Keratoconic and (de)formed vision: Re-thinking the limits of perspectival drawing

In this project the limitations of perspectival drawing are revised and reconsidered through a particular visual (dis)ability: keratoconus. Perspectival representation is based not only on a single and immobile eye, but also on an ‘able’ eye. The de-formation of keratoconic vision offers a new means to consider the perspectival drawing by extending beyond the limitations of its structure. The degenerative keratoconic eye thus calls attention to the intricate mechanism of sight and to the eye’s machinic functioning. By referring to Creative Evolution by Henri Bergson and The Large Glass by Marcel Duchamp it becomes possible to articulate the nuanced relations between the complexity of the eye as a complex structure and the simplicity of its unitary function. Through keratoconic vision, one experiences the formations and (de)formations of the visual image due to the eyes’ functioning and dysfunctioning. This then leads to the search for an alternative medium that is similar to such a nuanced embodied visual experience. The interval between the machinations of vision and the simplicity of its function is more closely resembled through the visual experience of the stereoscope. The digitization of the stereoscope further unfolds this notion of the durational interval that lies between the machinations of vision and their unitary function, increasingly veering towards the former. Emerging digital stereoscopic imaging begin to utilize feedback and interaction and thus produce new ways to imagine the complexity of the eye(s) and visuality more broadly.

In silico validation and fabrication of matrix diffusion based polymeric transdermal films for repurposing gabapentin hydrochloride in oncogenic neuropathic pain

ABSTRACTBackgroundGabapentin (GBP) is an FDA approved drug for the treatment of partial and secondary generalized seizures, apart from also being used for diabetic neuropathy. GBP displays highly intricate mechanism of action and its inhibitory response in elevated antagonism of NMDA (N-methyl-D-aspartate receptor) receptor and has potential in controlling neuropathic pain of cancer origin.ObjectiveTherefore, in the present study, we have selected BCATc (Pyridoxal 5’-phosphate dependent branched-chain aminotransferase cytosolic) enzyme that is highly expressed in neuropathic stress conditions and have analysed the GBP as its competitive inhibitor by modeling, docking and checking its pharmacokinetic suitability through ADMET. Though in this study the results exhibited higher efficacy of GBP in controlling neuropathic pain, the drug shows certain potential therapeutic limitations like shorter half-life, repetitive dosing, high inter subjective variability.MethodsTherefore, a suitable and equally efficacious drug delivery method was also designed and developed by loading GBP transdermal patches (GBP-TDP) by solvent evaporation method using PVP and HPMC in ratio of 2:1 as a polymer base for reservoir type of TDP. Also, PEG 400 was used as a plasticizer and PVA (4%) was taken for backing membrane preparation and then the optimized GBP-TDP was subjected for physical characterization, optimization and ex vivo release kinetics.Results and conclusionThe results showed desired specifications with uneven and flaky surface appearance giving avenue for controlled release of the drugs with 75.58% of drug release in 12 hrs., further suggesting that GBP-TDP can be used as an effective tool against diabetic neuropathy pain.

Single-cell-resolved dynamics of chromatin architecture delineate cell and regulatory states in wildtype and cloche/npas4l mutant zebrafish embryos

DNA accessibility of cis regulatory elements (CREs) dictates transcriptional activity and drives cell differentiation during development. While many of the genes that regulate embryonic development have been described, the underlying CRE dynamics controlling their expression remain largely unknown. To address this, we applied single-cell combinatorial indexing ATAC-seq (sci-ATAC-seq) to whole 24 hours post fertilization (hpf) stage zebrafish embryos and developed a new computational tool, ScregSeg, that selects informative genome segments and classifies complex accessibility dynamics. We integrated the ScregSeg output with bulk measurements for histone post-translational modifications and 3D genome organization, expanding knowledge of regulatory principles between chromatin modalities. Sci-ATAC-seq profiling of npas4l/cloche mutant embryos revealed novel cellular roles for this hemato-vascular transcriptional master regulator and suggests an intricate mechanism regulating its expression. Our work constitutes a valuable resource for future studies in developmental, molecular, and computational biology.

Local Ca2+ signals couple activation of TRPV1 and ANO1 sensory ion channels

ANO1 (TMEM16A) is a Ca2+-activated Cl− channel (CaCC) expressed in peripheral somatosensory neurons that are activated by painful (noxious) stimuli. These neurons also express the Ca2+-permeable channel and noxious heat sensor TRPV1, which can activate ANO1. Here, we revealed an intricate mechanism of TRPV1-ANO1 channel coupling in rat dorsal root ganglion (DRG) neurons. Simultaneous optical monitoring of CaCC activity and Ca2+ dynamics revealed that the TRPV1 ligand capsaicin activated CaCCs. However, depletion of endoplasmic reticulum (ER) Ca2+ stores reduced capsaicin-induced Ca2+ increases and CaCC activation, suggesting that ER Ca2+ release contributed to TRPV1-induced CaCC activation. ER store depletion by plasma membrane–localized TRPV1 channels was demonstrated with an ER-localized Ca2+ sensor in neurons exposed to a cell-impermeable TRPV1 ligand. Proximity ligation assays established that ANO1, TRPV1, and the IP3 receptor IP3R1 were often found in close proximity to each other. Stochastic optical reconstruction microscopy (STORM) confirmed the close association between all three channels in DRG neurons. Together, our data reveal the existence of ANO1-containing multichannel nanodomains in DRG neurons and suggest that coupling between TRPV1 and ANO1 requires ER Ca2+ release, which may be necessary to enhance ANO1 activation.

