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The study evaluated the long-term effect on vision-related quality-of-life (VRQoL) of routinely treated neovascular age-related macular degeneration (nAMD) in first and second eyes. The FASBAT (Observing Fibrosis, macular Atrophy and Subretinal highly reflective material Before and After Treatment with anti-VEGF treatment) study followed individuals with new unilateral nAMD (first eye) undergoing routine treatment for up to 4.5 years. Visual acuity (VA) was measured as part of routine care and VRQoL was assessed using the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25). Of the 424 participants, 307 had only the first eye affected by nAMD (mean age = 76.5, SD = 8.4 years). The mean VA was 58.1 (SD = 15.5) and 79.4 (SD = 5.6) letters at baseline, and 58.4 (SD = 20.9)/78.5 (SD = 7.8) letters at 36-months in the affected and unaffected eyes, respectively. The mean composite NEI-VFQ-25 score was 87.1 (SD = 11.9) at baseline and 85.2 (SD = 13.5) at 36-months. One hundred and seventeen participants (mean age = 77.6, SD = 7.3 years) developed second eye nAMD, with a mean of 18.9 (SD = 10.2) months following the first eye. Mean VA in first and second eye was 56.3 (SD = 19.3)/74.1 (SD = 9.9) letters at the time of second eye development, and 51.1 (SD = 22.5)/73.6 (SD = 8.9) letters after 24-months. Mean composite NEI-VFQ-25 score was 81.4 (SD = 14.6) and 79.1 (SD = 17.2) at these time points. Long-term VRQoL remains stable in unilateral treated nAMD. However, a clinically meaningful reduction in VRQoL occurs following development and treatment in the second eye which does not recover. It is important to offer appropriate support when the first and then second eye develop nAMD.
A class of organic, naturally occurring compounds known as phytohormones affects physiological functions in plants at trace levels. Phytohormones play important roles in plant growth, development, nutrient transport, and survival by regulating plant responses to abiotic stress and form the basis of ability of plants for adapting to changing conditions. To carry out some specific and distinct functions, cells of complex organisms implement gene regulation dynamics according to their cell types, including during the synthesis and control of various plant hormones. Rather than the traditional approaches for phytohormone quantification, single-cell RNA sequencing (scRNA-seq) and/or single-nucleus RNA sequencing (snRNA-seq) technologies that enable high-resolution mapping of cellular heterogeneity at the transcriptomic level, provide a novel approach for the phytohormone signaling. Here, we detailed the methodology of single cell/nucleus technologies to investigate underlying gene regulatory networks of plant hormone biology.
The welfare of non-human animals is central to ethical discussions on animal use, with increasing attention to fish welfare across research, aquaria, aquaculture, and fisheries. This paper reviews current theoretical approaches to animal welfare and recent advances in defining and assessing fish welfare since the seminal paper by Huntingford et al. (2006; J Fish Biol 68: 332-372), highlighting the growing role of cognitive and affective processes. It also includes the concept of positive welfare and some of the current research advances in this field. Methods for measuring, monitoring and assessing welfare via the utilisation of outcome- and input-based indicators are outlined, ranging from practical operational tools to laboratory-based measures. Welfare concerns in wild-capture fisheries are examined in relation to stress, flesh quality and sustainability, including the welfare of released fish. Recent advances in fish neurobiology, cognition and pain perception are summarised, together with technological innovations that enhance welfare monitoring and management. The paper also explores the relationship between fish welfare, sustainability, public concerns and consumer demand, and legal and moral recognition across contexts, situating fish welfare within the 'One Health' and 'One Welfare' frameworks that link animal welfare, environmental stewardship and human well-being. Ongoing challenges include climate change, cultural factors and the interpretation of fish sentience and cognition among others.
Bacteria exhibit extraordinary evolutionary and ecological diversity. They range from dominant, well-characterized phyla to rare lineages that are known only through environmental sequencing. This chapter reviews four key bacterial phyla, including Pseudomonadota, Bacillota, Actinomycetota, and Bacteroidota. These phyla are widely distributed, metabolically versatile, and play a central role in ecosystem functioning and human health. We discuss unique phyla within the PVC superphylum (Planctomycetota, Verrucomicrobiota, Chlamydiota) for their unusual cell biology, compartmentalization, and host associations. We also highlight hyperthermophilic phyla, such as Thermotogota, Aquificota, and Thermodesulfobacteriota, that thrive in geothermal ecosystems and drive sulfur and carbon cycling. We consider less-cultivated lineages, including Deinococcota, Acidobacteriota, Nitrospirota, Fusobacteriota, Fibrobacterota, Synergistota, Deferribacterota, and Chrysiogenota, in terms of their ecological niches, metabolic specializations, and roles in biogeochemical cycles, symbiosis, and disease. Collectively, these examples demonstrate the remarkable metabolic flexibility and ecological impact of bacteria, ranging from host-associated commensals and pathogens to free-living autotrophs in extreme environments. Despite advances in genomics and cultivation-independent methods, vast portions of bacterial diversity remain uncultured and poorly understood. Continued exploration of both dominant phyla and rare lineages promises to refine bacterial taxonomy, expand our understanding of microbial evolution, and reveal novel metabolic pathways with implications for ecology, medicine, and biotechnology.
