Vision Modulates Corticospinal Suppression in a Functionally Specific Manner during Movement of the Opposite Limb

The effect of vision on the excitability of corticospinal projections to the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles of right human forearm was investigated before and during discrete movement of the opposite limb. An external force opposed the initial phase of the movement (wrist flexion) and assisted the reverse phase, so that recruitment of the wrist extensors was minimized. Three conditions were used as follows: viewing the inactive right limb (Vision), viewing the mirror image of the moving left limb (Mirror), and with vision of the right limb occluded (No Vision). Transcranial magnetic stimulation was delivered to the left motor cortex: before, at the onset of, or during the left limb movement to obtain motor evoked potentials (MEPs) in the muscles of the right forearm. At and following movement onset, MEPs obtained in the right FCR were smaller in the Vision condition than in the Mirror and No Vision conditions. A distinct pattern of variation was obtained for the ECR. In all conditions, MEPs in this muscle were elevated upon or following movement of the opposite limb. An additional analysis of ipsilateral silent periods indicated that interhemispheric inhibition plays a role in mediating these effects. Activity-dependent changes in corticospinal output to a resting limb during discrete actions of the opposite limb are thus directly contingent upon where one looks. Furthermore, the extent to which vision exerts an influence upon projections to specific muscles varies in accordance with the functional contribution of their homologs to the intended action.

Missions and Institutions: Henri-Philippe Junod, Anthropology, Human Rights and Academia between Africa and Switzerland, 1921–1966

Drawing on a cultural, transnational and genealogical approach, this article studies the work of a Swiss missionary, Henri-Philippe Junod, between Europe and Africa. It tries not to look at what he brought to Africa, or brought back from Africa, but to see how his back-and-forth movement contributed to the formation of new ideas and institutions globally. The article looks at Junod’s contribution in three domains in particular, namely anthropology, human rights worldwide, and African studies in Switzerland.

Interpreting pedestrian behaviour by visualising and clustering movement data

Recent technological advances have increased the quantity of movement data being recorded. While valuable knowledge can be gained by analysing such data, its sheer volume creates challenges. Geovisual analytics, which helps the human cognition process by using tools to reason about data, offers powerful techniques to resolve these challenges. This paper introduces such a geovisual analytics environment for exploring movement trajectories, which provides visualisation interfaces, based on the classic space-time cube. Additionally, a new approach, using the mathematical description of motion within a space-time cube, is used to determine the similarity of trajectories and forms the basis for clustering them. These techniques were used to analyse pedestrian movement. The results reveal interesting and useful spatiotemporal patterns and clusters of pedestrians exhibiting similar behaviour.

DEAD-box helicase DP103 defines metastatic potential of human breast cancers

Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β-activated kinase-1 (TAK1) phosphorylation of NF-κB-activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB-mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.

TNF-α Sensitizes Mechanoreceptors in Human Odontoblasts

Background: Mechanotransduction in the dental pulp is mediated by mechano-sensitive trigeminal afferents but accumulating evidence suggests odontoblasts also contribute to mechano-sensory functions of the pulp as evidenced by expression of TRP channels, calcium-activated potassium channels and TREK-1 potassium channels. Activation of these mechano-sensitive channels is considered critical for the mechanotransduction of fluid movement within dentinal tubules into electrical signals transmitted by the pulpal afferents to elicit tooth sensitivity and pain. Since tooth pain and sensitivity are potentiated by inflammation we hypothesise that the inflammatory cytokine TNF-α sensitizes odontoblast responses to mechanical stimuli. Objective: To investigate the effect of TNF-α on the response of odontblast-like cells to mechanical stimuli. Method: Odontoblast-like cells were derived from dental pulp cells of immature third molars as previously described (El-karim et al 20112011 Pain, 152, 2211-2223). Odontoblast response to mechanical stimuli (application of hypotonic solution) was determined using ratiometric calcium imaging. Cells were treated with TNF-α for either 24hrs or short application for 10 mins prior to calcium imaging. Result: Odontoblast-like cells responded to hypotonic solution (230 mOSM) by increase in cytoplasmic Ca2+ concentration [Ca+2]i that was reduced to near base line in the presence of the TRPV4 antagonist RN-1734. Incubation of odontoblast -like cells with TNFα for 24 hrs resulted in a significant increase in cytoplasmic Ca2+ concentration in response to hypotonic stimuli compared to untreated cells. Similar results were obtained when cells were treated with TNF-α for 10 mins prior to imaging. Conclusion: Both short and long term treatment of odontoblasts-like cells with TNF-α resulted in enhanced responses to mechanical stimuli mediated via TRPV4 channel suggesting a role for this channel in inflammatory dental pain.

