bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Assessment and Mapping in a Space Analog Station: Collaborations to Ensure Safety and Minimize Failures
Authors: Cabral Iris Campanella , de Oliveira Santana Ana Carolina Seixas , de Rezende Júlio Francisco Dantas , Chucair Soraya , Santos Gabriel Matheus Dutra , Fürstenau Cristina Ribas
Published: December 2024

The development of Map Assessments, especially in analog space missions, plays a fundamental role in identifying, assessing, and mitigating potential threats and challenges that may arise during space operations in extraterrestrial environments. These missions are designed to simulate real space flight conditions, allowing space agencies and exploration teams to test and refine procedures, technologies, and protocols before implementing them in actual space missions. During the risk analysis, various factors are considered, including: i) Environmental Risks: the context in which the mission will occur, as extreme weather conditions; ii) Health and Safety Risks: health and safety of the team members, as exposure to radiation; iii) Operational Risks: associated with operational procedures, communications, resource management, team coordination, and decision-making during the mission; iv) Psychosocial Risks: interpersonal conflicts, and emotion management along with the crew. Based on the analysis of these risks, strategies and mitigation measures are developed to minimize the likelihood of adverse events and their potential consequences. This study aims to analyze occupation risks, divided into physical, chemical, ergonomic, biological, and mechanical, at the analog space station Habitat Marte, located in Rio Grande do Norte, Brazil. As a result, various sources of danger and vulnerabilities in analog space operations were identified, which include: a. identification of the biological risk group, which includes symptoms associated with transmitted diseases or infections, the possibilities of contamination and spread of transmissible diseases; b. identification of the chemical risk group, which includes the presence of harmful gases, such as carbon dioxide and methane, symptoms of exposure, such as breathing difficulties; c. Identification of the mechanical risk group, where insect bites, possible fires, structural collapses, d. Identification of the physical risk group, which includes exposure to extreme temperatures, dehydration, fatigue and falls, e. Identification of the ergonomic risk group, strongly present in issues such as work in confined spaces and repetitive movements, f. Identification of the psychological risk group, which ultimately encompasses stress due to confinement, lack of rest, and fear of incidents during the journey. By conducting this comprehensive and multidisciplinary risk analysis, space agencies and exploration teams can significantly increase the safety, efficacy, and success of their future missions in space. These results provide a solid foundation for the continuous development of risk management strategies and safety measures for long-duration space missions, contributing to the viability and success of future human expeditions to Mars and beyond.
Non-invasive Temporal Interference Stimulation of the Hippocampus Suppresses Epileptic Biomarkers in Patients with Epilepsy: Biophysical Differences between Kilohertz and Amplitude Modulated Stimulation
Authors: Missey Florian , Acerbo Emma , Dickey Adam S. , Trajlinek Jan , Studnička Ondřej , Lubrano Claudia , de Araújo e Silva Mariane , Brady Evan , Všianský Vit , Szabo Johanna , Dolezalova Irena , Fabo Daniel , Pail Martin , Gutekunst Claire-Anne , Migliore Rosanna , Migliore Michele , Lagarde Stanislas , Carron Romain , Karimi Fariba , Astorga Raul Castillo , Cassara Antonino M. , Kuster Niels , Neufeld Esra , Bartolomei Fabrice , Pedersen Nigel P. , Gross Robert E. , Jirsa Viktor , Drane Daniel L. , Brázdil Milan , Williamson Adam
Published: December 2024

Medication-refractory focal epilepsy creates a significant challenge, with approximately 30% of patients ineligible for surgery due to the involvement of eloquent cortex in the epileptogenic network. For such patients with limited surgical options, electrical neuromodulation represents a promising alternative therapy. In this study, we investigate the potential of non-invasive temporal interference (TI) electrical stimulation to reduce epileptic biomarkers in patients with epilepsy by comparing intracerebral recordings obtained before, during, and after TI stimulation, to recordings during low and high kHz frequency (HF) sham stimulation. Thirteen patients with symptoms of mesiotemporal epilepsy (MTLE) and implanted with stereoelectroencephalography (sEEG) depth electrodes received TI stimulation with an amplitude modulation (AM) frequency of 130Hz (Δf), where the AM was delivered with lower frequency kHz carriers (1kHz + 1.13kHz), or higher frequency carriers (9kHz + 9.13kHz), targeting the hippocampus – a common epileptic focus and consequently stimulation target in MTLE. Our results show that TI stimulation yields a statistically significant decrease in interictal epileptiform discharges (IEDs) and pathological high-frequency oscillations (HFOs) – specifically fast-ripples (FR) –, where the suppression is apparent in the hippocampal focus and propagation from the focus is reduced brain-wide. HF sham stimulation at 1kHz frequency also impacted the IED rate in the cortex, but without reaching the hippocampal focus. The HF sham effect diminished with increasing frequencies (2, 5, and 9kHz, respectively), specifically as a function of depth into the cortex. This depth dependence was not observed with the TI, independent of the employed carrier frequency (low or high kHz). Furthermore, a strong carry-over effect, i.e., suppression of epileptic biomarkers for a period of time after the end of stimulation, was observed for TI but not for kHz. Our findings underscore the possible application of TI in epilepsy, as an additional non-invasive brain stimulation tool, potentially offering opportunities to assess brain region response to electrical neuromodulation before committing to a deep brain stimulation (DBS) or responsive neurostimulation (RNS) implants. Our results further demonstrate distinct biophysical differences between kHz and focal AM stimulation.