The pancreatic β-cell contains several functional subpopulations of insulin secretory granules (ISGs). These subpopulations vary in maturity, age, and secretory capacity. Differences in protein and lipid composition of ISGs are correlated with disease but require further study to understand how ISG remodeling regulates normal biology. Due to limitations in traditional separation methods, the extent of these subpopulations, any overlap between them, and how they are affected by insulinotropic signals have not been determined. In this work, we adapted direct current insulator-based dielectrophoresis (DC-iDEP) to separate ISGs isolated from INS-1E cells, an immortalized rat insulinoma cell line model, according to their electrokinetic mobility ratio (EKMr). We were able to separate ISG subpopulations from unstimulated cells to determine a baseline distribution and identify characteristic profiles for immature, young, and old ISGs. We then analyzed distributions of subpopulations from cells stimulated with insulin secretion signals known to induce biophysical remodeling and maturation. We found significant changes in each subpopulation studied in response to stimulation, consistent with the increases in maturation, crystallization, and changes in size reported in the literature. This work provides new insights into how the cell controls ISG remodeling and may drive future development of more effective therapies.
Positron emission tomography (PET), particularly with prostate-specific membrane antigen (PSMA) tracers, has revolutionized the clinical management of prostate cancer (PCa). This review highlights the pivotal role of PET molecular imaging in guiding radiotherapy (RT) across diverse clinical scenarios, from postoperative biochemical recurrence to oligometastatic disease. Growing evidence shows that PET excels in lesion detection, enhances target volume delineation, enables focal dose escalation, and guides treatment intensification. PSMA PET increases the precision of RT planning, supports personalized therapeutic approaches, and is associated with improved outcomes, including biochemical recurrence-free and metastasis-free survival. The integration of PET with advanced RT technologies, including biology-guided radiotherapy (BgRT), is paving the way for real-time, biologically adaptive treatment paradigms. However, challenges remain, including the need for standardized protocols, management of tracer variability, and clinical translation of innovations such as PET-linear accelerator (LINAC) into routine practice. Future research should prioritize large-scale, prospective studies to establish the clinical efficacy, cost-effectiveness, and optimal integration of PET-guided RT in PCa care.
The coppery titi monkey (Plecturocebus cupreus) is an essential nonhuman primate model for social neuroscience, yet neuroimaging studies have been severely constrained by the paucity of standardized atlases. We address this gap by introducing the first MRI-based atlas package for the titi monkey brain that includes a single-subject atlas (UC Davis Titi monkey Neuroimaging Atlas (UCD-TiNA)), alongside a population atlas (UCD-TiNA_group) and a manually-segmented atlas compilation (UCD-TiNA_mac). UCD-TiNA comprises 74 hierarchically organized regions delineated from the MRI of a representative adult brain, along with whole brain, gray and white matter masks. These segmentations were propagated to the population template (UCD-TiNA_group, N = 17 monkeys) generated to enhance generalizability. A manually-segmented atlas compilation (UCD-TiNA_mac, N = 6 monkeys, 14 regions) was created to enable multi-atlas segmentation approaches. UCD-TiNA and UCD-TiNA_mac were evaluated in a [11C]GR103545 PET and MRI study (N = 42 monkeys) to quantify regional kappa opioid binding. The warped UCD-TiNA achieved a high concordance with the manually-segmented UCD-TiNA_mac labels (median Dice = 0.74). Regional [11C]GR103545 binding potential was consistent with published patterns. Quantitative PET analyses showed <1% median error and a high correlation (Spearman r = 0.99) between the warped and manually-segmented labels. This work delivers the first in vivo atlas package to enable standardized, reproducible and cross-modal analyses of titi monkey neuroimaging data. By providing a common anatomical reference, this atlas package should facilitate rigorous and harmonized data processing, supporting high-throughput and longitudinal investigations in social neurobiology and informing translational research on social behavior.
