bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Perioperative Glucagon-like Peptide-1 Receptor Agonist Use and Postoperative Outcomes
Authors: Aschen Seth Z. , Zhang Ashley , O’Connell Gillian M. , Salingaros Sophia , Andy Caroline , Rohde Christine H. , Spector Jason A.
Published: December 2024

Objective:

To assess rates of surgical complications and postoperative readmission in diabetic patients with and without active perioperative prescriptions for GLP-1 RA medications.

Background:

With the rapid growth of glucagon-like peptide-1 receptor agonist (GLP-1 RA) use in the United States, it is important to understand the potential effect of these drugs on surgical outcomes broadly.

Methods:

In this retrospective, observational cohort analysis, patients with a diagnosis of type 1 or type 2 diabetes undergoing a surgical procedure at a multicenter quaternary-care healthcare system between February 2020 to July 2023 were included. Propensity score matching was performed between procedures in patients with and without an active GLP-1 RA prescription. The primary outcome was 30-day readmission, and secondary outcomes were documented dehiscence, infection, hematoma, and bleeding within 180 days after surgery.

Results:

Among 74,425 surgical procedures in 21,772 patients included in the analysis, 27.2% were performed in the setting of an active GLP-1 RA prescription. 35,020 procedures in 13,129 patients (48.0% men, 52.0% women; median [IQR] age, 67 [57, 75]) were propensity score matched. After matching, the active GLP-1 RA prescription group had a significantly reduced risk of 30-day readmission (RR, 0.883; 95% CI, 0.789-0.987; P=0.028; NNT, 219; 95% CI, 191-257), postoperative wound dehiscence (RR, 0.711; 95% CI, 0.577-0.877; P=0.001; NNT, 266; 95% CI, 202-391), and postoperative hematoma (RR, 0.440; 95% CI, 0.216-0.894; P=0.023; NNT, 1786; 95% CI, 652-2416). No significant differences were seen in rates of infection and bleeding.

Conclusions:

An active perioperative GLP-1 RA prescription in patients with diabetes was associated with significant reductions in risk-adjusted readmission, wound dehiscence, and hematoma, and no difference in infection and bleeding rates. Further study is warranted to elucidate any causal association.
Optical coherence tomography: implications for neurology
Authors: Al-Ani Abdullah , Benard-Seguin Étienne , Costello Fiona
Published: December 2024

Purpose of review

This article explores the role of optical coherence tomography (OCT) in neurology practice, particularly in diagnosing and monitoring conditions such as papilledema, optic neuritis, and retinal artery occlusion. OCT has been increasingly utilized as a noninvasive and effective tool for detecting and monitoring neuroaxonal damage in the visual pathway, which is important for early intervention and improved patient outcomes across a variety of neurologic conditions.

Recent findings

OCT as an imaging modality continues to demonstrate its utility in quantifying optic nerve and retinal changes reflecting neuroaxonal injury, including, peripapillary retinal nerve fiber layer (pRNFL) thickness and macular ganglion cell layer thickness (or volume). This review focuses on recent evidence regarding the utilization of this modality in diagnosing, monitoring, and quantifying treatment responses in patients with papilledema, optic neuritis, and retinal artery occlusion. Advances in OCT technology, including deep learning algorithms, continue to enhance the diagnostic accuracy and predictive capabilities in the field of neuro-ophthalmology.

In recent years, OCT has become an essential tool in neuro-ophthalmic assessment, offering precise structural and anatomical assessments that support diagnosis, treatment planning, and monitoring of conditions affecting the visual pathway. Ongoing advances in OCT technology are expected to further enhance its clinical utility.
Clinical trials in Leber hereditary optic neuropathy: outcomes and opportunities
Authors: Chen Benson S. , Newman Nancy J.
Published: December 2024

Purpose of review

Leber hereditary optic neuropathy (LHON) is a mitochondrial DNA disease characterised by sequential bilateral vision loss due to loss of retinal ganglion cells. The purpose of this review is to provide an update on the results of recent clinical trials for LHON, focusing on studies of idebenone and lenadogene nolparvovec gene therapy.

Recent findings

Evidence from three clinical studies (RHODOS, RHODOS-OFU, and LEROS) suggest that idebenone should be started early and continued for at least 24 months. Treatment effect varies according to the stage of LHON and the underlying mutation. Favourable outcomes are associated with the m.11778G>A mutation and chronic eyes with the m.14484T>C mutation. Caution should be taken in subacute/dynamic eyes with the m.3460G>A mutation, due to possible clinical worsening with idebenone. Compared to eyes from an external natural history cohort, pooled data from four clinical studies (RESCUE, REVERSE, RESTORE and REFLECT) show that a single intravitreal injection of lenadogene nolparvovec can result in sustained bilateral visual improvement in m.11778G>A LHON patients aged ≥15 years when treated within 1 year of onset. Although the treatment effect is modest, the final visual acuity of treated patients (∼1.2 logMAR) significantly differs from the published natural history of LHON and the treatment benefit is more pronounced than the effect of idebenone alone in patients with the m.11778G>A mutation.

