INVESTIGATING THE ROLES OF MECHANORECEPTIVE CHANNELS IN TACTILE APPARENT MOTION PERCEPTION: A VIBROTACTILE STUDY

Tactile apparent motion (TAM) is a perceptual phenomenon in which consecutive presentation of multiple tactile stimuli creates an illusion of motion. Employing a novel tactile display device, the Latero, allowed us to investigate this. The current study focused on the Rapidly Adapting (RA) channel and Slowly Adapting I (SAI) channel on the index finger. The experiment implemented vibrotactile masking stimuli to target the mechanoreceptive channels with the goal of gaining better insight into the involvement of mechanoreceptive channels in the perception of TAM. Masking stimuli were used because previous studies have used them to differentiate between different channels; a certain masking stimulus will impact a mechanoreceptive channel more than others. The experiment began by measuring participants’ threshold for TAM stimuli by varying the stimulus intensity in a two-choice task (left vs right); participants received test trials consisting of TAM stimuli with 25 Hz and 6 Hz testing for the RA and SAI channels, respectively. Next, participants performed a series of test trials with vibrotactile masking stimuli that preceded the TAM stimuli mentioned above. The vibrotactile masking stimulus varied in duration (4 seconds vs 8 seconds) and intensity (two times vs three times the intensity of the TAM stimuli). The results suggest that there was no difference in accuracy when testing for the RA and SAI channels. The results also showed that the introduction of the masking stimuli significantly lowered accuracy. Overall, neither the RA nor the SAI channel may be uniquely involved in TAM perception. However, further improvement on the current design may aid in isolating each channel to help better understand the channel’s role in TAM perception

A differential genome-wide transcriptome analysis : impact of cellular copper on complex biological processes like aging and development

The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS) and of adenosine triphosphate (ATP). We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to explain the underlying mechanisms controlling complex biological processes like aging and development

TMS-induced Neural Noise in Sensory Cortex Interferes with Short-term Memory Storage in Prefrontal Cortex

In a previous study, Harris et al. (2002) found disruption of vibrotactile short-term memory after applying single-pulse transcranial magnetic stimulation (TMS) to primary somatosensory cortex (SI) early in the maintenance period, and suggested that this demonstrated a role for SI in vibrotactile memory storage. While such a role is compatible with recent suggestions that sensory cortex is the storage substrate for working memory, it stands in contrast to a relatively large body of evidence from human EEG and single-cell recording in primates that instead points to prefrontal cortex as the storage substrate for vibrotactile memory. In the present study, we use computational methods to demonstrate how Harris et al.\u27s results can be reproduced by TMS-induced activity in sensory cortex and subsequent feedforward interference with memory traces stored in prefrontal cortex, thereby reconciling discordant findings in the tactile memory literature

Ultrahigh Nanoparticle Stability against Salt, pH, and Solvent with Retained Surface Accessibility via Depletion Stabilization

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemistry Society copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Zhang, X., Servos, M. R., & Liu, J. (2012). Ultrahigh Nanoparticle Stability against Salt, pH, and Solvent with Retained Surface Accessibility via Depletion Stabilization. Journal of the American Chemical Society, 134(24), 9910–9913. https://doi.org/10.1021/ja303787eFor many applications, it is desirable to stabilize colloids over a wide range of buffer conditions while still retaining surface accessibility for adsorption and reaction. Commonly used charge or steric stabilization cannot achieve this goal since the former is sensitive to salt and the latter blocks the particle surface. We use depletion stabilization in the presence of high molecular weight polyethylene glycol (PEG) to stabilize a diverse range of nanomaterials, including gold nanoparticles (from 10 to 100 nm), graphene oxide, quantum dots, silica nanoparticles, and liposomes in the presence of Mg2+ (>1.6 M), heavy metal ions, extreme pH (pH 1–13), organic solvents, and adsorbed nucleosides and drugs. At the same time, the particle surface remains accessible for adsorption of both small molecules and macromolecules. Based on this study, high loading of thiolated DNA was achieved in one step with just 2% PEG 20 000 in 2 h.University of Waterloo || Canadian Foundation for Innovation || Ontario Ministry of Research & Innovation || Canadian Institutes of Health Research || Natural Sciences and Engineering Research Council |

