Highly Sensitive Flexible Modulus Sensor for Softness Perception and Clinical Application

The wearable sensors for softness measuring are emerging as a solution of softness perception, which is an intrinsic function of human skin, for electronic skin and human-machine interaction. However, these wearable sensors suffer from a key challenge: the modulus of an object can not be characterized directly, which originates from the complicated transduction mechanism. To address this key challenge, we developed a flexible and wearable modulus sensor that can simultaneously measure the pressure and modulus without mutual interference. The modulus sensing was realized by merging the electrostatic capacitance response from the pressure sensor and the ionic capacitance response from the indentation sensor. Via the optimized structure, our sensor exhibits high modulus sensitivity of 1.9 × 102 in 0.06 MPa, a fast dynamic response time of 100 ms, and high mechanical robustness for over 2500 cycles. We also integrated the sensor onto a prosthetic hand and surgical probe to demonstrate its capability for pressure and modulus sensing. This work provides a new strategy for modulus measurement, which has great potential in softness sensing and medical application.

p57Kip2 regulates embryonic haematopoietic stem cell numbers by controlling the size of the sympathoadrenal progenitor pool

ABSTRACTHaematopoietic stem cells (HSCs) are of major clinical importance, and finding methods for their in vitro generation is a prime research focus. We demonstrate that the cell cycle inhibitor p57Kip2/Cdkn1c limits HSC numbers by restricting the size of the sympathetic nervous system (SNS) and the amount of HSC-supportive catecholamines secreted by these cells, specifically in the aorta-gonads-mesonephros (AGM) region via β2-adrenergic receptor signalling. This regulation occurs at the SNS progenitor level and is in contrast to the cell-intrinsic function of p57Kip2 in maintaining adult HSCs. Using single-cell RNA-Seq we dissect the differentiation pathway of neural crest cells into SNS cells in the AGM and reveal that they are able to take an alternative differentiation pathway, giving rise to a subset of mesenchymal cells expressing HSC-supportive factors. Neural crest cells thus appear to contribute to the AGM HSC niche via two different mechanisms: SNS-mediated catecholamine secretion and HSC-supportive mesenchymal cell production.

Threat imminence reveals links among unfolding of anticipatory physiological response, cortical-subcortical intrinsic functional connectivity, and anxiety

Excessive expression of threat-anticipatory defensive responses is central in anxiety. Animal research indicates that anticipatory responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from translational work on threat imminence could guide mechanistic research mapping abnormal function in this circuitry to aberrant defensive responses in anxiety. Here, we initiate such research. Fifty pediatric anxiety patients and healthy-comparisons (33 females) completed a threat-anticipation task whereby cues signaled delivery of highly-painful (threat) or non-painful (safety) heat. Temporal changes in skin-conductance indexed defensive responding as function of threat imminence. Resting-state functional connectivity data were used to identify intrinsic-function correlates of anticipatory response within a specific functional network derived from translational research. Results indicate that anxiety was associated with greater increase in anticipatory response as threats became more imminent. Magnitude of increase in threat-anticipatory responses corresponded to intrinsic connectivity within a cortical-subcortical circuit; importantly, more severe anxiety was associated with greater connectivity between ventromedial prefrontal cortex and hippocampus and basolateral amygdala, a circuit implicated in animal models of anxiety. These findings link basic-translational and clinical research, highlighting aberrant intrinsic function in conserved defensive circuitry as potential pathophysiological mechanism in anxiety.

Reduced synchroneity of intra-islet Ca2+ oscillations in vivo in Robo-deficient β cells

The spatial architecture of the islets of Langerhans is hypothesized to facilitate synchronized insulin secretion among β cells yet testing this in vivo in the intact pancreas is challenging. Robo βKO mice, in which the genes Robo1 and Robo2 are deleted selectively in β cells, provide a unique model of altered islet spatial architecture without loss of β cell differentiation or islet damage from diabetes. Combining Robo βKO mice with intravital microscopy, we show here that Robo βKO islets have reduced synchronized intra-islet Ca2+ oscillations among β cells in vivo. We provide evidence that this loss is not due to a β cell-intrinsic function of Robo, mis-expression or mis-localization of Cx36 gap junctions, or changes in islet vascularization or innervation, suggesting that the islet architecture itself is required for synchronized Ca2+ oscillations. These results have implications for understanding structure-function relationships in the islets during progression to diabetes as well as engineering islets from stem cells.

