Early growth response 2 (EGR2) is a novel regulator of the senescence programme.

Senescence, a state of stable growth arrest, plays an important role in ageing and age-related diseases in vivo. Although the INK4/ARF locus is known to be essential for senescence programmes, the key regulators driving p16 and ARF transcription remain largely underexplored. Using siRNA screening for modulators of the p16/pRB and ARF/p53/p21 pathways in deeply senescent human mammary epithelial cells (DS HMECs) and fibroblasts (DS HMFs), we identified EGR2 as a novel regulator of senescence. EGR2 expression is up-regulated during senescence, and its ablation by siRNA in DS HMECs and HMFs transiently reverses the senescent phenotype. We demonstrate that EGR2 activates the ARF and p16 promoters and directly binds to both the ARF and p16 promoters. Loss of EGR2 down-regulates p16 levels and increases the pool of p16- p21- 'reversed' cells in the population. Moreover, EGR2 overexpression is sufficient to induce senescence. Our data suggest that EGR2 is a direct transcriptional activator of the p16/pRB and ARF/p53/p21 pathways in senescence and a novel marker of senescence

Mid-Ocean Outbreaks of COVID-19 with Tell-Tale Signs of Aerial Incidence

DOI: 10.37421/Virol Curr Res.2020.4.114 is not valid yet [https://doi.org/10.37421/Virol%20Curr%20Res.2020.4.114].Copyright © 2022 The Authors. Outbreaks of COVID-19 in passengers and crew in ships at sea continue to pose a problem for conventional epidemiology. In one instance the crew of an Argentinian fishing trawler, who were quarantined and tested negative before sailing, contracted the disease after 35 days at sea. In another instance a livestock ship had crew that was isolated and confined becoming sick with presumed COVID-19 whilst sailing in mid-ocean

Overview SARS-CoV-2 Pandemic as January-February 2022: Likely Cometary Origin, Global Spread, Prospects for Future Vaccine Efficacy

Copyright © The Athors 2022. As the SARS-CoV-2 pandemic is nearing its eventual end we focus on what we believe are two key omissions from the mainstream scientific literature and which have significant implications for how mankind manages the next global pandemic. We therefore review data, observations, analyses and conclusions from our series of papers published through 2020 and 2021 on its likely cometary origin and global spread. We also revisit our long held understanding of the superior effectiveness of intra-nasal vaccines against respiratory tract pathogens that involve induction of dimeric secretory IgA antibodies. While these two oversights seem disparate, together they provide us with new insights into our collective awareness of how we might view and address the next global pandemic. We begin with our hypothesis of the likely cometary origin of the SARS-CoV-2 virus via a bolide strike in the stratosphere on the night of October 11 2019 on the 40o N line over Jilin in NE China. Further global spread most likely occurred via prevailing wind systems transporting both the pristine cometary virus followed by continuing strikes from the same primary source as well as prior human-passaged virus transmitted by person to person spread and through contaminated dust in global wind systems. We also include a discussion of our prior work on data relating to vaccine protective efficacy. Finally we review the totality of evidence concerning the likely origin and global spread of the predominant variants of the virus ‘Omicron’ (+Delta mix?) from early to mid-December 2021 and extending into the first week January 2022. We describe the striking data showing the large numbers of infectious cases per day and outline the scale of what appears to be a global pandemic phenomenon, the causes of which are unclear and not completely understood. Firstly, these essentially simultaneous and sudden global-wide epidemic COVID-19 out breaks, appear to be largely correlated with events external to the Earth, probably causing globally correlated precipitation events. They appear related broadly to “Space Weather” events that render the Earth vulnerable to cosmic pandemic pathogen attack particularly during times of the minima of the Sunspot Solar Cycle which we are now currently passing through. Secondly, we argue that these sudden global-wide epidemic outbreaks of COVID-19 are specifically largely influenced by global wind transport and deposition mechanisms, the physics of which we need to further explore and comprehend. We conclude on an optimistic note for mankind. Given our prior knowledge of the effectiveness against respiratory tract pathogens of mucosal immunity involving induction of dimeric secretory IgA antibodies, we consider that the recently published intra-nasal vaccine data from laboratories based at the University of California, San Francisco and, independently at Yale University. These latter studies hold out great promise for the future development of both pan-specific and specific immunity against future pandemics caused by suddenly emergent respiratory pathogens, whether viral, bacterial or fungal

(Working title) Are We Meeting Oral Health Needs of Care Home Populations?

Aim: To evaluate care home (N) staff knowledge of oral care in comparison to NHS Quality Improvement Scotland (NHS QIS) guidelines. To identify barriers to delivering oral care and determine if Oral Health Educator (OHE) training had an effect upon staff knowledge of oral care delivery. Setting: The study was undertaken within Greater Glasgow, 2005 to 2007. Subjects and Methods: From 33 care homes (N), 28 participated in data gathering comprising 109 staff. A ‘knowledge check-list’ based upon daily oral care protocol from NHS QIS Best Practice Statement (BPS) served as template for knowledge assessment. An OHE undertook small group discussions related to the BPS in a sub-group of original participants and a second round of data collected. Results: The majority of staff (n=86, 79%) agreed that residents required assistance with oral care and placed oral care (n=85, 78%) as a moderate to high priority. Only 57% of managers and 49% of nurses had received training in oral care. Most staff (79% of managers, 85% of nurses) were unaware of the NHS QIS BPS. Deficiencies in knowledge of key areas within the BPS were identified. Between pre- and post-OHE training, significant differences were identified in prioritisation of oral care (p =0.009), perceived competence (p =0.005) and confidence giving advice (p =0.004). Following OHE intervention, knowledge of BPS protocol increased by 45%. Conclusion: Knowledge of oral care provision by carers for home residents requires substantial improvement. An OHE training programme structured around the NHS QIS BPS demonstrated a measurable increase in levels of staff knowledge of oral care

