Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysregulation of Astrocyte Ion Homeostasis and Its Relevance for Stroke-Induced Brain Damage

Ischemic stroke is a leading cause of mortality and chronic disability. Either recovery or progression towards irreversible failure of neurons and astrocytes occurs within minutes to days, depending on remaining perfusion levels. Initial damage arises from energy depletion resulting in a failure to maintain homeostasis and ion gradients between extra- and intracellular spaces. Astrocytes play a key role in these processes and are thus central players in the dynamics towards recovery or progression of stroke-induced brain damage. Here, we present a synopsis of the pivotal functions of astrocytes at the tripartite synapse, which form the basis of physiological brain functioning. We summarize the evidence of astrocytic failure and its consequences under ischemic conditions. Special emphasis is put on the homeostasis and stroke-induced dysregulation of the major monovalent ions, namely Na+, K+, H+, and Cl−, and their involvement in maintenance of cellular volume and generation of cerebral edema.
Determinants of Bird Species Literacy—Activity/Interest and Specialization Are More Important Than Socio-Demographic Variables

Simple Summary Biodiversity is declining around the world and knowledge about biodiversity declines in a similar way. In this study, we addressed predictors of species knowledge, i.e., the question of what influences or causes species knowledge. The focus was knowledge about common bird species in Germany. Data were collected from July to October 2020 via an online questionnaire, containing demographic data, engagement in birdwatching, interest/activity, and images of 28 bird species native to Germany. Data were collected from adult students, lecturers and administrative staff of the Eberhard Karls University Tübingen. Men identified more species than women, garden owners more than non-owners. Hometown size had no influence. Employees scored higher than students. However, we found that birding specialization was the most important predictor, followed by bird-related interest/activity. We suggest including such questions in addition to conventional demographic questions in the future. Abstract Biodiversity is declining, and knowledge about biodiversity declines in a similar way. Previous studies have already addressed predictors of species knowledge. Here, we studied bird species knowledge related to demographics, but also to individual differences in affinity to nature, by including (i) birding specialization and (ii) bird-related activities/interest. Data were collected from July to October 2020 via an online questionnaire, containing demographic data, birding specialization, interest/activity, and images of 28 bird species native to Germany. Participants were adult students, lecturers and administrative staff of the Eberhard Karls University Tübingen. A total of 1967 questionnaires were returned in this study (35.3% male, 53.8% students, 69% had access to a garden). Mean identification score was 16.31 ± 6.38. Thus, participants were able to identify more than half of the species (total species n = 28). Men identified more species than women, garden owners had higher identification scores than non-owners, while hometown size was not significant. A distance to the next forest patch >10 km was related to lower identification scores. Employees scored higher than students. Correlation between species knowledge and birding specialization was high, as was the correlation with bird interest/activity. Higher scores were found in older people. In the linear univariate model, birding specialization and bird interest were the most influential predictors of species knowledge, followed by distance to next forest patch and occupation (student vs employees). Other variables were not significant. We suggest including such measures (interest, attitude, etc.) into further studies and move forward from the urban–rural narrative to more complex analyses of living circumstances.
Colossal challenges to healthcare workers combating the second wave of coronavirus disease 2019 (COVID-19) in India

To the Editor — Since April 2021, India has been experiencing a massive surge in coronavirus disease 2019 (COVID-19) cases caused by the double mutant or B.1. 617 variant. This sudden spike in the number of cases, deemed the second pandemic wave, with a record-breaking > 400,000 cases daily, has proven to be much more alarming and devastating than the first wave. 1 The Indian healthcare community is facing major setbacks due to a lack of necessary resources to fight this outbreak, 2 and healthcare workers (HCWs) are also reaping the consequences. This fight is not only against the virus but also against ignorance. Ignorance and a false sense of normalcy, caused by lack of planning and education, have led to leaders and healthcare institutions being unprepared and people behaving carelessly. 3 HCWs,
Sex-Specific Cannabidiol- and Iloperidone-Induced Neuronal Activity Changes in an In Vitro MAM Model System of Schizophrenia