Timing of response differentiation in human motor cortex during a speeded Go/No-go task

We explored the brain's ability to quickly prevent a pre-potent but unwanted motor response. To address this, transcranial magnetic stimulation was delivered over the motor cortex (hand representation) to probe excitability changes immediately after somatosensory cues prompted subjects to either move as fast as possible or withhold movement. Our results showed a difference in motor cortical excitability 90 ms post-stimulus contingent on cues to either promote or prevent movement. We suggest that our study design emphasizing response speed coupled with well-defined early probes allowed us to extend upon similar past investigations into the timing of response inhibition.

Functional expression of TRPV4 in human periodontal ligament cells

Background: Periodontal ligament (PDL) cells are exposed to physical forces in vivo in response to mastication, parafunction, speech and orthodontic tooth movement. Although it has been shown that PDL cells perceive and respond directly to mechanical stimulation, the nature of the ion channels that mediate this mechanotransduction remain to be fully elucidated. The transient receptor potential (TRP) superfamily of ion channels is believed to play a critical role in sensory physiology, where they act as transducers for thermal, chemical and mechanical stimuli. Recent studies have shown that members of the vanilloid (TRPV) and ankyrin (TRPA) subfamilies encode mechanosensitive TRPs. The vanilloid family member TRPV4 is one such non selective calcium permeable cationic channel which has been shown to be activated by chemical ligands, hypotonicity, and mechanical stimuli. Objectives: The objective of the current study was to investigate functional expression of TRPV4 in cultured human PDL cells. Methods: Human PDL cells were grown in Dulbecco's Modified Eagle Medium with L-glutamine supplemented with 10% fetal bovine serum (FBS), 100UI/ml penicillin and 100μg/ml streptomycin. Cells in passage 4-6 were used in all experiments. TRPV4 functional expression was determined using ratiometric calcium imaging. Cultured cells were loaded with intracellular Ca2+ probe fura-2 and cells were then stimulated with the TRPV4 agonists, 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), GSK1016790A or hypotonic solution. The TRPV4 antagonist RN 1734 was used to block the corresponding agonist responses. Results: PDL fibroblasts responded to application of TRPV4 agonists and hypotonic stimuli by an increase in intracellular calcium which was attenuated in the presence of the TRPV4 antagonist. Conclusions: We have shown for the first time the functional expression of the mechanosensitive TRPV4 channel in human PDL cells. The molecular identity and mechanisms of activation of mechanosensitive TRP channels in PDL cells merit further investigation.

Expert players accurately detect an opponent's movement intentions through sound alone

Sounds offer a rich source of information about events taking place in our physical and social environment. However, outside the domains of speech and music, little is known about whether humans can recognize and act upon the intentions of another agent’s actions detected through auditory information alone. In this study we assessed whether intention can be inferred from the sound an action makes, and in turn, whether this information can be used to prospectively guide movement. In two experiments experienced and novice basketball players had to virtually intercept an attacker by listening to audio recordings of that player’s movements. In the first experiment participants had to move a slider, while in the second one their body, to block the perceived passage of the attacker as they would in a real basketball game. Combinations of deceptive and non-deceptive movements were used to see if novice and/or experienced listeners could perceive the attacker’s intentions through sound alone. We showed that basketball players were able to more accurately predict final running direction compared to non-players, particularly in the second experiment when the interceptive action was more basketball specific. We suggest that athletes present better action anticipation by being able to pick up and use the relevant kinematic features of deceptive movement from event-related sounds alone. This result suggests that action intention can be perceived through the sound a movement makes and that the ability to determine another person’s action intention from the information conveyed through sound is honed through practice.