bluuebunny/crossref_metadata_2025 huggingface dataset:
Wilting Wildflowers and Bummed-Out Bees: Climate Change Threatens U.S. State Symbols
Authors: Ge Xuezhen , Zou Ya , Hager Heather A , Newman Jonathan A
Published: September 2024

Species designated as state symbols in the United States carry cultural importance and embody historical heritage. However, they are threatened by climate change and even face the risk of local or global extinction. The responses of these species to climate change have received little attention. In this study, we examine the effects of climate change on state flowers and insects in the United States by employing correlative species distribution models (SDMs). We select a variety of commonly used SDM algorithms to construct an ensemble forecasting framework aimed at predicting the potential habitats for each species under both historical and future climate scenarios, and how these changes might influence the distributions of state flower and insect species. Our results show that more than half of the state flowers (∼ 66%) and insects (∼ 51%) are predicted to experience a substantial decrease in regions with favorable climates within the states they represent. Conversely, only a small number (Flowers: ∼ 2%; Insects: ∼ 10%) are projected to see an increase in habitat suitability in the future. Certain states may no longer possess suitable habitats for their state-designated species. Our findings indicate that cultural heritage might be at risk due to reduced habitat suitability and local extinctions driven by climate change. These findings can provide guidance regarding the protection or replacement of state species to preserve cultural heritage.

Significance Statement

We have known for decades that climate change may lead to species’ local or global extinction. However, the vast majority of such research has focused on species of ecological or economic importance. Only recently have researchers begun to seriously consider the impacts of climate change on our cultural heritage, and that research has mainly focused on tangible cultural assests such as buildings and anthropological sites. Here, we consider the impacts of climate change on species of cultural significance, namely U.S. state flowers and insects. We find that the majority of these species are threatened with local extinction from climate change, and the loss of these species will take with them important aspects of our history and culture.
Differential Impact of Multiple Sensory Deprivation on Spatial-coding Cells in Medial Entorhinal Cortex
Authors: Tian Jiayi , Wen Shidan , Zhou Yuqian , Yao Shuyang , Zhang Xuan , Miao Chenglin
Published: September 2024

Summary

Spatial navigation depends on anchoring internal spatial maps to external environments, guided by sensory cues such as visual and tactile stimuli. The Medial Entorhinal Cortex (MEC) is crucial for integrating these sensory inputs during the formation of spatial maps. While the responsiveness of many spatial-coding cells to visual stimuli is well-established, the role of tactile sensation in spatial representation is less understood. Rodents primarily gather tactile information through their whiskers, which provide essential spatial and textural details via whisking movements, potentially vital for constructing accurate spatial map. In our study, we employed advanced miniature two-photon microscopy to monitor neural activity in the MEC of freely moving mice subjected to sensory deprivation. Our findings revealed that head direction cells and border cells exhibited impaired spatial representation after either light deprivation or whisker trimming. In contrast, grid cells and speed cells were less affected by whisker trimming compared to visual deprivation, suggesting a stronger dependence on visual cues for these cell types. Notably, distinct subpopulations within each type of spatial-coding cell exhibited varying sensitivity to sensory deprivation—some neurons significantly changed their spatial-coding patterns, while others remained unaffected. This indicates that cells within the MEC may differ in their spatial-coding based on their sensitivity to external sensory inputs. Additionally, we observed a strong correlation between the activity of certain MEC neurons and whisker movement. Collectively, these findings enhance our understanding of how the MEC processes spatial information, particularly in relation to tactile sensation.
Differentiating wild and domesticated enset (Musaceae) using phytolith analysis
Authors: Castillo Cobo Cristina , Beldados Alemseged , Ryan Philippa , Bond Sandra , Vrydaghs Luc , Lulekal Molla Ermias , Borrell James , Hunt Harriet , Fuller Dorian Q
Published: September 2024

