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Encephalitic alphaviruses, including eastern, Venezuelan, and western equine encephalitis virus (EEEV, VEEV, and WEEV, respectively) are New World alphaviruses primarily transmitted by mosquitos that cause debilitating and lethal central nervous system (CNS) disease in both humans and horses. Despite over one hundred years of research on these viruses, the underpinnings of the molecular mechanisms driving virally induced damage to the CNS remain unresolved. Moreover, virally induced encephalitis following exposure to these viruses causes catastrophic damage to the CNS, and survivors of infection often suffer from permanent neurological sequelae as a result of sustained neuroinflammation and neurological insults encountered. Animal models are undoubtedly invaluable tools in biomedical research, where physiologically relevant models are required to study pathogenesis and host–pathogen interactions. Here, we review the literature to examine nonhuman primate (NHP) and mouse models of infection for EEEV, VEEV, and WEEV. We provide a brief overview of relevant background information for each virus, including geography, epidemiology, and clinical disease. The primary focus of this review is to describe neuropathological features associated with CNS disease in NHP and mouse models of infection and compare CNS invasion and neuropathogenesis for aerosol, intranasal, and subcutaneous routes of exposure to EEEV, VEEV, and WEEV. Full article

Marek’s disease (MD), characterized by the rapid onset of T-cell lymphomas in chickens, is caused by Mardivirus gallidalpha2, an oncogenic alphaherpesvirus commonly known as Marek’s disease virus (MDV). MDV encodes a bZIP protein, Meq, which contains a bZIP domain (basic DNA-binding and leucine zipper dimerization domain) at the amino terminus and a transcriptional regulatory domain at the carboxyl end. Meq can transform murine and chicken fibroblasts in vitro and is essential for tumor formation in chickens. Meq homodimerization and heterodimerization through its bZIP domain are involved in Meq-mediated transformation. However, the role of Meq DNA-binding and transcriptional regulatory domains in transformation has not been investigated. In this study, we constructed recombinant Md5 (very virulent MDV) viruses expressing chimeric Meq proteins generated by swapping the DNA-binding and transcriptional regulatory domains of Meq of Md5 and vaccine (CVI988/Rispens) strains. Our results show that these recombinant viruses, rMd5-Md5/CVI-Meq (Md5 DNA-binding domain and CVI transcriptional regulatory domain) and rMd5-CVI/Md5-Meq (CVI DNA-binding domain and Md5 transcriptional regulatory domain), replicated at levels similar to parental rMd5 in cell culture and chickens and could transmit efficiently among chickens. Interestingly, parental rMd5 and chimeric viruses exhibited distinct pathogenic phenotypes in chickens: rMd5 caused 100% mortality, a moderate level of tumor incidence in visceral organs and small visceral tumors; rMd5-Md5/CVI-Meq caused 100% mortality, a high level of tumor incidence in visceral organs, and very large visceral tumors; while rMd5-CVI/Md5-Meq caused an average of 37% mortality, rarely induced tumors in visceral organs, and the visceral tumors were small. In conclusion, our study suggests that the DNA-binding domain of Meq plays an essential role in transformation (tumor incidence), while the transcriptional regulatory domain of Meq influences the distribution and size of MDV-induced tumors. Full article

Animal manure is a desirable fertilizer because of its rich nitrogen, but it also contains a large and diverse reservoir of antimicrobial resistance (AMR) genes (ARGs). To reduce this AMR reservoir, five treatments (passive aeration, forced aeration, static or anaerobic incubations, autoclaving) were assessed for their impact on the poultry litter resistome. Bacterial DNA was extracted from the litter and the qPCR-estimated copy number of 16S rrs, class1 integrons (intI1) and associated resistance genes (aadA, sul1). Then, 16S amplicon metagenomic sequencing was used to determine community diversity and composition. Depending on incubation conditions, class 1 integrons and their associated ARGs were reduced by 0.5 to 1.0 Log₁₀/g poultry litter. Only autoclaving reduced integrons and associated AMR genes by three Log₁₀. Changes in AMR abundance reflected fluctuations in litter bacteriome composition at the family, genus, and sequence variant level. There was a negative correlation between class 1 integron and AMR genes, with genera belonging to Actinobacteria, Firmicutes, and Proteobacteria phyla. While these poultry litter treatments failed to reduce AMR abundance, aerobic and anaerobic treatments reduced taxons that contained pathogenic species. The approach to remediating resistance in poultry litter may be more effective if is focused on reducing bacterial pathogens. Full article

