Toll-like receptor 4-dependent innate immune responses are mediated by intracrine corticosteroids and activation of glycogen synthase kinase-3ß in astrocytes.

Reactive astrocytes are important pathophysiologically and synthesize neurosteroids. We observed that LPS increased immunoreactive TLR4 and key steroidogenic enzymes in cortical astrocytes of rats and investigated whether corticosteroids are produced and mediate astrocytic TLR4-dependent innate immune responses. We found that LPS increased steroidogenic acute regulatory protein (StAR) and StAR-dependent aldosterone production in purified astrocytes. Both increases were blocked by the TLR4 antagonist TAK242. LPS also increased 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) and corticosterone production, and both were prevented by TAK242 and by siRNAs against 11ß-HSD1, StAR, or aldosterone synthase (CYP11B2). Knockdown of 11ß-HSD1, StAR, or CYP11B2 or blocking either mineralocorticoid receptors (MR) or glucocorticoid receptors (GR) prevented dephosphorylation of p-Ser9GSK-3ß, activation of NF-κB, and the GSK-3ß-dependent increases of C3, IL-1ß, and TNF-α caused by LPS. Exogenous aldosterone mimicked the MR- and GSK-3ß-dependent pro-inflammatory effects of LPS in astrocytes, but corticosterone did not. Supernatants from astrocytes treated with LPS reduced MAP2 and viability of cultured neurons except when astrocytic StAR or MR was inhibited. In adrenalectomized rats, intracerebroventricular injection of LPS increased astrocytic TLR4, StAR, CYP11B2, and 11ß-HSD1, NF-κB, C3 and IL-1ß, decreased astrocytic p-Ser9GSK-3ß in the cortex and was neurotoxic, except when spironolactone was co-injected, consistent with the in vitro results. LPS also activated NF-κB in some NeuN+ and CD11b+ cells in the cortex, and these effects were prevented by spironolactone. We conclude that intracrine aldosterone may be involved in the TLR4-dependent innate immune responses of astrocytes and can trigger paracrine effects by activating astrocytic MR/GSK-3ß/NF-κB signaling.

Case report: Abdominal mesothelioma in Atelerix albiventris.

Hedgehogs, as exotic species, are more susceptible to various neoplastic conditions affecting diverse bodily systems, particularly the tegumentary, hemolymphatic, and digestive systems. Among these conditions, epithelial tumors are the most prevalent, followed by round cell tumors and mesenchymal tumors. A striking characteristic is the malignant nature of over 8% of these tumors, leading to a generally unfavorable prognosis. This study aims to present a unique case involving a 2.5 year-old male African pygmy hedgehog in Concepción, Biobío District, Chile, diagnosed with a mesenchymal neoplasia originating from mesothelial cells. The hedgehog presented to the veterinary clinic with acute abdominal pain, prompting ultrasound imaging, and comprehensive cytological, histopathological, and immunohistochemical analyses. During abdominal ultrasound, a mass was observed, and its cytological examination revealed the presence of malignant cells. The histopathological examination unveiled a diffuse mesothelial cell tissue interwoven with abundant fibrous tissue and small cysts containing serous fluid, all enveloped by flattened or cuboidal cells of mesothelial origin. Immunohistochemistry further confirmed the diagnosis, demonstrating positive immunostaining for calretinin and mesothelin markers, corroborating the diagnosis of fibrous malignant peritoneal mesothelioma. This case highlights the complexity of neoplastic conditions in hedgehogs and emphasizes the importance of multimodal diagnostic approaches for accurate identification and understanding of these rare diseases.

Differences in Out-of-Hospital Cardiac Arrest Outcomes Among 5 Racial/Ethnic Groups.