There is increasing evidence for the potential therapeutic benefit of idebenone and lenadogene nolparvovec gene therapy.
A comparative study of depressive and anxiety symptoms, insomnia, and sleepiness in patients with obstructive sleep apnea, restless legs syndrome, or both (CO-ROSA): preliminary findings from a retrospective study
Authors: DelRosso Lourdes M. , Bradshaw Sam , Singh Amitoj , Jain Viraj , Mogavero Maria P. , Ferri Raffaele
Published: December 2024

Patients with obstructive sleep apnea (OSA), restless legs syndrome (RLS), or both may exhibit varied manifestations of depressive and anxiety symptomatology, reflecting the complex interplay between sleep disturbances, neurotransmitter imbalances, and psychosocial stressors in these often overlapping conditions. The aim of this study was to compare depressive and anxiety symptomatology, insomnia severity, and sleepiness in these conditions. Patients were enrolled and subdivided into those with OSA, RLS, and OSA + RLS. All were evaluated using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7), Insomnia Severity Index, and Epworth Sleepiness Scale. A total of 159 patients were enrolled, with OSA (n = 85), RLS (n = 11), and OSA + RLS (n = 63). A significant difference was observed for PHQ-9 (higher in patients with RLS, associated or not with OSA); however, the groups also differed for age (older in RLS) and apnea–hypopnea index (AHI) (higher in OSA). The group difference in PHQ-9 persisted also after ruling out the confounding effects of age and AHI. Our study highlights the significant burden of depressive symptomatology in patients with OSA, RLS, or both. RLS patients consistently exhibited higher levels of depressive symptomatology compared with OSA patients, emphasizing the need for comprehensive assessment and tailored management strategies targeting both sleep-related and psychiatric symptoms in this population.
MEGA12: Molecular Evolutionary Genetic Analysis version 12 for adaptive and green computing
Authors: Kumar Sudhir , Stecher Glen , Suleski Michael , Sanderford Maxwell , Sharma Sudip , Tamura Koichiro
Published: December 2024

We introduce the 12th version of the Molecular Evolutionary Genetics Analysis (MEGA) software. This latest version brings many significant improvements by reducing the computational time needed for selecting optimal substitution models and conducting bootstrap tests on phylogenies using maximum likelihood (ML) methods. These improvements are achieved by implementing heuristics that minimize likely unnecessary computations. Analyses of empirical and simulated datasets show substantial time savings by using these heuristics without compromising the accuracy of results.MEGA12also implements an evolutionary sparse learning approach to identify fragile clades and associated sequences in evolutionary trees inferred through phylogenomic analyses. In addition, this version includes fine-grained parallelization for ML analyses, support for high-resolution monitors, and an enhancedTree Explorer. TheMEGA12beta version can be downloaded fromhttps://www.megasoftware.net/beta_download.
Inbreeding and demography interact to impact population recovery from bottlenecks
Authors: Zheng Jia , Rees-Baylis Ella , Janzen Thijs , Zhang Zhengwang , Zhan Xiangjiang , Wang Daiping , Li Richter Xiang-Yi
Published: December 2024

Biodiversity loss driven by climate change and human activities poses a critical global challenge. Population restoration and reintroduction programs are essential for mitigating this threat, yet their outcomes are often unpredictable due to poorly understood success factors. The conservation program of the crested ibis (Nipponia nippon) marks a successful example where the population rose from seven survivors to over 9,000 in the past four decades. To learn whether this successful restoration was due to chance or largely repeatable, we developed an individual-based model that simulates the restoration process by incorporating life-history parameters from empirical data. Our simulation results closely mirror empirical findings, including the time taken to reach the current population size and population-level inbreeding coefficients. We further analyzed the model to compare the effectiveness of two reintroduction strategies and analyzed how inbreeding depression interacts with demography to influence the chance of recovery from bottlenecks. The reintroduction simulations reveal that the ‘firework’ approach (one-source translocations) outperforms the ‘stepping-stone’ (serial translocations) approach in restoration effectiveness. Our simulations over broad demographic parameters demonstrate that the net effect of inbreeding varies with species-specific demography, and highlight the importance of considering this interaction when interpreting conservation outcomes and designing future reintroduction programs.
Machine Learning Predictions Surpass Individual mRNAs as a Proxy of Single-cell Protein Expression
Authors: Fisher Josephine , Wood Oliver , Bullers Samuel , Murray Lynne , Li Li , Jackson-Wood Matthew A.
Published: December 2024

Background

Expansive repositories of single-cell RNA-seq data are now available. These data are often analysed assuming that mRNA abundance reflects the expression of their cognate proteins. However, post-transcriptional and translational regulation make mRNA an inadequate proxy for protein. High sparsity in low abundance mRNAs from single-cell transcriptomics data further complicates the extrapolation of protein expression levels. Although methods for single-cell surface protein quantification exist, they incur additional technical steps at greater expense and have yet to see wide-spread adoption. Computational approaches for protein imputation from scRNAseq data have been published, which learn transcriptome-wide patterns that predict protein expression. These models can then be applied to infer surface protein expression on RNA-seq only data, to increase the utility of existing data repositories.

