Hydrophobic and ionic-interactions in bulk and confined water with implications for collapse and folding of proteins

Water and water-mediated interactions determine thermodynamic and kinetics of protein folding, protein aggregation and self-assembly in confined spaces. To obtain insights into the role of water in the context of folding problems, we describe computer simulations of a few related model systems. The dynamics of collapse of eicosane shows that upon expulsion of water the linear hydrocarbon chain adopts an ordered helical hairpin structure with 1.5 turns. The structure of dimer of eicosane molecules has two well ordered helical hairpins that are stacked perpendicular to each other. As a prelude to studying folding in confined spaces we used simulations to understand changes in hydrophobic and ionic interactions in nano droplets. Solvation of hydrophobic and charged species change drastically in nano water droplets. Hydrophobic species are localized at the boundary. The tendency of ions to be at the boundary where water density is low increases as the charge density decreases. Interaction between hydrophobic, polar, and charged residue are also profoundly altered in confined spaces. Using the results of computer simulations and accounting for loss of chain entropy upon confinement we argue and then demonstrate, using simulations in explicit water, that ordered states of generic amphiphilic peptide sequences should be stabilized in cylindrical nanopores

Time evolution and asymmetry of a laser produced blast wave

Studies of a blast wave produced from carbon rods and plastic spheres in an argon background gas have been conducted using the Vulcan laser at the Rutherford Appleton Laboratory. A laser of 1500 J was focused onto these targets, and rear-side observations of an emission front were recorded using a fast-framing camera. The emission front is asymmetrical in shape and tends to a more symmetrical shape as it progresses due to the production of a second shock wave later in time, which pushes out the front of the blast wave. Plastic spheres produce faster blast waves, and the breakthrough of the second shock is visible before the shock stalls. The results are presented to demonstrate this trend, and similar evolution dynamics of experimental and simulation data from the FLASH radiation-hydrodynamics code are observed

Monte Carlo simulation for the prediction of precision of absorbance measurements with a miniature CCD spectrometer

The precision characteristics of the absorbance measurements obtained with a low-cost miniature spectrometer incorporating an array detector were evaluated. Uncertainties in absorbance measurements were due to a combination of non-uniform light intensity and detector response over the wavelength range examined (350-850 nm), in conjunction with the digitization of the intensity indications and the intrinsic noise of the detecting elements. The precision characteristics are presented as contour plots displaying the expected RSD% of absorbances on the absorbance versus wavelength plane. The minimum RSD% for the spectrometer configuration tested was observed within the 0.2-1.5 absorbance units and 500-750 nm wavelength range. Without invoking signal enhancement features of the data-acquisition program (scan average, higher integration times, smoothing based on averaging the signal detected by adjacent pixels), the attainable precision within this range was 0.4-0.8%. A computer program based on Monte Carlo simulations was developed for the prediction of absorbance precision characteristics under various conditions of measurements

Exposure during embryonic development to Roundup® Power 2.0 affects lateralization, level of activity and growth, but not defensive behaviour of marsh frog tadpoles

As glyphosate-based herbicides, sold under the commercial name Roundup®, represent the most used herbicides in the world, contamination of the freshwater environment by glyphosate has become a widespread issue. In Italy, glyphosate was detected in half of the surface waters monitoring sites and its concentrations were higher than environmental quality standards in 24.5% of them. It can last from days to months in water, leading to exposure for aquatic organisms and specifically to amphibians’ larvae that develop in shallow water bodies with proven effects to development and behaviour. In this study, we tested the effects of a 96 h exposure during embryonic development of marsh frog's tadpoles to three ecologically relevant Roundup® Power 2.0 concentrations. As expected, given the low concentrations tested, no mortality was observed. Morphological measurements highlighted a reduction in the total length in tadpoles exposed to 7.6 mg a.e./L, while an increase was observed at lower concentrations of 0.7 and 3.1 mg a.e./L compared to control group. Tadpoles raised in 7.6 mg a.e./L also showed a smaller tail membrane than those raised in the control solution. Regarding behaviour, we tested tadpoles in two different sessions (Gosner stages 25 and 28/29) for lateralization, antipredator response and basal activity. Lower intensity of lateralization was detected in tadpoles raised at the highest Roundup® concentration in the first session of observation, while no significant difference among treatments was observed in the second one. In both sessions, effects of Roundup® Power 2.0 embryonic exposure on antipredator response, measured as the proportional change in activity after the injection of tadpole-fed predator (Anax imperator) cue, were not detected. Tadpoles exposed during embryonic development to Roundup® exhibited lower basal activity than the control group, with the strongest reduction for the 7.6 mg a.e./L treatment. Our results reinforce the concern of Roundup® contamination impact on amphibians

Developmental perspectives on interpersonal affective touch

In the last decade, philosophy, neuroscience and psychology alike have paid increasing attention to the study of interpersonal affective touch, which refers to the emotional and motivational facets of tactile sensation. Some aspects of affective touch have been linked to a neurophysiologically specialised system, namely the C tactile (CT) system. While the role of this sys-tem for affiliation, social bonding and communication of emotions have been widely investigated, only recently researchers have started to focus on the potential role of interpersonal affective touch in acquiring awareness of the body as our own, i.e. as belonging to our psychological ‘self’. We review and discuss recent developmental and adult findings, pointing to the central role of interpersonal affective touch in body awareness and social cognition in health and disorders. We propose that interpersonal affective touch, as an interoceptive modality invested of a social nature, can uniquely contribute to the ongoing debate in philosophy about the primacy of the relational nature of the minimal self