Graphical Abstract
Impact of disease-associated chromatin accessibility QTLs across immune cell types and contexts
Authors: Mu Zepeng , Randolph Haley E. , Aguirre-Gamboa Raúl , Ketter Ellen , Dumaine Anne , Locher Veronica , Brandolino Cary , Liu Xuanyao , Kaufmann Daniel E. , Barreiro Luis B. , Li Yang I.
Published: December 2024

Only a third of immune-associated loci from genome-wide association studies (GWAS) colocalize with expression quantitative trait loci (eQTLs). To learn about causal genes and mechanisms at the remaining loci, we created a unified single-cell chromatin accessibility (scATAC-seq) map in peripheral blood comprising a total of 282,424 cells from 48 individuals. Clustering and topic modeling of scATAC data identified discrete cell-types and continuous cell states, which helped reveal disease-relevant cellular contexts, and allowed mapping of genetic effects on chromatin accessibility across these contexts. We identified 37,390 chromatin accessibility QTLs (caQTL) at 10% FDR across eight cell groups and observed extensive sharing of caQTLs across immune cell contexts, finding that fewer than 20% of caQTLs are specific to a single cell type. Notably, caQTLs colocalized with ∼50% more GWAS loci compared to eQTLs, helping to nominate putative causal genes for many unexplained loci. However, most GWAS-caQTL colocalizations had no detectable downstream regulatory effects on gene expression levels in the same cell type. We find evidence that the higher rates of colocalization between caQTLs and GWAS signals reflect missing disease-relevant cellular contexts among existing eQTL studies. Thus, there remains a pressing need for identifying disease-causing cellular contexts and for mapping gene regulatory variation in these cells.
Enzyme-Regulated Non-Thermal Fluctuations Enhance Ligand Diffusion and Receptor-Mediated Endocytosis
Authors: Nividha  , Maiti Arnab , Parihar Kshitiz , Chakraborty Rik , Agarwala Pratibha , Sasmal Dibyendu K. , Radhakrishnan Ravi , Bhatia Dhiraj , Dey Krishna Kanti
Published: December 2024

Active enzymes during catalyzing chemical reactions, have been found to generate significant mechanical fluctuations, which can influence the dynamics of their surroundings. These phenomena open new avenues for controlling mass transport in complex and dynamically inhomogeneous environments through localized chemical reactions. To explore this potential, we studied the uptake of transferrin molecules in retinal pigment epithelium (RPE) cells via clathrin-mediated endocytosis. In the presence of enzyme catalysis in the extracellular matrix, we observed a significant enhancement in the transport of fluorophore-tagged transferrin inside the cells. Fluorescence correlation spectroscopy measurements showed substantial increase in transferrin diffusion in the presence of active fluctuations. This study sheds light on the possibility that enzyme-substrate reactions within the extracellular matrix may induce long-range mechanical influences, facilitating targeted material delivery within intracellular milieu more efficiently than passive diffusion. These insights are expected to contribute to the development of better therapeutic strategies by overcoming limitations imposed by slow molecular diffusion under complex environments.
Eukaryotic Translation Initiation Factor Loaded Extracellular Vesicles Promotes Macrophage Cholesterol Metabolism in ovarian cancer
Authors: Mittal Sonam , Nenwani Minal , Kadamberi Ishaque Pulikkal , Kumar Sudhir , Animasahun Olamide , George Jasmine , Tsaih Shirng-Wern , Gupta Prachi , Singh Mona , Geethadevi Anjali , Dey Chandrima , Meurs Noah , Shankaran Ajay , Chaluvally Raghavan Pradeep , Nagrath Deepak , Pradeep Sunila
Published: December 2024

Tumor-driven immune suppression poses a significant impediment to the success of immunotherapy in ovarian cancer. Among the various mechanisms contributing to immune suppression, intracellular communication facilitated by tumor-derived extracellular vesicles (EVs) within the tumor microenvironment (TME) emerges as a pivotal factor influencing tumor growth.

We discovered that EVs from both ovarian tumor cell lines and the plasma of ovarian cancer patients are encapsulated with eukaryotic translation initiation factor 4E (eIF4E). Our study revealed a new mechanism showing how these EVs are loaded with eIF4E and its impact on ovarian cancer progression. We also demonstrated that eIF4E-containing EVs (eIF4E-EVs) alter protein translation in macrophages, contributing to anti-tumor immune response.

Treatment of macrophages with eIF4E-EVs induces an immunosuppressive phenotype marked by the release of cytokines such as IL-6 and an elevated expression of Programmed death-ligand 1 (PD-L1). Notably, eIF4E-packaged EVs enhance the expression of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) a pivotal enzyme in cholesterol biosynthesis, resulting in increased cholesterol levels within macrophages. Inhibition of HMGCR or reduction of cholesterol in macrophages effectively restores their antitumor activity by decreasing PD-L1 on macrophages.