Results

We tested 8 such methods and compared the accuracy of predictions between approaches, and against cognate mRNAs as a direct proxy. Predictions from the trained models outperformed the use of mRNA expression as a proxy. We identify notable cases of cell surface proteins with very poor correlation with their mRNA that were predicted very successfully by imputation using the whole transcriptome. We find cell type signatures are a major determinant of predicted protein levels and, as such, prediction methods require representative training data.

Conclusions

These results reiterate that mRNA level is not a reliable predictor of cell surface protein expression, and that whole-transcriptome informed imputation can improve protein estimations given appropriately trained models.
Prefrontal cortex dopamine responds to the total valence of stimuli
Authors: Yang Yating , Parent Willem , Rice Hunter , Mark Risa , Desimone Matthew , Rahman Monzilur , Ellwood Ian T.
Published: December 2024

The prefrontal cortex (PFC) dopamine system plays an essential role in cognitive flexibility, working memory and psychiatric disease, but determining the conditions under which dopamine in the PFC is released remains an open problem. Both rewarding and aversive stimuli have been found to trigger release, but studies have disagreed on whether the valence of a stimulus or other variables like novelty and salience are the most important. Here we report on recordings of dopamine-dependent fluorescence using a high-sensitivity dopamine indicator. We deliver an array of rewarding, aversive and mixed valence stimuli, as well as stimuli without any obvious valence. We observe that stimuli without valence, as well as the omission of expected stimuli, do not lead to large changes in fluorescence, even when these stimuli and omissions are both novel and engaging. In contrast, both rewarding and aversive stimuli lead to increases in fluorescence, with the most rewarding and most aversive stimuli leading to the largest increases. We test the effect of adding an aversive component to a rewarding stimulus and find that the increases in fluorescence are consistent with a summation of the rewarding and aversive components. We propose that dopamine release in the PFC responds to the total valence of a stimulus, in contrast with the traditional view of basal ganglia dopamine release that depends on the net valence.
Sending mixed signals: convergent iridescence and divergent chemical signals in sympatric sister-species of Amazonian butterflies
Authors: Ledamoisel Joséphine , Buatois Bruno , Mauxion Rémi , Andraud Christine , McClure Melanie , Debat Vincent , Llaurens Violaine
Published: December 2024

Closely-related species are often partitioned into different geographic areas or micro-habitats as a result of competition and reproductive interference. Here, we investigate how the evolution of shared adaptive traits may shape ecological interactions and genetic divergence, and facilitate co-existence in sympatry. In closely-relatedMorphobutterfly species living in the understory of the neo-tropical rainforest, the blue iridescent coloration of the wings is likely involved in predation evasion as well as in mating recognition and courtship. These contrasted selective pressures acting on this visual trait shared between closely-related species has likely shaped their coexistence. We used spectrophotometry, behavioral experiments, visual modeling and chemical analyses applied to samples from allopatric and sympatric populations ofMorpho helenorandMorpho achillesto characterize how the evolution of visual and chemical traits might favor their coexistence in sympatry: we quantified the differences in wing iridescence and tested for variations in the sexual preference for this trait between allopatricvs.sympatric populations. We found a strong similarity in iridescence among species in sympatry, suggesting convergence driven by predation. Although behavioral results suggest that iridescent signals could also be used as visual cues during mate choice, convergent iridescent signals may impair the visual recognition of sympatricMorphospecies. In contrast, divergent chemical bouquets among species suggest that the visual similarity of sympatricMorphospecies might have favored the divergence of alternative traits involved in species recognition such as chemical cues. This study underlines how ecological interactions and trait evolution can shape species coexistence in sympatry.
Biomechanics of stem cell fate decisions in multilayered tissues
Authors: Sahu Preeti , Canato Sara , Soares Raquel , Sánchez-Danés Adriana , Hannezo Edouard
Published: December 2024

Tissue homeostasis relies on a precise balance of fate choices between renewal and differentiation, which is dysregulated during tumor initiation. Although much progress has been done over recent years to characterize the dynamics of cellular fate choices at the single cell level, their underlying mechanistic basis often remains unclear. In particular, although physical forces are increasingly characterized as regulators of cell behaviors, a unifying description of how global tissue mechanics interplays with local cellular fate choices is missing. Concentrating on skin epidermis as a paradigm for multilayered tissues with complex fate choices, we develop a 3D vertex-based model with proliferation restrained in the basal layer, showing that mechanics and competition for space naturally gives rise to homeostasis and neutral drift dynamics that are seen experimentally. We then explore the effect of introducing mechanical inhomogeneities, whereby subpopulations have differential tensions. We uncover that relatively small mechanical disparities can be sufficient to heavily tilt cellular towards symmetric renewal and exponential growth. Importantly, the simulations predict that such mechanical inhomogeneities are reflected by distinct morphological changes in single-cell shapes. This led us to derive a master relationship between two very different experimentally measurable parameters, cell shape and long-term clonal dynamics, which we validated using a model of basal cell carcinoma (BCC) consisting in clonal Smoothened overexpression in mouse tail epidermis. Altogether, we propose a theoretical framework to link mechanical forces, quantitative cellular morphologies and cellular fate outcomes in complex tissues.
Modulatory Effects of Mdivi-1 on OxLDL-Induced Metabolic Alterations, Inflammatory Responses, and Foam Cell Formation in Human Monocytes
Authors: Mosalmanzadeh Negin , Maurmann Rafael Moura , Davis Kierstin , Schmitt Brenda Landvoigt , Makowski Liza , Pence Brandt D.
Published: December 2024