Mitochondria of the Yeasts Saccharomyces cerevisiae and Kluyveromyces lactis Contain Nuclear rDNA-Encoded Proteins

In eukaryotes, the nuclear ribosomal DNA (rDNA) is the source of the structural 18S, 5.8S and 25S rRNAs. In hemiascomycetous yeasts, the 25S rDNA sequence was described to lodge an antisense open reading frame (ORF) named TAR1 for Transcript Antisense to Ribosomal RNA. Here, we present the first immuno-detection and sub-cellular localization of the authentic product of this atypical yeast gene. Using specific antibodies against the predicted amino-acid sequence of the Saccharomyces cerevisiae TAR1 product, we detected the endogenous Tar1p polypeptides in S. cerevisiae (Sc) and Kluyveromyces lactis (Kl) species and found that both proteins localize to mitochondria. Protease and carbonate treatments of purified mitochondria further revealed that endogenous Sc Tar1p protein sub-localizes in the inner membrane in a Nin-Cout topology. Plasmid-versions of 5′ end or 3′ end truncated TAR1 ORF were used to demonstrate that neither the N-terminus nor the C-terminus of Sc Tar1p were required for its localization. Also, Tar1p is a presequence-less protein. Endogenous Sc Tar1p was found to be a low abundant protein, which is expressed in fermentable and non-fermentable growth conditions. Endogenous Sc TAR1 transcripts were also found low abundant and consistently 5′ flanking regions of TAR1 ORF exhibit modest promoter activity when assayed in a luciferase-reporter system. Using rapid amplification of cDNA ends (RACE) PCR, we also determined that endogenous Sc TAR1 transcripts possess heterogeneous 5′ and 3′ ends probably reflecting the complex expression of a gene embedded in actively transcribed rDNA sequence. Altogether, our results definitively ascertain that the antisense yeast gene TAR1 constitutes a functional transcription unit within the nuclear rDNA repeats

Nature and consequences of interactions between Salmonella enterica serovar Dublin and host cells in cattle

International audienceAbstractSalmonella enterica is a veterinary and zoonotic pathogen of global importance. While murine and cell-based models of infection have provided considerable knowledge about the molecular basis of virulence of Salmonella, relatively little is known about salmonellosis in naturally-affected large animal hosts such as cattle, which are a reservoir of human salmonellosis. As in humans, Salmonella causes bovine disease ranging from self-limiting enteritis to systemic typhoid-like disease and exerts significant economic and welfare costs. Understanding the nature and consequences of Salmonella interactions with bovine cells will inform the design of effective vaccines and interventions to control animal and zoonotic infections. In calves challenged orally with S. Dublin expressing green fluorescent protein (GFP) we observed that the bacteria were predominantly extracellular in the distal ileal mucosa and within gut-associated lymph nodes 48 h post-infection. Intracellular bacteria, identified by flow cytometry using the GFP signal, were predominantly within MHCII+ macrophage-like cells. In contrast to observations from murine models, these S. Dublin-infected cells had elevated levels of MHCII and CD40 compared to both uninfected cells from the same tissue and cells from the cognate tissue of uninfected animals. Moreover, no gross changes of the architecture of infected lymph nodes were observed as was described previously in a mouse model. In order to further investigate Salmonella-macrophage interactions, net replication of S. enterica serovars that differ in virulence in cattle was measured in bovine blood-derived macrophages by enumeration of gentamicin-protected bacteria and fluorescence dilution, but did not correlate with host-specificity

Impacts of savanna trees on forage quality for a large African herbivore

Recently, cover of large trees in African savannas has rapidly declined due to elephant pressure, frequent fires and charcoal production. The reduction in large trees could have consequences for large herbivores through a change in forage quality. In Tarangire National Park, in Northern Tanzania, we studied the impact of large savanna trees on forage quality for wildebeest by collecting samples of dominant grass species in open grassland and under and around large Acacia tortilis trees. Grasses growing under trees had a much higher forage quality than grasses from the open field indicated by a more favourable leaf/stem ratio and higher protein and lower fibre concentrations. Analysing the grass leaf data with a linear programming model indicated that large savanna trees could be essential for the survival of wildebeest, the dominant herbivore in Tarangire. Due to the high fibre content and low nutrient and protein concentrations of grasses from the open field, maximum fibre intake is reached before nutrient requirements are satisfied. All requirements can only be satisfied by combining forage from open grassland with either forage from under or around tree canopies. Forage quality was also higher around dead trees than in the open field. So forage quality does not reduce immediately after trees die which explains why negative effects of reduced tree numbers probably go initially unnoticed. In conclusion our results suggest that continued destruction of large trees could affect future numbers of large herbivores in African savannas and better protection of large trees is probably necessary to sustain high animal densities in these ecosystems

Perivascular Adipose Tissue and Its Role in Type 2 Diabetes and Cardiovascular Disease

Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity. Adipose tissue-derived substances (adipokines) and especially inflammatory products of adipose tissue control insulin sensitivity and vascular function. In the past years, adipose tissue associated with the vasculature, or perivascular adipose tissue (PAT), has been shown to produce a variety of adipokines that contribute to regulation of vascular tone and local inflammation. This review describes our current understanding of the mechanisms linking perivascular adipose tissue to vascular function, inflammation, and insulin resistance. Furthermore, we will discuss mechanisms controlling the quantity and adipokines secretion by PAT