Analysis of tumor tissue from ovarian cancer patients revealed a positive correlation between HMGCR and TAM in ovarian cancer. In summary, we have characterized the mechanism of how eIF4E loaded EVs induced cholesterol synthesis, creating an immunosuppressive environment by upregulating PD-L1 expression in macrophages.
Alterations in topology, cost and dynamics of gamma-band EEG functional networks in a preclinical model of traumatic brain injury
Authors: Tsikonofilos Konstantinos , Bruyns-Haylett Michael , May Hazel G. , Donat Cornelius K. , Kozlov Andriy S.
Published: December 2024

Traumatic brain injury is a major cause of disability leading to multiple sequelae in cognitive, sensory, and physical domains, including post-traumatic epilepsy. Despite extensive research, our understanding of its impact on macroscopic brain circuitry remains incomplete. We analyzed electrophysiological functional connectomes in the gamma band using a preclinical model of blast-induced traumatic brain injury over multiple time points after injury. We revealed differences in small-world propensity and rich-club structure compared to age-matched controls, indicating functional reorganization following injury. We further investigated cost-efficiency trade-offs, propose a computationally efficient normalization procedure for quantifying cost of spatially embedded networks that controls for connectivity strength differences, and suggest metabolic drivers as a candidate for the observed differences. Furthermore, we employed a brain-wide computational model of seizure dynamics and attribute brain reorganization to a homeostatic mechanism of activity regulation with the potential unintended consequence of driving generalized seizures. Finally, we demonstrated post-injury hyperexcitability that manifests as an increase in sound-evoked response amplitudes at the cortical level. Our work characterizes for the first time gamma-band functional network reorganization in a model of brain injury and proposes potential causes of these changes, thus identifying targets for future therapeutic interventions.
Inkube: An all-in-one solution for neuron culturing, electrophysiology, and fluidic exchange
Authors: Maurer Benedikt , Fassbind Selina , Ruff Tobias , Duru Jens , Spacone Giusy , Rodde Theo , Vörös János , Ihle Stephan J.
Published: December 2024

Culturing neuronal networksin vitrois a tedious and time-consuming endeavor. In addition, how the composition of the culture medium and environmental variables such as temperature, osmolarity, and pH affect the spiking behavior of neuronal cultures is difficult to study using electrophysiology. In this work, we present “inkube”, an incubation system that has been combined with an electrophysiology setup and a fully automatic perfusion system. This setup allows for the precise measurement and control of the temperature of up to 4 microelectrode arrays (MEAs) in parallel. In addition, neuronal activity can be electrically induced and recorded from the MEAs. inkube can continuously monitor the medium level to automatically readjust osmolarity. Using inkube’s unique capability to precisely control the environmental variables of a neural culture, we found that medium evaporation influences the spiking response. Moreover, decreasing medium temperature by only 1.5°C significantly affected spike latency, a measure commonly used to show plasticity inin vitroexperiments. We finally provide a proof-of-concept experiment for drug screening applications, where inkube automatically and precisely varies the concentration of magnesium ions in the medium. Given its high level of autonomy, the system can record, stimulate, and control the medium continuously without user intervention. Both the hardware and the software of inkube are completely open-source.

Highlights

Low-cost, open-hardware/open-software electrophysiology setup

Full incubation solution: Temperature, CO2, and humidity control

Perfusion system for automatic fluidic exchange and drug testing with volume feedback
Orchids, hawkmoths and Darwin revisited: How adaptation to pollination by hawk-moths spurred the speciation of Old and New World angraecoids
Authors: Farminhão João , Collobert Géromine , Perez-Lamarque Benoît , Verlynde Simon , Ramandimbisoa Brigitte , Kaymak Esra , Azandi Laura , Droissart Vincent , Simo-Droissart Murielle , Johnson Steve , Martos Florent , Stévart Tariq
Published: December 2024

Specialised pollination has often been proposed as a major driver of the unrivalled diversification of angiosperms. With its unparalleled variation in flower depth, ranging from spurless to 40 cm spurred flowers pollinated by hawkmoths, angraecoid orchids (Angraecinae) provide unique opportunities to reveal the impact of floral specialisation on diversification rates in the Afrotropics and Neotropics. We compiled floral characters for 327 angraecoid species, and assigned these species to newly formalised floral syndrome categories calibrated against pollination case studies. We then estimated ancestral character states and state-dependent speciation rates using the latest time-calibrated phylogeny of angraecoids. We found that white flowers consistent with micro-sphingophily (2 cm≥ spurs <8.7 cm), macro-sphingophily (8.7 cm≥ spurs <18.6 cm) and mega-sphingophily (spurs ≥18.6 cm) evolved repeatedly in angraecoids, and are ancestral in some non-sphingophilous clades. Reversals to non-sphingophily and pigmented flowers suggest higher evolutionary lability of these traits than what is traditionally thought. Increasing floral specialisation with long spurs does not seem to enhance angraecoid orchids’ speciation rates, since micro-sphingophily appears to be associated with the highest speciation rates. An abundance of short-proboscid hawkmoths in Madagascar, as an ecological opportunity, may have accelerated the speciation of micro-sphingophilous taxa.
Virtual clinical trial reveals significant clinical potential of targeting tumour-associated macrophages and microglia to treat glioblastoma
Authors: Mongeon Blanche , Craig Morgan
Published: December 2024

