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Upon infection, human papillomavirus (HPV) manipulates host cell gene expression to create an environment that is supportive of a productive and persistent infection. The virus-induced changes to the host cell's transcriptome are thought to contribute to carcinogenesis. Here, we show by RNA-sequencing that oncogenic HPV18 episome replication in primary human foreskin keratinocytes (HFKs) drives host transcriptional changes that are consistent between multiple HFK donors. We have previously shown that HPV18 recruits the host protein CTCF to viral episomes to control the differentiation-dependent viral transcriptional programme. Since CTCF is an important regulator of host cell transcription via coordination of epigenetic boundaries and long-range chromosomal interactions, we hypothesised that HPV18 may also manipulate CTCF to contribute to host transcription reprogramming. Analysis of CTCF binding in the host cell genome by ChIP-Seq revealed that while the total number of CTCF binding sites is not altered by the virus, there are a sub-set of CTCF binding sites that are either enriched or depleted of CTCF. Many of these altered sites are clustered within regulatory elements of differentially expressed genes, including the tumour suppressor gene cell adhesion molecule 1 (CADM1), which supresses epithelial cell growth and invasion. We show that HPV18 establishment results in reduced CTCF binding at the CADM1 promoter and upstream enhancer. Loss of CTCF binding is coincident with epigenetic repression of CADM1, in the absence of CpG hypermethylation, while adjacent genes including the transcriptional regulator ZBTB16 are activated. These data indicate that the CADM1 locus is subject to topological rearrangement following HPV18 establishment. We tested this hypothesis using 4C-Seq (circular chromosome confirmation capture-sequencing) and show that HPV18 establishment causes a loss of long-range chromosomal interactions between the CADM1 transcriptional start site and the upstream transcriptional enhancer. These data show that HPV18 manipulates host cell promoter-enhancer interactions to drive transcriptional reprogramming that may contribute to HPV-induced disease progression.

IntroductionSoil microbial communities, including biological soil crust microbiomes, play key roles in water, carbon and nitrogen cycling, biological weathering, and other nutrient releasing processes of desert ecosystems. However, our knowledge of microbial distribution patterns and ecological drivers is still poor, especially so for the Chihuahuan Desert.MethodsThis project investigated the effects of trampling disturbance on surface soil microbiomes, explored community composition and structure, and related patterns to abiotic and biotic landscape characteristics within the Chihuahuan Desert biome. Composite soil samples were collected in disturbed and undisturbed areas of 15 long-term ecological research plots in the Jornada Basin, New Mexico. Microbial diversity of cross-domain microbial groups (total Bacteria, Cyanobacteria, Archaea, and Fungi) was obtained via DNA amplicon metabarcode sequencing. Sequence data were related to landscape characteristics including vegetation type, landforms, ecological site and state as well as soil properties including gravel content, soil texture, pH, and electrical conductivity.ResultsFilamentous Cyanobacteria dominated the photoautotrophic community while Proteobacteria and Actinobacteria dominated among the heterotrophic bacteria. Thaumarchaeota were the most abundant Archaea and drought adapted taxa in Dothideomycetes and Agaricomycetes were most abundant fungi in the soil surface microbiomes. Apart from richness within Archaea (p = 0.0124), disturbed samples did not differ from undisturbed samples with respect to alpha diversity and community composition (p ≥ 0.05), possibly due to a lack of frequent or impactful disturbance. Vegetation type and landform showed differences in richness of Bacteria, Archaea, and Cyanobacteria but not in Fungi. Richness lacked strong relationships with soil variables. Landscape features including parent material, vegetation type, landform type, and ecological sites and states, exhibited stronger influence on relative abundances and microbial community composition than on alpha diversity, especially for Cyanobacteria and Fungi. Soil texture, moisture, pH, electrical conductivity, lichen cover, and perennial plant biomass correlated strongly with microbial community gradients detected in NMDS ordinations.DiscussionOur study provides first comprehensive insights into the relationships between landscape characteristics, associated soil properties, and cross-domain soil microbiomes in the Chihuahuan Desert. Our findings will inform land management and restoration efforts and aid in the understanding of processes such as desertification and state transitioning, which represent urgent ecological and economical challenges in drylands around the world.

