Human Animal Research Articles

Discovery of the 1-naphthylamine biodegradation pathway reveals a broad-substrate-spectrum enzyme catalyzing 1-naphthylamine glutamylation.

1-Naphthylamine (1NA), which is harmful to human and aquatic animals, has been used widely in the manufacturing of dyes, pesticides, and rubber antioxidants. Nevertheless, little is known about its environmental behavior and no bacteria have been reported to use it as the growth substrate. Herein, we describe a pathway for 1NA degradation in the isolate Pseudomonas sp. strain JS3066, determine the structure and mechanism of the enzyme NpaA1 that catalyzes the initial reaction, and reveal how the pathway evolved. From genetic and enzymatic analysis, a five gene-cluster encoding a dioxygenase system was determined to be responsible for the initial steps in 1NA degradation through glutamylation of 1NA. The γ-glutamylated 1NA was subsequently oxidized to 1,2-dihydroxynaphthalene which was further degraded by the well-established pathway of naphthalene degradation via catechol. A glutamine synthetase-like (GS-like) enzyme (NpaA1) initiates 1NA glutamylation, and this enzyme exhibits a broad substrate selectivity toward a variety of anilines and naphthylamine derivatives. Structural analysis revealed that the aromatic residues in the 1NA entry tunnel and the V201 site in the large substrate-binding pocket significantly influence NpaA1's substrate preferences. The findings enhance understanding of degrading polycyclic aromatic amines, and will also enable the application of bioremediation at naphthylamine contaminated sites.

Genetic and Pathophysiological Basis of Cardiac and Skeletal Muscle Laminopathies.

Nuclear lamins, a type V intermediate filament, are crucial components of the nuclear envelope's inner layer, maintaining nuclear integrity and mediating interactions between the nucleus and cytoplasm. Research on human iPSC-derived cells and animal models has demonstrated the importance of lamins in cardiac and skeletal muscle development and function. Mutations in lamins result in laminopathies, a group of diseases including muscular dystrophies, Hutchison-Gilford progeria syndrome, and cardiomyopathies with conduction defects. These conditions have been linked to disrupted autophagy, mTOR, Nrf2-Keap, and proteostasis signaling pathways, indicating complex interactions between the nucleus and cytoplasm. Despite progress in understanding these pathways, many questions remain about the mechanisms driving lamin-induced pathologies, leading to limited therapeutic options. This review examines the current literature on dysregulated pathways in cardiac and skeletal muscle laminopathies and explores potential therapeutic strategies for these conditions.

Applying the V.E.R.A. method to entheses of the humerus: An assessment of repeatability and reproducibility

AbstractThe “Validated Entheses‐based Reconstruction of Activity” (V.E.R.A.) method has proven to be a reliable method for the quantification and analysis of entheses. However, this method has only been successfully applied to human hand bones and animal long bones. This study tests the general applicability of the V.E.R.A. method to the human humerus, focusing on evaluating its reliability and repeatability. The sample included 23 humeri of unknown origin and background. The V.E.R.A. method was applied to six entheses of the humerus, comprising the subscapularis, supraspinatus, infraspinatus, teres minor, common extensor origin, and common flexor origin. Lin's concordance correlation coefficient (CCC) and percentage of error statistics were used to measure intraobserver error. Interobserver error was assessed through analysis of variance (ANOVA) tests, the intraclass correlation coefficient (ICC), and Lin's CCC. Intraobserver rates were between 1.83% and 3.23%. Interobserver error values were excellent, with no significant differences found in the ANOVA tests; Lin's CCC values were all above 0.90, with only the common extensor origin being 0.87; and ICC values were all above 0.97. Our results showed that the V.E.R.A. method is highly reliable and reproducible for the six entheses of the human humerus selected for this study. These results demonstrate the vast potential for the V.E.R.A. method to be applied to other parts of the human skeleton.