Enset (Ensete ventricosum, Musaceae) is an important economic crop from Ethiopia which accounts for 20% of the staple diet in Ethiopia today. However, its evolutionary history and spread is poorly understood. Archaeology could provide evidence of past use and contribute to our understanding of its early history, but so far, this has not transpired. Cultivated enset is clonally reproduced and seed production rarely occurs, therefore, looking for seed remains is futile and instead archaeobotanical research should focus on microfossils such as phytoliths. Phytoliths have been shown to be diagnostic for the presence of banana (Musa) and are expected to be similarly useful for identifying enset, but we need a better understanding of phytolith production and variability, and the extent to which this may be used to track domestication. The current study provides a fundamental baseline for the identification of Ensete phytoliths through the examination of phytoliths from leaves and other plant parts based on their size and shape. We consider the differentiation of phytoliths across a single plant, based on location in the leaf, the age of the leaf, and different organs of the plant. We also compare phytoliths in the Musaceae Family, and between the enset cultivar and wild samples.
Idiosyncrasy in gestural communication: a case study of hand-clapping in a Barbary macaque (Macaca sylvanus)
Authors: Bosshard Tiffany Claire , Hirel Marie , Meunier Hélène , Fischer Julia
Published: September 2024

While it is well established that apes invent or individually learn new gestures, cases of development and use of novel gestures in monkeys are more rarely described. We report a case of a novel, idiosyncratic gesture in a Barbary macaque (Macaca sylvanus) at ‘La Forêt des Singes’, Rocamadour, France. One adult male, Jomanix, was observed hand-clapping. To our knowledge, hand-clapping has never been described before in this species. To hand-clap, the male briefly shifted his weight onto his legs, lifted his upper body, and clapped both hands together. We recorded 30 instances of hand-clapping. Twenty-five of these hand-claps occurred in combination with other agonistic signals, such as lunges and open mouth threats. Recipients either responded with counter-aggression (N= 9) or a submissive response (N= 16). In five of the 30 events, the context was unclear. These observations suggest that the gesture constitutes an agonistic signal. According to the staff at ‘La Forêt des Singes’, the hand-clapping may have been copied from staff members who occasionally hand-clap to shoo the animals away from areas where they were not supposed to be, but that notion remains speculative. In the meantime, another subject from the same group reportedly started to hand-clap, but the subject had passed away before we could document the behaviour. The observations show that Jomanix can flexibly combine a novel gesture with other established communicative signals. The hand-clap is goal-directed and fulfils the criteria for first-order intentional communication. This case, as well as anecdotal reports from a Tonkean macaque (Macaca tonkeana) hand-clapping to get attention, reveals greater flexibility in the gestural communication of this genus than previously assumed but also underscores that social learning of the production of communicative gestures occurs rarely in this taxon.
Crop productivity of Central European Permaculture is within the range of organic and conventional agriculture
Authors: Reiff Julius , Jungkunst Hermann F. , Antes Nicole , Entling Martin H
Published: September 2024

1

Permaculture is a promising framework to design and manage sustainable food production systems based on mimicking ecosystems. However, there is still a lack of scientific evidence especially on the crop productivity of permaculture systems. In this first study on permaculture yield, we collected yield data of eleven permaculture sites in Germany and surrounding countries, that also work according to organic guidelines. We used the Land Equivalent Ratio (LER) as index to compare mixed cropping systems of permaculture sites with average monoculture yield data of the overall German agricultural sector, as well as that of only organic German agriculture. An LER of 1 indicates equal yields of the compared polyculture and monoculture, while an LER of 1.2 would indicate a 20% higher productivity of the polyculture. Mean permaculture LER as compared to total German agriculture was 0.80 ± 0.27 and 1.44 ± 0.52 as compared to German organic agriculture, both with no significant difference to 1. Our results imply, that yields of permaculture sites are comparable to predominant industrial agriculture. The observed productivity may result from the application of key permaculture principles, such as utilizing diversity and mutually supportive species and improving soil health, which contribute to system stability and resource efficiency. Provided that future studies will support our findings, permaculture could combine soil, biodiversity and climate protection with agricultural productivity. Most importantly, the variables that determine the difference in crop productivity among permaculture sites need to be identified and evaluated.
IL-34 empowers regulatory T cells with novel non-canonical function to safeguard brain barrier integrity during neuro-inflammation
Authors: Van Hoecke Lien , Verreycken Janne , Van Acker Lore , Amelinck Laura , Xie Junhua , Castelein Jonas , Van Wonterghem Elien , Van Imschoot Griet , Burgelman Marlies , Vanherle Sarah , Dewachter Ilse , Baeten Paulien , Broux Bieke , Vandenbroucke Roosmarijn E.
Published: September 2024

