Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia Brain

BACKGROUND: Transcriptomic studies of the brains of schizophrenia (SZ) patients have produced abundant but largely inconsistent findings about the disorders pathophysiology. These inconsistencies might stem not only from the heterogeneous nature of the disorder, but also from the unbalanced focus on particular cortical regions and protein-coding genes. Compared to protein-coding transcripts, long intergenic non-coding RNA (lincRNA) display substantially greater brain region and disease response specificity, positioning them as prospective indicators of SZ-associated alterations. Further, a growing understanding of the systemic character of the disorder calls for a more systematic screening involving multiple diverse brain regions. AIM: We aimed to identify and interpret alterations of the lincRNA expression profiles in SZ by examining the transcriptomes of 35 brain regions. METHODS: We measured the transcriptome of 35 brain regions dissected from eight adult brain specimens, four SZ patients, and four healthy controls, using high-throughput RNA sequencing. Analysis of these data yielded 861 annotated human lincRNAs passing the detection threshold. RESULTS: Of the 861 detected lincRNA, 135 showed significant region-dependent expression alterations in SZ (two-way ANOVA, BH-adjusted p 0.05) and 37 additionally showed significant differential expression between HC and SZ individuals in at least one region (post hoc Tukey test, p 0.05). For these 37 differentially expressed lincRNAs (DELs), 88% of the differences occurred in a cluster of brain regions containing axon-rich brain regions and cerebellum. Functional annotation of the DEL targets further revealed stark enrichment in neurons and synaptic transmission terms and pathways. CONCLUSION: Our study highlights the utility of a systematic brain transcriptome analysis relying on the expression profiles measured across multiple brain regions and singles out white matter regions as a prospective target for further SZ research

Hot-Melt and Pressure-Sensitive Adhesives Based on Styrene-Isoprene-Styrene Triblock Copolymer, Asphaltene/Resin Blend and Naphthenic Oil

Asphaltene/resin blend (ARB) extracted from heavy crude oil was used to modify poly(styrene-block-isoprene-block-styrene) (SIS) to make it an adhesive. There were prepared double and triple mixtures containing 10–60% SIS, 10–40% ARB, and 10–50% naphthenic oil used as an additional plasticizer. The viscoelasticity of the mixtures at 25 °C and 120 °C was studied, their flow curves were obtained, and the temperature dependences of the loss tangent and the components of the complex modulus were measured. In addition, the mixtures were used as hot-melt adhesives (HMAs) and pressure-sensitive adhesives (PSAs) in the shear, peel, and pull-off tests of the adhesive bonds that they formed with steel. Both naphthenic oil and ARB act as plasticizers for SIS and make it sticky. However, only the combined use of ARB and the oil allows for achieving the best set of adhesive properties of the SIS-based mixture. High-quality HMA requires low oil content (optimal SIS/ARB/oil ratio is 50/40/10, pull-off adhesion strength (τt) of 1990 kPa), whereas a lot of the oil is needed to give SIS characteristics of a PSA (SIS/ARB/oil is 20/40/40, τt of 100 kPa). At the same time, the resulting PSA can be used as a hot-melt pressure-sensitive adhesive (HMPSA) that has many times lower viscosity than HMA (13.9 Pa·s versus 2640 Pa·s at 120 °C and 1 s−1) but provides a less strong adhesive bond (τt of 960 kPa)

Asphaltene-Stabilized Polyisobutylene Pressure-Sensitive Adhesives for Ultraviolet Protection and Surface Bonding

The usual way to protect indoor areas from solar UV radiation is to use UV-absorbing materials, which are applied as a thin film on the surface of the windowpane. Asphaltenes are useless wastes from crude oil refining that absorb UV radiation well, which gave the idea of their use in protective coatings. Pressure-sensitive adhesives based on polyisobutylene containing from 5 to 30 wt% of asphaltenes were obtained. Deterioration of the adhesive properties with the introduction of 5–20 wt% of asphaltenes was shown by adhesion tests, which can be associated with the plasticization of the polymer matrix. At the same time, the use of 30 wt% of asphaltenes leads to the polymer matrix reinforcement with the restoration of adhesive properties to the original level or even slightly higher. The rheological study of adhesives at 25 °C and 120 °C showed the structural network formation by asphaltenes at a content of 30 wt%, explaining the increase in adhesion performance. According to microscopy, asphaltenes are flat brown glass shards in a polymer matrix. They absorb electromagnetic radiation, predominantly in the UV range, while maintaining relative translucency in the visible range. This makes it possible to obtain thin films from the asphaltene-filled adhesive for bonding glass sheets to produce UV-blocked and tinted windowpanes