Prostate-specific antigen, androgen, progesterone and oestrogen receptors in Benign prostatic hyperplasia: human tissues and animal model study

Background Direct evidence for the relationship between a large prostate (≥80 ml) and androgen receptor/PSA signal remains lacking in benign prostatic hyperplasia (BPH). Our aim is to identify whether the cause of a large prostate is related to progesterone receptor (PGR) androgen receptor (AR), oestrogen receptor α, β (ERα,β) and prostate-specific antigen (PSA). Materials and methods Surgical specimens of BPH in plasmakinetic resection of the prostate (PKRP) with three groups of different prostate-sizes with mean volumes of 25.97 ml, 63.80 ml, and 122.37 ml were collected for immunohistochemical analysis of the tissue microarray with PGR, AR, PSA and ERs. Rats were castrated and treated with testosterone replacement to explore androgen and PGR, AR and ERs expression levels in the prostate. Quantitative real-time reverse transcription polymerase chain reaction (Rt-PCR) for mRNA detection of above genes was conducted. Results Immunoblotting, Rt-PCR and immunohistochemistry assays showed that PGR, PSA, AR, ERα expression levels were positively correlated with prostate size and that ERβ expression levels were negatively correlated with prostate volume. Animal experiments have shown that prostate volume is decreased in castrated rats with decreased PGR, AR, ERα and increased ERβ expression levels. Conclusion PGR, AR, ERs signals can be regarded as important factors for large-sized prostates in BPH patients (≥100 ml).

Chinese White Dolphins in the Anthropocene: Human-animal Relations Among the Islands of the Pearl River Delta

Chinese White Dolphins in the Anthropocene: Human-animal Relations Among the Islands of the Pearl River Delta

Self-assembled metal-polyphenolic based multifunctional nanomedicine to improve therapy treatment of pancreatic cancer by inhibition of glutamine metabolism

Cancer poses a significant threat to human health and life. Chemotherapy, immunotherapy and chemodynamic therapy (CDT) are effective treatments for cancer. However, the presence of metabolic reprogramming via glutamine in tumor cells limits their therapeutic effectiveness. Herein, we propose an effective assembly strategy to synthesize a novel metal-polyphenolic based multifunctional nanomedicine (Fe-DBEF) containing Pluronic F127 stable ferric ion crosslinked epigallocatechin gallate (EGCG) nanoparticles loaded with GLS1 inhibitor bis-2-(5-phenylacetamino-1,3,4-thiadiazole-2-yl) ethyl sulfide (BPTES) and chemotherapy drug doxorubicin (DOX). Our study demonstrates that Fe-DBEF nanomedicine exhibits high efficiency anti-proliferation properties in pancreatic cancer through a combination of in vitro cell experiments, human organoid experiments and KPC animal experiments. Notably, Fe-DBEF nanomedicine can reduce the production of glutathione (GSH) in tumor cells, thereby reducing their resistance to ROS therapy. Additionally, excessive ROS production also aggravates DNA damage caused by DOX, synergistically sensitizing chemotherapy and promoting apoptosis for efficient treatment of pancreatic cancer. Overall, our findings suggest that inhibiting glutamine metabolism to increase the sensitivity of chemotherapy/CDT using metal-polyphenolic based multifunctional nanomedicine provides a promising combination of multiple therapeutic means for treating pancreatic cancer.

The role of BTG2/PI3K/AKT pathway-mediated microglial activation in T-2 toxin-induced neurotoxicity

T-2 toxin is one of the mycotoxins widely distributed in human food and animal feed. Our recent work has shown that microglial activation may contribute to T-2 toxin-induced neurotoxicity. However, the molecular mechanisms involved need to be further clarified. To address this, we employed high-throughput transcriptome sequencing and found altered B cell translocation gene 2 (BTG2) expression levels in microglia following T-2 toxin treatment. It has been shown that altered BTG2 expression is involved in a range of neurological pathologies, but whether it’s involved in the regulation of microglial activation is unclear. The aim of this study was to investigate the role of BTG2 in T-2 toxin-induced microglial activation. The results of animal experiments showed that T-2 toxin caused neurobehavioral disorders and promoted the expression of microglial BTG2 and pro-inflammatory activation of microglia in hippocampus and cortical, while microglial inhibitor minocycline inhibited these changes. The results of in vitro experiments showed that T-2 toxin enhanced BTG2 expression and pro-inflammatory microglial activation, and inhibited BTG2 expression weakened T-2 toxin-induced microglial activation. Moreover, T-2 toxin activated PI3K/AKT and its downstream NF-κB signaling pathway, which could be reversed after knock-down of BTG2 expression. Meanwhile, the PI3K inhibitor LY294002 also blocked this process. Therefore, BTG2 may be involved in T-2 toxin's ability to cause microglial activation through PI3K/AKT/NF-κB pathway.