Atherosclerosis, a major contributor to cardiovascular disease, involves lipid accumulation and inflammatory processes in arterial walls, with oxidized low-density lipoprotein (OxLDL) playing a central role. OxLDL is increased during aging and stimulates monocyte transformation into foam cells and induces metabolic reprogramming and pro-inflammatory responses, accelerating atherosclerosis progression and contributing to other age-related diseases. This study investigated the effects of Mdivi-1, a mitochondrial fission inhibitor, and S1QEL, a selective complex I-associated reactive oxygen species (ROS) inhibitor, on OxLDL-induced responses in monocytes. Healthy monocytes isolated from participants were treated with OxLDL, with or without Mdivi-1 or S1QEL, and assessed for metabolic shifts, inflammatory cytokine expression, foam cell formation, and ROS production. OxLDL treatment elevated glycolytic activity (ECAR) and expression of pro-inflammatory cytokines IL1B and CXCL8, promoting foam cell formation and mitochondrial ROS (mtROS) production. Mdivi-1 and S1QEL effectively reduced OxLDL-induced glycolytic reprogramming, inflammatory cytokine levels, and foam cell formation while limiting mtROS. These findings suggest that both Mdivi-1 and S1QEL modulate key monocyte responses to OxLDL, providing insights into potential therapeutic approaches for age-related diseases.
Epigenomics of embryogenesis in turbot (Scophthalmus maximus)
Authors: Aramburu Oscar , Pardo Belén G. , Jimenez-Gonzalez Ada , Blanco-Hortas Andrés , Macqueen Daniel J. , Bouza Carmen , Martínez Paulino
Published: December 2024

Embryogenesis is the crucial first step of ontogeny, where an organism with a complex body plan arises from a single undifferentiated totipotent cell. This process is orchestrated by dynamic changes in transcriptional regulation, influenced by chromatin accessibility and nucleotide and histone modifications constituting epigenetic signals enabling access to transcription factors. The epigenomic regulation of embryogenesis has been studied in model fishes, but little attention has been paid to farmed fish - where traits of importance to aquaculture rely on early developmental processes. This study, framed within the AQUA-FAANG consortium, reports a comprehensive regulatory atlas of embryogenesis for turbot (Scophthalmus maximus), a farmed flatfish representing order Pleuronectiformes. 14,560 genes were expressed in the embryonic transcriptome with > 90% showing differential expression across consecutive stages. By integrating multi-histone ChIP-Seq marks with ATAC-Seq, we built a genome-wide chromatin state model, defining promoter and enhancer activity across stages. Transcription factor binding motif (TFBM) analysis of differentially active promoters and enhancers revealed dynamism in regulated gene functions, with more than half the TFBM enriched in a single developmental transition. Significant shifts in chromatin accessibility occurred across stages, most notably during the transition from shield to early segmentation, suggesting a profound chromatin reorganization underpins somitogenesis and early organ development. Most changes in chromatin accessibility across stages did not involve promoter regions of differentially expressed genes, suggesting a trend of promoter accessibility preceding gene transcriptional activity. Comparative analyses with zebrafish revealed a global transcriptomic correlation of single copy orthologs at matched stages of embryogenesis across species. While conserved expression dynamics were revealed for many orthologous Hox genes, notable cross-species differences were identified from before zygotic genome activation leading up to hatching. This multi-omics investigation provides a novel atlas of non-coding regulatory elements controlling turbot development, with key applications for flatfish biology and enhancing sustainable aquaculture.
Condensates act as translation hubs to coordinate multinucleate cell growth
Authors: Geisterfer Zachary M. , Jalihal Ameya P. , Cole Sierra J. , Gladfelter Amy S.
Published: December 2024

Coordination between growth and division is a fundamental feature of cells. In many syncytia, cell growth must couple with multiple nuclear divisions in one cytoplasm. In the fungus,Ashbya gossypii,cell-cycle progression and hyphal elongation require condensates formed by the protein Whi3 in complex with distinct mRNA species. We hypothesized the condensates may act through local translation regulation and find that Whi3 target mRNAs show distinct spatial biases in translation in vivo. Whi3-RNA condensates can both promote and repress RNA translation in an RNA- and condensate size-dependent manner in vitro. Interestingly, we observe a sub-condensate enrichment of translation that is tunable by RNA valency and protein phospho-state. Together, these data suggest that Whi3 condensates generate a continuum of translation states, resulting in asynchronous nuclear divisions coordinated with growth. This local regulation requires a minimal complement of molecular components at the nano scale to support global coordination at the cell scale.
SpecificSOX10enhancer elements modulate phenotype plasticity and drug resistance in melanoma
Authors: DeGeorgia Sophia “Noah” , Kaufman Charles K.
Published: December 2024