The Effect of Non-Solvent Nature on the Rheological Properties of Cellulose Solution in Diluted Ionic Liquid and Performance of Nanofiltration Membranes

The weak point of ionic liquids is their high viscosity, limiting the maximum polymer concentration in the forming solutions. A low-viscous co-solvent can reduce viscosity, but cellulose has none. This study demonstrates that dimethyl sulfoxide (DMSO), being non-solvent for cellulose, can act as a nominal co-solvent to improve its processing into a nanofiltration membrane by phase inversion. A study of the rheology of cellulose solutions in diluted ionic liquids ([EMIM]Ac, [EMIM]Cl, and [BMIM]Ac) containing up to 75% DMSO showed the possibility of decreasing the viscosity by up to 50 times while keeping the same cellulose concentration. Surprisingly, typical cellulose non-solvents (water, methanol, ethanol, and isopropanol) behave similarly, reducing the viscosity at low doses but causing structuring of the cellulose solution and its phase separation at high concentrations. According to laser interferometry, the nature of these non-solvents affects the mass transfer direction relative to the forming membrane and the substance interdiffusion rate, which increases by four-fold when passing from isopropanol to methanol or water. Examination of the nanofiltration characteristics of the obtained membranes showed that the dilution of ionic liquid enhances the rejection without changing the permeability, while the transition to alcohols increases the permeability while maintaining the rejection

Bacterial Metabolites of Human Gut Microbiota Correlating with Depression

Depression is a global threat to mental health that affects around 264 million people worldwide. Despite the considerable evolution in our understanding of the pathophysiology of depression, no reliable biomarkers that have contributed to objective diagnoses and clinical therapy currently exist. The discovery of the microbiota-gut-brain axis induced scientists to study the role of gut microbiota (GM) in the pathogenesis of depression. Over the last decade, many of studies were conducted in this field. The productions of metabolites and compounds with neuroactive and immunomodulatory properties among mechanisms such as the mediating effects of the GM on the brain, have been identified. This comprehensive review was focused on low molecular weight compounds implicated in depression as potential products of the GM. The other possible mechanisms of GM involvement in depression were presented, as well as changes in the composition of the microbiota of patients with depression. In conclusion, the therapeutic potential of functional foods and psychobiotics in relieving depression were considered. The described biomarkers associated with GM could potentially enhance the diagnostic criteria for depressive disorders in clinical practice and represent a potential future diagnostic tool based on metagenomic technologies for assessing the development of depressive disorders

Alterations of the Composition and Neurometabolic Profile of Human Gut Microbiota in Major Depressive Disorder

Major depressive disorder (MDD) is among the most prevalent mental disorders worldwide. Factors causing the pathogenesis of MDD include gut microbiota (GM), which interacts with the host through the gut–brain axis. In previous studies of GM in MDD patients, 16S rRNA sequencing was used, which provided information about composition but not about function. In our study, we analyzed whole metagenome sequencing data to assess changes in both the composition and functional profile of GM. We looked at the GM of 36 MDD patients, compared with that of 38 healthy volunteers. Comparative taxonomic analysis showed decreased abundances of Faecalibacterium prausnitzii, Roseburia hominis, and Roseburia intestinalis, and elevated abundances of Escherichia coli and Ruthenibacterium lactatiformans in the GM of MDD patients. We observed decreased levels of bacterial genes encoding key enzymes involved in the production of arginine, asparagine, glutamate, glutamine, melatonin, acetic, butyric and conjugated linoleic acids, and spermidine in MDD patients. These genes produced signature pairs with Faecalibacterium prausntizii and correlated with decreased levels of this species in the GM of MDD patients. These results show the potential impact of the identified biomarker bacteria and their metabolites on the pathogenesis of MDD, and should be confirmed in future metabolomic studies

Genome instability in MCF-7 cells exposed to gDNA^OX at final concentration 50 ng/mL for 24 hours.