Aedes (Ochlerotatus) scapularis, Aedes japonicus japonicus, and Aedes (Fredwardsius) vittatus (Diptera: Culicidae): Three Neglected Mosquitoes with Potential Global Health Risks.

More than 3550 species of mosquitoes are known worldwide, and only a fraction is involved in the transmission of arboviruses. Mosquitoes in sylvatic and semi-sylvatic habitats may rapidly adapt to urban parks and metropolitan environments, increasing human contact. Many of these mosquitoes have been found naturally infected with arboviruses from the Alphaviridae, Flaviviridae, and Bunyaviridae families, with many being the cause of medically important diseases. However, there is a gap in knowledge about the vector status of newly invasive species and their potential threat to human and domestic animal populations. Due to their rapid distribution, adaptation to urban environments, and anthropophilic habits, some neglected mosquito species may deserve more attention regarding their role as secondary vectors. Taking these factors into account, we focus here on Aedes (Ochlerotatus) scapularis (Rondani), Aedes japonicus japonicus (Theobald), and Aedes (Fredwardsius) vittatus (Bigot) as species that have the potential to become important disease vectors. We further discuss the importance of these neglected mosquitoes and how factors such as urbanization, climate change, and globalization profoundly alter the dynamics of disease transmission and may increase the participation of neglected species in propagating diseases.

Linking One Health to 3R. Culture of Care as a bridge towards Russell and Burch's highest goal: Replacement

Animal testing has long been ethically controversial, initially due to religious and cultural beliefs and increasingly because of the obvious suffering inflicted. The 3Rs principles are now a central part of laboratory practice and have prompted discussions about adding further Rs to take account of societal values. However, this expansion can lead to contradictions, such as the emphasis on reproducibility, which implies the continued use of animals and thus conflicts with the original highest goal of the 3Rs, replacement. At the same time, the Culture of Care approach associated with the 3Rs promotes a change in the human-animal relationship but has not significantly challenged the use of animals in research. The One Health approach, which recognizes the connection between human, animal and environmental health, is also often criticized for prioritizing human health over animal welfare. This article aims to show how the One Health approach can be consistently extended to interdisciplinarity and intersectionality to include animals as stakeholders in the debate. It will also discuss the potential of the Culture of Care approach to transfer the implications of a consistently conceived One Health approach to the field of animal experimentation, in order to bring the complete renunciation of the use of sentient beings back into the focus of 3R research

An in vitro evaluation of the effect of antimicrobial treatment on bovine mammary microbiota

Antimicrobial-resistant bacteria have been an increasing problem in human medicine and animal husbandry since the introduction of antimicrobials on the market in the 1940s. Over the last decades, efforts to reduce antimicrobial usage in animal husbandry have been shown to limit the development of resistant bacteria. Despite this, antimicrobial-resistant bacteria are still commonly detected and isolated worldwide. In this study, we investigated the presence of antimicrobial-resistant bacteria in bovine milk samples using a multiple approach based on culturing and amplicon sequencing. We first enriched milk samples obtained aseptically from bovine udders in the presence of two antimicrobials commonly used to treat mastitis and then described the resistant microbiota by amplicon sequencing and isolate characterization. Our results show that several commensal species and mastitis pathogens harbor antimicrobial resistance and dominate the enriched microbiota in milk in presence of antimicrobial agents. The use of the two different antimicrobials selected for different bacterial taxa and affected the overall microbial composition. These results provide new information on how different antimicrobials can shape the microbiota which is able to survive and reestablish in the udder and point to the fact that antimicrobial resistance is widely spread also in commensal species.