Inflammation is a major cause of morbidity and mortality in Western societies. Despite use of multiple drugs, both chronic and acute inflammation still represent major health burdens. Inflammation produces highly reactive dicarbonyl lipid peroxidation products such as isolevuglandins which covalently modify and cross-link proteins via lysine residues. Mitochondrial dysfunction has been associated with inflammation; however, its molecular mechanisms and pathophysiological role are still obscure. We hypothesized that inflammation-induced isolevuglandins contribute to mitochondrial dysfunction and mortality. To test this hypothesis, we have (a) investigated the mitochondrial dysfunction in response to synthetic 15-E2-isolevuglandin (IsoLG) and its adducts; (b) developed a new mitochondria-targeted scavenger of isolevuglandins by conjugating 2-hydroxybenzylamine to the lipophilic cation triphenylphosphonium, (4-(4-aminomethyl)-3-hydroxyphenoxy)butyl)-triphenylphosphonium (mito2HOBA); (c) tested if mito2HOBA protects from mitochondrial dysfunction and mortality using a lipopolysaccharide model of inflammation. Acute exposure to either IsoLG or IsoLG adducts with lysine, ethanolamine or phosphatidylethanolamine inhibits mitochondrial respiration and attenuates Complex I activity. Complex II function was much more resistant to IsoLG. We confirmed that mito2HOBA markedly accumulates in isolated mitochondria and it is highly reactive with IsoLGs. To test the role of mitochondrial IsoLGs, we studied the therapeutic potential of mito2HOBA in lipopolysaccharide mouse model of sepsis. Mito2HOBA supplementation in drinking water (0.1 g/L) to lipopolysaccharide treated mice increased survival by 3-fold, improved complex I-mediated respiration, and histopathological analyses supported mito2HOBA-mediated protection of renal cortex from cell injury. These data support the role of mitochondrial IsoLG in mitochondrial dysfunction and inflammation. We conclude that reducing mitochondrial IsoLGs may be a promising therapeutic target in inflammation and conditions associated with mitochondrial oxidative stress and dysfunction.

Abstract Disability prevention and preservation of independence is crucial for successful aging of older adults. To date, relatively little is known regarding disparities in independent aging in a disadvantaged older adult population despite widely recognized health disparities reported in other populations and disciplines. In the U.S., the Southeastern region also known as “the Deep South”, is an economically and culturally unique region ravaged by pervasive health disparities – thus it is critical to evaluate barriers to independent aging in this region along with strategies to overcome these barriers. The objective of this narrative review is to highlight unique barriers to independent aging in the Deep South and to acknowledge gaps and potential strategies and opportunities to fill these gaps. We have synthesized findings of literature retrieved from searches of computerized databases and authoritative texts. Ultimately, this review aims to facilitate discussion and future research that will help to address the unique challenges to the preservation of independence among older adults in the Deep South region.

Upon infection, human papillomavirus (HPV) manipulates host cell gene expression to create an environment that is supportive of a productive and persistent infection. The virus-induced changes to the host cell's transcriptome are thought to contribute to carcinogenesis. Here, we show by RNA-sequencing that oncogenic HPV18 episome replication in primary human foreskin keratinocytes (HFKs) drives host transcriptional changes that are consistent between multiple HFK donors. We have previously shown that HPV18 recruits the host protein CTCF to viral episomes to control the differentiation-dependent viral transcriptional programme. Since CTCF is an important regulator of host cell transcription via coordination of epigenetic boundaries and long-range chromosomal interactions, we hypothesised that HPV18 may also manipulate CTCF to contribute to host transcription reprogramming. Analysis of CTCF binding in the host cell genome by ChIP-Seq revealed that while the total number of CTCF binding sites is not altered by the virus, there are a sub-set of CTCF binding sites that are either enriched or depleted of CTCF. Many of these altered sites are clustered within regulatory elements of differentially expressed genes, including the tumour suppressor gene cell adhesion molecule 1 (CADM1), which supresses epithelial cell growth and invasion. We show that HPV18 establishment results in reduced CTCF binding at the CADM1 promoter and upstream enhancer. Loss of CTCF binding is coincident with epigenetic repression of CADM1, in the absence of CpG hypermethylation, while adjacent genes including the transcriptional regulator ZBTB16 are activated. These data indicate that the CADM1 locus is subject to topological rearrangement following HPV18 establishment. We tested this hypothesis using 4C-Seq (circular chromosome confirmation capture-sequencing) and show that HPV18 establishment causes a loss of long-range chromosomal interactions between the CADM1 transcriptional start site and the upstream transcriptional enhancer. These data show that HPV18 manipulates host cell promoter-enhancer interactions to drive transcriptional reprogramming that may contribute to HPV-induced disease progression. Author summary: Infection with oncogenic HPV is the cause of numerous cancer types, which generally arise after persistent HPV infection. Upon infection, HPV alters the gene expression profile of infected cells to facilitate virus replication and persistence. Multiple mechanisms of HPV-induced host cell reprogramming have been previously suggested. Here, we show that HPV infection induces rearrangement of specific genomic loci by altering the chromatin binding of the host cell protein CTCF, an important regulator of chromatin architecture. Loss of CTCF binding to a cluster of binding sites at the CADM1 locus on chromosome 11 is coincident with epigenetic reprogramming and disruption of long-range chromatin interactions, resulting in transcriptional repression of CADM1. Our data show that repression of CADM1 is an early event in HPV-driven disease, preceding hypermethylation of the CADM1 transcriptional promoter that is frequently observed in HPV-driven cancers, demonstrating a novel mechanism of HPV-induced host cell transcriptional reprogramming. [ABSTRACT FROM AUTHOR]