Fast pH-assisted functionalization of silver nanoparticles with monothiolated DNA

Attaching monothiolated DNA to silver nanoparticles has been achieved at pH 3.0 in 30 minutes and difficulties associated with DNA attachment to AgNPs at neutral pH have been revealed by studying DNA adsorption kinetics.University of Waterloo || Canadian Foundation for Innovation || Canadian Institutes of Health Research || Natural Sciences and Engineering Research Council || Ontario Ministry of Research and Innovation |

Instantaneous and Quantitative Functionalization of Gold Nanoparticles with Thiolated DNA Using a pH-Assisted and Surfactant-Free Route

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Zhang, X., Servos, M. R., & Liu, J. (2012). Instantaneous and Quantitative Functionalization of Gold Nanoparticles with Thiolated DNA Using a pH-Assisted and Surfactant-Free Route. Journal of the American Chemical Society, 134(17), 7266–7269. https://doi.org/10.1021/ja3014055The attachment of thiolated DNA to gold nanoparticles (AuNPs) has enabled many landmark works in nanobiotechnology. This conjugate chemistry is typically performed using a salt-aging protocol where, in the presence of an excess amount of DNA, NaCl is gradually added to increase DNA loading over 1–2 days. To functionalize large AuNPs, surfactants need to be used, which may generate difficulties for downstream biological applications. We report herein a novel method using a pH 3.0 citrate buffer to complete the attachment process in a few minutes. More importantly, it allows for quantitative DNA adsorption, eliminating the need to quantify the number of adsorbed DNA and allowing the adsorption of multiple DNAs with different sequences at predetermined ratios. The method has been tested for various DNAs over a wide range of AuNP sizes. Our work suggests a synergistic effect between pH and salt in DNA attachment and reveals the fundamental kinetics of AuNP aggregation versus DNA adsorption, providing a novel means to modulate the interactions between DNA and AuNPs.University of Waterloo || Canadian Foundation for Innovation || Ontario Ministry of Research & Innovation || Canadian Institutes of Health Research || Natural Sciences and Engineering Research Council |

Instantaneous Attachment of an Ultrahigh Density of Nonthiolated DNA to Gold Nanoparticles and Its Applications

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see http://dx.doi.org/10.1021/la3035424The last 16 years have witnessed the landmark development of polyvalent thiolated DNA-functionalized gold nanoparticles (AuNP's) possessing striking properties within the emerging field of nanobiotechnology. Many novel properties of this hybrid nanomaterial are attributed to the dense DNA shell. However, the question of whether nonthiolated polyvalent DNA–AuNP could be fabricated with a high DNA density and properties similar to those of its thiolated counterpart has not been explored in detail. Herein, we report that by simply tuning the pH of the DNA–AuNP mixture an ultrahigh capacity of nonthiolated DNA can be conjugated to AuNP's in a few minutes, resulting in polyvalent DNA–AuNP conjugates with cooperative melting behavior, a typical property of polyvalent thiolated DNA-functionalized AuNP's. With this method, large AuNP's (e.g., 50 nm) can be functionalized to achieve the colorimetric detection of sub-nanometer DNA. Furthermore, this fast, stable DNA loading was employed to separate AuNP's of different sizes. We propose that a large fraction of the attached DNAs are adsorbed via one or a few terminal bases to afford the high loading capacity and the ability to hybridize with the complementary DNA. This discovery not only offers a time- and cost-effective way to functionalize AuNP's with a high density of nonthiolated DNA but also provides new insights into the fundamental understanding of how DNA strands with different sequences interact with AuNP's.University of Waterloo || Canadian Foundation for Innovation || Ontario Ministry of Research & Innovation || Canadian Institutes of Health Research || Natural Sciences and Engineering Research Counci