Feline immunodeficiency virus (FIV) is the domestic cat analogue of HIV infection in humans. Both viruses induce oral disease in untreated individuals, with clinical signs that include gingivitis and periodontal lesions. Oral disease manifestations in HIV patients are abated by highly effective combination antiretroviral therapy (cART), though certain oral manifestations persist despite therapy. Microorganisms associated with oral cavity opportunistic infections in patients with HIV cause similar pathologies in cats. To further develop this model, we evaluated characteristics of feline oral health and the oral microbiome during experimental FIV infection over an 8-month period following cART. Using 16S rRNA sequencing, we evaluated gingival bacterial communities at four timepoints in uninfected and FIV-infected cats treated with either cART or placebo. Comprehensive oral examinations were also conducted by a veterinary dental specialist over the experimental period. Gingival inflammation was higher in FIV-infected cats treated with placebo compared to cART-treated cats and the controls at the study endpoint. Oral microbiome alpha diversity increased in all groups, while beta diversity differed among treatment groups, documenting a significant effect of cART therapy on microbiome community composition. This finding has not previously been reported, and indicates cART ameliorates immunodeficiency virus-associated oral disease via the preservation of oral mucosal microbiota. Further, this study illustrates the value of the FIV animal model for investigations of mechanistic associations and therapeutic interventions for HIV’s oral manifestations. Full article

ΦV10 is an Escherichia coli O157:H7-specific bacteriophage that has been used to develop luminescent reporter assays for the detection of this important foodborne pathogen. Previous work demonstrated the specificity of ΦV10 for infection of E.coli O157:H7 through interaction with the O157 antigen. In addition, modification of the lipopolysaccharide (LPS) via O-acetylation prevents ΦV10 infection in an E. coli O157:H7 expressing a phage-encoded O-acetylase gene. Through assays for phage binding, plaque formation, and lysogeny using non-O157:H7 and O157: non-H7 strains, as well as complementation of an O157:H⁻ strain, it is demonstrated in this study that both the somatic O157 antigen and flagellar H7 antigen are required for productive infection of E. coli O157:H7 by ΦV10. Together, the results indicate that the O157 antigen is required for phage binding and that the H7 antigen is necessary to complete the infection process. Full article

Salmonellosis in humans is a public health threat and cattle are important reservoirs for the pathogen. Cattle products such as ground beef have been linked to human salmonellosis outbreaks, and some disease investigations have been traced back to infected animal herds on farms and animal markets as the origin of infection. It is now common to isolate Salmonella from many cattle operations as the pathogen once introduced onto a farm can establish an undesirable endemic condition among herds. It is, therefore, essential to adopt measures to mitigate or prevent the introduction and spread of zoonotic disease agents like Salmonella in animal populations. With this background, the potential sources and risks of Salmonella infection in cattle, the control of already established infection, and other preventative measures are discussed in this article. We conclude that a holistic approach involving all stakeholders in cattle production is needed to safeguard public health, eventually forestalling human salmonellosis from cattle sources. In achieving this, it will be essential to consider the farm as a critical control point in preventing the introduction of Salmonella into the food chain. Full article

