This paper introduces the ARCH model—Behavior = Archetype × Drive × Culture—as a biologically grounded framework for understanding emotion and behavior across species. Rooted in Tinbergen’s ethological paradigm, the model formalizes emotion as the emergent outcome of conserved behavioral scripts (archetypes), motivational systems (drives), and sociocultural modulation (culture). Neurobiologically anchored in systems such as the amygdala, hypothalamus, and mesolimbic pathways, the model accounts for affective expression across phylogeny, from bacteria to primates, and includes applications in psychiatric diagnosis, comparative ethology, and cognitive neuropsychology. The ARCH model reframes psychopathology as misalignment within the triad, offering explanatory value for conditions such as dissociation, addiction, and violent extremism. By unifying neural substrates, motivational states, and symbolic environments, ARCH provides a scalable, testable, and evolutionarily conserved law of behavior, with implications for psychiatry, AI, and behavioral science.
<b>Background/Objectives:</b> Oleuropein (OLP), the key bioactive in olive leaf extracts, has demonstrated various biological benefits. We previously reported on the pro-melanogenic action with increased dendricity of a patented olive leaf extract (Benolea<sup>®</sup>) that was standardized to 16–24% OLP. In this study, purified OLP was evaluated to identify if it might be the bioactive responsible for the stimulating effects on melanocytes. Moreover, previous studies on OLP have never reported the effects on melanocyte dendricity or melanin export in the medium. <b>Methods:</b> Herein, the effect of OLP on melanogenesis was first evaluated using the B16F10 cell model and validated using the physiological model of normal human melanocytes from Caucasian (lightly pigmented; LP) and Asian (moderately pigmented; MP) skin. The effects of OLP on melanin export in LP and MP cells were indirectly evaluated by dendricity indices. <b>Results:</b> OLP lowered the intracellular melanin content in B16F10 cells by 26.36%, 24.48%, and 27.71% at 100, 150, and 200 µg/mL (all <i>p</i> < 0.01), respectively, with no effect on the intracellular melanin contents of LP or MP cells. OLP treatment did not influence tyrosinase activity in B16F10 cells or MP cells but significantly enhanced the activity in LP cells. The measurement of extracellular melanin showed significantly higher levels for all three cells, although the levels were considerably higher in MP cells, after the adjustment for OLP autoxidation observed in the cell-free system, which caused melanin-like brown coloration. Furthermore, OLP induced morphological alterations of extended dendrites of B16F10 cells that were retained in LP and MP cells. The quantitation of the dendricity of cells treated with OLP at 200 μg/mL revealed that the total dendrite length was increased by 35.24% (<i>p</i> < 0.05) in LP cells and by 58.45% (<i>p</i> < 0.001) in MP cells without any change in the dendrite number. <b>Conclusions:</b> This is the first study to demonstrate the novel finding that OLP possesses a hitherto unreported unique capacity to stimulate melanocyte dendricity, hence establishing the efficacy for use in increasing human pigmentation. Our findings show significance, with a potential application of the compound OLP for addressing human hypopigmentation disorders in clinical settings or for cosmetic uses related to sunless tanning.
Marília I. Figueira, Tiago M. A. Carvalho, Joana Macário-Monteiro
et al.
The role of estrogens in prostate cancer (PCa) is shrouded in mystery, with its actions going from angelic to devilish. The findings by Huggins and Hodges establishing PCa as a hormone-sensitive cancer have provided the basis for using estrogens in therapy. However, despite the clinical efficacy in suppressing tumor growth and the panoply of experimental evidence describing its anticarcinogenic effects, estrogens were abolished from PCa treatment because of the adverse secondary effects. Notwithstanding, research work over the years has continued investigating the effects of estrogens, reporting their pros and cons in prostate carcinogenesis. In contrast with the beneficial therapeutic effects, many reports have implicated estrogens in the disruption of prostate cell fate and tissue homeostasis. On the other hand, epidemiological data demonstrating the lower incidence of PCa in Eastern countries associated with a higher consumption of phytoestrogens support the beneficial role of estrogens in counteracting cancer development. Many studies have investigated the effects of phytoestrogens and the underlying mechanisms of action, which may contribute to developing safe estrogen-based anti-PCa therapies. This review compiles the existing data on the anti- and protumorigenic actions of estrogens and summarizes the anticancer effects of several phytoestrogens, highlighting their promising features in PCa treatment.