Cluster of differentiation 38 (CD38) is a multifunctional ectoenzyme regulating immune functions, calcium signaling, and nicotinamide adenine dinucleotide (NAD+) metabolism. Through rapid hydrolytic degradation of NAD+, CD38 drives cellular NAD+ depletion during aging, inflammation, and tumor growth, contributing to mitochondrial dysfunction and immune suppression. Consequently, CD38 inhibition has been emerging as a potential approach for disease control by restoring NAD+ homeostasis and immunometabolic balance. This review summarizes current advances in the development of small-molecule CD38 inhibitors. Mechanism-based nucleotides and nucleosides enable potent inhibition of CD38 in a covalent manner. From NAD+ analogues and synthetic molecules to natural products, non-covalent inhibitors represent versatile strategies for elevating tissue NAD+ levels with great efficacy by blocking CD38 catalysis. These discoveries establish a diverse chemical landscape for CD38 modulation and provide tools for studying CD38 biology as well as insight into the identification of therapeutic candidates with promising pharmacological activities.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, and diagnosis typically occurs after substantial neuronal loss, underscoring the need for biomarkers capable of detecting early pathological changes. The endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have been proposed as potential PD biomarkers; however, only their free fractions are biologically active. In this study, an in vivo solid-phase microextraction (SPME) method was developed to quantify free and total concentrations of AEA and 2-AG in rat brain under conditions of negligible depletion. Under these conditions, the SPME probe functions analogously to a sensor, extracting only minute amounts of analyte without perturbing the equilibrium between free and matrix-bound species. Extractions were performed at equilibrium, and experimentally determined distribution constants in PBS were used to calculate free concentrations. Matrix-binding percentages exceeded 99% for both analytes and were used alongside with free concentration measurements to estimate total concentration levels. In vivo analyses in a 6-OHDA rat model of PD revealed significant elevated striatal AEA levels in lesioned animals relative to controls, supporting its potential as a biomarker of early neurochemical alterations. In contrast, ex vivo SPME extractions in dissected brain did not show increased AEA levels in the PD group, indicating loss of physiologically relevant information post-mortem. Although 2-AG was not detected in vivo, it was quantified ex vivo, suggesting limited active release under the examined conditions. Overall, these findings highlight the capability of in vivo SPME to capture changes in heavily bound hydrophobic neurochemicals, thereby supporting its application in studies of endocannabinoid dysregulation.
Animals can use predation-risk experiences to modulate their antipredator responses and improve survival under future risk conditions, a phenomenon known as behavioural carryover. However, different contexts, such as group living, may alter both risks and associated responses for an individual. A group can provide multiple antipredator benefits, including dilution and confusion effects, potentially modifying the payoffs of behavioural carryover. Despite the prevalence of both antipredator strategies, we know little about how group living and behavioural carryover interact. We tested the influence of group living on the behavioural carryover of predation-risk experience in Aedes aegypti. Previous work showed that predation-risk experience shapes future behaviour when individuals are solitary. We hypothesized that these carryover effects would become redundant in groups due to the protective benefits of group living. To test this, we compared the behaviour of risk-experienced and naive individuals in groups, both in the presence and absence of an immediate threat, and contrasted it with that of solitary individuals. As expected, past predation-risk experience did not influence behaviour in a group. Surprisingly, both experienced and naive individuals altered their behaviour in response to an immediate threat. These results suggest that predation-risk experience is more relevant when prey are solitary than in groups.
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Skill is the ability to do a challenging behaviour well. We examined how contest skill influences contest success, costs and whether skilful behaviour enhances welfare. We measured skill across three domains: accuracy, appropriateness (selecting suitable agonistic tactics when the optimal choice varies) and efficiency, alongside vigour, sex and body weight. Skill was weakly correlated across domains. Winners were heavier relative to their opponent, displayed greater vigour and were more skilful at blocking, but other skill measures did not predict contest win/loss outcome. Appropriate blocking by winners reduced the number of lesions received by reducing exposure to attacks, suggesting it can both reduce costs and improve competitive success, with potential welfare benefits. Losers received more lesions when they adopted appropriate postures after submission; however, this unambiguous submission may have resulted from more costly contests. For winners, being heavy relative to the opponent tended to reduce skin lesions received, but otherwise, having a weight advantage did not reduce contest costs. Fighting with increased vigour led to a considerable increase in contest costs, particularly in losers. Compared to other resource-holding potential traits, skill has moderate effects on winning and injuries but nevertheless modulated energetic costs of fighting.