Hyperalgesic priming is a model of the transition from acute to chronic pain. Whether a similar mechanism exists for “pruritic priming” of itch is unknown. Here, we tested the hypothesis that itchy skin in a commonly used mouse model of dry skin pruritus develops latent sensitization after resolution. Acetone–ether–water (AEW) treatment induced a dry and itchy skin condition in the mouse cheek that elicited site-directed scratching behavior. After cessation of treatment and the complete resolution of AEW-induced scratching, histaminergic and non-histaminergic pruritogens were administered to the cheek to test for altered site-directed scratching and wiping behavior. Each pruritogen was also tested following the resolution of carrageenan-induced nociceptor hypersensitivity to test for cross-modality priming. Peak AEW-induced scratching occurred 24 h after the final day of treatment, and 5 days were required for scratching levels to return to baseline. Likewise, epidermal thickening was the greatest on the final treatment day and completely returned to baseline after 5 days. After the resolution of itchy cheek skin, acute histamine- and non-histamine-evoked scratching and wiping behaviors were unchanged, nor were scratching and wiping behaviors to acute pruritogens altered after the resolution of carrageenan-induced hypersensitivity. The results indicate that persistent itch due to dry skin likely resolves completely, without producing a latent primed response to subsequent pruritic stimuli. We conclude that the mechanisms regulating hyperalgesic priming are likely distinct from pruritic signaling in the dry and itchy skin model. Full article

Biological activities, including cell viability, oxidative stress, genotoxicity/antigenotoxicity, and antimicrobial activity, were evaluated for a visible-light-responsive TiO₂-based ICT complex with dihydroquercetin (DHQ) and compared with pristine TiO₂, its inorganic component. Pristine TiO₂ did not induce cytotoxicity in MRC-5 or HeLa cells within the tested concentration range (1–20 mg/mL), while TiO₂/DHQ displayed a significant reduction in cell viability in both cell lines at higher concentrations (≥10 mg/mL). The analysis of reactive oxygen species (ROS) production revealed that TiO₂/DHQ significantly reduced ROS levels in both cell types (MRC-5 and HeLa), with HeLa cells showing a more substantial reduction at lower concentrations. Genotoxicity assessment using the comet assay demonstrated that TiO₂ induced DNA damage in MRC-5 cells, while TiO₂/DHQ did not, indicating that DHQ mitigates the genotoxic potential of TiO₂. Furthermore, TiO₂/DHQ exhibited antigenotoxic effects by reducing H₂O₂-induced DNA damage in MRC-5 cells, supporting its protective role against oxidative stress. Preliminary antimicrobial tests revealed that TiO₂/DHQ exhibits antimicrobial activity against E. coli under visible-light excitation, while TiO₂ does not. These findings suggest that the TiO₂-based ICT complex with DHQ with enhanced antioxidant properties can potentially serve as a safe, non-toxic biocide agent. Full article

Fusobacterium necrophorum subspecies necrophorum, a resident of the rumen, is the causative agent of bovine liver abscesses. Currently, tylosin, a macrolide, is used in the feed to reduce liver abscesses. Because macrolides are medically important antibiotics, their use in food animal production is of public health concern. There is significant interest in finding antimicrobial alternatives. Bacteriophages that lyse subsp. necrophorum have the potential to replace tylosin. Our objective was to isolate bacteriophages lytic to subsp. necrophorum. Pooled ruminal fluid from slaughtered cattle and pooled sewage samples were collected and incubated overnight with lysine, and subsp. necrophorum strains and filtrates were spotted on F. necrophorum lawns. Phage plaques were harvested and purified. Bacteriophage isolation frequencies were compared between sample types, sampling dates, and necrophorum strains. Overall relative frequency of isolated bacteriophages lytic to subsp. necrophorum was 17.1%. The frequency of bacteriophage isolation ranged from 0 to 25.4% for ruminal fluid, and from 13.7 to 32.0% for sewage. Isolation frequency was significantly higher in sewage than in ruminal fluid samples (p < 0.01). Isolation rates varied significantly between necrophorum strains. Sewage was a rich source of bacteriophages lytic to necrophorum, which have the potential to be used to prevent liver abscesses. Full article

Endometrial cancer (EC) is a growing public health concern. This secondary data study of a case series leveraged existing samples and data to explore the potential link between exposure to heavy metals/essential elements and stage of EC. We analyzed urine samples from women with EC, measuring levels of toxic metals (cadmium, mercury, and lead) and essential elements (zinc and copper). Our findings revealed that higher levels of mercury, cadmium, and lead are associated with more advanced EC stages. Conversely, zinc showed a protective effect, potentially mitigating EC stage progression. Copper levels did not show a clear association with EC stage. These results highlight the potential impact of environmental exposures on EC stage and the crucial need for advanced statistical methods to understand the combined effects of these pollutants on health and the need for public health interventions. Further research is needed to explore the mechanisms by which these metals influence EC stage and long-term outcomes. Full article

