Unique gene expression profiles of microglia and astrocytes following innate immune activation

Both astrocytes and microglia are often activated in association with diseases of the central nervous system (CNS), including virus-induced neurological disease. Understanding how activation alters the transcriptome of these cells may offer valuable insight in regards to how activated cells mediate neurological damage. Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation. In the current study, we utilized microarray analysis to examine the response of astrocyte and microglia to specific innate immune stimuli. Since virus infections often induce activation of toll-like receptor 7 (TLR7), we used the TLR7 agonist imiquimod that has been shown to induce activation of both microglia and astrocytes in vivo and in vitro. We found that microglia generate a much stronger response to TLR7 activation than astrocytes, with the upregulation and downregulation of substantially more genes in microglia than that observed in astrocytes. We identified genes that were uniquely upregulated by each cell type and examined these genes for upregulation by other factors including virus infection. These data provide new insights into innate immune activation of astrocytes and microglia that will be useful in characterizing the cellular responses of these genes during infection or insult of the CNS

effect of dimethylacetamide and n methylacetamide on the quality and fertility of frozen thawed chicken semen

ABSTRACT The aim was to compare the effect of dimethylacetamide (DMA) and N-methylacetamide (NMA) concentrations on the quality and fertility of post-thaw chicken semen. Ejaculates were obtained from 30 Hi-Line White roosters and processed according to the following treatments: lake pre-freezing extender + 0.1M trehalose (LPF-T) + 6% DMA (control treatment), LPF-T + 9% DMA, LPF-T + 6% NMA, and LPF-T + 9% NMA. Sperm quality (viability, motility, and kinetic traits) was assessed before and after cryopreservation. A total of 15 laying hens per treatment were inseminated to assess fertility and embryo viability. Sperm cryopreserved in presence of DMA had significantly better in vitro quality compared to NMA, showing the highest proportion of viable and progressive motile sperm recovered after thawing. Furthermore, proportion of progressive motile sperm and the VCL, LIN, ALH, and WOB mean values were significantly improved in semen samples frozen/thawed with 6% compared to 9% cryoprotectant concentration. However, the best cryoprotective action on sperm quality played by DMA and the lowest cryoprotectant concentration did not translate into a concomitant advantage in in vivo semen fertility that showed no differences between cryoprotectant and cryoprotectant concentration treatments. Finally, the cryoprotectant DMA and NMA showed an opposite effect on embryo viability in comparison with the effect played on in vitro semen quality, being NMA more efficient than DMA on preserving viable embryos. The present results suggest the urgency to further decrease the cryoprotectant concentration in poultry semen freezing procedures and to assess the specific toxic effect of cryoprotectant on sperm integrity, fertility, and embryo development

Breeding performance in the Italian chicken breed Mericanel della Brianza

In Italy, 90 local avian breeds were described; the majority (61%) were classified as extinct and only 8.9% as still widely spread. Therefore, efforts for conservation of Italian avian breeds are urgently required. The aim of this study was to record the breeding performance of the Italian breed Mericanel della Brianza to multiply a small population, in order to develop a conservation programme. Fourteen females and eight males were available at the beginning of the reproductive season in 2009 and organised into eight families (1 male/1-2 females) kept in floor pens. Birds received a photoperiod of 14L:10D and were fed ad libitum. Breeding performance was recorded from March to June. Egg production and egg weight were recorded daily; eggs were set every two weeks and fertility, embryo mortality and hatchability were recorded. Mean egg production was 37% and mean egg weight was 34±3.49 g. High fertility values from 94% to 87% were recorded in the first three settings and the overall mean fertility value was 81.6%. Overall hatchability was only 49.6% owing to a high proportion of dead embryos. Embryo mortality occurred mainly between days 2 and 7 of incubation and during hatching. The highest hatchability values were recorded in settings 1 and 2, 69% and 60% respectively, and a large decrease was found in the subsequent settings. Marked variations in egg production, fertility, hatchability and embryo mortality were found among families. The present results represent the basic know ledge of reproductive parameters necessary to improve the reproductive efficiency of the breed within a conservation plan

The CO2 reduction potential for the European industry via direct electrification of heat supply (power-to-heat)

The decarbonisation of industry is a bottleneck for the EU's 2050 target of climate neutrality. Replacing fossil fuels with low-carbon electricity is at the core of this challenge; however, the aggregate electrification potential and resulting system-wide CO2 reductions for diverse industrial processes are unknown. Here, we present the results from a comprehensive bottom-up analysis of the energy use in 11 industrial sectors (accounting for 92% of Europe's industry CO2 emissions), and estimate the technological potential for industry electrification in three stages. Seventy-eight per cent of the energy demand is electrifiable with technologies that are already established, while 99% electrification can be achieved with the addition of technologies currently under development. Such a deep electrification reduces CO2 emissions already based on the carbon intensity of today's electricity (∼300 gCO2 kWhel−1). With an increasing decarbonisation of the power sector IEA: 12 gCO2 kWhel−1 in 2050), electrification could cut CO2 emissions by 78%, and almost entirely abate the energy-related CO2 emissions, reducing the industry bottleneck to only residual process emissions. Despite its decarbonisation potential, the extent to which direct electrification will be deployed in industry remains uncertain and depends on the relative cost of electric technologies compared to other low-carbon options