Cortical circuit dysfunction is thought to be an underlying mechanism of schizophrenia (SZ) pathophysiology with normalization of aberrant circuit activity proposed as a biomarker for antipsychotic efficacy. Cannabidiol (CBD) shows potential as an adjunctive antipsychotic therapy; however, potential sex effects in these drug interactions remain unknown. In the present study, we sought to elucidate sex effects of CBD coadministration with the atypical antipsychotic iloperidone (ILO) on the activity of primary cortical neuron cultures derived from the rat methylazoxymethanol acetate (MAM) model used for the study of SZ. Spontaneous network activity measurements were obtained using a multielectrode array at baseline and following administration of CBD or ILO alone, or combined. At baseline, MAM male neurons displayed increased bursting activity whereas MAM female neurons exhibited no difference in bursting activity compared to sex-matched controls. CBD administered alone showed a rapid but transient increase in neuronal activity in the MAM networks, an effect more pronounced in females. Furthermore, ILO had an additive effect on CBD-induced elevations in activity in the MAM male neurons. In the MAM female neurons, CBD or ILO administration resulted in time-dependent elevations in neuronal activity, but the short-term CBD-induced increases in activity were lost when CBD and ILO were combined. Our findings indicate that CBD induces rapid increases in cortical neuronal activity, with sex-specific drug interactions upon ILO coadministration. This suggests that sex should be a consideration when implementing adjunct therapy for treatment of SZ.
Evaluation of Misalignment Effect in Vehicle-to-Vehicle Visible Light Communications: Experimental Demonstration of a 75 Meters Link

The use of visible light communications technology in communication-based vehicle applications is gaining more and more interest as the research community is constantly overcoming challenge after challenge. In this context, this article addresses the issues associated with the use of Visible Light Communications (VLC) technology in Vehicle-to-Vehicle (V2V) communications, while focusing on two crucial issues. On the one hand, it aims to investigate the achievable communication distance in V2V applications while addressing the least favorable case, namely the one when a standard vehicle rear lighting system is used as a VLC emitter. On the other hand, this article investigates another highly unfavorable use case scenario, i.e., the case when two vehicles are located on adjacent lanes, rather than on the same lane. In order to evaluate the compatibility of the VLC technology with the usage in inter-vehicle communication, a VLC prototype is intensively evaluated in outdoor conditions. The experimental results show a record V2V VLC distance of 75 m, while providing a Bit Error Ratio (BER) of 10−7–10−6. The results also show that the VLC technology is able to provide V2V connectivity even in a situation where the vehicles are located on adjacent lanes, without a major impact on the link performances. Nevertheless, this situation generates an initial no-coverage zone, which is determined by the VLC receiver reception angle, whereas in some cases, vehicle misalignment can generate a BER increase that can go up to two orders of magnitude.
Risk Factors for the Structural Progression of Myopic Glaucomatous Eyes with a History of Laser Refractive Surgery

As laser refractive surgeries (LRS) have been widely performed to correct myopia, ophthalmologists easily encounter patients with glaucoma who have a history of LRS. It is well known that intraocular pressure (IOP) in eyes with glaucoma is not accurate when measured using Goldmann applanation tonometry. However, risk factors for glaucoma progression, particularly those associated with measured IOP, have rarely been studied. We analysed data for 40 patients with a history of LRS and 50 age-matched patients without a history of LRS. Structural progression was defined as significant changes in thickness in the peripapillary retinal nerve fibre layer as identified using optical coherence tomography event-based guided progression analysis. Risk factors were determined via Cox regression analysis. Disc haemorrhage (DH) was associated with glaucoma progression in both the non-LRS group and LRS group (hazard ratio (HR): 4.650, p = 0.012 and HR: 8.666, p = 0.019, respectively). However, IOP fluctuation was associated with glaucoma progression only in the LRS group (HR: 1.452, p = 0.023). Our results show that DH was a significant sign of progression in myopic glaucoma eyes. When treating patients with myopia and glaucoma, IOP fluctuation should be monitored more carefully, even if IOP seems to be well controlled.
Synthesis of Optically Tunable and Thermally Stable PMMA–PVA/CuO NPs Hybrid Nanocomposite Thin Films

