Human Animal Research Articles

Ethical Implications of Social Science Research on Xenotransplantation.

Social science research has generated extensive knowledge on xenotransplantation, encompassing the perspectives of actual and potential patients, other stakeholders, public opinion and debate, human-animal relationships, animal production and husbandry, bioeconomy, as well as biotechnology governance and regulation. We therefore convened social science researchers to discuss the latest developments in xenotransplantation research and practice in late 2023. Based on a brief workshop report, we aim to highlight the various ethical implications of this debate. After outlining the role of social science research in the ethical evaluation of xenotransplantation, we elaborate three critical points that may become pivotal in the future evolution of xenotransplantation: the framing of xenotransplantation in the clinical setting and in the public, the potential impact of religious beliefs on patients' transplant choices, and the consequences for the allotransplantation system if xenotransplantation becomes clinically established, including the allocation of allo- and xeno-organs.

Perinatal behavioral patterns during and after human-animal interactions in rangeland breeding ewes

Perinatal behavioral patterns during and after human-animal interactions in rangeland breeding ewes

Managing forage for grain: Strategies and mechanisms for enhancing forage production to ensure feed grain security 1

The “Greater Food” approach has replaced the older “taking grain production as a top priority” approach. The importance of feed and forage as the material basis for guaranteeing high-quality development of the livestock industry has gradually become prominent. However, owing to the tradition of “both human staple food and animal feed relying on grain production” in China and the decoupling of feed crop planting and livestock farming, the risk of feed grain security has increased, especially as it relates to the supply of high-quality protein feed ingredients from abroad, which is facing a bottleneck. To ensure food security, effective domestic agricultural production should be adopted. Nevertheless, guaranteeing the supply of high-quality protein feed through domestic soybean production is difficult because of limited arable land; furthermore, pressure on the staple food supply is still extreme. In this article, the historical and realistic implications for the security risks of feed grain in China are analyzed. Proposals are made to separate staple food grains for humans from the feed grain supply for animals and to develop high-quality forage to reduce feed grain use. High-quality forage can be supplied via intercropping with grain crops in arable land and reseeding perennial legumes or grasses into natural grasslands. However, “managing forage for grain” needs to be supported via technical paths and policies as the forage industry develops to effectively increase the capacity to ensure feed grain security.

Dynamin-1 is a potential mediator in cancer-related cognitive impairment

Dynamin-1 (DNM1) is crucial for synaptic activity, neurotransmission, and associative memory, positioning it as a potential biomarker of cancer-related cognitive impairment (CRCI), a neurological consequence of cancer treatment characterized by memory loss, poor concentration, and impaired executive function. Through a stepwise approach, this study investigated the role of DNM1 in CRCI pathogenesis, incorporating both human data and animal models. The human study recruited newly diagnosed, chemotherapy-naïve adolescent and young adult cancer and non-cancer controls to complete a cognitive instrument (FACT-Cog) and blood draws for up to three time points. Following that, a syngeneic young-adult WT (C57BL/6) female mouse model of breast cancer chemobrain was developed to study DNM1 expression in the hippocampus. Samples from eighty-six participants with 30 adolescent and young adult (AYA) cancer and 56 non-cancer participants were analyzed. DNM1 levels were 32 ​% lower (P ​= ​0.041) among cancer participants compared to non-cancer prior to treatment. After receiving cytotoxic treatment, cognitively impaired cancer patients were found to have 46 ​% lower DNM1 levels than those without impairment (P ​= ​0.049). In murine breast cancer-bearing mice receiving chemotherapy, we found a greater than 40 ​% decline (P ​< ​0.0001) in DNM1 immunoreactivity in the hippocampal CA1 and CA3 subregions concurrent with a deterioration in spatial recognition memory (P ​< ​0.02), compared to control mice without exposure to cancer and chemotherapy. Consistently observed in both human and animal studies, the downregulation of DNM1 is linked with the onset of CRCI. DNM1 might be a biomarker and therapeutic target for CRCI.

Is There an Association between 5a Reductase Inhibitors and Metabolic Syndrome? A Narrative Review of the Literature.