Teresa Soda, Teresa Pasqua, Giovambattista De Sarro
et al.
Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in synaptic strength. This plasticity often manifests as long-term potentiation (LTP) and long-term depression (LTD), which are bidirectional modulations of synaptic efficacy. Strong epidemiological and experimental evidence show that the heart–brain axis could be severely compromised by both neurological and cardiovascular disorders. Particularly, cardiovascular disorders, such as heart failure, hypertension, obesity, diabetes and insulin resistance, and arrhythmias, may lead to cognitive impairment, a condition known as cardiogenic dementia. Herein, we review the available knowledge on the synaptic and molecular mechanisms by which cardiogenic dementia may arise and describe how LTP and/or LTD induction and maintenance may be compromised in the CA1 region of the hippocampus by heart failure, metabolic syndrome, and arrhythmias. We also discuss the emerging evidence that endothelial dysfunction may contribute to directly altering hippocampal LTP by impairing the synaptically induced activation of the endothelial nitric oxide synthase. A better understanding of how CV disorders impact on the proper function of central synapses will shed novel light on the molecular underpinnings of cardiogenic dementia, thereby providing a new perspective for more specific pharmacological treatments.
Navid Saidi, Fateme Davarzani, Zahra Yousefpour
et al.
Background: Bacterial virulence factors may be influenced by sub-minimum inhibitory concentrations (sub-MICs) of antibiotics. The main purpose of this study was to investigate the effects of gentamicin at sub-MICs (0.5 MIC and 0.25 MIC) on alginate production of clinical isolates of Pseudomonas aeruginosa.
Materials and Methods: The minimum inhibitory concentrations of gentamicin against 88 clinical isolates of P. aeruginosa were determined using the broth microdilution method. Alginate production of the isolates in the absence and presence of gentamicin at sub-MICs was assessed by the carbazole method. The presence of alginate in clinical isolates was confirmed by the detection of alginate genes (algD and algU) using the PCR method.
Results: All the isolates had the ability of alginate production and were positive for algD and algU genes. sub-MICs of gentamicin significantly increased alginate production of 34 isolates (38.6%). On the other hand, in 49 isolates (55.7%), alginate production was significantly increased after treatment with sub-MICs of gentamicin. In five isolates (5.7%), the alginate production was reduced in exposure to 0.5 MIC of gentamicin while it was increased by gentamicin at 0.25 MIC.
Conclusion: This study showed different effects of gentamicin at sub-MICs on the alginate production of clinical isolates of P. aeruginosa. Further research is highly recommended to understand the mechanism of different responses of P. aeruginosa isolates to the exposure of sub-MICs of gentamicin.
Asier Léniz, Alfredo Fernández-Quintela, Sara Arranz
et al.
Background: Adipokines, as well as the fatty acid profile of red blood cell (RBC) membranes, are known to play important roles in the development and progression of metabolic complications induced by obesity. Thus, the objective of this study is to compare the serum adipokine profile and the RBC membrane fatty acid profile of normal-weight and obese adults, and to analyze their relationship with serum biochemical parameters. Methods: An observational case–control study was performed in 75 normal-weight and obese adult subjects. Biochemical serum parameters, eight serum adipokines and the RBC membrane fatty acid profiles were measured. Associations between parameters were established using regression analysis. Results: Subjects with obesity showed increased levels of leptin, fibroblast growth factor 21 (FGF21) and overexpressed nephroblastoma (NOV/CCN3), decreased adiponectin, and similar levels of vaspin and chemerin compared to normal-weight subjects. Significant positive and negative correlations were found with triglycerides and high-density lipoprotein-cholesterol (HDL-c), respectively. An increase in the total ω-6 fatty acids in the RBC membrane fatty acid profiles in subjects with obesity was observed, because of higher levels of both dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), and decreased total ω-3 fatty acids, mainly due to lower levels of docosahexaenoic acid (DHA). The ω-6/ω-3 ratio in the RBCs was significantly higher, suggesting an inflammatory status, as was also suggested by a reduced adiponectin level. A negative association between DGLA and adiponectin, and a positive association between DHA and serum triglycerides, was observed. Conclusions: Important alterations in serum adipokine and RBC fatty acid profiles are found in subjects with obesity.