Inter-dependency between surface morphology and sensitive low RH detection: exploration of an intricate mechanism to extend the lower detection limit

Water vapor molecular dynamics, pore size, and anion concentration within the pores are interdependent and together affect the lower detection limit (LOD) and sensitivity of a humidity sensor.

mTOR-RhoA signalling impairments in direct striatal projection neurons induce altered behaviours and striatal physiology in mice

As an integrator of molecular pathways, mTOR has been associated with diseases including neurodevelopmental, psychiatric and neurodegenerative disorders as autism, schizophrenia, and Huntington’s disease. An important brain area involved in all these diseases is the striatum. However, the mechanisms behind how mTOR is involved in striatal physiology and its relative role in distinct neuronal populations in these striatal-related diseases still remain to be clarified.Taking advantage of the D1-mTOR KO mice (males), we combined behavioural, biochemical, electrophysiological and morphological analysis aiming to untangle the role of mTOR in direct pathway striatal projection neurons (dMSNs) and how this would impact on striatal physiology.Our results indicate deep behavioural changes in absence of mTOR in dMSNs such as decreased spontaneous locomotion, impaired social interaction and repetitive behaviour. These were accompanied by a Kv1.1-induced increase in the fast phase of afterhyperpolarization and decreased distal spines density that were mechanistically independent of protein synthesis but dependent of RhoA activity.These results identify mTOR RhoA signaling as an important regulator of striatal functions through an intricate mechanism involving RhoA and culminating in Kv1.1 overfunction, which could be targeted to treat striatal-related mTORopathies.

IMMIGRATION PROBLEMATICS IN THE NARRATIVE DISCOURSE OF JOSEF IGNACY KRASZEWSKI

The article devotes to the immigration problematics in the creative work of Józef Ignacy Kraszewski – the leading spiritual and intellectual leader of Polish immigration after the January uprising. The contribution of a writer to the development of the cultural life of the Polish immigration of the 19-th century in the field of fiction, literary criticism, journalism, publishing and public activities were characterized as the theme of the January uprising determined the direction and problematics of the journalistic and public activities of the writer of the Dresden period of life and work. Peculiarities of creative rethinking of consequences of the Polish Insurrection of 1863 in the large-scale artistic heritage of Josef Ignacy Kraszewski, in particular, in the cycle of novels on political issues that were published under the pseudonym Bogdan Boleslavit “The Child of the Old City” (1863), “We and They” (1865), “Moscal” (1865), “The Jew” (1866), “Travelers “(1968-1970),” In a Strange Land “(1871). In the Dresden period the creativity of Josef Ignacy Kraszewski acquired new features – profound analytic and critical judiciousness of judgements. It should be noted the richness of the problematics and genre variety of the creative work of Kraszewski in this period. The novel “In a Strange Land” contains abundance of social realities, emotional images of conflicts and characters of the work. The narrative strategy of the novel is determined by the emotionality, sensuality and high degree of the presence of the narrator in the work through the indirect representation of his personal feelings, ideas and the declaration of a personal social position On the material of the novel “In a Strange Land” the motive of expulsion, martyrdom, involuntary journey, travel-escape is analyzed both in the literature of the mentioned period and in the narrative discourse of Josef Ignacy Kraszewski. The writer demonstrates the intersection of Polish and foreign culture from his own position of emigrant. The article analyzes the intricate mechanism of saving national identity in such political situation after January uprising

Do Osmolytes Impact the Structure and Dynamics of Myoglobin?

Osmolytes are small organic compounds that can affect the stability of proteins in living cells. The mechanism of osmolytes’ protective effects on protein structure and dynamics has not been fully explained, but in general, two possibilities have been suggested and examined: a direct interaction of osmolytes with proteins (water replacement hypothesis), and an indirect interaction (vitrification hypothesis). Here, to investigate these two possible mechanisms, we studied myoglobin-osmolyte systems using FTIR, UV-vis, CD, and femtosecond IR pump-probe spectroscopy. Interestingly, noticeable changes are observed in both the lifetime of the CO stretch of CO-bound myoglobin and the spectra of UV-vis, CD, and FTIR upon addition of the osmolytes. In addition, the temperature-dependent CD studies reveal that the protein’s thermal stability depends on molecular structure, hydrogen-bonding ability, and size of osmolytes. We anticipate that the present experimental results provide important clues about the complicated and intricate mechanism of osmolyte effects on protein structure and dynamics in a crowded cellular environment.