Finasteride and dutasteride are 5a Reductase Inhibitors (5a-RIs) and comprise the mainstay of treatment for the management of patients with benign prostatic hyperplasia. 5a-RIs are expressed in a variety of tissues, such as adipose tissues and liver, resulting in a reduction of glucocorticoid levels and affecting androgen regulation and metabolic function. As a result, the administration of these regimens may generate adverse metabolic events, such as liver disease, hyperglycemia, hyperlipidemia, and diabetes mellitus. Although several studies have tried to record these adverse metabolic events both in human subjects and animal models, the exact mechanisms of these actions have not been well described yet in the literature. Further well-designed clinical trials are needed to elucidate the exact role of 5a reductase inhibitors in the progression of the metabolic syndrome. The aim of this study was to systematically review the literature concerning the role of dutasteride or finasteride in the progression of metabolic adverse events and further investigate possible pathophysiologic mechanisms.

Integrated mRNA-seq and miRNA-seq analysis reveals key transcription factors of HNF4α and KLF4 in ADPKD

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most prevalent genetic disorder affecting the kidneys. Understanding epigenetic regulatory mechanisms and the role of microRNAs (miRNAs) is crucial for developing therapeutic interventions. Two mRNA datasets (GSE7869 and GSE35831) and miRNA expression data (GSE133530) from ADPKD patients were used to find differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs), with a focus on genes regulated by hub transcription factors (TFs) and their target genes. The expression of hub TFs was validated in human kidneys and animal models through Western Blot (WB) and RT-PCR analysis. The location of the hub TF proteins in kidney cells was observed by a laser confocal microscope. A total of 2037 DEGs were identified. DEM analysis resulted in 59 up-regulated and 107 down-regulated miRNAs. Predicted target DEGs of DEMs indicated two top dysregulated TFs: hepatocyte nuclear factor 4 alpha (HNF4α) and Kruppel-like factor 4 (KLF4). RT-PCR, WB, and immunochemistry results showed that mRNA and protein levels of HNF4α were significantly decreased while KLF4 levels were significantly up-regulated in human ADPKD kidneys and Pkd1 conditional knockout mice compared with normal controls. Laser confocal microscopy revealed that KLF4 was mainly located in the cytoplasm while HNF4α was in the nucleus. Functional enrichment analysis indicated that genes regulated by HNF4α were mainly associated with metabolic pathways, while KLF4-regulated genes were linked to kidney development. Drug response prediction analysis revealed potential drug candidates for ADPKD treatment, including BI-2536, Sepantronium, and AZD5582. This integrated analysis provides new epigenetic insights into the complex miRNA-TF-mRNA network in ADPKD and identifies HNF4α and KLF4 as key TFs. These findings offer valuable resources for further research and potential drug development for ADPKD.

ICTV Virus Taxonomy Profile: Peribunyaviridae 2024.

Peribunyavirids produce enveloped virions with three negative-sense RNA segments comprising 10.7-12.5 kb in total. The family includes globally distributed viruses in multiple genera. While most peribunyavirids are maintained in geographically restricted vertebrate-arthropod transmission cycles, others are arthropod-specific or do not have a known vector. Arthropods can be persistently infected. Human and other vertebrate animal infections occur through blood feeding by an infected vector arthropod, resulting in diverse human and veterinary clinical outcomes in a strain-specific manner. Reassortment can occur between members of the same genus. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Peribunyaviridae, which is available at ictv.global/report/peribunyaviridae.

Insights into trypanosomiasis transmission: Age, infection rates, and bloodmeal analysis of Glossina fuscipes fuscipes in N.W. Uganda.