Vasiliki Zoi, Vasiliki Galani, Pericles Tsekeris
et al.
Radiation therapy plays an important role in almost every cancer treatment. However, radiation toxicity to normal tissues, mainly due to the generation of reactive free radicals, has limited the efficacy of radiotherapy in clinical practice. Curcumin has been reported to possess significant antitumor properties. Although curcumin can sensitize cancer cells to irradiation, healthy cells are much less sensitive to this effect, and thus, curcumin is thought to be a potent, yet safe anti-cancer agent. In this review, a summary of the role of curcumin as both a radiosensitizer and radioprotector has been presented, based on the most recent data from the experimental and clinical evaluation of curcumin in different cancer cell lines, animal models, and human patients.
Bryan A Johnson, Yiyang Zhou, Kumari G Lokugamage
et al.
While SARS-CoV-2 continues to adapt for human infection and transmission, genetic variation outside of the spike gene remains largely unexplored. This study investigates a highly variable region at residues 203-205 in the SARS-CoV-2 nucleocapsid protein. Recreating a mutation found in the alpha and omicron variants in an early pandemic (WA-1) background, we find that the R203K+G204R mutation is sufficient to enhance replication, fitness, and pathogenesis of SARS-CoV-2. The R203K+G204R mutant corresponds with increased viral RNA and protein both in vitro and in vivo. Importantly, the R203K+G204R mutation increases nucleocapsid phosphorylation and confers resistance to inhibition of the GSK-3 kinase, providing a molecular basis for increased virus replication. Notably, analogous alanine substitutions at positions 203+204 also increase SARS-CoV-2 replication and augment phosphorylation, suggesting that infection is enhanced through ablation of the ancestral 'RG' motif. Overall, these results demonstrate that variant mutations outside spike are key components in SARS-CoV-2's continued adaptation to human infection.
Abstract Over the last two decades, southwestern North America (SWNA) has been in the grip of one of the most severe droughts of the last 1,200 years, with one third to nearly one half of its severity attributable to climate change. We analyze how the risk of extreme soil moisture droughts in SWNA, analogous to the most severe 21‐year (≥ in magnitude to 2000–2020) and single‐year (≥ in magnitude to 2002) events of the last several decades, changes in projections from Phase 6 of the Coupled Model Intercomparison Project. By the end of the 21st century, SWNA experiences robust (R ≥ 0.80) soil moisture drying and substantial increases in extreme single‐year drought risk that scale strongly with warming, spanning an 8%–26% probability of occurrence across +2–4 K. Notably, our results show that 21‐year droughts analogous to 2000–2020 are up to 5 times more likely than extreme single‐year droughts under all levels of warming (≈50%). These high levels of 21‐year drought risk are largely invariant across scenarios because of large spring precipitation declines in half the models, shifting SWNA into a drier mean state. Despite projections of this sweeping and ostensibly inevitable increase in 21‐year drought risk, climate mitigation reduces their severity by reducing the magnitude of extreme single‐year droughts during these events. Our results emphasize both the importance of preparing SWNA for imminent increases in persistent drought events and constraining projected precipitation uncertainty to better resolve future long‐term drought risk.
Abstract Feedback control is a fundamental underpinning of life, underlying homeostasis of biological processes at every scale of organization, from cells to ecosystems. The ability to evaluate the contribution and limitations of feedback control mechanisms operating in cells is a critical step for understanding and ultimately designing feedback control systems with biological molecules. Here, we introduce CoRa –or Co ntrol Ra tio –, a general framework that quantifies the contribution of a biological feedback control mechanism to adaptation using a mathematically controlled comparison to an identical system that does not contain the feedback. CoRa provides a simple and intuitive metric with broad applicability to biological feedback systems.