Glioblastoma is the most aggressive primary brain tumour, with a median survival of just fifteen months with treatment. Standard-of-care (SOC) for glioblastoma consists of resection followed by radio- and chemotherapy. Clinical trials involving PD-1 inhibition with nivolumab in combination with SOC failed to increase overall survival. A quantitative understanding of the interactions between the tumour and its immune environment driving treatment outcomes is currently lacking. As such, we developed a mathematical model of tumour growth that considers cytotoxic CD8+ T cells, pro- and antitumoral tumour-associated macrophages and microglia (TAMs), SOC, and nivolumab. Our results show that PD-1 inhibition fails due to a lack of CD8+ T cell recruitment during treatment explained by TAM-driven immunosuppressive mechanisms. Using our model, we studied five TAM-targeting strategies currently under investigation for solid tumours. Our model predicts that while reducing TAM numbers does not improve prognosis, altering their functions to counter their protumoral properties has the potential to considerably reduce post-treatment tumour burden. In particular, restoring antitumoral TAM phagocytic activity through anti-CD47 treatment in combination with SOC was predicted to nearly eradicate the tumour. By studying time-varying efficacy with the same half-life as the anti-CD47 antibody Hu5F9-G4, our model predicts that repeated dosing of anti-CD47 provides sustained control of tumour growth. Thus, we propose that targeting TAMs by enhancing their antitumoral properties is a highly promising avenue to treat glioblastoma and warrants future clinical development. Together, our results provide proof-of-concept that mechanistic mathematical modelling can uncover the mechanisms driving treatment outcomes and explore the potential of novel treatment strategies for hard-to-treat tumours like glioblastoma.
Staying on track: collagen fibers orientation strongly affects thrombi formation at high shear
Authors: Melnikova E.A. , Mangin P.H. , Panteleev M.A. , Nechipurenko D.Y.
Published: December 2024

Objective

Subendothelial matrix exhibits a distinctive organization, with collagen fibers beneath the endothelium oriented primarily parallel to the flow and comprising mainly types III and I collagen in arteries and arterioles. However, the significance of such organization in initiating rapid thrombus formation remains unclear.

Approach and Results

To investigate the role of collagen fibers orientation in triggering thrombus formation we utilized thein vitromicrofluidic model of thrombosis. Human whole blood was perfused through a system with collagen fibers oriented either parallel or perpendicular to the flow, and the primary stages of platelet adhesion and thrombi growth were analyzed using a high-speed fluorescence microscopy.

At the shear rates of 200 and 1000 s-1no significant difference in thrombogenicity was observed between the collagen fibers orientations. However, at a high shear rate of 2000 s-1, thrombi on the parallel fibers were higher and covered a much larger area than those on the perpendicular ones. High-speed microscopy revealed that platelets were able to achieve stable adhesion only after translocating for over several seconds under all studied conditions. Analysis of single platelets dynamics revealed that platelets interacted longer and translocated farther during their interaction with parallel fibers at high shear, suggesting that flow-aligned fibers facilitate stable adhesion by enabling platelets to translocate along them and stay in contact with collagen. Importantly, only a small fraction of collagen fibers belonging to type III collagen admixture - a common component of a standard type I collagen preparation - accumulated plasma vWF and supported platelet adhesion at high shear rate.

Conclusion

Type III, but not type I collagen fibers oriented parallel to the flow facilitate stable platelet adhesion at high shear rates. Thus, axial orientation of subendothelial collagen fibers observedin vivomay have physiological relevance for triggering rapid thrombus formation at high shear rates.

Graphical abstract
Ionic Liquid-Induced Modulation of Ubiquitin Stability: The Dominant Role of Hydrophobic Interactions
Authors: Shrivastava Aditya , Kamma Harika , Das Ranabir , Ainavarapu Sri Rama Koti
Published: December 2024

Despite the widespread use of imidazolium-based ionic liquids (ILs) in biotechnology, pharmaceuticals, and green chemistry, their detailed interactions with proteins, particularly affecting structural stability, remain poorly understood. This study examines the effects of ILs on ubiquitin, a thermodynamically robust protein with a β-grasp structure. We found that IL-induced destabilisation follows a consistent order with previous findings: [BF4]-> [MeSO4]-> [Cl]-for anions and [BMIM]+> [BMPyr]+> [EMIM]+for cations. Through pH and ionic strength-dependent studies, we observed that hydrophobic interactions predominantly influence the stability of positively charged ubiquitin, with electrostatic interactions playing a secondary role. NMR studies identified residues impacted by [BMIM][BF4]; however, mutagenesis of these residues showed minimal changes in destabilisation, suggesting a global effect. This led us to conduct a broader empirical analysis, incorporating solvent-accessible surface area evaluations, which confirmed that hydrophobic residues are the primary drivers of stability alterations in ubiquitin, with charged residues playing a minimal role. Additionally, single-molecule force spectroscopy results indicate that imidazolium ILs decrease the unfolding barrier without altering transition state structures, offering insights into protein folding dynamics. ILs appear to modulate the stability landscape of proteins by energetically and kinetically favouring the unfolded state over the folded state. These insights offer potential strategies for the selective tuning of protein stability, which could be exploited to modulate protein-protein or protein-substrate interactions in various applications of ILs.
OrthoHMM: Improved Inference of Ortholog Groups using Hidden Markov Models
Authors: Steenwyk Jacob L , Buida Thomas J. , Rokas Antonis , King Nicole
Published: December 2024

