binds weakly to DNA that harbors a double overhang mimicking an unwinding intermediate. Consistently, RecBCD binds weakly to ADP in the presence of the same DNA. We did not observe coupling between DNA and nucleotide binding for DNA molecules having only a single overhang, suggesting that RecBCD subunits must both bind DNA to "sense" the nucleotide state. Excitingly, we observed weak coupling for AMPpNp as RecBCD remains strongly bound to DNA in its presence. Detailed thermodynamic analysis of RecBCD reaction mechanism suggests an energetic compensation between RecB and RecD, which may be essential for rapid unwinding. Our findings provide the basis for a stepping mechanism during the processive translocation of RecBCD.

biochemistry↗

bioRxiv2017

Single-molecule DNA unzipping reveals asymmetric modulation of the transcription factor Egr-1 by its binding site sequence and context

Most functional transcription factor (TF) binding sites deviate from their \"consensus\" recognition motif, although their sites and flanking sequences are often conserved across species. Here, we used single-molecule DNA unzipping with optical tweezers to study how Egr-1, a TF harbouring 3 zinc fingers (ZF1,ZF2 and ZF3), is modulated by the sequence and context of its functional sites in the Lhb gene promoter. We find that both the core 9 base pairs bound to Egr-1 in each of the sites, and the base pairs flanking them, modulate the affinity and structure of the protein-DNA complex. The effect of the flanking sequences is asymmetric, with a stronger effect for the sequence flanking ZF3. Characterization of the dissociation time of Egr-1 revealed that a local, mechanical perturbation of the interactions of ZF3 destabilizes the complex more effectively than a perturbation of the ZF1 interactions. Our results reveal a novel role for ZF3 in the interaction of Egr-1 with other proteins and the DNA, providing insight on the regulation of Lhb and other genes by Egr-1. Moreover, our findings reveal the potential of small changes in DNA sequence to alter transcriptional regulation, and may shed light on the organization of regulatory elements at promoters.

biophysics↗

bioRxiv2017

Mobile nucleosomes and the accessibility of transcription factors to DNA: a modified dynamic equilibrium model

Nucleosomes, the basic building block of chromatin, regulate the accessibility of the transcription machinery to DNA. Recent studies have revealed that the nucleosome's spontaneous, thermally driven positional dynamics are modulated by different factors, and exploited by the cell as a regulatory mechanism. In particular, enrichment of mobile nucleosomes at the promoters of genes suggests that the mobility of nucleosomes may affect the ability of transcription factors to bind DNA. However, a quantitative model describing the effect nucleosome mobility on the effective affinity of transcription factors is lacking. We present here a simple equilibrium model that captures the essence of the effect, and show that modulation of the nucleosome's mobility can be a potent and versatile regulator of transcription factor binding.

biophysics↗