OBJECTIVE: Out-of-hospital cardiac arrest (OHCA) is a major health problem and one of the leading causes of death in adults older than 40. Multiple prior studies have demonstrated survival disparities based on race/ethnicity, but most of these focus on a single racial/ethnic group. This study evaluated OHCA variables and outcomes among on 5 racial/ethnic groups. METHODS: This is a retrospective review of data for adult patients in the Cardiac Arrest Registry to Enhance Survival (CARES) from 3 racially diverse urban counties in the San Francisco Bay Area from May 2009 to October 2021. Stratifying by 5 racial/ethnic groups, we evaluated patient survival outcomes based on patient demographics, emergency medical services response location, cardiac arrest characteristics, and hospital interventions. Adjusted risk ratios were calculated for survival to hospital discharge, controlling for sex, age, response locations, median income of response location, arrest witness, shockable rhythm, and bystander cardiopulmonary resuscitation as well as clustering by census tract. RESULTS: There were 10,757 patient entries analyzed: 42% White, 24% Black, 18% Asian, 9.3% Hispanic, 6.0% Pacific Islander, 0.7% American Indian/Alaska Native, and 0.1% multiple races selected; however, only the first 5 racial/ethnic groups had sufficient numbers for comparison. The adjusted risk ratio for survival to hospital discharge was lower among the 4 racial/ethnic groups compared with the White reference group: Black (0.79, p = 0.003), Asian (0.78 p = 0.004), Hispanic (0.79, p = 0.018), and Pacific Islander (0.78, p = 0.041) groups. The risk difference for positive neurologic outcome was also lower among all 4 racial/ethnic groups compared with the White reference group. CONCLUSIONS: The Black, Asian, Hispanic, and Pacific Islander groups were less likely to survive to hospital discharge from OHCA when compared with the White reference group. No variables were associated with decreased survival across any of these 4 groups.

Molecular characterization and demographic insights into soybean bud borer (Lepidoptera: Tortricidae) in Brazil.

The soybean bud borer, a soybean pest in Brazil, was initially identified as Crocidosema aporema (Walsingham 1914) (Lepidoptera: Tortricidae). Outbreaks of this species have recently increased, but identification of this pest remains uncertain, and the historical factors associated with its geographic distribution in Brazil are little known. Here, we conducted a species characterization and phylogeographic analysis based on molecular and morphological evidence. Ninety individuals of bud-borers Lepidoptera were collected in different regions of Brazil. We sequenced COI and COII mitochondrial genes and examined wing patterns and male genital morphology. DNA barcoding approach revealed that 10 individuals were Argyrotaenia sphaleropa (Meyrick 1909) (Lepidoptera: Tortricidae) and 80 were a species of the genus Crocidosema Zeller. The morphology of the adult genitalia and wings proved to be insufficient to confirm the identification of Brazilian individuals as C. aporema, a species originally described from a high-elevation site in Costa Rica. Furthermore, the genetic distance between putative C. aporema specimens from Brazil and Costa Rica (ranging from 5.2% to 6.4%) supports the hypothesis that the Brazilian specimens are not referable to C. aporema. Our analysis revealed a single genetic strain (i.e., species) with low genetic diversity on soybean crops. We found no indication that the genetic structure was related to geographic distance among populations or edaphoclimatic regions. The population expansion of the soybean bud borer coincides with the increase in the area of soybean production in Brazil, suggesting that expanded soybean farming has allowed a significant increase in the effective population size of this pest.

Assessment of the radionuclide remediation potential of novel miscanthus hybrids.