Tsetse flies (Glossina) transmit species of Trypanosoma which cause human African trypanosomiasis (HAT) and animal African trypanosomiasis (AAT). Understanding the epidemiology of this disease and controlling the vector rationally requires analysis of the abundance, age structure, infection rates and feeding patterns of tsetse populations. We analysed a population of G. fuscipes fuscipes in the Koboko district of Uganda. Seasonal variation in the abundance of tsetse was assessed from the numbers of tsetse caught in pyramidal traps. The age structure of the population was assessed by dissecting female tsetse to estimate their ovarian categories. Classical and PCR-based methods were utilised to determine the presence of the three major pathogenic species of salivarian trypanosomes: T. vivax, T. congolense and T. brucei in a subset (n = 2369) of flies. Further, bloodmeal analysis was carried using PCR to amplify and sequence a portion of the vertebrate cytb gene. The abundance and age structure of tsetse populations were relatively stable and a slight seasonal four-fold variation in abundance appeared to be correlated with rainfall. Analyses of age structure suggests a low natural daily mortality of 1.75% (1.62-1.88). Infection rates estimated were significantly greater (1.9-9.3 times) using the PCR-based method compared to the classical dissection-based method. Positive rates for T. brucei sl, T. congolense and T. vivax were 1.6% (1.32-2.24), 2.4% (1.83-3.11and 2.0% (1.46-2.63), respectively by PCR. The majority of bloodmeals were identified as cattle (39%, 30.5-47.8) and human (37% of meals, 28.4-45.6). The seasonally stable abundance, low mortality rate and high proportion of bloodmeals from humans may explain, in part, why this district has historically been a focus of sleeping sickness. Additionally, the high rates of cattle feeding indicate insecticide treated cattle may prove to be a useful vector control strategy in the area.

EFEITOS DE FÁRMACOS PSICOTRÓPICOS NO TRATAMENTO DE DISTÚRBIOS COMPORTAMENTAIS EM CÃES (CANIS FAMILIARIS)

With the strengthening of human-animal interaction and the scientific recognition of sentience, there has been a significant increase in the perception of atypical behaviors in companion animals, as observed by legal guardians and veterinarians. In general terms, such changes occur due to excessive humanization, stress, fear, or inappropriate environments, leading to variations in temperament, emotional dependency, and/or inhibition of species-specific natural behaviors. The class of psychotropic drugs offers pharmacological treatment for the mental state of these animals by modulating neurotransmitters such as serotonin and dopamine. The objective of this study was to evaluate the pharmacological impact of psychotropic drugs on the social development and emotional resilience of these animals, in conjunction with behavioral therapy. For this purpose, domestic dogs (Canis familiaris) diagnosed with compulsive disorders secondary to other behavioral dysfunctions were treated with trazodone hydrochloride (Group 1) and extracts from Psilocybe cubensis mushrooms (Group 2), and compared to conventional treatment with fluoxetine hydrochloride. The animals were diagnosed and evaluated using questionnaires aimed at diagnosing and monitoring the evolution of treatment, based on the literature referenced in this study. Atypical behaviors associated with primary and secondary disorders were mitigated or eliminated in Group 1 (n=4), Group 2 (n=4), and the conventional treatment group. However, fluoxetine hydrochloride showed a reduction in appetite as a side effect.

Coordination of Pharyngeal and Esophageal Phases of Swallowing.

Although swallowing has been reviewed extensively, the coordination of the phases of swallowing have not. The phases are controlled by the brainstem, but peripheral factors help coordinate the phases. The occurrence, magnitude, and duration of esophageal phase depends upon peripheral feedback activated by the bolus. The esophageal phase does not occur without peripheral feedback from the esophagus. This feedback is mediated by esophageal slowly-adapting mucosal tension receptors through the recurrent and superior laryngeal nerves. A similar reflex mediated by the same peripheral pathway is the activation of swallowing by stimulation of the cervical esophagus. This reflex occurs primarily in human infants and animals, and this reflex may be important for protecting against aspiration after esophago-pharyngeal reflux. Not only are there inter-phase excitatory processes, but also inhibitory processes. A significant inhibitory process is deglutitive inhibition. When one swallows faster than peristalsis ends, peristalsis is inhibited by the new pharyngeal phase. This process prevents the ongoing esophageal peristaltic wave from blocking the bolus being pushed into the esophagus by the new wave. The esophageal phase returns during the last swallow of the sequence. This process is probably mediated by mucosal tension receptors through the superior laryngeal nerves. A similar reflex exists, the pharyngo-esophageal inhibitory reflex, but studies indicate that it is controlled by a different neural pathway. The pharyngo-esophageal inhibitory reflex is mediated by mucosal tension receptors through the glossopharyngeal nerve. In summary, there are significant peripheral processes that contribute to swallowing, whereby one phase of swallowing significantly affects the other.

Comparative Analysis of Skim Milk and Milk Fat Globule Membrane Proteomes between Human and Farm Animal Milk for Infant Formula Production.