Recent studies indicate that the development of drug resistance and increased invasiveness in melanoma is largely driven by transcriptional plasticity rather than canonical coding mutations. Understanding the mechanisms behind cell identity shifts in oncogenic transformation and cancer progression is crucial for advancing our understanding of melanoma and other aggressive cancers. While distinct melanoma phenotypic states have been well characterized, the processes and transcriptional controls that enable cells to shift between these states remain largely unknown. In this study, we initially leverage the well-established zebrafish melanoma model as a high-throughput system to dissect and analyze transcriptional control elements that are hijacked by melanoma. We identify key characteristics of these elements, making them translatable to human enhancer identification despite the lack of direct sequence conservation. Building on our identification of a zebrafishsox10enhancer necessary for melanoma initiation, we extend these findings to human melanoma, identifying two human upstream enhancer elements that are critical for fullSOX10expression. Stable biallelic deletion of these enhancers using CRISPR-Cas9 induces a distinct phenotype shift across multiple human melanoma cell lines from a melanocytic phenotype towards an undifferentiated phenotype and is also characterized by an increase in drug resistance that mirrors clinical data including an upregulation of NTRK1, a tyrosine kinase, and potential therapeutic target. These results provide new insights into the transcriptional regulation ofSOX10in human melanoma and underscore the role of individual enhancer elements and potentially NTRK1 in driving melanoma phenotype plasticity and drug resistance. Our work lays the groundwork for future gene-based and combination kinase-inhibitor therapies targetingSOX10regulation and NTRK1 as a potential avenue for enhancing the efficacy of current melanoma treatments.
Plasmo3Net: A Convolutional Neural Network-Based Algorithm for Detecting Malaria Parasites in Thin Blood Smear Images
Authors: Owoloye Afolabi J. , Ligali Funmilayo C. , Enejoh Ojochenemi A. , Agosile Oluwafemi , Musa Adesola Z. , Aina Oluwagbemiga , Idowu Emmanuel T. , Oyebola Kolapo M.
Published: December 2024

Early diagnosis of malaria is crucial for effective control and elimination efforts. Microscopy is a reliable field-adaptable malaria diagnostic method. However, microscopy results are only as good as the quality of slides and images obtained from thick and thin smears. In this study, we developed deep learning algorithms to identify malaria-infected red blood cells (RBCs) in thin blood smears. Three algorithms were developed based on a convolutional neural network (CNN). The CNN was trained on 15,060 images and evaluated using 4,000 images. After a series of fine-tuning and hyperparameter optimization experiments, we selected the top-performing algorithm, which was named Plasmo3Net. The Plasmo3Net architecture was made up of 13 layers: three convolutional, three max-pooling, one flatten, four dropouts, and two fully connected layers, to obtain an accuracy of 99.3%, precision of 99.1%, recall of 99.6%, and F1 score of 99.3%. The maximum training accuracy of 99.5% and validation accuracy of 97.7% were obtained during the learning phase. Four pre-trained deep learning models (InceptionV3, VGG16, ResNet50, and ALexNet) were selected and trained alongside our model as baseline techniques for comparison due to their performance in malaria parasite identification. The topmost transfer learning model was the ResNet50 with 97.9% accuracy, 97.6% precision, 98.3 % recall, and 97.9% F1 score. The accuracy of the Plasmo3Net in malaria parasite identification highlights its potential for automated malaria diagnosis in the future. With additional validation using more extensive and diverse datasets, Plasmo3Net could evolve into a diagnostic workflow suitable for field applications.
Assessing group size and the demographic composition of unhabituated northern muriqui (Brachyteles hypoxanthus) using non-invasive biomonitoring
Authors: Kaizer Mariane C. , Sales Naiara G. , Alvim Thiago H. G. , Strier Karen B. , de Melo Fabiano R. , Boubli Jean P. , Young Robert J. , McDevitt Allan D.
Published: December 2024

Obtaining accurate population measures of endangered species is critical for effective conservation and management actions and to evaluate their success overtime. However, determining the population size and demographic composition of most canopy forest-dwelling species has proven to be challenging. Here, we apply two non-invasive biomonitoring methods, arboreal camera trap and genetic tagging of faecal samples, to estimate the population size of a critically endangered primate, the northern muriqui (Brachyteles hypoxanthus), in the Caparaó National Park, Brazil. When comparing population sizes between camera trapping and genetic tagging, the genetic tagging survey estimated fewer individuals for one of the muriqui groups studied but showed slightly higher population size estimates for the other group. In terms of the cost-efficiency of both methods, arboreal camera trapping had high initial costs but was more cost-effective in the long-term. Genetic tagging on the other hand did not require expensive equipment for data collection but had higher associated expenses for laboratory consumables and data processing. We recommend the use of both methods for northern muriqui monitoring and provide suggestions for improving the implementation of these non-invasive methods for future routine monitoring. Our findings also highlight the potential of arboreal camera trapping and genetic tagging to other arboreal mammals in tropical forests.
Targeting and anchoring the mechanosensitive ion channel Piezo to facilitate its inhibition of axon regeneration
Authors: Wang Qin , Miles Leanne , Wang Shuo , Noristani Harun N. , Monahan Vargas Ernest J. , Powell Jackson , O’Rourke-Ibach Sean J , Li Shuxin , Song Yuanquan
Published: December 2024