Iron regulatory protein 1 is required for the propagation of inflammation in inflammatory bowel disease

Inflammatory bowel diseases (IBD) are complex disorders. Iron accumulates in the inflamed tissue of IBD patients, yet neither a mechanism for the accumulation nor its implication on the course of inflammation are known. We hypothesized that the inflammation modifies iron homeostasis, affects tissue iron distribution and that this in turn perpetuates the inflammation. This study analyzed human biopsies, animal models and cellular systems to decipher the role of iron homeostasis in IBD. We found inflammation-mediated modifications of iron distribution, and iron-decoupled activation of the iron regulatory protein (IRP)1. To understand the role of IRP1 in the course of this inflammation-associated iron pattern, a novel cellular co-culture model was established, that replicated the iron-pattern observed in vivo, and supported involvement of nitric oxide in the activation of IRP1 and the typical iron pattern in inflammation. Importantly, deletion of IRP1 from an IBD mouse model completely abolished both, the misdistribution of iron and intestinal inflammation. These findings suggest that IRP1 plays a central role in the coordination of the inflammatory response in the intestinal mucosa and that it is a viable candidate for therapeutic intervention in IBD.

Unveiling the High Diversity of Clones and Antimicrobial Resistance Genes in Escherichia coli Originating from ST10 across Different Ecological Niches.

In this pioneering in silico study in Peru, we aimed to analyze Escherichia coli (E. coli) genomes for antimicrobial resistance genes (ARGs) diversity and virulence and for its mobilome. For this purpose, 469 assemblies from human, domestic, and wild animal hosts were investigated. Of these genomes, three were E. coli strains (pv05, pv06, and sf25) isolated from chickens in our previous study, characterized for antimicrobial susceptibility profile, and sequenced in this study. Three other genomes were included in our repertoire for having rare cgMLSTs. The phenotypic analysis for antimicrobial resistance revealed that pv05, pv06, and sf25 strains presented multidrug resistance to antibiotics belonging to at least three classes. Our in silico analysis indicated that many Peruvian genomes included resistance genes, mainly to the aminoglycoside class, ESBL-producing E. coli, sulfonamides, and tetracyclines. In addition, through Multi-locus Sequence Typing, we found more than 180 different STs, with ST10 being the most prevalent among the genomes. Pan-genome mapping revealed that, with new lineages, the repertoire of accessory genes in E. coli increased, especially genes related to resistance and persistence, which may be carried by plasmids. The results also demonstrated several genes related to adhesion, virulence, and pathogenesis, especially genes belonging to the high pathogenicity island (HPI) from Yersinia pestis, with a prevalence of 42.2% among the genomes. The complexity of the genetic profiles of resistance and virulence in our study highlights the adaptability of the pathogen to different environments and hosts. Therefore, our in silico analysis through genome sequencing enables tracking the epidemiology of E. coli from Peru and the future development of strategies to mitigate its survival.

Understanding the Cryptosporidium species and their challenges to animal health and livestock species for informed development of new, specific treatment strategies

Cryptosporidium species are parasitic organisms of vertebrates with a worldwide distribution. They have an important impact globally upon human and animal health, and livestock productivity. The life cycle of these species is complex and difficult to disrupt to improve human health, animal health, food security and economic growth. This may contribute to the fact that no new treatment strategy has been widely accepted or applied in livestock for years. Here we consider the natural history of these parasites, their biochemistry and economic impact. Using recent developments in understanding these parasites we then consider viable and affordable approaches to enhancing control of their effects on livestock. These are based on advances in drug discovery, omics research and artificial intelligence applications to human and veterinary medicine that indicate putative new therapeutic approaches.