Human and animal milk contain a rich variety of milk proteins that meet the needs of their newborns. In total, 1263 skim milk proteins and 1754 MFGM proteins were identified in human milk and six types of animal milk, respectively. Both similarities and differences were observed among the species. Human milk contained more immunoglobulins involved in the adaptive immune response, playing a crucial role in mucosal defense in newborn babies. In contrast, ruminant milk contained higher amounts of antimicrobial proteins, which protect newborns from bacterial infections. The most dominant difference in MFGM proteins between human and animal milk was related to protein processing in the endoplasmic reticulum. Goat milk and camel milk were more similar to human milk in terms of skim milk and MFGM proteins compared to the other five types of animal milk. Moreover, immunoglobulins and complement and coagulation cascade proteins in goat milk were most similar to those in human milk. A higher content of immunoglobulin A was observed in donkey milk, which could be considered as a source of IgA in infant formula. These results provide more comprehensive and novel insights into protein variation among animal milk, which may support improving dairy products such as infant formula.

Euthanasia of dogs as control of Visceral Leishmaniasis: brazilian law from a technical and ethical-moral view

Dogs participate in the maintenance of leishmaniasis as a reservoir in urban areas. The Visceral Leishmaniasis Surveillance and Control Program (PVCLV) of the Ministry of Health determines the euthanasia of seroactive dogs. The human-animal relationship has become closer to the point that zoonoses are gaining greater attention from health services, and the euthanasia of these animals has an impact on the multispecies family. The maintenance of euthanasia as an action to control the disease is questioned. With the approval of medication and the development of prevention methods, guardians question the action recommended by PVCLV. This review highlights the importance of health education, environmental management, responsible custody and public policies, highlighting current legislation and its controversies, in addition to the fact that the emotional impact of euthanasia is not limited to the animal's family, but also to the professional who performs it, and that as the only action to control leishmaniasis it is ineffective and may worsen the epidemiological situation of the disease.

Review: Human-Animal Relations and the Hunt in Korea and Northeast Asia, by George Kallander

Review: <i>Human-Animal Relations and the Hunt in Korea and Northeast Asia</i>, by George Kallander

Comparing the mental effects of interacting with farm animals and walking in a botanical garden.

Over the past two decades, farm animal-assisted therapies have become popular. However, the effects of farm animals on healthy people's mental states have not yet been investigated. In Study 1, we aimed to explore whether positive effects of human-animal interaction (HAI) can be detected in healthy farm volunteers even after short-term (2-3 hours) work with goats and goatlings on a goat farm. We found that the participants' state anxiety decreased (p < 0.001) while their trust levels increased (p < 0.001) after interacting with goats. Nevertheless, it is possible that time spent in nature alone can have a beneficial effect on well-being. Therefore, in Study 2, we compared the results of Study 1 with those of a similar short-term outdoor treatment, walking in a botanical garden as a visitor. Similar but smaller effects were found for garden visitors. Decreases in anxiety scores and increases in trust scores were more pronounced in farm volunteers (anxiety: 25% vs 13%, p < 0.001; trust: 13% vs 3%, p = 0.002) after the treatments. Overall, the results suggest that the novel experience of interacting with goats and goatlings has a more positive effect on the mental state of healthy humans than walking in a botanical garden. This finding offer a strong foundation for developing animal assisted therapy methods for individuals with short or long term mental problems, but they can also enhance the wellbeing of mentally healthy people.

Late-Holocene hydroclimatic change and its effect on human activity at Xiada Co on the western Tibetan Plateau

The scarcity of paleoclimate records in the western Tibetan Plateau (TP) hinders our understanding of how environmental evolution affects past human population, agriculture, and animal husbandry. Here, we utilized a range of materials to investigate the impact of climate change on human activities in the Xiada Co basin on the western TP during the Late-Holocene. We presented a continuous compound-specific hydrogen isotope record of sedimentary leaf waxes (δ2Hwax) from a sediment core of Xiada Co, and compared it to XRF core-scanning elements, brGDGT-based mean annual air temperature (MAAT) record, and fecal stanol-based human population proxy record from the same sediment core, as well as archeological evidence from the TP. The δ2Hwax exhibited a sustained increasing trend during the period from 4700 to 900 cal yr BP, followed by a generalized decrease in δ2Hwax values during 900–0 cal yr BP. The multi-proxy analysis of Xiada Co sediments revealed that the δ2Hwax values mainly reflect changes in the ISM precipitation, and are also influenced to some extent by glacier meltwater. Furthermore, a warm and humid climate condition was conducive to human habitation. Appropriate adaptation strategies, such as the herding of cold-tolerant and dry-tolerant sheep and the cultivation of barley in the western TP, led to a surge in population density during 3400–2900 cal yr BP, despite the slightly deteriorated climate background. This study confirmed the importance of choosing the right adaptive strategies to cope with climate change for human survival and development on the Tibetan Plateau.