Mechanical force orchestrates a myriad of cellular events including inhibition of axon regeneration, by locally activating the mechanosensitive ion channel Piezo enriched at the injured axon tip. However, the cellular mechanics underlying Piezo localization and function remains poorly characterized. We show that the RNA repair/splicing enzyme Rtca acts upstream of Piezo to modulate its expression and transport/targeting to the plasma membrane via Rab10 GTPase, whose expression also relies on Rtca. Loss or gain of function of Rab10 promotes or impedesDrosophilasensory neuron axon regeneration, respectively. Rab10 mediates the cell surface expression of integrin β1 (Itgb1)/mys, which colocalizes and genetically interacts with Piezo, facilitating its anchorage and engagement with the microenvironment, and subsequent activation of mechanotransduction to inhibit regeneration. Importantly, loss of Rtca, Rab10 or Itgb1 promotes CNS axon regeneration after spinal cord injury or optic nerve crush in adult mice, indicating the evolutionary conservation of the machinery.
Curcuma longaEssential Oil Topically Mitigates Inflammatory Markers in Acetone-Induced Atopic Dermatitis in Wistar Albino Rats
Authors: Namale Nathiim , Tusubira Deusdedit , Male Kenneth , Musyoka Angela Mumbua , Aja Patrick Maduabuchi
Published: December 2024

Background

Atopic dermatitis ranks number one in skin diseases worldwide. It is challenging to treat; associated with burdens such as sleeping difficulties, depression, and anxiety and impairs life quality due to finances. This study aims to evaluate the potential of topicalCurcuma LongaEssential Oil in the management of atopic dermatitis. It was driven by overwhelming side effects that present with the use of topical corticosteroids in the management of the condition yet they present a variety of side effects.

Methods

Curcuma LongaEssential Oil was extracted by hydro-distillation of fresh rhizomes in a Clevenger apparatus. Thirty Wistar Albino rats; Male and Female; were divided into 5 groups, n=6. Atopic dermatitis was induced by rubbing a cotton ball soaked in acetone on rat skin for 5 minutes for three days. Groups were treated withCurcuma Longa Essential oil (1), 0.1% hydrocortisone (2), bothCurcuma LongaEssential oil and hydrocortisone (3) and the remaining two groups were positive and negative control. The effect ofCurcuma LongaTopical Essential oil was analysed using its effect on pruritus, Mast cell infiltration in skin biopsies and CRP levels in serum.

Results

Pruritus decreased with theCurcuma Longaessential oil (CLEO) topical treatment and significantly compared to that in the positive group (P <0.0001.). Negative Control VsCurcuma longaessential oil treatment showed a significant difference (P = 0.0001) in CRP levels. Mast cells significantly decreased in groups that had treatment compared to the Positive control.

Conclusion

Curcuma longaTopical essential oil has the potential treat Acetone induced Atopic Dermatitis in Wistar Albino rats.

Recommendation

2%Curcuma Longatopical Essential oil on Atopic dermatitis should be studied on a Clinical trial.
Structural Characterization and Functional Assessment of the Alpha-Expansin Precursor inOryza sativa
Authors: Nayem Rofiqul Islam , Saha Mridha , Sourav Md. Touhidul Islam
Published: December 2024

Expansins are vital proteins that facilitate cell wall loosening, playing a crucial role in plant growth and development. This study investigates the structural and functional characteristics of the alpha-expansin precursor (GenBank ID: AAL79710.1) inOryza sativa(Japanese rice). Through bioinformatics analyses, including ProtParam, CELLO, and conserved domain identification, we identified key biochemical properties, such as a molecular weight of approximately 28 kDa, a basic isoelectric point (pI 9.40), and significant levels of alanine and glycine. The CELLO analysis predicted the protein’s localization primarily in the extracellular space, consistent with its role in modifying the cell wall. Homology searches revealed high similarity to expansin-A29 proteins in related species, while phylogenetic analysis indicated a close evolutionary relationship among monocots. Structural modeling predicted a well-folded protein, though refinement is necessary to address certain discrepancies highlighted in the QMEANDisCo analysis. Our findings underscore the evolutionary conservation of alpha-expansins and their integral role in plant physiology, particularly in cell wall dynamics and stress responses. This research enhances our understanding of alpha-expansins in rice and lays the groundwork for future studies aimed at manipulating these proteins to improve crop resilience and yield under changing environmental conditions.
Mechanical stress induces anatomical changes, tomato early flowering, and increased yield involving ethylene and auxins
Authors: Castro-Estrada Jenifer , Salazar Sergio M. , Cabello Julieta V. , Mariotti-Martínez Jorge A. , Chan Raquel L. , Welchen Elina
Published: December 2024

Plants have evolved mechanisms to perceive and face mechanical stress (MS) caused by physical forces, including compacted soils, winds, rain, pathogens, and interactions with animals and plants. Previous research indicated that applying mechanical treatment (MT) to Arabidopsis increases both xylem area and seed yield. To explore sustainable tomato production, we applied MT - combining stem bending, weighting, and particular touching - to 10-day-old seedlings, using a specific weight on the upper stem for 48 h. Two days after the treatment, we observed stem enlargement and increased the number of xylem vessels and area in MT plants. Additionally, we noticed earlier flowering, leading to increased tomato production. The transcriptome of MT-treated plants revealed significant changes in the expression of several essential genes involved in central metabolism, growth responses, and crucial phytohormone signalling. By studying different tomato mutants in the ethylene and auxin signalling pathways, we demonstrated that both hormones play essential roles in the plant responses to combined MT. Our findings suggest that combined MT generates a beneficial MS in tomato plants that induces plant morphoanatomical changes that promote early flowering and increased yield, providing a promising strategy for sustainable agriculture.