In efforts to find reparative strategies for brain damage, brain-associated regulatory T cells (Tregs) have gained increasing attention in recent years. Beyond their textbook immunoregulatory function, Tregs have emerged as key players in the response to brain trauma and the restoration of damaged brain tissue. Here, we are the first to describe a novel, non-canonical function of Tregs in maintaining the sealing capacity of both the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier. Moreover, we identified the cytokine IL-34 as a critical determinant in this newly unveiled Treg function. Mechanistically, IL-34 exerts its influence by modulating the expression and localization of the tight junction protein ZO-1 in both BBB endothelial cells and choroid plexus epithelial cells, thereby reinforcing the strength of the brain barriers. Given the well-established notion of leaky brain barriers and the involvement of immunological components in neurological diseases such as Alzheimer’s disease (AD) and multiple sclerosis (MS), we further demonstrate diminished IL-34 expression in Tregs derived from patients with relapsing-remitting MS (RR-MS) and patients with AD and even mild cognitive impairment (MCI). Remarkably, our study reveals the potential of IL-34 treatment in reinstating the integrity of brain barriers within murine models mimicking these neurological disorders. These ground-breaking findings shed light on the intricate relationship between Tregs, IL-34, and the integrity of brain barriers. They offer novel avenues for therapeutic approaches to ameliorate brain barrier dysfunction in the context of neurological disorders.
Leveraging large language models for metabolic engineering design
Authors: Li Xiongwen , Liang Zhu , Guo Zhetao , Liu Ziyi , Wu Ke , Luo Jiahao , Zhang Yuesheng , Liu Lizheng , Sun Manda , Huang Yuanyuan , Tang Hongting , Chen Yu , Yu Tao , Nielsen Jens , Li Feiran
Published: September 2024

Establishing efficient cell factories involves a continuous process of trial and error due to the intricate nature of metabolism. This complexity makes predicting effective engineering targets a challenging task. Therefore, it is vital to learn from the accumulated successes of previous designs for advancing future cell factory development. In this study, we developed a method based on large language models (LLMs) to extract metabolic engineering strategies from research articles on a large scale. We created a database containing over 29006 metabolic engineering entries, 1210 products and 751 organisms. Using this extracted data, we trained a hybrid model combining deep learning and mechanistic approaches to predict engineering targets. Our model outperformed traditional metabolic engineering target prediction algorithms, excelled in predicting the effects of gene modifications, and generalized well to out-of-distribution products and multiple gene combinations. Our study provides a valuable dataset, a chatbot, and an engineering target prediction model for the metabolic engineering field and exemplifies an efficient method for leveraging existing knowledge for future predictions.
Downy mildew effector HaRxL106 interacts with the transcription factor BIM1 altering plant growth, BR signaling and susceptibility to pathogens
Authors: Bogino Maria Florencia , Senz Juan Marcos Lapegna , Kourdova Lucille Tihomirova , Tamagnone Nicolas , Romanowski Andres , Wirthmueller Lennart , Fabro Georgina
Published: September 2024

Hyaloperonospora arabidopsidis (Hpa) is an oomycete pathogen that causes downy mildew disease on Arabidopsis. This obligate biotroph manipulates the homeostasis of its host plant by secreting numerous effector proteins, among which are the RxLR-effectors. Identifying the host targets of effectors and understanding how their manipulation facilitates colonization of plants is key to improve plant resistance to pathogens. Here we characterize the interaction between the RxLR effector HaRxL106 and BIM1, an Arabidopsis transcription factor (TF) involved in Brassinosteroid (BR) signaling. We report that HaRxL106 interacts with BIM1 in vitro and in planta. BIM1 is required by the effector to increase the host plant susceptibility to (hemi)biotrophic pathogens, and thus can be regarded as a susceptibility factor. Mechanistically, HaRxL106 requires BIM1 to induce the transcriptional activation of BR-responsive genes and cause alterations in plant growth patterns that phenocopy the shade avoidance syndrome. Our results support previous observations of antagonistic interactions between activation of BR signaling and suppression of plant immune responses and reveal that BIM1, a new player in this crosstalk, is manipulated by the pathogenic effector HaRxL106.
The resilience of the oral microbiome and lability of the hair microbiome across host environments in wild and captive lemurs
Authors: Burten Rachel B. , Lawler Richard R. , Ratsirarson Joelisoa , Ranaivonasy Jeannin , Leduc Rebecca , Bhagat Ankita , Lopez Amelia , Kamilar Jason M.
Published: September 2024