There are few studies related to the radionuclide remediation options, which comply to the demands of the environmentally non-destructive physical remediation methods. So far, most of the research was conducted on the phytoremediation capacity of different energy crops, as well as the established miscanthus hybrids which involved metal and heavy metal contaminants. Hence, the objective of this research was the radioecological characterization of the examined agroecosystem, including the initial source of the radionuclides (soil) as well as different miscanthus hybrids grown on the same soil. The results have shown that the radioactive content of soil was similar to the global averages. All measurements of the activity concentration of 137Cs in miscanthus samples were below the detection limits. There is also an indication that 210Pb is leaching into the lower layers (or is being taken up by miscanthus plant from the upper layers). Moreover, transfer factors (TFs) for radionuclides, as a more precise parameter for evaluating the phytoremediation potential, were calculated; the TFs were found to be very low for 226Ra (≤0.07), TFs for 40K (≤0.39) and for 232Th (≤0.21) were in the lower limits, whereas the TFs for 238U were found to be the highest (≤0.92). For 210Pb, the TFs were not calculated, since the expectation was that a significant part of the measured quantity came from the air, and not through the soil. Having in mind the sustainability and the circularity aspect of the radionuclide phytoremediation system, the appropriate management method should be applied for the disposal and utilization of the biomass contaminated with radionuclides. This research has shown that the radiological content in miscanthus is high enough and the ash content is low enough that miscanthus ash could be considered as a NORM (Naturally Occurring Radioactive Material), and it can be further used for the construction industry (i.e. concrete, tiles), in mixtures with other materials with certain limitations, similar to the utilization of ash from other sources such as coal or wood.

Two new species of the hyperdiverse geometrid moth genus Eois (Lepidoptera, Geometridae, Larentiinae) from Ecuador, with descriptions of early stages.

The hyperdiverse geometrid genus Eois Hübner, estimated to encompass more than 1,000 species, is among the most species-rich genera in all of Lepidoptera. While the genus has attracted considerable attention from ecologists and evolutionary biologists in recent decades, limited progress has been made on its alpha taxonomy. This contribution focuses on the Olivacea clade, whose monophyly has been recognized previously through molecular analyses. We attempt to define the clade from a morphological perspective and recognize the following species based on morphology and genomic data: E.olivacea (Felder & Rogenhofer); E.pseudolivacea Doan, sp. nov.; E.auruda (Dognin), stat. rev.; E.beebei (Fletcher, 1952), stat. rev.; E.boliviensis (Dognin), stat. rev.; and E.parumsimii Doan, sp. nov. Descriptions and illustrations of the immature stages of E.pseudolivacea reared from Piper (Piperaceae) in Ecuador are provided.

Salidroside directly activates HSC70, revealing a new role for HSC70 in BDNF signalling and neurogenesis after cerebral ischemia.

Salidroside, a principal bioactive component of Rhodiola crenulata, is neuroprotective across a wide time window in stroke models. We investigated whether salidroside induced neurogenesis after cerebral ischemia and aimed to identify its primary molecular targets. Rats, subjected to transient 2 h of middle cerebral artery occlusion (MCAO), received intraperitoneal vehicle or salidroside ± intracerebroventricular HSC70 inhibitor VER155008 or TrkB inhibitor ANA-12 for up to 7 days. MRI, behavioural tests, immunofluorescent staining and western blotting measured effects of salidroside. Reverse virtual docking and enzymatic assays assessed interaction of salidroside with purified recombinant HSC70. Salidroside dose-dependently decreased cerebral infarct volumes and neurological deficits, with maximal effects by 50 mg/kg/day. This dose also improved performance in beam balance and Morris water maze tests. Salidroside significantly increased BrdU+/nestin+, BrdU+/DCX+, BrdU+/NeuN+, BrdU-/NeuN+ and BDNF+ cells in the peri-infarct cortex, with less effect in striatum and no significant effect in the subventricular zone. Salidroside was predicted to bind with HSC70. Salidroside dose-dependently increased HSC70 ATPase and HSC70-dependent luciferase activities, but it did not activate HSP70. HSC70 immunoreactivity concentrated in the peri-infarct cortex and was unchanged by salidroside. However, VER155008 prevented salidroside-dependent increases of neurogenesis, BrdU-/NeuN+ cells and BDNF+ cells in peri-infarct cortex. Salidroside also increased BDNF protein and p-TrkB/TrkB ratio in ischemic brain, changes prevented by VER155008 and ANA-12, respectively. Additionally, ANA-12 blocked salidroside-dependent neurogenesis and increased BrdU-/NeuN+ cells in the peri-infarct cortex. Salidroside directly activates HSC70, thereby stimulating neurogenesis and neuroprotection via BDNF/TrkB signalling after MCAO. Salidroside and similar activators of HSC70 might provide clinical therapies for ischemic stroke.