Dynamic coloration is one of the most striking visual displays in the animal kingdom. While reversible colour changes are well characterized in animal communication, more passive effects of climate on baseline coloration remain poorly understood. Here, we present a novel experimental demonstration of reversible, humidity-induced colour change in bees. In controlled lab experiments, we show that relative humidity affects cuticle colour of the sweat bee Agapostemon subtilior, changing dramatically within 24 h from a deep blue-green at low humidity to a pale, coppery green at high humidity. Older specimens experienced greater magnitude colour shifts, suggesting that cuticular degradation may increase water permeability and amplify moisture effects. To understand whether these effects shape colour variation in the wild, we extracted colour data from a large dataset of crowd-sourced field images. We found that ambient humidity weakly predicts colour variation across A. subtilior's western range, in a manner consistent with the direction of colour change established in lab experiments. While the structural basis for this colour change is still unknown, these shifts are directionally consistent with moisture-induced swelling of multilayer structures that causes reflection of longer wavelengths, a mechanism described in other insects and cephalopods. Together, these results demonstrate that climate modulates structural coloration in bees, emphasizing the role of abiotic conditions in shaping dynamic visual traits.
Efforts to control malaria face several challenges, including the presence of parasite reservoirs within the community that contribute to disease transmission. This study aimed to assess malaria prevalence among community members using microscopy and nested polymerase chain reaction (PCR) to detect parasite reservoirs in malaria-endemic settings. A community-based cross-sectional study was conducted in malaria-endemic districts of the Gamo Zone in the southern Rift Valley of Ethiopia. The research was conducted as part of a baseline assessment for a trial evaluating the impact of house screening and ivermectin treatment of domestic animals on malaria incidence. Capillary blood samples were collected from the study participants to prepare blood films and dried blood spots. Malaria parasite detection and species identification were performed using both microscopy and nested PCR. Of 4745 participants screened by microscopy, malaria prevalence was 2.7% (126/4745; 95% CI: 2.2-3.2%). Nested PCR was performed on 1183 samples, including 97 microscopy-positive and 1,086 microscopy-negative samples. PCR confirmed 67% (65/97) of microscopy-positive cases, yielding a PCR-corrected microscopy prevalence of 1.4% (65/4745). Submicroscopic infections were detected in 6.1% (66/1086) of microscopy-negative samples. Malaria prevalence across Kebeles ranged from 0.5-2.3% by microscopy and 4.1-9.6% by PCR. Species misclassification by microscopy was common: 19.5% of P. falciparum infections were misidentified as P. vivax, 14.0% of P. vivax as P. falciparum, and 33.0% of microscopy-positive samples were PCR-negative. These findings emphasize that community-based malaria diagnosis using microscopy underestimates malaria prevalence, highlighting the need for improved diagnostic methods.
The early Palaeozoic saw a dramatic diversification of shelly epibenthic metazoans adapted to suspension and filter feeding, but the extent to which these radiations affected the evolution of non-biomineralized suspension-feeding taxa is uncertain because these organisms are not typically well represented in the fossil record. Luolishaniids are a highly derived and disparate clade of (typically) armoured lobopodians, widely interpreted as suspension feeders based on the presence of five or six anterior pairs of setulose appendages. Luolishaniids are globally widespread and represent the only Cambrian non-biomineralized free-living epibenthic bilaterians suggested to have a suspension-feeding mode of life, but their proposed ecology relies solely on a qualitative interpretation of their functional morphology. Here we test the hypothesis that the setulose appendages of luolishaniids were adapted for a suspension-feeding function. Quantitative morphological comparisons reveal a positive and statistically significant relationship between body length and the mesh spacing of the setulose anterior limbs of luolishaniids. Standardized comparisons indicate that the body size disparity between luolishaniids (predators) and Cambrian mesoplankton (prey) is consistent with patterns observed in modern suspension-feeding organisms. We provide quantitative evidence for suspension feeding in luolishaniids, which represents the first statistically supported example of modern-like predator-prey scaling patterns observed in Cambrian soft-bodied metazoans. Despite the uncanny appearance of luolishaniids, and Cambrian organisms more broadly, our results suggest their adaptations and mode of life feature ecological attributes shared with modern marine invertebrates.