Highlight

A combined mechanical treatment applied to tomato seedlings enhances stem width, increases the number of vascular bundles, promotes early flowering, and improves fruit yield, involving auxin and ethylene pathways.
Plasma proteome demonstrates sex-specific associations with mental health risks in adolescents
Authors: Afonin Alexey M. , Piironen Aino-Kaisa , Julvez Jordi , van Kamp Irene , Kanninen Katja M.
Published: December 2024

Adolescence is a critical developmental period marked by significant physiological, psychological, and behavioural changes. Sex-specific biological factors can play a major role in their progression. Liquid chromatography – tandem mass spectrometry proteomic analysis was used to measure the plasma proteome abundances in 197 adolescents (11-16 years old) from the WALNUTs cohort. Orthogonal partial least squares discriminant analysis (OPLS-DA) revealed clear sex-based proteomic distinctions, with 76 proteins significantly differing between males and females after correcting for age and BMI. Gene Ontology enrichment analysis of these proteins highlighted pathways related to cell adhesion and extracellular matrix organization reflecting sex-specific developmental trajectories during puberty. Bioinformatic analysis revealed 37 proteins significantly associated with the total score of the Strengths and Difficulties Questionnaire (SDQ), with additional sex-specific associations emerging in subgroup analyses. Plasma protein abundancies in males exhibited stronger correlations with SDQ externalizing subscale scores, while in females the associations with the internalizing score were more prominent, consistent with known behavioural sex differences. Immune response and blood coagulation pathways were implicated in these associations, particularly in females, while no significant pathway enrichment was observed for males. These findings highlight both shared and sex-specific proteomic features associated with the SDQ scores in adolescents, emphasising the need to consider sex differences in proteomic studies. The results provide a critical step toward identifying biomarkers and pathways underlying sex-specific psychological and developmental processes in adolescence.
TMEM55A-mediated PI5P signaling regulates α-cell actin depolymerization and glucagon secretion
Authors: Liu Xiong , dos Santos Theodore , Spigelman Aliya F. , Duckett Shawn , Smith Nancy , Suzuki Kunimasa , MacDonald Patrick E.
Published: December 2024

Diabetes is associated with the dysfunction of glucagon-producing pancreatic islet α-cells, although the underlying mechanisms regulating glucagon secretion and α-cell dysfunction remain unclear. While insulin secretion from pancreatic β-cells has long been known to be partly controlled by intracellular phospholipid signaling, very little is known about the role of phospholipids in glucagon secretion. Here we show that TMEM55A, a lipid phosphatase that dephosphorylates phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-5-phosphate (PI5P), regulates α-cell exocytosis and glucagon secretion. TMEM55A knockdown in both human and mouse α-cells reduces exocytosis at low glucose, and this is rescued by the direct reintroduction of PI5P. This does not occur through an effect on Ca2+channel activity, but through a re-modelling of cortical F-actin dependent upon TMEM55A lipid phosphatase activity which occurs in response to oxidative stress. In summary, we reveal a novel pathway by which TMEM55A regulates α-cell exocytosis by manipulating intracellular PI5P level and the F-actin network.
Cross validation coordinate meta-analysis: contrast analysis
Authors: Tench C.R.
Published: December 2024

Coordinate based meta-analysis (CBMA) can be used to estimate where a future neuroimaging study testing a particular hypothesis might report summary results (activation foci, for example). However, current methods cannot be validated for all possible analyses because of empirical features that might not be appropriate. Furthermore, the use of voxel-wise null hypothesis significance testing (NHST) in the algorithms is not in keeping with meta-analysis, where statistical significance is secondary to the primary aim of effect estimation.

Cross-validation coordinate analysis (CVCA) has been described, which can eliminate the need for the empirical use of spatial uncertainty and avoid voxel-wise p values. The result is an estimated effect that is not based on voxel-wise statistical significance, and which allows the uncertainty to reduce with larger numbers of studies as expected.

Here an additional function of CVCA is detailed, which uses cross-validation to contrast two different meta-analyses produced using two sets of studies (A & B) to identify differences. Such contrast analysis is common in CBMA. The results are a contrast image with regions that differentiate studiesAfrom studiesB.