We report the synthesis and comprehensive characterization of polymethylmethacrylate (PMMA)/polyvinylalcohol (PVA) polymeric blend doped with different concentrations of Copper oxide (CuO) nanoparticles (NPs). The PMMA–PVA/CuO nanocomposite hybrid thin films containing wt. % = 0%, 2%, 4%, 8%, and 16% of CuO NPs are deposited on glass substrates via dip-coating technique. Key optical parameters are measured, analyzed, and interpreted. Tauc, Urbach, Spitzer–Fan, and Drude models are employed to calculate the optical bandgap energy (Eg) and the optoelectronic parameters of PMMA–PVA/CuO nanocomposites. The refractive index and Eg of undoped PMMA–PVA are found to be (1.5–1.85) and 4.101 eV, respectively. Incorporation of specific concentrations of CuO NPs into PMMA–PVA blend leads to a considerable decrease in Eg and to an increase of the refractive index. Moreover, Fourier Transform Infrared Spectroscopy (FTIR) transmittance spectra are measured and analyzed for undoped and doped polymeric thin films to pinpoint the major vibrational modes in the spectral range (500 and 4000 cm−1) as well as to elucidate the nature of chemical network bonding. Thermogravimetric analysis (TGA) is conducted under appropriate conditions to ensure the thermal stability of thin films. Doped polymeric thin films are found to be thermally stable below 105 °C. Therefore, controlled tuning of optoelectronic and thermal properties of doped polymeric thin films by introducing an appropriate concentration of inorganic fillers leads to a smart design of scaled multifunctional devices.
Structural insights into dpCoA-RNA decapping by NudC

ABSTRACT Various kinds of cap structures, such as m7G, triphosphate groups, NAD and dpCoA, protect the 5′ terminus of RNA. The cap structures bond covalently to RNA and affect its stability, translation, and transport. The removal of the caps is mainly executed by Nudix hydrolase family proteins, including Dcp2, RppH and NudC. Numerous efforts have been made to elucidate the mechanism underlying the removal of m7G, triphosphate group, and NAD caps. In contrast, few studies related to the cleavage of the RNA dpCoA cap have been conducted. Here, we report the hydrolytic activity of Escherichia coli NudC towards dpCoA and dpCoA-capped RNA in vitro. We also determined the crystal structure of dimeric NudC in complex with dpCoA at 2.0 Å resolution. Structural analysis revealed that dpCoA is recognized and hydrolysed in a manner similar to NAD. In addition, NudC may also remove other dinucleotide derivative caps of RNA, which comprise the AMP moieties. NudC homologs in Saccharomyces cerevisiae and Arabidopsis thaliana exhibited similar dpCoA decapping (deCoAping) activity. These results together indicate a conserved mechanism underpinning the hydrolysis of dpCoA-capped RNA in both prokaryotes and eukaryotes.
Non-viral Vectors in Gene Therapy: Recent Development, Challenges, and Prospects

Gene therapy has been experiencing a breakthrough in recent years, targeting various specific cell groups in numerous therapeutic areas. However, most recent clinical studies maintain the use of traditional viral vector systems, which are challenging to manufacture cost-effectively at a commercial scale. Non-viral vectors have been a fast-paced research topic in gene delivery, such as polymers, lipids, inorganic particles, and combinations of different types. Although non-viral vectors are low in their cytotoxicity, immunogenicity, and mutagenesis, attracting more and more researchers to explore the promising delivery system, they do not carry ideal characteristics and have faced critical challenges, including gene transfer efficiency, specificity, gene expression duration, and safety. This review covers the recent advancement in non-viral vectors research and formulation aspects, the challenges, and future perspectives.
Anti-EGFR VHH Antibody under Thermal Stress Is Better Solubilized with a Lysine than with an Arginine SEP Tag