<div><p>A – multiple micronuclei [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B1" target="_blank">1</a>], chromatin bridges [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B2" target="_blank">2</a>], M-phase chromatin decondensation [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B3" target="_blank">3</a>], non-treated control cells [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B4" target="_blank">4</a>] (x100). </p> <p>B – proportions of cells with micronuclei in non-treated control cells, cells exposed to gDNA, cells exposed to gDNA<b>^OX</b>. Grey columns: non-confluent, actively proliferating MCF-7 culture. Black columns: MCF-7 cells at high confluency. *p < 0.05 against control group of cells, non-parametric U-test.</p> <p>С - Exposure to gDNA<b>^OX</b> (50 ng/mL, 2 hours) induces formation of 8-oxodG-containing micronuclei (x100). </p></div

The exposure to gDNA^OX leads to an increase in the production of ROS.

<p>А – Microscopy-based evaluation of MCF-7 cells sequentially treated with DNA (50 ng/mL) and H2DCFH-DA (control, gDNA, gDNA^ox [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B1" target="_blank">1</a>]) and incubated for 30 minutes (x100). Alternatively, MCF-7 cells were incubated with DNA (50 ng/mL) for 1 hour followed by addition of H2DCFH-DA and photography 30 minutes later (gDNA^ox [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B2" target="_blank">2</a>]). B - MCF-7 cells exposed to gDNA^ox (0.5h; 50ng/mL), were sequentially treated with Mito-tracker TMRM (15 min) and H2DCFH-DA (15 min) (x200). C - Co-detection of labeled probe gDNA^red (50 ng/mL) and DCF after 30 minutes of incubation. D - The results of the quantification of fluorescence using plate reader [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B1" target="_blank">1</a>]. The time kinetics of fluorescence outputs in cells sequentially treated with H2DCFH-DA and, three minutes later, a DNA sample at final concentration of 5 or 50 ng/mL [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B2" target="_blank">2</a>]. The same for cells pretreated with DNA (final concentration 5 ng/mL) for one hour, with subsequent addition of H2DCFH-DA. *) p < 0.05 against control group of cells, non-parametric U-test.</p

The exposure to gDNA^OX (50 ng/mL) leads to a transient increase in expression cytoplasmic DNA sensor AIM2, while not changing expression levels of TLR9.

<div><p>A - intracellular localization of AIM2 (FITC-conjugated antibodies) and labeled probe gDNA<b>^red-ox</b> (x40). B – the ratio of the levels of AIM1 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B1" target="_blank">1</a>] and TLR9 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B2" target="_blank">2</a>] – encoding RNAs to the levels TBP-encoding reference mRNA in cells exposed to gDNA or gDNA^OX for 2 hrs (grey columns) and 48 hrs (black columns).</p> <p>C and D – Flow cytometry detection of AIM2 (C) and TLR9 (D) expression in MCF-7. Cells were stained with AIM2 (C) or TLR9 (D) antibody (secondary PE-conjugated antibodies). Panels D [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B1" target="_blank">1</a>] and E [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B1" target="_blank">1</a>] – control cells plots: FL2 versus SSC. R: gated area. Panels C [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B2" target="_blank">2</a>] and D [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B2" target="_blank">2</a>]: median signal intensity of FL2 (R) in MCF-7 cells (mean value for three independent experiments). Panels C [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B3" target="_blank">3</a>] and D [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B3" target="_blank">3</a>]: relative proportions of AIM2- or TLR9-positive cells in R gates [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077469#B1" target="_blank">1</a>]. Background fluorescence was quantified using PE-conjugated secondary antibodies. </p> <p>*p < 0.05 against control group of cells, non-parametric U-test.</p></div