Cassie M. Hazell, Christina J. Jones, Aparajita Pandey
et al.
Abstract Objective Carers play an important role within the UK mental health system. Those carers who support persons with psychosis can experience a reduction in their own physical and mental health. As part of the Caring for Caregivers (C4C) trial, we piloted a writing intervention (Positive Written Disclosure) that has been shown to improve wellbeing in other populations. Although we reached our recruitment target, we encountered several barriers that made recruitment slower than anticipated. This paper synthesises the process data collected during the C4C trial that relates to the barriers to recruiting and retaining psychosis carers. Results We encountered four main carer-specific barriers to the recruitment and retention of participants in our study. These were: (1) poor relationship with mental health clinicians, (2) conflicting with the care recipient’s (CR) needs, (3) lack of spare time, and (4) lack of services for mental health carers. The interventions to assist carers need to be informed by robust evidence and this requires trials that reach their recruitment targets. By sharing our practical experiences other researchers and clinicians can modify their practices to minimise recruitment difficulties and delay. Trial registration ISRCTN79116352. Retrospectively registered (before the final participant was recruited) on 23rd January 2017
Eduardo J Contijoch, Graham J Britton, Chao Yang
et al.
To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn’s disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
Zaman Subhi Madlool, Satar Abood Faris, Ali M. Hussein
The present study was designed to know the effect of sertraline and fluoxetine on the reproductive abilities of male rats. The experiment consisted of five groups (each group contains of 5 males), the first (control) group was injected (I.P) with 0.25ml of normal saline, the second group was injected with sertraline (10 mg / kg), the third group was injected with sertraline (20 mg / kg), the fourth group was injected with fluoxetine (5 mg / kg) and the fifth group was injected with fluoxetine (10 mg / kg). .The results showed a significant decrease (P?0.05) in the number of sperms and in the level of testosterone hormone and a significant increase (P?0.05) in the percentage of sperm deformities in all treated groups when compared with control group. The histologically examination showed that there was changes in the testis including the dissociation of the connective tissue in second and fifth groups, decrease in the number of spermatgonia, and Leydig cells, bloody congestion in third and fifth groups, hemorrhage and necrosis in forth group.
Abstract The endosymbiotic bacterium Wolbachia infects a wide range of arthropods and their relatives. It is an intracellular parasite transmitted through the egg from mother to offspring. Wolbachia can spread and persist through various means of host reproductive manipulation. How these different mechanisms of host manipulation evolved in Wolbachia is unclear. Which host reproductive phenotype is most likely to be ancestral and whether evolutionary transitions between some host phenotypes are more common than others remain unanswered questions. Recent studies have revealed multiple cases where the same Wolbachia strain can induce different reproductive phenotypes in different hosts, raising the question to what degree the induced host phenotype should be regarded as a trait of Wolbachia. In this study, we constructed a phylogenetic tree of Wolbachia and analyzed the patterns of host phenotypes along that tree. We were able to detect a phylogenetic signal of host phenotypes on the Wolbachia tree, indicating that the induced host phenotype can be regarded as a Wolbachia trait. However, we found no clear support for the previously stated hypothesis that cytoplasmic incompatibility is ancestral to Wolbachia in arthropods. Our analysis provides evidence for heterogeneous transition rates between host phenotypes.
Kimberly A. Dowd, Christina R. DeMaso, Rebecca S. Pelc
et al.