Accurate orthology inference is essential for comparative genomics and phylogenomics. However, orthology inference is challenged by sequence divergence, which is pronounced among anciently diverged organisms. We present OrthoHMM, an algorithm that infers orthologous gene groups using Hidden Markov Models parameterized from substitution matrices, which enables better detection of remote homologs. Benchmarking indicates OrthoHMM outperforms currently available methods; for example, using a curated set of Bilaterian orthogroups, OrthoHMM showed a 10.3 – 138.9% improvement in precision. Rank-based benchmarking using Bilaterian orthogroups and a novel dataset of orthogroups from organisms in three major eukaryotic kingdoms revealed OrthoHMM had the best overall performance (6.7 – 97.8% overall improvement). These findings suggest that Hidden Markov Models improve orthogroup inference.
Vitrification and rapid rewarming of precision-cut liver slices for pharmacological and biomedical research
Authors: Ramesh Srivasupradha , Rao Joseph Sushil , Namsrai Bat-Erdene , Fisher Benjamin , Tobolt Diane K. , Megaly Michael , Etheridge Michael L. , Pruett Timothy L. , Seelig Davis , Murugan Paari , Aldaraiseh Bashar , Finger Erik B. , Bischof John C.
Published: December 2024

Background and Aims

High-throughput in vitro pharmacological toxicity testing is essential for drug discovery. Precision-cut liver slices (PCLS) provide a robust system for screening that is more representative of the complex 3D structure of the whole liver than isolated hepatocytes. However, PCLS are not available as off-the-shelf products, significantly limiting their translational potential. Cryopreservation could solve this bottleneck by effectively preserving PCLS indefinitely until their time of use. Conventional cryopreservation (slow cooling in DMSO-forming ice) results in poor PCLS viability and function and, therefore, has proven unsuitable. Here, we explore an “ice-free” cryopreservation approach called vitrification and focus on culturing and assessing PCLS for 3 days post-vitrification and rewarming, given that most acute drug toxicity tests are conducted over 24h.

Methods

Rat liver slices were diffusively loaded with a cryoprotective agent (CPA) cocktail consisting of EG and Sucrose. The CPA-loaded PCLS were placed on a polymer cryomesh, vitrified in liquid nitrogen (LN2), and rapidly rewarmed in CPA. The vitrified and rewarmed PCLS were subsequently cultured in a controlled volume of serum-free, chemically defined media for 3 days.

Results

The cryopreserved PCLS maintained high viability, morphology, function, enzymatic activity, and drug toxicity response. Results show that the vitrified PCLS perform comparably to untreated controls and significantly outperform conventionally cryopreserved PCLS in all assessments (p< 0.05).

Conclusions

Rapid vitrification and rewarming of PCLS using cryomesh enabled successful preservation and culture. This approach maintained high viability, function, enzymatic activity, and drug response for 3 days in culture, similar to controls.

Impact and Implications

The implications of using vitrification to store PCLS are extensive. This technology provides an exciting opportunity for the development of an “off-the-shelf” cold supply chain of human PCLS from organs declined for transplant, which are sliced, cryopreserved, and stored in a repository and available for on-demand shipping for industrial and academic biomedical research. This would also allow PCLS to become a scalable, reproducible, wide-ranging, and population-representative source of tissue that can accurately mimic in-vivo conditions of the human liver. These transformative technologies could revolutionize our practice in studying not just the metabolism of drugs but also increase our capacity to study the zonal progression of many liver diseases and conduct other exciting biomedical research.
Biophysical modeling of thalamic reticular nucleus subpopulations and their differential contribution to network dynamics
Authors: Litvak Polina , Hartley Nolan D. , Kast Ryan , Feng Guoping , Fu Zhanyan , Arnaudon Alexis , Hill Sean L.
Published: December 2024

The burst firing mode of thalamic reticular neurons plays a pivotal role in the generation and maintenance of sleep rhythms and is implicated in sleep-related deficits characteristic of neurodevelopmental disorders. Although several models of reticular neurons have been developed to date, we currently lack a biophysically detailed model able to accurately reproduce the heterogeneity of burst firing observed experimentally. Using electrophysiology recordings of patch-clamped fluorescently tagged Spp1+ and Ecel1+ reticular neurons, we leverage a previously established statistical framework to introduce differentiation of cell types in model thalamic reticular neurons. We developed a population of biophysically detailed models of thalamic reticular neurons that capture the diversity of their firing properties, particularly their ability to generate rebound bursts. These models incorporate key ion channels, such as T-type Ca2+and small conductance potassium channels (SK), and enable systematic investigations into the impact of these channels on single-cell dynamics. By integrating these models into a thalamic microcircuit, we demonstrate that T-type Ca2+and SK channel conductances have opposing effects on spindle oscillations. We identify a simple relationship between these conductances and the peak firing frequency of spindles, maintained across circuits with mixed reticular neuron populations, providing a framework for understanding how ion channel expression influences thalamic network dynamics. Collectively, these models establish a foundation for relating intrinsic cellular properties of reticular cell populations to network-level activity in both healthy and pathological conditions.
Validating Atlantic salmon (Salmo Salar) scale reading by genetic parent assignment and PIT-tagging
Authors: Utne Kjell Rong , Brieuc Marine Servane Ono , Fjeldheim Per Tommy , Urdal Kurt , Østborg Gunnel Marie , Glover Kevin A. , Harvey Alison , Skaala Øystein
Published: December 2024