Lysine-36 of Drosophila histone H3.3 supports adult longevity.

Aging is a multifactorial process that disturbs homeostasis, increases disease susceptibility, and ultimately results in death. Although the definitive set of molecular mechanisms responsible for aging remain to be discovered, epigenetic change over time is proving to be a promising piece of the puzzle. Several post-translational histone modifications have been linked to the maintenance of longevity. Here, we focus on lysine-36 of the replication-independent histone protein, H3.3 (H3.3K36). To interrogate the role of this residue in Drosophila developmental gene regulation, we generated a lysine-to-arginine mutant that blocks the activity of its cognate-modifying enzymes. We found that an H3.3BK36R mutation causes a significant reduction in adult lifespan, accompanied by dysregulation of the genomic and transcriptomic architecture. Transgenic co-expression of wild-type H3.3B completely rescues the longevity defect. Because H3.3 is known to accumulate in nondividing tissues, we carried out transcriptome profiling of young vs aged adult fly heads. The data show that loss of H3.3K36 results in age-dependent misexpression of NF-κB and other innate immune target genes, as well as defects in silencing of heterochromatin. We propose H3.3K36 maintains the postmitotic epigenomic landscape, supporting longevity by regulating both pericentric and telomeric retrotransposons and by suppressing aberrant immune signaling.

Complete genome sequences of Streptomyces griseus phages Spelly and Phredrick.

We present the complete genome sequences of two viruses with siphovirus morphology, isolated from soils collected in Southwestern Indiana using the host Streptomyces griseus. Spelly is a BE2 cluster phage with a 131,347-bp genome. Phredrick is a BK1 cluster phage with a 128,873-bp genome.

REVEILLE2 thermosensitive splicing: a molecular basis for the integration of nocturnal temperature information by the Arabidopsis circadian clock.

Cold stress is one of the major environmental factors that limit growth and yield of plants. However, it is still not fully understood how plants account for daily temperature fluctuations, nor how these temperature changes are integrated with other regulatory systems such as the circadian clock. We demonstrate that REVEILLE2 undergoes alternative splicing after chilling that increases accumulation of a transcript isoform encoding a MYB-like transcription factor. We explore the biological function of REVEILLE2 in Arabidopsis thaliana using a combination of molecular genetics, transcriptomics, and physiology. Disruption of REVEILLE2 alternative splicing alters regulatory gene expression, impairs circadian timing, and improves photosynthetic capacity. Changes in nuclear gene expression are particularly apparent in the initial hours following chilling, with chloroplast gene expression subsequently upregulated. The response of REVEILLE2 to chilling extends our understanding of plants immediate response to cooling. We propose that the circadian component REVEILLE2 restricts plants responses to nocturnal reductions in temperature, thereby enabling appropriate responses to daily environmental changes.

Assessment of Drought and Zinc Stress Tolerance of Novel Miscanthus Hybrids and Arundo donax Clones Using Physiological, Biochemical, and Morphological Traits.

High-yield potential perennial crops, such as Miscanthus spp. and Arundo donax are amongst the most promising sources of sustainable biomass for bioproducts and bioenergy. Although several studies assessed the agronomic performance of these species on diverse marginal lands, research to date on drought and zinc (Zn) resistance is scarce. Thus, the objective of this study was to investigate the drought and Zn stress tolerance of seven novel Miscanthus hybrids and seven Arundo clones originating from different parts of Italy. We subjected both species to severe drought (less than 30%), and Zn stress (400 mg/kg-1 of ZnSO4) separately, after one month of growth. All plants were harvested after 28 days of stress, and the relative drought and Zn stress tolerance were determined by using a set of morpho-physio-biochemical and biomass attributes in relation to stress tolerance indices (STI). Principal component analysis (PCA), hierarchical clustering analysis (HCA) and stress tolerance indices (STI) were performed for each morpho-physio-biochemical and biomass parameters and showed significant relative differences among the seven genotypes of both crops. Heatmaps of these indices showed how the different genotypes clustered into four groups. Considering PCA ranking value, Miscanthus hybrid GRC10 (8.11) and Arundo clone PC1 (11.34) had the highest-ranking value under both stresses indicating these hybrids and clones are the most tolerant to drought and Zn stress. In contrast, hybrid GRC3 (-3.33 lowest ranking value) and clone CT2 (-5.84) were found to be the most sensitive to both drought and Zn stress.