Aberrant computational mechanisms of social learning and decision-making in schizophrenia and borderline personality disorder

Psychiatric disorders are ubiquitously characterized by debilitating social impairments. These difficulties are thought to emerge from aberrant social inference. In order to elucidate the underlying computational mechanisms, patients diagnosed with major depressive disorder (N = 29), schizophrenia (N = 31), and borderline personality disorder (N = 31) as well as healthy controls (N = 34) performed a probabilistic reward learning task in which participants could learn from social and nonsocial information. Patients with schizophrenia and borderline personality disorder performed more poorly on the task than healthy controls and patients with major depressive disorder. Broken down by domain, borderline personality disorder patients performed better in the social compared to the non-social domain. In contrast, controls and MDD patients showed the opposite pattern and SCZ patients showed no difference between domains. In effect, borderline personality disorder patients gave up a possible overall performance advantage by concentrating their learning in the social at the expense of the non-social domain. We used computational modeling to assess learning and decision-making parameters estimated for each participant from their behavior. This enabled additional insights into the underlying learning and decision-making mechanisms. Patients with borderline personality disorder showed slower learning from social and non-social information and an exaggerated sensitivity to changes in environmental volatility, both in the non-social and the social domain, but more so in the latter. Regarding decision-making the modeling revealed that compared to controls and major depression patients, patients with borderline personality disorder and schizophrenia showed a stronger reliance on social relative to non-social information when making choices. Depressed patients did not differ significantly from controls in this respect. Overall, our results are consistent with the notion of a general interpersonal hypersensitivity in borderline personality disorder and schizophrenia based on a shared computational mechanism characterized by an over-reliance on beliefs about others in making decisions and by an exaggerated need to make sense of others during learning specifically in borderline personality disorder

Exploring the role of NONO in transcriptional regulation of cellular pathways in Multiple Myeloma: insights into its paraspeckle-dependent and independent regulatory mechanisms

BACKGROUND: Multiple myeloma (MM) is a malignant proliferation of bone marrow plasma cells (BMPCs) with variable clinical outcome, which, despite treatment advances, still remains incurable. LncRNA NEAT1, the scaffold of paraspeckle (PS) organelle, has been linked to cancer development and progression, by playing a critical role in DNA repair and cell survival in MM. NONO, a protein involved in NEAT1 stability and PS, is essential for several cellular functions and gene regulation. Notably, NONO is upregulated in MM patients, and its high expression correlates with poor OS and PFS. In addition to its essential role within PSs, NONO may also have independent functions in MM cells. AIM: To dissect the role of NONO in modulating the transcriptomic landscape of MM plasma cells through next-generation sequencing, and elucidate its contribution both in relation to the PS and independently of it. MATERIAL AND METHODS: RNA was extracted from NONO-KD, NEAT1-KD, and scramble AMO1 and LP1 cells. RNA-seq libraries were prepared following Illumina Stranded TotalRNA PrepLigation with Ribo-zero Plus protocol (Illumina). Sequencing was performed on Illumina Novaseq 6000 S2 cartridge. CoMMpass data were retrieved from the Interim Analysis 15a (MMRF_CoMMpass_IA15a, accessed on 16 October 2020). RESULTS: To explore the role of NONO in both PS-related and independent pathways, we compared data from NONO-KD or NEAT1-KD AMO1 and LP1 cells; overlapping pathways between NONO and NEAT1 should be suggestive of a NONO’s involvement in PS-related functions. In NEAT1 and NONO silenced cells we highlighted a significant downregulation of gene sets associated with chromatin modifications, as well as pathways related to WNT/β-catenin and NOTCH signalling. These findings were further confirmed by analyzing RNAseq data from AMO1 cells, which were previously engineered to overexpress NEAT1 and PSs. This analysis revealed a significant positive modulation of the same pathways (NES ≥ 1.5, padj < 0.05). Further confirmation was obtained by stratifying samples from the CoMMpass dataset based on NONO expression levels, comparing the expression profiles between the two extreme quartiles, and conducting GSEA on the list of differentially expressed coding genes. Since NONO is essential for protecting NEAT1 from degradation, its silencing results in a marked downregulation of NEAT1 expression levels, thereby impacting the transcriptome of NONO-silenced cells in a NEAT1-dependent manner. As a result, all the pathways modulated in the NONO-KD MM cell lines (HMCLs) were also confirmed in the NEAT1-KD samples, making it impossible to identify any pathways regulated by NONO independently of PSs. However, the analysis of data from the extreme quartile of NONO in the CoMMpass dataset enabled the identification of specific pathways not shared with NEAT1-KD HMCLs, which may suggest pathways that NONO regulates independently of PS in MM cells. This analysis revealed NONO's involvement in RNA splicing or maturation, cellular RNA trafficking to the cytoplasm, as well as its role in mitochondrial biogenesis and cell-matrix adhesion. CONCLUSION: This study underscores the complex transcriptional roles of NONO in MM and its potential as a therapeutic target, particularly in pathways critical for disease progression. The in-silico validation further supports the clinical relevance of these findings, highlighting the value of the HMCLs model in advancing our understanding of MM