Understanding changes in abundance and survival in Atlantic salmon populations requires knowledge of growth rates and age. Salmon are typically aged through scale reading, but such estimates are rarely validated against age-verified fish from the wild. Here, we present a unique dataset of scales from 254 PIT-tagged Atlantic salmon with known sea-age. In addition, the freshwater age is known for 81 of these fish, through genetic parent-offspring identification. This dataset was used to estimate precision and bias in age readings and back-calculated length, as estimated by three independent experienced salmon scale readers. Overall, readers had an accuracy of 97.1% for sea-age and 71.7% for freshwater-age. For sea-age, scale reading was less accurate for salmon that had spent 2 or more years at sea than for salmon that had spent 1 year at sea. Freshwater age did however not affect scale reading accuracy. None of the scale readers erroneously misclassified freshwater-or sea-age with more than one year, and there was no significant pattern of misclassified ages to be under-or overestimate by the scale readers. Back-calculated smolt length was significantly different to length when measured as a smolt prior to seaward migration: it was shorter than the measured body-length for small smolts and longer for large smolts. This unique dataset, including the age-validated images of all scales, is now made openly available providing an important resource for training and testing salmon scale readers globally.
Simulating the diffusion of PPR-like disease to improve surveillance
Authors: Mesdour Asma , Ijoma Sandra , Bolajoko Muhammad-Bashir , Ciss Mamadou , Cardinale Eric , Eubank Stephen , Andraud Mathieu , Apolloni Andrea
Published: December 2024

Animal mobility is a founding element of pastoral culture and fundamental to the economy in West Africa. Herds’ movement, involving mainly cattle, sheep, and goats, is vital for adapting to climate fluctuations, optimizing natural resources, and managing risks in livestock production, as well as livestock trade and exchanges. However, these movements contribute to the spread of transboundary animal diseases such as Peste des petits ruminants (PPR). Nigeria experienced its first PPR outbreak in the 1960s-1970s, and outbreaks have regularly occurred since then. Yet, no adequate surveillance system has been put in place, and the absence of proper animal movement tracking remains a critical shortcoming in addressing this ongoing threat. Because of this, we rely onad-hocactivities, like mobility surveys, to collect this information. However, these data could be partial and limited in time and space, hindering the capacity to identify suitable areas for monitoring disease circulation (sentinel nodes). Market survey data from three northern states are collected once to reconstruct the small ruminant mobility network. A group of areas with a high potential to infect each other were identified (Contagion Cluster). A stochastic Susceptible-Infected-Recovered (SIR) was used to simulate the spread of a PPR-like disease through movements. Sentinel nodes and their key characteristics were identified using Random Forest classification. The network (missing movement) was predicted with a hierarchical random graph (HRG), and uncertainty analysis assessed the effects of missing movements on the epidemic extent and identity and characteristics of sentinel nodes. The number of sentinel nodes varied with the epidemic’s severity, but their characteristics remained consistent. The uncertainty analysis results showed that adding 1% of the most probable missing links did not affect the final size of the epidemic. However, a significant difference appears when adding more than 3% of the missing links, causing a gradual fluctuation in the epidemic’s final size. The final size of the epidemic stabilized when adding more than 50% of the most probable links. The challenge posed by incomplete animal movement data underscores the need for further research and data collection efforts. However, predicting missing links presents a promising method for enhancing the reliability of epidemic prediction and sentinel node identification. This potential to improve disease surveillance and control strategies is a significant implication of our study.
Rats pursue food and leisure following the same rational principles
Authors: Logue Raegan S. , Garcia Ana K. , Bejarano Brissa A. , Kendall Riley K. , Wikenheiser Andrew M.
Published: December 2024

Animals in the wild must balance multiple, potentially mutually-exclusive goals simultaneously in order to survive. Yet laboratory tests of decision making often investigate how animals optimize their behavior to achieve a single, well-defined goal, which is often a nutritive reward. Thus, how animals solve multi-objective optimization problems is not well understood. Here, we devised an ethologically-inspired decision making task to examine how rats balance the pursuit of food and non-food reinforcement. Rats performed a free-choice patch-foraging task, in which they could earn food in one location (food patch) or interact with a rodent play structure in a different location (toy patch). The cost of switching between patches was manipulated by requiring rats to endure a long or short “travel time” penalty during which they were not able to access either patch. Rats devoted a considerable amount of their limited foraging time to patches of both types, showing a small but significant preference for food patches. In accordance with theoretical models of foraging, when the cost of switching patches was high rats chose longer stay durations in both types of patches, suggesting that similar rational principles guided their pursuit of food and non-food rewards. Examining the within-session dynamics of time allocation revealed that rats showed an early preference for spending time in toy patches that reversed over the course of the session. These results validate a naturalistic approach to testing decision making in rats over a range of food and non-food goods.
Enhancing Two-Dimensional Control via Single-Channel Haptic Feedback: A Multi-dimensional Encoding Strategy
Authors: Benigni T R , Pena A , Kuntaegowdanahalli S , Abbas J J , Jung R
Published: December 2024