Water is crucial to human survival in general, and determining the WQI (water quality index) is one of the primary aspects. The existing water quality classification models are facing various challenges and gaps that are impeding their effectiveness. These challenges include limited data availability, the intricate nature of water systems, spatial and temporal variability, non-linear relationships, sensor noise, and error, interpretability, and explainability. It is imperative to address these challenges to improve the accuracy and efficacy of the models and to ensure that they continue to serve as reliable tools for monitoring and safeguarding water quality. To solve the issues, this paper proposes a Stacked Ensemble efficient long short-term memory (StackEL) model for an efficient water quality index classification. At first, the raw input data is pre-processed to rescale the input data using data normalization and one-hot encoding. After that, the process known as variational mode decomposition (VMD) is applied to get at the intrinsic mode functions (IMFs). Consequently, feature selection is performed using an extended coati optimization (EX-CoA) algorithm to select the most significant attributes from the feature selection. Here, publicly available datasets, namely the water quality dataset from Kaggle, are used for classification and performed using are used to perform the Stacked Ensemble efficient long short-term memory (StackEL) classification process effectively. To further perfect the proposed prediction model, the Dwarf Mongoose optimization (DMO) method is implemented. Several measures of effectiveness are examined. When compared to other existing models, the suggested model can achieve a high accuracy of 98.85% of the water quality dataset.

IntroductionSoil microbial communities, including biological soil crust microbiomes, play key roles in water, carbon and nitrogen cycling, biological weathering, and other nutrient releasing processes of desert ecosystems. However, our knowledge of microbial distribution patterns and ecological drivers is still poor, especially so for the Chihuahuan Desert.MethodsThis project investigated the effects of trampling disturbance on surface soil microbiomes, explored community composition and structure, and related patterns to abiotic and biotic landscape characteristics within the Chihuahuan Desert biome. Composite soil samples were collected in disturbed and undisturbed areas of 15 long-term ecological research plots in the Jornada Basin, New Mexico. Microbial diversity of cross-domain microbial groups (total Bacteria, Cyanobacteria, Archaea, and Fungi) was obtained via DNA amplicon metabarcode sequencing. Sequence data were related to landscape characteristics including vegetation type, landforms, ecological site and state as well as soil properties including gravel content, soil texture, pH, and electrical conductivity.ResultsFilamentous Cyanobacteria dominated the photoautotrophic community while Proteobacteria and Actinobacteria dominated among the heterotrophic bacteria. Thaumarchaeota were the most abundant Archaea and drought adapted taxa in Dothideomycetes and Agaricomycetes were most abundant fungi in the soil surface microbiomes. Apart from richness within Archaea (p = 0.0124), disturbed samples did not differ from undisturbed samples with respect to alpha diversity and community composition (p ≥ 0.05), possibly due to a lack of frequent or impactful disturbance. Vegetation type and landform showed differences in richness of Bacteria, Archaea, and Cyanobacteria but not in Fungi. Richness lacked strong relationships with soil variables. Landscape features including parent material, vegetation type, landform type, and ecological sites and states, exhibited stronger influence on relative abundances and microbial community composition than on alpha diversity, especially for Cyanobacteria and Fungi. Soil texture, moisture, pH, electrical conductivity, lichen cover, and perennial plant biomass correlated strongly with microbial community gradients detected in NMDS ordinations.DiscussionOur study provides first comprehensive insights into the relationships between landscape characteristics, associated soil properties, and cross-domain soil microbiomes in the Chihuahuan Desert. Our findings will inform land management and restoration efforts and aid in the understanding of processes such as desertification and state transitioning, which represent urgent ecological and economical challenges in drylands around the world.