Lysine-36 of Drosophila histone H3.3 supports adult longevity.

Aging is a multifactorial process that disturbs homeostasis, increases disease susceptibility, and ultimately results in death. Although the definitive set of molecular mechanisms responsible for aging remain to be discovered, epigenetic change over time is proving to be a promising piece of the puzzle. Several posttranslational histone modifications (PTMs) have been linked to the maintenance of longevity. Here, we focus on lysine-36 of the replication-independent histone protein, H3.3 (H3.3K36). To interrogate the role of this residue in Drosophila developmental gene regulation, we generated a lysine to arginine mutant that blocks the activity of its cognate modifying enzymes. We found that an H3.3BK36R mutation causes a significant reduction in adult lifespan, accompanied by dysregulation of the genomic and transcriptomic architecture. Transgenic co-expression of wild-type H3.3B completely rescues the longevity defect. Because H3.3 is known to accumulate in non-dividing tissues, we carried out transcriptome profiling of young vs aged adult fly heads. The data show that loss of H3.3K36 results in age-dependent misexpression of NF-κB and other innate immune target genes, as well as defects in silencing of heterochromatin. We propose H3.3K36 maintains the postmitotic epigenomic landscape, supporting longevity by regulating both pericentric and telomeric retrotransposons and by suppressing aberrant immune signaling.

Novel Miscanthus hybrids: Modelling productivity on marginal land in Europe using dynamics of canopy development determined by light interception.

New biomass crop hybrids for bioeconomic expansion require yield projections to determine their potential for strategic land use planning in the face of global challenges. Our biomass growth simulation incorporates radiation interception and conversion efficiency. Models often use leaf area to predict interception which is demanding to determine accurately, so instead we use low-cost rapid light interception measurements using a simple laboratory-made line ceptometer and relate the dynamics of canopy closure to thermal time, and to measurements of biomass. We apply the model to project the European biomass potentials of new market-ready hybrids for 2020-2030. Field measurements are easier to collect, the calibration is seasonally dynamic and reduces influence of weather variation between field sites. The model obtained is conservative, being calibrated by crops of varying establishment and varying maturity on less productive (marginal) land. This results in conservative projections of miscanthus hybrids for 2020-2030 based on 10% land use conversion of the least (productive) grassland and arable for farm diversification, which show a European potential of 80.7-89.7 Mt year-1 biomass, with potential for 1.2-1.3 EJ year-1 energy and 36.3-40.3 Mt year-1 carbon capture, with seeded Miscanthus sacchariflorus × sinensis displaying highest yield potential. Simulated biomass projections must be viewed in light of the field measurements on less productive land with high soil water deficits. We are attempting to model the results from an ambitious and novel project combining new hybrids across Europe with agronomy which has not been perfected on less productive sites. Nevertheless, at the time of energy sourcing issues, seed-propagated miscanthus hybrids for the upscaled provision of bioenergy offer an alternative source of renewable energy. If European countries provide incentives for growers to invest, seeded hybrids can improve product availability and biomass yields over the current commercial miscanthus variety.

Perennial biomass cropping and use: Shaping the policy ecosystem in European countries.