Recently a multidimensional encoding approach to direct stimulation of a single site in the median nerve showed that an intensity and flutter frequency could be perceived and graded. It is unclear whether these two dimensions are able to convey useful information to participants performing control tasks or whether they improve on typical intensity only modulation approach. Eleven participants performed experiments to assess the efficacy of multidimensional stimulation. In a set of discrete matching tasks, participants were able to correctly identify all thirteen discrete stimulation points better than chance. In a modified center-out task, and three separate extremes-in tasks, all seventeen changes in the stimulation parameters could be detected better than chance. Performance of the discrete task using a multidimensional approach showed increased information transfer compared to the individual modulation of intensity or flutter frequency. The results suggest that multidimensional encoding is a promising approach for increasing information throughput in sensory feedback systems. By investigating a multimodal encoding approach, this study offers valuable insights into haptic feedback through peripheral nerve stimulation. This haptic feedback might offer pronounced benefits for virtual reality applications and individuals with upper limb amputations opening avenues for an enhanced sensory feedback experience.
De-medicalising gluten-free products through a subsidy card scheme: a qualitative study of service users
Authors: Sha’aban Abubakar , Mazzaschi Francesca , Ingram Beti-Jane , Joseph-Williams Natalie
Published: December 2024

Introduction

Coeliac disease requires a strict gluten-free diet to prevent complications. In the late 1960s, Gluten free foods (GFF) became available on prescription to support adherence when these foods were scarce in shops. Today, gluten-free foods are more accessible in large supermarkets, making it easier for patients to obtain them without prescriptions. In 2019, Hywel Dda University Health Board introduced the GFF subsidy card as an alternative to prescriptions, a method still used by other health boards in Wales.

Aims

This study aimed to explore individuals’ perspectives on a new subsidy card scheme for GFF, identify key barriers and facilitators, and provide recommendations to enhance the scheme’s implementation and effectiveness.

Method

A qualitative approach was employed, involving in-depth interviews with coeliac patients and parents of coeliac children. Participants included current users of the subsidy card, those relying on prescriptions, and individuals who opted out of the card scheme.

Results

Participants using the subsidy card valued its flexibility, variety of products, and convenience over the prescription system. Challenges included managing card balances, limited retailer acceptance, and geographical disparities. Non-users appreciated the potential for increased choice and mostly showed interest in switching but some raised concerns about inflation, misuse, and the additional burden on taxpayers.

Conclusion

Most participants view the subsidy card as an acceptable alternative to GFF prescriptions. To improve the subsidy card uptake, recommendations include enhancing digital tools for balance management, card value reviews, expanding retailer partnerships, promoting safer food practices, targeted communication, and ensuring prescription continuity for those who prefer it. These measures can optimize the scheme’s impact and better support individuals with coeliac disease.
Connectome-based symptom mapping andin silicorelated gene expression in children with autism and/or attention-deficit/hyperactivity disorder
Authors: Segura Patricia , Pagani Marco , Bishop Somer L. , Thomson Phoebe , Colcombe Stanley , Xu Ting , Factor Zekiel Z. , Hector Emily C. , Kim So Hyun , Lombardo Michael V. , Gozzi Alessandro , Castellanos Xavier F. , Lord Catherine , Milham Michael P. , Di Martino Adriana
Published: December 2024

Clinical, neuroimaging and genomics evidence have increasingly underscored a degree of overlap between autism and attention-deficit/hyperactivity disorder (ADHD). This study explores the specific contribution of their core symptoms to shared biology in a sample of N=166 verbal children (6-12 years) with rigorously-established primary diagnoses of either autism or ADHD (without autism). We investigated the associations between inter-individual differences in clinician-based dimensional measures of autism and ADHD symptoms and whole-brain low motion intrinsic functional connectivity (iFC). Additionally, we explored their linked gene expression patternsin silico. Whole-brain multivariate distance matrix regression revealed a transdiagnostic association between autism severity and iFC of two nodes: the middle frontal gyrus of the frontoparietal network and posterior cingulate cortex of the default mode network. Across children, the greater the iFC between these nodes, the more severe the autism symptoms, even after controlling for ADHD symptoms. Results from segregation analyses were consistent with primary findings, underscoring the significance of internetwork iFC interactions for autism symptom severity across diagnoses. No statistically significant brain-behavior relationships were observed for ADHD symptoms. Genetic enrichment analyses of the iFC maps associated with autism symptoms implicated genes known to:(i)have greater rate of variance in autism and ADHD, and(ii)be involved in neuron projection, suggesting shared genetic mechanisms for this specific brain-clinical phenotype. Overall, these findings underscore the relevance of transdiagnostic dimensional approaches in linking clinically-defined phenomena to shared presentations at the macroscale circuit- and genomic-levels among children with diagnoses of autism and ADHD.
Genetic Variants and Alteration inTranscription Factor 7-Like 2 (TCF7L2)mRNA level in Ischemic Stroke Patients: An Indian Scenario
Authors: Sadhukhan Dipanwita , Roy Arunima , Nath Sukla , Basu Esha , Mukherjee Joydeep , Ghosh Kartik Chandra , Banerjee Tapas Kumar , Krishnan Prasad , Chatterjee Sourya Kishore , Desai Soaham , Patel Vishal Ajitbhai , Ray Debes , Hui Subhra Prakash , Gupta Soma , Biswas Arindam
Published: December 2024