In this study, we assessed the potential of arginine and lysine solubility-enhancing peptide (SEP) tags to control the solubility of a model protein, anti-EGFR VHH-7D12, in a thermally denatured state at a high temperature. We produced VHH-7D12 antibodies attached with a C-terminal SEP tag made of either five or nine arginines or lysines (7D12-C5R, 7D12-C9R, 7D12-C5K and 7D12-C9K, respectively). The 5-arginine and 5-lysine SEP tags increased the E. coli expression of VHH-7D12 by over 80%. Biophysical and biochemical analysis confirmed the native-like secondary and tertiary structural properties and the monomeric nature of all VHH-7D12 variants. Moreover, all VHH-7D12 variants retained a full binding activity to the EGFR extracellular domain. Finally, thermal stress with 45-minute incubation at 60 and 75 °C, where VHH-7D12 variants are unfolded, showed that the untagged VHH-7D12 formed aggregates in all of the four buffers, and the supernatant protein concentration was reduced by up to 35%. 7D12-C5R and 7D12-C9R did not aggregate in Na-acetate (pH 4.7) and Tris-HCl (pH 8.5) but formed aggregates in phosphate buffer (PB, pH 7.4) and phosphate buffer saline (PBS, pH 7.4). The lysine tags (either C5K or C9K) had the strongest solubilization effect, and both 7D12-C5K and 7D12-C9K remained in the supernatant. Altogether, our results indicate that, under a thermal stress condition, the lysine SEP tags solubilization effect is more potent than that of an arginine SEP tags, and the SEP tags did not affect the structural and functional properties of the protein.
SETD2-mediated H3K14 trimethylation promotes ATR activation and stalled replication fork restart in response to DNA replication stress

Significance ATR is a central molecule involved in the DNA replication stress response and repair that ensures genome stability. Whether chromatin modifiers or chromatin modifications also regulate ATR activation, however, is unclear. We conclude that SETD2-mediated H3K14me3 recruits the RPA complex to chromatin and thus promotes ATR activation during conditions of replication stress. Using a series of biological and molecular approaches, we carefully delineated this new SETD2-H3K14me3-RPA-ATR axis that promotes ATR activation and improves cancer cell survival in response to DNA replication stress. Our data open up future opportunities to generate cancer therapeutics strategies based on this pathway. Ataxia telangiectasia and Rad3 related (ATR) activation after replication stress involves a cascade of reactions, including replication protein A (RPA) complex loading onto single-stranded DNA and ATR activator loading onto chromatin. The contribution of histone modifications to ATR activation, however, is unclear. Here, we report that H3K14 trimethylation responds to replication stress by enhancing ATR activation. First, we confirmed that H3K14 monomethylation, dimethylation, and trimethylation all exist in mammalian cells, and that both SUV39H1 and SETD2 methyltransferases can catalyze H3K14 trimethylation in vivo and in vitro. Interestingly, SETD2-mediated H3K14 trimethylation markedly increases in response to replication stress induced with hydroxyurea, a replication stress inducer. Under these conditions, SETD2-mediated H3K14me3 recruited the RPA complex to chromatin via a direct interaction with RPA70. The increase in H3K14me3 levels was abolished, and RPA loading was attenuated when SETD2 was depleted or H3K14 was mutated. Rather, the cells were sensitive to replication stress such that the replication forks failed to restart, and cell-cycle progression was delayed. These findings help us understand how H3K14 trimethylation links replication stress with ATR activation.
Elevation of CD40/CD40L Inflammatory Pathway Molecules in Carotid Plaques from Moderate-and-Severe Obstructive Sleep Apnea Patients