Demand for sustainably produced biomass is expected to increase with the need to provide renewable commodities, improve resource security and reduce greenhouse gas emissions in line with COP26 commitments. Studies have demonstrated additional environmental benefits of using perennial biomass crops (PBCs), when produced appropriately, as a feedstock for the growing bioeconomy, including utilisation for bioenergy (with or without carbon capture and storage). PBCs can potentially contribute to Common Agricultural Policy (CAP) (2023-27) objectives provided they are carefully integrated into farming systems and landscapes. Despite significant research and development (R&D) investment over decades in herbaceous and coppiced woody PBCs, deployment has largely stagnated due to social, economic and policy uncertainties. This paper identifies the challenges in creating policies that are acceptable to all actors. Development will need to be informed by measurement, reporting and verification (MRV) of greenhouse gas emissions reductions and other environmental, economic and social metrics. It discusses interlinked issues that must be considered in the expansion of PBC production: (i) available land; (ii) yield potential; (iii) integration into farming systems; (iv) R&D requirements; (v) utilisation options; and (vi) market systems and the socio-economic environment. It makes policy recommendations that would enable greater PBC deployment: (1) incentivise farmers and land managers through specific policy measures, including carbon pricing, to allocate their less productive and less profitable land for uses which deliver demonstrable greenhouse gas reductions; (2) enable greenhouse gas mitigation markets to develop and offer secure contracts for commercial developers of verifiable low-carbon bioenergy and bioproducts; (3) support innovation in biomass utilisation value chains; and (4) continue long-term, strategic R&D and education for positive environmental, economic and social sustainability impacts.

Use of volume-targeted non-invasive bilevel positive airway pressure ventilation in a patient with amyotrophic lateral sclerosis, / Utilização de ventilação não invasiva com dois níveis de pressão positiva nas vias aéreas e volume alvo em paciente com esclerose lateral amiotrófica

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which most patients die of respiratory failure. Although volume-targeted non-invasive bilevel positive airway pressure (BPAP) ventilation has been studied in patients with chronic respiratory failure of various etiologies, its use in ALS has not been reported. We present the case of a 66-year-old woman with ALS and respiratory failure treated with volume-targeted BPAP ventilation for 15 weeks. Weekly data downloads showed that disease progression was associated with increased respiratory muscle weakness, decreased spontaneous breathing, and increased use of non-invasive positive pressure ventilation, whereas tidal volume and minute ventilation remained relatively constant.

A esclerose lateral amiotrófica (ELA) é uma doença neurodegenerativa progressiva. A maioria dos pacientes com ELA falece por insuficiência respiratória. Embora a ventilação não invasiva com dois níveis de pressão positiva nas vias aéreas e volume alvo tenha sido estudada em pacientes com insuficiência respiratória crônica de diferentes etiologias, sua utilização em ELA não foi relatada. Apresentamos o caso de uma mulher de 66 anos com ELA e insuficiência respiratória tratada com ventilação com dois níveis de pressão positiva e volume alvo por 15 semanas. Os dados obtidos semanalmente mostraram que a progressão da doença estava associada com aumento da fraqueza muscular respiratória, redução da respiração espontânea e maior uso de ventilação não invasiva com pressão positiva, enquanto o volume corrente e a ventilação minuto permaneceram relativamente constantes.

Avaliaçäo "in vitro" da eficiência do selamento marginal pela vibraçäo aplicada na face ou no cone de guta-percha quando da obturaçäo de canais radiculares / In vitro evaluation of marginal apical leakage throught vibration aplied on gutta percha points or patient face during root canal obturation

Propomo-nos a avaliar "in vitro", pela montagem de dentes em manequim, a infiltraçäo apical do azul-de-metileno utilizado como indicador das condiçöes de selamento marginal na porçäo apical das obturaçöes realizadas com cimento N-Rickert e cones de guta-percha aplicados de forma convencional ou quando acompanhado de vibraçäo na face, ou no próprio cone de guta-percha. Os resultados permitem afirmar que a eficácia do selamento é maior na seqüência dos testes efetuados