Effect of Cancer-Related Cachexia and Associated Changes in Nutritional Status, Inflammatory Status, and Muscle Mass on Immunotherapy Efficacy and Survival in Patients with Advanced Non-Small Cell Lung Cancer

Immune checkpoint inhibitor (ICI)-based immunotherapy has significantly improved the survival of patients with advanced non-small cell lung cancer (NSCLC); however, a significant percentage of patients do not benefit from this approach, and predictive biomarkers are needed. Increasing evidence demonstrates that cachexia, a complex syndrome driven by cancer-related chronic inflammation often encountered in patients with NSCLC, may impair the immune response and ICI efficacy. Herein, we carried out a prospective study aimed at evaluating the prognostic and predictive role of cachexia with the related changes in nutritional, metabolic, and inflammatory parameters (assessed by the multidimensional miniCASCO tool) on the survival and clinical response (i.e., disease control rate) to ICI-based immunotherapy in patients with advanced NSCLC. We included 74 consecutive patients. Upon multivariate regression analysis, we found a negative association between IL-6 levels (odds ratio (OR) = 0.9036; 95%CI = 0.8408–0.9711; p = 0.0025) and the miniCASCO score (OR = 0.9768; 95%CI = 0.9102–0.9999; p = 0.0310) with the clinical response. As for survival outcomes, multivariate COX regression analysis found that IL-6 levels and miniCASCO-based cachexia severity significantly affected PFS (hazard ratio (HR) = 1.0388; 95%CI = 1.0230–1.0548; p < 0.001 and HR = 1.2587; 95%CI = 1.0850–1.4602; p = 0.0024, respectively) and OS (HR = 1.0404; 95%CI = 1.0221–1.0589; p < 0.0001 and HR = 2.3834; 95%CI = 1.1504–4.9378; p = 0.0194, respectively). A comparison of the survival curves by Kaplan–Meier analysis showed a significantly lower OS in patients with cachexia versus those without cachexia (p = 0.0323), as well as higher miniCASCO-based cachexia severity (p = 0.0428), an mGPS of 2 versus those with a lower mGPS (p = 0.0074), and higher IL-6 levels (>6 ng/mL) versus those with lower IL-6 levels (≤6 ng/mL) (p = 0.0120). In conclusion, our study supports the evidence that cachexia, with its related changes in inflammatory, body composition, and nutritional parameters, is a key prognostic and predictive factor for ICIs. Further larger studies are needed to confirm these findings and to explore the potential benefit of counteracting cachexia to improve immunotherapy efficacy

Human Enterovirus B: Selective Inhibition by Quinoxaline Derivatives and Bioinformatic RNA-Motif Identification as New Targets

The Enterovirus genus includes many viruses that are pathogenic in humans, including Coxsackie viruses and rhinoviruses, as well as the emerging enteroviruses D68 and A71. Currently, effective antiviral agents are not available for the treatment or prevention of enterovirus infections, which remain an important threat to public health. We recently identified a series of quinoxaline derivatives that were provento be potent inhibitors of coxsackievirus B5, the most common and a very important human pathogen belonging to the enterovirus genus. We have shown how most active derivatives interfere with the earliest stages of viral replication, blocking infection. Considering the broad antiviral spectrum, a very attractive property for an antiviral drug, we aimed to investigate the antiviral activity of the most promising compounds against other Enterovirus species. Here, we investigated the susceptibility of a panel of representatives of Enterovirus genus (enterovirus A71, belonging to A species; coxsackieviruses B4 and B3;echovirus 9, belonging to B species; and enterovirus D68, belonging to D species) to quinoxaline inhibitors. We also tested cytotoxicity and selectivity indices of the selected compounds, as well as their effects on virus yield.We also investigated their potential mechanism of action by a time course assay. In addition, a bioinformatic analysis was carried out to discover potential new conserved motifs in CVB3 and CVB4 compared to the other enterovirus species that can be used as new targets

Genome sequences of 10 SARS-CoV-2 viral strains obtained by nanopore sequencing of nasopharyngeal swabs in Malta

The genome sequences of 10 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from Sliema, Malta, were obtained by Nanopore sequencing using the amplicon sequencing approach developed by the Artic Network. The assembled genomes were analyzed with Pangolin software and assigned to the B.1 lineage, which is widely circulating in Europe.peer-reviewe