Adoption of the Improved Sorghum Variety (Melkame) in the West Hararghe, Mieso District

Sorghum bicolor, also known as sorghum, is a type of grass that is grown for its grain. This grain is used for various purposes, such as human consumption, animal feed, and ethanol production. The study aims to identify the factors that influence the adoption of the Melkam sorghum variety in the Mieso district by collecting primary data from 160 randomly selected respondents through a structured questionnaire. Econometric models were then employed to analyze the relationship and determine the adoption factors of the Melkam Sorghum variety using STATA 13 software. The study utilized frequencies, percentages, correlation, and regression to analyze the data. The findings indicated that the use of improved sorghum (Melkam) resulted in a positive correlation with the availability of an active working labor force in the household. Farmers were more inclined to adopt new technologies when they frequently interacted with extension agents. The size of the family and the frequency of contact with extension agents significantly influenced farmers' decisions to adopt the improved sorghum (Melkam) variety (t = 5.07, P>0.005) and (t = 6.73, P>0.005) at 1 percent, respectively. The study recommends that the government should increase their contact with farmers to at least once a month through extension agents to promote the adoption of improved sorghum (Melkam). Therefore, to improve communication with farmers, extension agents should utilize local community organizations and effective traditional knowledge-sharing methods in conjunction with modern extension systems. It is recommended that extension agents prioritize households with larger family sizes as potential adopters of new technologies, while also paying special attention to households with smaller family sizes.

Comparative genomic analysis of an emerging Pseudomonadaceae member, Thiopseudomonas alkaliphila.

Thiopseudomonas alkaliphila, an organism recently classified within the Pseudomonadaceae family, has been detected in diverse sources such as human tissues, animal guts, industrial fermenters, and decomposition environments, suggesting a diverse ecological role. However, a large knowledge gap exists in how T. alkaliphila functions. In this comparative genomic analysis, adaptations indicative of habitat specificity among strains and genomic similarity to known opportunistic pathogens are revealed. Genomic investigation reveals a core metabolic utilization of multiple oxidative and non-oxidative catabolic pathways, suggesting adaptability to varied environments and carbon sources. The genomic repertoire of T. alkaliphila includes secondary metabolites, such as antimicrobials and siderophores, indicative of its involvement in microbial competition and resource acquisition. Additionally, the presence of transposases, prophages, plasmids, and Clustered Regularly Interspaced Short Palindromic Repeats-Cas systems in T. alkaliphila genomes suggests mechanisms for horizontal gene transfer and defense against viral predation. This comprehensive genomic analysis expands our understanding on the ecological functions, community interactions, and potential virulence of T. alkaliphila, while emphasizing its adaptability and diverse capabilities across environmental and host-associated ecosystems.IMPORTANCEAs the microbial world continues to be explored, new organisms will emerge with beneficial and/or pathogenetic impact. Thiopseudomonas alkaliphila is a species originally isolated from clinical human tissue and fluid samples but has not been attributed to disease. Since its classification, T. alkaliphila has been found in animal guts, animal waste, decomposing remains, and biogas fermentation reactors. This is the first study to provide an in-depth view of the metabolic potential of publicly available genomes belonging to this species through a comparative genomics and draft pangenome calculation approach. It was found that T. alkaliphila is metabolically versatile and likely adapts to diverse energy sources and environments, which may make it useful for bioremediation and in industrial settings. A range of virulence factors and antibiotic resistances were also detected, suggesting T. alkaliphila may operate as an undescribed opportunistic pathogen.

Hearing Animals’ Stories: Interspecies Bond in Sanjeev Upreti’s Hansa

This paper analyzes Sanjeev Upreti’s Hansa (Duck), published in 2076 BS (2019 AD) from the perspective of Literary Animal Studies with a major objective of unveiling the author’s awareness of the exigency of an equitable and sustainable animal-human bond in the contemporary Anthropocene. The novel unfolds twin narratives in which one is a human protagonist and another a duck. In both narratives, stories of animals are foregrounded. Animal characters narrate their own stories that consist of their grievances of cruelties and indifference they face at the hand of humans. The human protagonist hears and understand these stories. It raises a question: why does he hear their stories? After analyzing the textual evidence through the theoretical perspective of Literary Animal Studies by focusing on Susan McHugh’s concept of animal narrative agency, the paper finds the answer that the human protagonist hears the animals’ stories because they underscore narrative agency. Unlike conventional roles of animals as metaphors and symbols for the making of human identity, these animals play an active role in resisting human exploitation against them. Finally, the paper claims that by offering narrative agency to animal characters, the author highlights the need of building an entangled interspecies bond among human and nonhuman animals. With this, the study expects to be useful for those readers and researchers interested in the field of Literary Animal Studies.