Recent epidemics of Zika virus (ZIKV) have been associated with congenital malformation during pregnancy and Guillain-Barré syndrome. There are two ZIKV lineages (African and Asian) that share >95% amino acid identity. Little is known regarding the ability of neutralizing antibodies elicited against one lineage to protect against the other. We investigated the breadth of the neutralizing antibody response following ZIKV infection by measuring the sensitivity of six ZIKV strains to neutralization by ZIKV-confirmed convalescent human serum or plasma samples. Contemporary Asian and early African ZIKV strains were similarly sensitive to neutralization regardless of the cellular source of virus. Furthermore, mouse immune serum generated after infection with African or Asian ZIKV strains was capable of neutralizing homologous and heterologous ZIKV strains equivalently. Because our study only defines a single ZIKV serotype, vaccine candidates eliciting robust neutralizing antibody responses should inhibit infection of both ZIKV lineages, including strains circulating in the Americas.
Kiessoun Konaté, Kassi Yomalan, Oksana Sytar
et al.
Objective: To evaluate anti-diarrhoeal and antimicrobial activities of the bioactive fraction of Trichilia emetica in order to provide a scientific basis for the management of gastroenteritis in Burkina Faso.
Methods: To do this, polyphenols content of extract and fractions were investigated. Folin-Ciocalteu, AlCl3 methods and tannic acid respectively were used for polyphenols content. The in vivo antidiarrhoeal activity was done using Swiss albino mice of both sexes. In vitro antimicrobial activity (disc-diffusion assay, minimum inhibitory concentration and minimum microbicidal concentration or minimal bactericidal concentration) was assessed using seven bacteria strains (Gram-negative and Gram-positive).
Results: About our study, it was found that ethyl acetate fraction effective attenuation factior (EAF) elicits the higher total phenolics and total flavonoids contents compared to the extracts of leaves of Trichilia emetica. EAF of Trichilia emetica Vahl., has positive effects in a dose dependent manner against diarrhoea induced by castor oil in experimental mice. The bioactive fraction also showed good antimicrobial activity against all tested Gram-negative and Gram-positive bacteria strains. It was shown that experimental bacteria strains were more sensitive to the EAF effect compared to the ciprofloxacin.
Conclusions: The obtained results allow justifying the traditional uses of Trichilia emetica and possess good antidiarrhoeal and antimicrobial activities of EAF from Trichilia emetica. Results of the present study have clearly supported the utilization of Trichilia emetica in Burkina Faso traditional medicine.
Setsuko Wakao, Brian L Chin, Heidi K Ledford
et al.
Singlet oxygen is a highly toxic and inevitable byproduct of oxygenic photosynthesis. The unicellular green alga Chlamydomonas reinhardtii is capable of acclimating specifically to singlet oxygen stress, but the retrograde signaling pathway from the chloroplast to the nucleus mediating this response is unknown. Here we describe a mutant, singlet oxygen acclimation knocked-out 1 (sak1), that lacks the acclimation response to singlet oxygen. Analysis of genome-wide changes in RNA abundance during acclimation to singlet oxygen revealed that SAK1 is a key regulator of the gene expression response during acclimation. The SAK1 gene encodes an uncharacterized protein with a domain conserved among chlorophytes and present in some bZIP transcription factors. The SAK1 protein is located in the cytosol, and it is induced and phosphorylated upon exposure to singlet oxygen, suggesting that it is a critical intermediate component of the retrograde signal transduction pathway leading to singlet oxygen acclimation.
Amino acid racemases are enzymes that invert the α-carbon stereochemistry of amino acids (AAs), interconverting amino acids between their L- and D-enantiomers in a reversible reaction. In bacteria, they are known to have catabolic physiological functions but are also involved in the synthesis of many D-AAs, including D-glutamate and D-alanine, which are necessary components of the peptidoglycan layer of the bacterial cell wall. As such, amino acid racemases represent significant targets for the development of bactericidal compounds. Amino acid racemases are also regarded by the biotechnological industry as important catalysts for the production of economically relevant D-AAs. Here, we provide a detailed protocol using high performance liquid chromatography (HPLC) and 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA, also Marfey’s reagent) for the characterization of novel amino acid racemases. The protocol described here was designed to obtain accurate kinetic parameters (kcat, KM values). Enzyme concentrations and reaction times were optimized so as to minimize the reverse reaction, which can confound results when measuring racemase reactions.