Background

Diabetes and Hyperlipidemia are major risk factors for stroke across the world population.TCF7L2, a key player of the WNT signaling pathway shows genetic association with both metabolic disturbances. However, its role in stroke pathogenesis (if any) is not well characterized.

Objectives

Thus, here we aim to (a) examine and correlate dysregulation ofTCF7L2expression with diabetes or hyperlipidemia-associated Ischemic Stroke, (b) identify genetic risk variants in theTCF7L2gene and (c) establish a correlation betweenTCF7L2mRNA expressions with biochemical parameters.

Methods

Based on radiological findings for Ischemic Stroke, a total of 50 unrelated subjects were recruited with diverse biochemical parameters for TCF7L2 mRNA expression study in PBMC, followed by correlation with fasting blood sugar and lipid profile. Furthermore, mutation screening and genetic association studies (rs7901695 & rs7903146) were performed among 326 cases and 258 controls from India.

Results

Here, we observed a significant downregulation ofTCF7L2gene expression among hyperlipidemic stroke patients than cases and control without dyslipidemia but no change between the cases with different diabetic statuses. Moreover, a strong negative correlation betweenTCF7L2mRNA level and total blood cholesterol but not for FBS was identified. The rs7901695T/C appeared as a promising genetic risk factor for stroke among eastern Indians.

Conclusion

Therefore, we can suggest that alteration inTCF7L2leading to stroke pathogenesis is more associated with hyperlipidemia than diabetes among Indians. Its expression level in PBMC is influenced by rs7901695T/C and holds a good promise to be used as a diagnostic marker.
Tools of Hibernation Measurement and Interpretation (TOHMIN) for quantifying various values from body temperature fluctuation during hibernation
Authors: Otsuka Reo , Shimoyama Yutaro , Nakagawa Satoshi , Yamaguchi Yoshifumi
Published: December 2024

Hibernation is a fascinating physiological phenomenon that dramatically reduces basal metabolism and thermogenesis, resulting in a large deviation in body temperature (Tb) from homeothermic ranges in mammals. Although high-resolution long-term Tb recording in wild or laboratory animals has become possible through data loggers, few standardized methods to analyze details of hibernation patterns are available, making it difficult to reproduce and compare the results across different studies and species. To facilitate the analysis of hibernation patterns and accelerate hibernation research, we developed an open-source program, tools of hibernation measurement and interpretation (TOHMIN). As a proof of concept, we analyzed a dataset from two pilot studies on (1) the effects of distinct diets on hibernation patterns and (2) differences in hibernation patterns between males and females in a mammalian hibernator, Syrian hamster (Mesocricetus auratus), and found previously undetectable fine-scale differences in hibernation patterns. First, different types of diets affected the duration of periodic arousal. Second, females maintained higher body temperatures during periodic arousal than males. Third, the duration of the pre-hibernation period was negatively correlated with the hibernation period for this species. Thus, TOHMIN accelerates studies to assess the effects of various experimental manipulations on hibernation phenotypes in mammals.
Age and sex influence seed dispersal of native and non-native plants by Lion-tailed MacaquesMacaca silenus
Authors: Bindu K , Kumara Honnavalli N. , Naniwadekar Rohit
Published: December 2024

While interspecific variation in seed dispersal, a critical ecosystem process in tropical forests, is relatively well-studied, intraspecific variation as a consequence of differences in body size, foraging behaviours, and ranging patterns among age-sex categories within a species is relatively understudied. Among vertebrates, primates play a critical role in seed dispersal and exhibit behavioural differences between age and sex categories, making them a suitable study system for intraspecific variation in seed dispersal. Lion-tailed macaquesMacaca silenus, an endemic and predominantly frugivorous primate species in the Western Ghats Biodiversity Hotspot, provide an excellent model for such studies. We examined the influence of age and sex on 1) the diversity and 2) the quantity of native and non-native fruits consumed, 3) the number of seeds dispersed, 4) seed dispersal distance, and 5) seed deposition substrates in lion-tailed macaques. We conducted over 375 hours of focal animal watches, distributed evenly across adult males, females, and subadults. Our findings showed that subadults consumed a higher diversity of native and non-native fruits than females and males. They dispersed fewerFicusseeds than females. We found differences in the proportions of non-native fruits in the diets of different age- sex categories. Males consumed moreCoffea liberica, whereas females and subadults fed onCoffeaandLantana. We found weak evidence suggesting that males were more likely to disperseFicusseeds on trees, which are suitable substrates forFicusestablishment. Our study highlights that age and sex significantly influence seed dispersal patterns of native and non- native species by an endemic, frugivorous primate species with potential influence on recruitment.