VEGFB ameliorates insulin resistance in NAFLD via the PI3K/AKT signal pathway

BackgroundNon-alcoholic fatty liver disease (NAFLD) is one of the most universal liver diseases with complicated pathogenesis throughout the world. Insulin resistance is a leading risk factor that contributes to the development of NAFLD. Vascular endothelial growth factor B (VEGFB) was described by researchers as contributing to regulating lipid metabolic disorders. Here, we investigated VEGFB as a main target to regulate insulin resistance and metabolic syndrome.MethodsIn this study, bioinformatics, transcriptomics, morphological experiments, and molecular biology were used to explore the role of VEGFB in regulating insulin resistance in NAFLD and its molecular mechanism based on human samples, animal models, and cell models. RNA-seq was performed to analyze the signal pathways associated with VEGFB and NAFLD; Palmitic acid and High-fat diet were used to induce insulin-resistant HepG2 cells model and NAFLD animal model. Intracellular glucolipid contents, glucose uptake, hepatic and serum glucose and lipid levels were examined by Microassay and Elisa. Hematoxylin-eosin staining, Oil Red O staining, and Periodic acid-schiff staining were used to analyze the hepatic steatosis, lipid droplet, and glycogen content in the liver. Western blot and quantitative real-time fluorescent PCR were used to verify the expression levels of the VEGFB and insulin resistance-related signals PI3K/AKT pathway.ResultsWe observed that VEGFB is genetically associated with NAFLD and the PI3K/AKT signal pathway. After VEGFB knockout, glucolipids levels were increased, and glucose uptake ability was decreased in insulin-resistant HepG2 cells. Meanwhile, body weight, blood glucose, blood lipids, and hepatic glucose of NAFLD mice were increased, and hepatic glycogen, glucose tolerance, and insulin sensitivity were decreased. Moreover, VEGFB overexpression reduced glucolipids and insulin resistance levels in HepG2 cells. Specifically, VEGFB/VEGFR1 activates the PI3K/AKT signals by activating p-IRS1Ser307 expression, inhibiting p-FOXO1pS256 and p-GSK3Ser9 expressions to reduce gluconeogenesis and glycogen synthesis in the liver. Moreover, VEGFB could also enhance the expression level of GLUT2 to accelerate glucose transport and reduce blood glucose levels, maintaining glucose homeostasis.ConclusionsOur studies suggest that VEGFB could present a novel strategy for treating NAFLD as a positive factor.Graphical

A Multidisciplinary One Health Approach to Addressing Unsanitary Conditions: The Case of Cascais

Abstract Unsanitary conditions in domiciles often stem from complex social and health-related issues, involving the elderly and/or individuals with mental health problems. These situations typically lead to a decreased quality of life for those involved, directly and indirectly, and may pose a risk to public health depending on their magnitude. In Cascais municipality, identified cases of unsanitary conditions undergo a multidisciplinary analysis. It has been established a Local Technical Group for Domiciliary Unsanitary Situations, comprising various institutions such as local authorities, law enforcement agencies, civil protection, health and social security ministries, and the animal rescue center. This group operates under a One Health approach, encompassing human health, environmental health, and animal health. Interventions are determined by the working group, with the aim of promoting health and enhancing citizens’ quality of life. Cases of unsanitary conditions reported are subsequently discussed within the technical group, which has regular meetings, and may organize joint assessment visits and appropriate actions. This social and environmental initiative responds to the growing need to address unsanitary and cluttered living conditions, which significantly impact individuals’ physical, emotional, and social well-being. The objective is to restore housing conditions in homes by removing waste and unnecessary items, contributing to general individual well-being. While international studies suggest a correlation between unsanitary conditions and hoarding disorder, it’s crucial to differentiate between distinct and independent situations caused by various physical, psychological, and cognitive processes. The establishment of a Local Technical Group for Domiciliary Unsanitary Situations exemplifies a proactive approach to addressing complex health and social challenges, emphasizing collaboration, and holistic intervention strategies, always with a One Health approach. Key messages • Addressing unsanitary conditions is crucial for safeguarding public health, impacting physical, emotional, and social well-being. • The establishment of a Local Technical Group for Domiciliary Unsanitary Situations, under a One Health framework, reflects a collaborative approach to addressing complex health and social challenges.