A chronic inflammatory process characteristic of obstructive sleep apnea promotes vascular endothelial dysfunction and atherogenesis. This process can lead to destabilization and rupture of cardiovascular plaques, which clinically manifests as an acute coronary syndrome or stroke. The aim of this study was to investigate the inflammatory pathway leading to plaque destabilization in non-to-mild and moderate-to-severe groups of OSA patients. This prospective study involved enrollment of patients scheduled for endarterectomy. A sleep study was performed prior to surgery. Immunohistochemistry was performed on atherosclerotic plaques from carotid arteries obtained during standard open endarterectomy to determine levels of CD40, CD40L receptors, MCP-1, and MMP-9. The 46 patients included 14 controls, 13 with mild, 11 with moderate, and 8 with severe OSA. Increased expression of CD40, CD40L receptors, MCP-1, and MMP-9 were found to be proportionate with OSA severity. However, significant differences among groups were observed only for MCP-1 (p = 0.014). Increased expression of inflammatory markers (CD40, CD40L, MCP-1, MMP-9) is associated with increasing OSA severity. This suggests the CD40-CD4-L inflammatory pathway may contribute to plaque instability and rupture in OSA patients.
Environmental Status of Cryptococcus neoformans and Cryptococcus gattii in Colombia

The genus Cryptococcus comprises more than 80 species, including C. neoformans and C. gattii, which are pathogenic to humans, mainly affecting the central nervous system. The two species differ in geographic distribution and environmental niche. C. neoformans has a worldwide distribution and is often isolated from bird droppings. On the contrary, C. gattii is reported in tropical and subtropical regions and is associated with Eucalyptus species. This review aims to describe the distribution of environmental isolates of the Cryptococcus neoformans species complex and the Cryptococcus gattii species complex in Colombia. A systematic investigation was carried out using different databases, excluding studies of clinical isolates reported in the country. The complex of the species of C. gattii is recovered mainly from trees of the genus Eucalyptus spp. , while the complex of the species of C. neoformans is recovered mainly from avian excrement, primarily Columba livia (pigeons) excrement. In addition, greater positivity was found at high levels of relative humidity. Likewise, an association was observed between the presence of the fungus in places with little insolation and cold or temperate temperatures compared to regions with high temperatures.
On-Line Remaining Useful Life Estimation of Power Connectors Focused on Predictive Maintenance

Connections are critical elements in power systems, exhibiting higher failure probability. Power connectors are considered secondary simple devices in power systems despite their key role, since a failure in one such element can lead to major issues. Thus, it is of vital interest to develop predictive maintenance approaches to minimize these issues. This paper proposes an on-line method to determine the remaining useful life (RUL) of power connectors. It is based on a simple and accurate model of the degradation with time of the electrical resistance of the connector, which only has two parameters, whose values are identified from on-line acquired data (voltage drop across the connector, electric current and temperature). The accuracy of the model presented in this paper is compared with the widely applied autoregressive integrated moving average model (ARIMA), showing enhanced performance. Next, a criterion to determine the RUL is proposed, which is based on the inflection point of the expression describing the electrical resistance degradation. This strategy allows determination of when the connector must be replaced, thus easing predictive maintenance tasks. Experimental results from seven connectors show the potential and viability of the suggested method, which can be applied to many other devices.
Structural Insights of Three 2,4-Disubstituted Dihydropyrimidine-5-carbonitriles as Potential Dihydrofolate Reductase Inhibitors

In this report, we describe the structural characterization of three 2,4-disubstituted-dihydropyrimidine-5-carbonitrile derivatives, namely 2-{[(4-nitrophenyl)methyl]sulfanyl}-6-oxo-4-propyl-1,6-dihydropyrimidine-5-carbonitrile 1, 4-(2-methylpropyl)-2-{[(4-nitrophenyl)methyl]sulfanyl}-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 2, and 2-[(2-ethoxyethyl)sulfanyl]-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile monohydrate 3. An X-ray diffraction analysis revealed that these compounds were crystallized in the centrosymmetric space groups and adopt an L-shaped conformation. One of the compounds (3) crystallized with a water molecule. A cyclic motif (R22(8)) mediated by N–H···O hydrogen bond was formed in compounds 1 and 2, whereas the corresponding motif was not favorable, due to the water molecule, in compound 3. The crystal packing of these compounds was analyzed based on energy frameworks performed at the B3LYP/6-31G(d,p) level of theory. Various inter-contacts were characterized using the Hirshfeld surface and its associated 2D-fingerprint plots. Furthermore, a molecular docking simulation was carried out to assess the inhibitory potential of the title compounds against the human dihydrofolate reductase (DHFR) enzyme.