Doxycycline (Dxy), a broad-spectrum antibiotic with anti-inflammatory effects, is commonly used in ophthalmology but is unstable as a topical eyedrop, degrading quickly into inactive forms and requiring frequent application. To address this, gelatin nanoparticles (GNPs) loaded with Dxy (DNPs) were developed as a stable ophthalmic nanomedicine for enhancing corneal wound healing by inhibiting matrix metalloproteinases (MMPs). In this study, female Sprague–Dawley rats underwent lamellar keratectomy, and various Dxy formulations—oral, conventional eyedrops, and DNP-containing eyedrops—were evaluated for corneal wound repair. Clinical assessments included fluorescein staining, slit-lamp biomicroscopy, spectral-domain optical coherence tomography (SD-OCT) imaging, histopathology, and immunohistochemistry for MMP-2, MMP-9, and α-SMA. The DNP group (0.01% Dxy in DNPs, applied twice daily) demonstrated faster corneal thickness recovery and epithelial healing on days 7 and 14 compared to 0.1% Dxy eyedrop treatments applied twice or four times daily. DNP-treated eyes also showed reduced angiogenesis intensity and lower MMP-2 and MMP-9 immunoreactive scores, with enhanced stromal recovery and reduced neovascularization. These results highlight DNPs’ potential as a superior treatment for corneal wounds, providing effective healing with less frequent dosing and lower drug concentrations. This study supports DNPs’ potential for clinical application as a stable and efficient therapeutic agent in ophthalmology. Full article

Sub-Saharan Africa has long been prone to widespread mosquito-borne diseases affecting both humans and animals. However, the presence and impact of West Nile virus (WNV) among livestock in Ethiopia have not been thoroughly investigated. The objective of this study was to investigate the seroprevalence of West Nile virus in livestock in the Afar region using serological methods. A total of 736 serum samples were collected from 224 cattle, 155 camels, 144 sheep, 121 goats, and 92 donkeys in the Amibara and Haruka districts of the Afar region selected using haphazard sampling. Among 736 tested livestock serum samples, 50.7% (373/736) showed anti-WNV IgG antibodies evaluated using the ID screen^® WNV competition multispecies ELISA kits (95% CI: 47–54.4%; p < 0.01). The seroprevalence was higher (p < 0.01) in donkeys (76.1%), followed by camels (69.1%), cattle (52.2%), goats (34.7%), and sheep (25.7%). The study showed a statistically significant difference of WNV seropositivity between species of animals AOR (1.5), 95% CI (1.038–2.212) (p < 0.01). Compared with sheep, donkeys had a seven-fold higher chance of being seropositive for WNV infection (OR: 6.447, 95% CI = 3.888–10.688) (p < 0.01). This study emphasizes how common WNV infection is in Ethiopia’s pastoral Afar region. It is imperative to consider consistent surveillance of WNV infection and prompt management of identified WNV disease in clinical practice. A clear need exists to build additional research capacity regarding WNV infections among both humans and animals. Full article

Bovine alphaherpesvirus 1 (BoHV-1) acute infection leads to latently infected sensory neurons in trigeminal ganglia. During lytic infection, the immediate early expression of infected cell protein 0 (bICP0) and bICP4 is regulated by an immediate early transcription unit 1 (IEtu1) promoter. A separate bICP0 early (E) promoter drives bICP0 as an early viral gene, presumably to sustain high levels during productive infection. Notably, bICP0 protein expression is detected before bICP4 during reactivation from latency, suggesting the bICP0 E promoter drives bICP0 protein expression during the early phases of reactivation from latency. The glucocorticoid receptor (GR) and Krüppel-like factor 4 (KLF4) cooperatively transactivate the bICP0 E promoter despite this promoter lacks a consensus GR response element (GRE). KLF and specificity protein (Sp) family members comprise a “super-family” of transcription factors. Consequently, we hypothesized Sp1 and Sp3 transactivated the bICP0 E promoter. These studies revealed GR and Sp3 or Sp1 cooperatively transactivated bICP0 E promoter activity. KLF4 and Sp3, but not Sp1, had an additive effect on bICP0 E promoter activity. Mutating the consensus Sp1 and CACCC binding sites proximal to the TATA box impaired promoter activity more than the Sp1 sites further upstream from the TATA box. Full article