Adoption of the Improved Sorghum Variety (Melkame) in the West Hararghe, Mieso District

Sorghum bicolor, also known as sorghum, is a type of grass that is grown for its grain. This grain is used for various purposes, such as human consumption, animal feed, and ethanol production. The study aims to identify the factors that influence the adoption of the Melkam sorghum variety in the Mieso district by collecting primary data from 160 randomly selected respondents through a structured questionnaire. Econometric models were then employed to analyze the relationship and determine the adoption factors of the Melkam Sorghum variety using STATA 13 software. The study utilized frequencies, percentages, correlation, and regression to analyze the data. The findings indicated that the use of improved sorghum (Melkam) resulted in a positive correlation with the availability of an active working labor force in the household. Farmers were more inclined to adopt new technologies when they frequently interacted with extension agents. The size of the family and the frequency of contact with extension agents significantly influenced farmers' decisions to adopt the improved sorghum (Melkam) variety (t = 5.07, P>0.005) and (t = 6.73, P>0.005) at 1 percent, respectively. The study recommends that the government should increase their contact with farmers to at least once a month through extension agents to promote the adoption of improved sorghum (Melkam). Therefore, to improve communication with farmers, extension agents should utilize local community organizations and effective traditional knowledge-sharing methods in conjunction with modern extension systems. It is recommended that extension agents prioritize households with larger family sizes as potential adopters of new technologies, while also paying special attention to households with smaller family sizes.

Interspecies Justice within a Normative Sustainable Development Framework–Animal-Friendly Energy Systems as a Test Case

This paper argues that existing human-animal relations contribute to the pressing socio-ecological crises of our time, and therefore, they should be discussed in the context of Sustainable Development. This holds true even from a purely anthropocentric perspective, as these crises are threats to humans. However, sentient nonhuman animals possess interests as well and should be included in the moral community. Therefore, ignoring their interests in Sustainable Development is falling short. Furthermore, the paper argues that the anthropocentric perspective of Sustainable Development is flawed because the normative foundations of Sustainable Development (intra- and intergenerational justice) can be convincingly applied to nonhuman animals. According to approaches of interspecies justice, the normative foundations of Sustainable Development not merely can but should be applied to nonhuman animals. The paper argues for including nonhuman animals into the scope of justice and, therefore, in a theory of Sustainable Development. What such inclusion means at the practical level is examined in the last section of the paper, which investigates a field of application important for transforming societies into more sustainable ones, namely energy systems. This last section discusses how more sustainable, more animal-friendly energy systems would look like.

Past shadows and gender roles: Human elephant relations and conservation in Southern India

Some conceptual thinking about human-wildlife relations has lacked translations into empirical studies with an in-depth enquiry into social, cultural, economic and ecological aspects. This study explores human-elephant relations in a cohabited landscape in the Western Ghats of India, with a focus on 'more than conflict' relations. The Valparai plateau, in the Indian Western Ghats, is a landscape dominated by tea estates and remnants of rainforest fragments where human communities cohabit and closely interact with wildlife. We offer an empirical contribution on the variegated and paradoxical relation between care and fear, between empathy and hate and between the residents and elephants of Valparai. Where conflicts occur between elephants and humans, they have multiple meanings. Gender and unpleasant memories serve as drivers of negative attitudes towards wildlife. A conservation intervention based on engagement and collaboration with local people was perceived as highly effective. Preventive and mitigative, rather than reactive conflict mitigation strategies may have a significant role to play in maintaining the social carrying capacity of local communities towards elephants. We explore the many facets of human-elephant relations, and the numerous entanglements between them, thereby adding multiple layers to the extant knowledge of human-animal relations in the Western Ghats.

Multi-level LSTM framework with hybrid sonic features for human–animal conflict evasion

Multi-level LSTM framework with hybrid sonic features for human–animal conflict evasion