Femicide definitions

Words constrain our perceptions and experiences. Our language builds our thoughts and is a powerful tool to describe the world. The words used in language represent an ambivalent tool that we can use to express our own perceptions, emotions and thoughts, and at the same time, they determine our experiences and social imaginary (cf. Castoriadis, 1975), using a previously established corpus of meanings and order. We can, however, do things and transform the world using language as a tool. Defining a social problem in a certain way leads to a specific possible solution, which is dependent on the way the problem is defined. Furthermore, we have to acknowledge that the perspective of those that pose the problem (such as individuals, groups, communities and so on) is affected by their view of the social system within which they perceive the problem (Foerster, 2003).peer-reviewe

Effects of Polyethylene Glycol on DNA Adsorption and Hybridization on Gold Nanoparticles and Graphene Oxide

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see http://dx.doi.org/10.1021/la302799sUnderstanding the interface between DNA and nanomaterials is crucial for rational design and optimization of biosensors and drug delivery systems. For detection and delivery into cells, where high concentrations of cellular proteins are present, another layer of complexity is added. In this context, we employ polyethylene glycol (PEG) as a model polymer to mimic the excluded volume effect of cellular proteins and to test its effects on DNA adsorption and hybridization on gold nanoparticles (AuNPs) and graphene oxide (GO), both of which show great promise for designing intracellular biosensors and drug delivery systems. We show that PEG 20000 (e.g., 4%) accelerates DNA hybridization to DNA-functionalized AuNPs by 50–100%, but this enhanced hybridization kinetics has not been observed with free DNA. Therefore, this rate enhancement is attributed to the surface blocking effect by PEG instead of the macromolecular crowding effect. On the other hand, DNA adsorption on citrate-capped AuNP surfaces is impeded even in the presence of a trace level (i.e., parts per billion) of PEG, confirming PEG competes with DNA for surface binding sites. Additional insights have been obtained by studying the adsorption of a thiolated DNA and a peptide nucleic acid. In these cases, the steric effects of PEG to impede adsorption are observed. Similar observations have also been made with GO. Therefore, PEG may be used as an effective blocking agent for both hydrophilic AuNP and for GO that also contains hydrophobic domains.University of Waterloo || Canadian Foundation for Innovation || Ontario Ministry of Research & Innovation || Canadian Institutes of Health Research || Natural Sciences and Engineering Research Council |

Polarity Control for Nonthiolated DNA Adsorption onto Gold Nanoparticles

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Zhang, X., Liu, B., Servos, M. R., & Liu, J. (2013). Polarity Control for Nonthiolated DNA Adsorption onto Gold Nanoparticles. Langmuir, 29(20), 6091–6098. https://doi.org/10.1021/la400617uGold nanoparticles (AuNPs) functionalized with thiolated DNA have enabled many studies in nanoscience. The strong thiol/gold affinity and the nanoscale curvature of AuNPs allow the attached DNA to adapt an upright conformation favorable for hybridization. Recently, it has been shown that nonthiolated DNA can also be attached via DNA base adsorption. Without a thiol label, both ends of the DNA and even internal bases could be adsorbed, decreasing the specificity of subsequent molecular recognition reactions. In this work, we employed a modular sequence design approach to systematically study the effect of DNA sequence on adsorption polarity. A block of poly adenine (poly-A) could be used to achieve a high density of DNA attachment. When the poly-A block length is short (e.g., below 5–7), the loading was independent of the block length, and the conjugate cannot hybridize to its cDNA effectively, suggesting a random attachment controlled by adsorption kinetics. Increasing the block length leads to reduced capacity but improved hybridization, suggesting that more DNA with the desired conformation was adsorbed due to the thermodynamic effects of poly-A binding. The design can be further improved by including capping sequences rich in T or G. Finally, a more general double-stranded DNA approach was described to be suitable for DNA that cannot satisfy the above-mentioned design requirements.University of Waterloo || Canadian Institutes of Health Research || Canadian Foundation for Innovation || Natural Sciences and Engineering Research Council || Ontario Ministry of Research and Innovation |