Background/Objectives: A mouse antibody directed against truncated Annexin A1 showed high tumor retention in pre-clinical cancer models and was approved by the National Cancer Institute Experimental Therapeutics (NExT) program for humanization and large batch cGMP production for toxicology and clinical trials. In this process, a contractor for Leidos accidentally produced a mutated version of humanized AnnA1 (hAnnA1-mut) with a single nucleotide deletion in the terminal Fc coding region that increased the translated size by eight amino acids with random alterations in the final twenty-four amino acids. We investigated the tissue distribution of hAnnA1-mut, hAnnA1, mAnnA1, and isotope-matched human IgG1 under various injection and conjugation conditions with C57BL/6, FVB, and BALB/c nude mice strains. Methods: Biodistribution studies were performed 24 h after injection of Tc-99m-HYNIC radiolabeled antibodies (purity > 98%). Non-reducing gel electrophoresis studies were conducted with IR680 labeled antibodies incubated with various mouse sera. Results: Our results showed that Tc-99m-HYNIC-hAnnA1 had low spleen and liver retention not statistically different from Tc-99m-HYNIC-IgG1 and Tc-99m-HYNIC-mAnnA1, with corresponding higher blood levels; however, Tc-99m-HYNIC-hAnnA1-mut had high levels in the spleen and liver with differences identified among the mouse strains, radiolabeling conditions, and injection routes. Histopathology showed no morphological change in the liver or spleen from any conditions. Gel electrophoresis showed an upward shift of hAnnA1-mut, consistent with the binding of blood serum protein. Conclusions: The changes in the Fc region of hAnnA1-mut led to higher liver and spleen uptake, suggesting the antibody’s recognition by the innate immune system (likely complement protein binding) and subsequent clearance. Future clinical translation using hAnnA1 and other antibodies needs to limit protein modifications that could drastically reduce blood clearance. Full article

Ticks are well-known vectors of pathogens, posing considerable risks to livestock health and productivity. In Cameroon, where livestock production is vital, established tick species such as Amblyomma variegatum and Hyalomma truncatum are prevalent in key cattle-rearing areas. The recent introduction of the invasive, acaricide-resistant Rhipicephalus microplus further complicates control efforts. In this study, we deliver baseline data on the composition of tick species and their shifts within agroecological zone I (AEZ I) and agroecological zone III (AEZ III) of Cameroon, providing a foundation for targeted vector control strategies to ultimately reduce the risk of pathogen transmission. From 1100 ticks collected across two Cameroonian agroecological zones, H. truncatum (39.9%), A. variegatum (31%), and R. microplus (10.64%) were the most prevalent species, along with Rhipicephalus lunulatus (4.45%), Hyalomma rufipes (1.45%), Hyalomma marginatum (1.09%), Hyalomma dromedarii (0.45%), and Rhipicephalus sanguineus (0.9%). Molecular identification using cytochrome C oxidase subunit 1 (cox1) and 16s led to the identification of five additional species, Hyalomma nitidum (0.73%), Rhipicephalus simus (3.54%), Rhipicephalus sulcatus (2.64%), Rhipicephalus praetextatus (2.1%), and Rhipicephalus pusillus (1.1%). R. microplus emerged as the most dominant Rhipicephalus spp. in AEZ I, comprising 67.5% of the total Rhipicephalus ticks. In conclusion, we demonstrate the further spread of R. microplus, which represents a major source of vector-borne diseases, affecting both humans and animals. Full article