Software to perform CVCA is freely available.
A key role of the EMC complex for mitochondrial respiration and quiescence in fission yeasts
Authors: Berraquero Modesto , Tallada Víctor A. , Jimenez Juan
Published: December 2024

In eukaryotes, oxygen consumption is mainly driven by the respiratory activity of mitochondria, which generates most of the cellular energy that sustains life. This parameter provides direct information about mitochondrial activity of all aerobic biological systems. Using the Seahorse analyzer instrument, we show here that deletion of theoca3/emc2gene (oca3Δ) encoding the Emc2 subunit of the ER membrane complex (EMC), a conserved chaperone/insertase which aids membrane protein biogenesis in the ER, severely affects oxygen consumption rates and quiescence survival inSchizosaccharomyces pombeyeast cells. Remarkably, the respiratory defects of theoca3Δmutation (EMC dysfunction) is rescued synergistically by the disruption of ergosterol biosynthesis (erg5Δ)and the action of the membrane fluidizing agent tween 20, suggesting a direct role of membrane fluidity and sterols composition in mitochondrial respiration in the fission yeast.
Immunometabolic analysis of primary murine Group 2 Innate Lymphoid Cells: a robust step-by-step approach
Authors: Krisna Sai Sakktee , Deagle Rebecca C. , Ismailova Nailya , Esomojumi Ademola , Roy-Dorval Audrey , Roth Frederik , Berberi Gabriel , del Rincon Sonia V. , Fritz Jörg H.
Published: December 2024

Group 2 Innate Lymphoid Cells (ILC2s) have recently been shown to exert key regulatory functions in innate and adaptive immune response networks that drive the establishment and progression of type 2 immunity and its associated pathologies. Although mainly tissue resident, ILC2s and their crosstalk within tissue microenvironments influences both local and systemic metabolism. In turn, the metabolic status shapes the diverse ILC2 phenotypes and effector functions. Hence, deciphering the metabolic networks of ILC2s is essential in understanding ILC2’s roles in health as well as pathophysiologies. Here we detail a framework of experimental approaches to study key immunometabolic states of primary murine ILC2s and link them to phenotypes and functionality. Utilizing flow cytometry, Single Cell ENergetIc metabolism by ProfilIng Translation inhibition (SCENITH) as well as the Seahorse platform we provide a framework that allows in-depth analysis of cellular bioenergetic states to determine the immunometabolic wiring of ILC2. Linking immunometabolic states and networks to ILC2 phenotypes and effector functions will allow in-depth studies that assess the potential of novel pharmaceutics to alter ILC2 functionality in experimental and clinical settings.
Dynamic relocalization and divergent expression of a major facilitator carrier subfamily in diatoms
Authors: Liu Shun , Yang Shun-Min , Bowler Chris , Obornik Miroslav , Dorrell Richard G.
Published: December 2024

Eukaryotic organisms, including microbial members such as protists and green algae, utilise suites of transporter proteins to move essential metabolites across cell organelle membranes. Amongst these different transporter families, the MCF (Mitochondrial Carrier Family) is one of the most diverse, encompassing essential NAD+ and ADP/ ATP translocators, as well as amino acid, sugar and cofactor transporters. They are typically associated with the mitochondrial inner membrane but some display more dynamic localization. Here, we perform a brief census of MCF domains in the genome of the model diatom algaPhaeodactylum tricornutum, identifying a new family of three proteins (termed here and elsewhere “MCFc”) with strong internal sequence conservation but limited similarity to other MCF proteins. Considering both phylogenetic data and experimental localization, we posit that MCFc is widespread across algae with complex red chloroplasts alongside some primary green algae, and contains multiple sub-families targeted to diatom mitochondria, plastids, and endomembranes. Finally, using data fromTaraOceans, we identify putative roles for MCFc in diatom cells, including a probable association of the plastid-targeted Phatr3_J46742 sub-family in cellular nitrate assimilation. Our data provide insights into the evolutionary diversification of the membrane transport mechanisms associated with diatoms and other eukaryotic algae.
Temporal Parameters Determine the Efficacy of Vagus Nerve Stimulation Directed Neural Plasticity
Authors: Addo Juliet J. A. , Neifert Connor L. , Danaphongse Tanya T. , Abe Stephanie T. , Ezhil Vikram , Kilgard Michael P. , Hays Seth A.
Published: December 2024

Combining vagus nerve stimulation (VNS) with rehabilitation represents an emerging treatment for a range of neurological disorders, and identifying stimulation parameters that maximize the effects of VNS may provide a means to optimize this therapy. A number of prior studies show that varying the intensity of stimulation, which influences the amount of neuromodulatory activation in response to VNS, determines the strength of VNS-dependent enhancement of synaptic plasticity in cortical circuits. The impact of the temporal parameters of stimulation, such as the frequency and distribution of pulses within a stimulation train, remains underexplored. In this study, we evaluated how varying these temporal parameters impacts the magnitude of VNS-directed plasticity. In the first experiment, rats received trains of VNS at one of three moderate pulse frequencies (20, 30, or 45Hz) timed to occur with movement during training on a simple motor task. After five days of training, we evaluated the cortical movement representations using intracortical microstimulation. All three moderate pulse frequencies produced equivalent increases in the cortical representation of the paired movement compared to sham stimulation. In a second experiment, we used a similar paradigm to explore whether burst stimulation would enhance VNS-dependent plasticity. Unexpectedly, we found that both burst stimulation or a matched number of pulses distributed evenly in time failed to produce significant enhancement of plasticity compared to sham stimulation, whereas moderate pulse frequency stimulation did. These findings illustrate the importance of the temporal dynamics of stimulation in determining the effects of VNS and provide guidelines for designing novel VNS sequences.