Sex as a biological variable in HIV-1 and schistosome co-infection.

The sex of people living with HIV-1 infection, schistosome infection, or both, is a fundamental determinant of their clinical outcomes and of how these two infections interact in the host. Data from longitudinal and cross-sectional human studies and animal models indicate that males with HIV-1 and schistosome co-infection excrete fewer schistosome eggs and might have higher HIV-1 RNA viral loads and greater liver damage. Females with schistosome infection appear to have higher risk of HIV-1 acquisition than females without, particularly in Schistosoma haematobium infection, and a greater risk of death in HIV-1 and schistosome co-infection. Greater transmission of HIV-1 to partners has been shown in both sexes in those with schistosome infection. Biological sex is a consequential factor affecting pathophysiological and clinical responses in HIV-1 and schistosome co-infection. Designing future analyses to incorporate sex is vital to optimise research and care for people living with HIV-1, schistosomes, and HIV-1 and schistosome co-infection.

The full transcription map of cottontail rabbit papillomavirus in tumor tissues.

Cottontail rabbit papillomavirus (CRPV), the first papillomavirus associated with tumor development, has been used as a powerful model to study papillomavirus pathogenesis for more than 90 years. However, lack of a comprehensive analysis of the CRPV transcriptome has impeded the understanding of CRPV biology and molecular pathogenesis. Here, we report the construction of a complete CRPV transcription map from Hershey CRPV-induced skin tumor tissues. By using RNA-seq in combination with long-reads PacBio Iso-seq, 5' and 3' RACE, primer-walking RT-PCR, Northern blot, and RNA in situ hybridization, we demonstrated that the CRPV genome transcribes its early and late RNA transcripts unidirectionally from at least five distinct major promoters (P) and polyadenylates its transcripts at two major polyadenylation (pA) sites. The viral early transcripts are primarily transcribed from three "early" promoters, P90, P156, and P907 and polyadenylated at nt 4368 by using an early polyadenylation signal (PAS) at nt 4351. Like other low-risk human papillomaviruses and animal papillomaviruses, CRPV E6 and E7 transcripts are transcribed from three separate early promoters. Transcripts from two "late" promoters, P7525, and P1225, utilize either an early PAS for E1^E4 or a late PAS at 7399 for L2 and L1 RNA polyadenylation at nt 7415 to express capsid L2 and L1 proteins respectively. By using the mapped four 5' splice sites and three 3' splice sites, CRPV RNA transcripts undergo extensive alternative splicing to produce more than 33 viral RNA isoforms for production of at least 12 viral proteins, some of which without codon optimization are expressible in rabbit RK13 and human HEK293T cells. The constructed full CRPV transcription map in this study for the first time will enhance our understanding of the structures and expressions of CRPV genes and their contribution to molecular pathogenesis and tumorigenesis.

Security, ethics, and animals: towards a sentientist security discourse

ABSTRACT This article argues that it is high time for the (extra)ordinary violence and insecurity that nonhuman animals are subjected to in today’s world to be taken seriously in studies on security. Through a sympathetic yet critical engagement with how animals have appeared in recent posthuman security scholarship, the article insists on the need to differentiate between sentient beings on the one hand, and other beings as well as things on the other; the need to acknowledge and seek ways of eliminating the violence and insecurity internal to entangled human-animal relations; the feasibility of treating individual animals as direct subjects of security; and the feasibility of adopting a strong animal rights position grounded in sentience to supplement the relational or entanglement ethic dominant in posthuman security scholarship. The article proceeds by developing a tentative outline of a sentientist security discourse in terms of referent objects, nature of threats, security agents and security practices, and concludes by discussing some scholarly implications and the potential impact of securitising existential threats to animals.