Genetic and phylogenetic uncoupling of structure and function in human transmodal cortex

Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in non-human primates had a similar spatial distribution, but we observed an increased coupling between structure and function in association regions in macaques relative to humans. Meta-analysis suggested regions with the least genetic control (low heritable correspondence and different across primates) are linked to social cognition and autobiographical memory. Our findings establish the genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex, culturally embedded forms of cognition.

Sufficient Niacin Supply: The Missing Puzzle Piece to COVID-19, and beyond?

Definitive antiviral properties are evidenced for niacin, i.e., nicotinic acid (NA), as coronavirus disease 2019 (COVID-19) therapy for both health restoration and prevention, to the level that progression of COVID-19 pathology may follow as an intrinsic function of NA supply. This detailed investigation proposes thorough disentanglement of how the downstream inflammatory propagation of ensuing severe acute respiratory virus 2 (SARS-CoV-2) infection can either be prohibited or reversed upstream out the body to expeditiously restore health with well-tolerated dynamic supplementation of sufficient NA (i.e., ~1-3 grams per day). Culmination of this research leads to realization of the potentially ubiquitous therapeutic and preventive powers of NA against inflammatory disease, in general.

Sufficient niacin supply: the missing puzzle piece to COVID-19, and beyond?

Definitive antiviral properties are evidenced for niacin, i.e., nicotinic acid (NA), as coronavirus disease 2019 (COVID-19) therapy for both disease recovery and prevention, to the level that reversal or progression of its pathology follows as an intrinsic function of NA supply. This detailed investigation provides a thorough disentanglement of how the downstream inflammatory propagation of ensuing severe acute respiratory virus 2 (SARS-CoV-2) infection is entirely prohibited or reversed upstream out the body to expeditiously restore health with well-tolerated dynamic supplementation of sufficient NA (i.e., ~1-3 grams per day). Culmination of this research leads to realization of the potentially ubiquitous therapeutic and preventive powers of NA against inflammatory disease, in general.

T cell-intrinsic role for Nod2 in protection against Th17-mediated uveitis

Mutations in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) cause Blau syndrome, an inflammatory disorder characterized by uveitis. The antimicrobial functions of Nod2 are well-established, yet the cellular mechanisms by which dysregulated Nod2 causes uveitis remain unknown. Here, we report a non-conventional, T cell-intrinsic function for Nod2 in suppression of Th17 immunity and experimental uveitis. Reconstitution of lymphopenic hosts with Nod2−/− CD4+ T cells or retina-specific autoreactive CD4+ T cells lacking Nod2 reveals a T cell-autonomous, Rip2-independent mechanism for Nod2 in uveitis. In naive animals, Nod2 operates downstream of TCR ligation to suppress activation of memory CD4+ T cells that associate with an autoreactive-like profile involving IL-17 and Ccr7. Interestingly, CD4+ T cells from two Blau syndrome patients show elevated IL-17 and increased CCR7. Our data define Nod2 as a T cell-intrinsic rheostat of Th17 immunity, and open new avenues for T cell-based therapies for Nod2-associated disorders such as Blau syndrome.

Argument is War Metaphor in the Qur’ān

This paper investigates the experiential basis of the concept of ‘argument’ in the language of the Holy Qur’ān in order to explore the cross-era dimensions of war as the source domain for argument. Conceptual metaphor approach has been applied to the data collected from the Holy Qur’ān through the technique of topical words to find out metaphor themes of argument. The findings reveal that ARGUMENT IS WAR metaphor is missing in classical Arabic of the Holy Qur’ān. However, the concept of argument is framed by other metaphors such as container schema, objects, and personification. It also serves as source domain for the invocation to Allah SWT. The findings also show that language has an intrinsic function in metaphor comprehension. The paper suggests further research of classical Arabic literature to make some definite theoretical conclusions on ARGUMENT IS WAR metaphor, and to explore more basic conceptual schemas in cross-era languages.