Herpes simplex virus type 1 (HSV-1) primarily targets the oral and nasal epithelia before establishing latency in the trigeminal ganglion (TG) and other peripheral ganglia. HSV-1 can also infect and become latent in the central nervous system (CNS) independent of latency in the TGs. Recent studies suggest entry to the CNS via two distinct routes: the TG-brainstem connection and olfactory nerve; however, to date, there is no characterization of brain regions targeted during HSV-1 primary infection. Furthermore, the immune response by microglia may also contribute to the heterogeneity between different brain regions. However, the response to HSV-1 by microglia has not been characterized in a region-specific manner. This study investigated the time course of HSV-1 spread within the olfactory epithelium (OE) and CNS following intranasal inoculation and the corresponding macrophage/microglial response in a C57BL/6 mouse model. We found an apical to basal spread of HSV-1 within the OE and underlying tissue accompanied by an inflammatory response of macrophages. OE infection was followed by infection of a small subset of brain regions targeted by the TG in the brainstem and other cranial nerve nuclei, including the vagus and hypoglossal nerve. Furthermore, other brain regions were positive for HSV-1 antigens, such as the locus coeruleus (LC), raphe nucleus (RaN), and hypothalamus while sparing the hippocampus and cortex. Within each brain region, microglia activation also varied widely. These findings provide critical insights into the region-specific dissemination of HSV-1 within the CNS, elucidating potential mechanisms linking viral infection to neurological and neurodegenerative diseases. IMPORTANCE This study shows how herpes simplex virus type 1 (HSV-1) spreads within the brain after infecting the nasal passages. Our data reveal the distinct pattern of HSV-1 through the brain during a non-encephalitic infection. Furthermore, microglial activation was also temporally and spatially specific, with some regions of the brain having sustained microglial activation even in the absence of viral antigens. Previous reports have identified specific brain regions found to be positive for HSV-1 infection; however, to date, there has not been a concise investigation of the anatomical spread of HSV-1 and the brain regions consistently vulnerable to viral entry and spread. Understanding these region-specific differences in infection and immune response is crucial because it links HSV-1 infection to potential triggers for neurological and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Food safety is crucial to attaining food security and sustainability. Unsafe foods for human and animal consumption lead to product recalls and rejection, negatively impacting the global economy and trade. Similarly, climate change can adversely affect the availability of safe and nutritious food at the table. The changing climatic conditions and global food trade and transport can make the movement of toxic plants possible, resulting in food crops being increasingly invaded by some species of plants that produce toxic secondary metabolites, such as tropane alkaloids (TAs). Datura stramonium from the Solanaceae plant family is an invasive and virulent plant that produces high amounts of two TAs, atropine and scopolamine. Various food poisoning events following accidental or deliberate ingestion of foods contaminated by atropine and scopolamine from seeds of D. stramonium have been recorded in different locations globally. Due to these incidents, regulatory agencies require the development of plant toxin detection methods that can be used in the food chain as early as possible. This systematic review thus focuses on the TA determination techniques in food and feeds published between 2013 and 2023. A particular focus was given to the sample preparation methods, the improvements of each technique claimed, and data to support the performance of each method, especially the ability to measure at or below the maximum level. The review concludes with other technological advancements, including rapid spectroscopy, electrophoresis, and colorimetric methods, as well as the possibility of coupling with smartphones for use in on‐farm detection and the challenges in applying them. [ABSTRACT FROM AUTHOR]