Fraternal cooperative organizations (FCOs), which encompass metazoan multicellularity and eusociality, rely on a division of labour among specialized members. I present a comprehensive framework to concretely classify FCO members by specialization, state transition and potency, which are associated with complexity, regeneration and defector susceptibility of the group. Across FCOs, specialization hinders plasticity, potency and regenerative capacity due to sophisticated fate-determination systems. In addition, such a sophisticated system is vulnerable to spontaneous malfunctions, generating dysfunctional or cheating group members (cancers or excessively produced queens) characterized by unregulated proliferation/reproduction. The framework explains why complex FCOs exhibit limited regeneration and why highly regenerative FCOs cannot become complex. As an exception, plants can be complex and regenerative owing to their structural robustness against cancer.
Wild edible plants (WEPs) play a crucial role in rural livelihoods, food security, and cultural heritage in Ethiopia. Despite their importance, comprehensive documentation of WEP diversity, utilization, and associated indigenous knowledge in Tegedie District remains limited. This study aimed to identify WEP species, evaluate their uses, assess knowledge distribution among community members, and identify threats to their sustainability. Ethnobotanical data were collected from 144 purposively selected informants across eight sites using semi-structured interviews, focus group discussions, and guided field observations. Quantitative indices, including the Relative Frequency of Citation (RFC) and Jaccard Similarity Index (JSI), were employed to assess species importance, cultural significance, and similarity with other Ethiopian districts. Preference ranking and direct matrix ranking were used to evaluate species preference, multifunctionality, and perceived threats. Data analysis was conducted using R software, and species identifications were cross-checked against the IUCN Red List. A total of 52 WEP species were documented, comprising trees, shrubs, herbs, and climbers. Fruit-bearing trees and shrubs were the most frequently cited, highly preferred, and culturally significant. The top-ranked WEPs included Cordia africana Lam., Syzygium guineense (Willd.) DC., Diospyros mespiliformis Hochst. ex A.DC., and Tamarindus indica L. Knowledge of WEPs was significantly higher among men, older individuals, illiterate participants, and key informants (P < 0.005), reflecting the cumulative and experiential nature of indigenous knowledge. Major threats to WEPs included agricultural expansion, overgrazing, firewood collection, charcoal production, and habitat degradation. WEPs were primarily harvested from forests, grazing lands, and uncultivated areas, with knowledge transferred orally and through hands-on participation in harvesting. WEPs in Tegedie District are vital for dietary diversity, food security, and cultural practices, but they face significant anthropogenic and environmental pressures. Conservation strategies, including habitat protection, sustainable harvesting, ex situ cultivation, and systematic documentation of indigenous knowledge, are urgently needed. Promoting intergenerational knowledge transfer is essential to ensure the continued availability and sustainable use of these valuable plant resources.
Vivien R, Martin P, Pawlowski J, Alther R. 2025 Adapting practices to accelerate the scientific description of invertebrate cryptic species. Biol. Lett. 21, 20250385. (doi:10.1098/rsbl.2025.0385) propose accelerating the formal description of cryptic invertebrate species by relaxing long-standing evidentiary requirements, including the type concept. While motivated by a desire for efficiency, this proposal is both unnecessary, because existing provisional labels already allow rapid communication, and undesirable, because genetic patterning alone does not justify naming species. Species are explanatory hypotheses that require names anchored to verifiable type material. Detaching names from types would destabilize nomenclature and erode the evidentiary standards that make systematics a scientific enterprise.
Morphological and low-coverage genomic data reveal that the shallow-water Swedish ribbon worm Tubulanus lutescens is conspecific with nemerteans collected from bathyal methane seeps along the Costa Rican margin, thus spanning two ocean basins and environmental extremes. Of approximately 1350 described nemertean species, only approximately 35 are known from below 500 m, and only six species are genetically confirmed as eurybathic. In 2022, we reported the Costa Rican material but withheld a species description because its cytochrome c oxidase subunit I (COI) closely matched that of T. lutescens. Here, we re-examined serial sections of the holotype plus its COI vouchers and generated mitochondrial genomes and hundreds of single-copy nuclear orthologues from one Costa Rican and one Swedish specimen using low-coverage whole-genome sequencing. Morphological and genome-scale comparisons support a single species spanning shallow to bathyal habitats across both the Atlantic and Pacific. This establishes T. lutescens as the first confirmed eurybathic palaeonemertean, exhibiting the widest geographic and bathymetric range among nemerteans and an exceptional range even among benthic marine invertebrates. Because one population inhabits a deep-sea seep, anthropogenic dispersal is unlikely. This unexpected conspecificity, despite increased genomic resolution that often reveals cryptic diversity, highlights how much remains to be discovered about marine invertebrate distributions.