Microbiome diversity and composition in mammals is affected by the host’s environment and has been linked to important immune and physiological host functions, yet most of these data come from the gut microbiome. Research on the oral and hair microbiome in nonhuman primates has been far less common, and information from wild primates is even rarer. These overlooked patterns of environmental effects on microbial communities across the body may have important implications for a range of host functions. Therefore, in this study we characterized the gut, oral, and hair microbiomes across nine different captive and wild lemur species:Eulemur collaris,Eulemur coronatus,Eulemur mongoz,Lemur catta,Microcebus griseorufus,Microcebus murinus,Propithecus coquereli,Propithecus verreauxi, andVarecia rubra. We explored how host environment affects the microbiome diversity of these three body regions using 16S rRNA sequencing and found significant differences in microbiome composition, diversity, and environmental influence across body regions. The oral microbiome was least diverse and most resilient to different environmental effects; conversely, the hair microbiome was both most diverse and most labile. Differentially abundant bacterial taxa across oral, gut, and hair microbiota may also reflect selective regimes unique to each body region. These results emphasize the importance of accounting for body region when conducting microbiome studies.

Importance

An organism’s microbiome plays important roles in a wide variety of the host animal’s physiological functions, yet how these microbial communities in body regions beyond the gut are affected by the host’s environment is not clearly understood. We therefore analyzed how the oral, gut, and hair microbiomes of nine lemur species (generaEulemur,Lemur,Microcebus,Propithecus, andVarecia) varied across wild and captive environments. We found that host environment affected the microbiomes of each body region in distinct ways, with the oral microbiome appearing conserved and more resilient to environmental effects, particularly compared to the diverse and widely variable hair microbiome. To our knowledge, this study is the most comprehensive multi-body-region analysis of the lemur microbiome to date. Our results demonstrate that the environment does not have a universal effect on the microbiome across body regions, but is instead mediated by body-region specific factors.
bayesReact: Expression-coupled regulatory motif analysis detects microRNA activity in cancer and at the single cell level
Authors: Rasmussen Asta Mannstaedt , Bouchard-Cote Alexandre , Pedersen Jakob Skou
Published: September 2024

Motivation: Regulatory constraints are crucial in maintaining tissue and cell integrity, and play important roles during developmental processes and environmental responses. Yet many regulatory mechanisms remain unobserved at the single-cell level and statistical inference may, in some cases, help elucidate their condition-specific activity and perturbation during disease progression. Results: We introduce bayesReact (BAYESian modeling of Regular Expression ACTivity), a generative model of motif occurrence across experimentally ranked sequences to infer motif-based regulatory activities. The method is evaluated for microRNAs (miRNAs), which perform post-transcriptional regulation through target mRNA destabilization and translational repression. Inferred miRNA activities positively correlate with the observed miRNA expressions in primary tumors from The Cancer Genome Atlas (TCGA) and mouse stem cells. The top miRNA activity profiles are as informative for TCGA cancer-type cluster identification as the top miRNA or mRNA expression profiles. The activity captures tissue-specific miRNA patterns observed in the matched expression, e.g., the expression of miR-122-5p in the liver and miR-124-3p in low-grade gliomas (LGG). We observe a negative association between the activity of the two miRNAs and their target gene expressions, including between the miR-124-3p activity and the anti-neuronal REST expression in LGG. bayesReact outperforms the existing method, miReact, on sparse count data, and shows a higher correlation with the miRNA expression in single-cell data. The method recovers temporal activities of prominent miRNAs during murine stem cell differentiation, including miR-298-5p, miR-92-2-5p, and the large Sfmbt2 cluster (miR-297-669). The bayesReact model is probabilistic and quantifies the uncertainty of all provided estimates. It is unsupervised and permits screens of bulk or single-cell data to identify condition-specific regulatory motif candidates. It further improves miRNA activity inference in single-cell data. Availability and implementation: bayesReact is implemented as an R-package, uses a Hamiltonian Monte-Carlo sampler for posterior approximation, and is available at https://github.com/astamr/bayesReact.
Synergistic DNA and RNA binding of the Hox transcription factor Ultrabithorax coordinates splicing and shapesin vivohomeotic functions
Authors: Blanco Constanza , Xiang Wan , Boumpas Panagiotis , Scorcelletti Maily , Hermon Ashley Suraj , Wong Jiemin , Merabet Samir , Carnesecchi Julie
Published: September 2024

The dual interaction of many transcription factors (TFs) with both DNA and RNA is an underexplored issue that could fundamentally reshape our understanding of gene regulation. We address this central issue by investigating the RNA binding activity of theDrosophilaHox TF Ultrabithorax (Ubx) in alternative splicing and morphogenesis. Relying on molecular and genetic interactions, we uncover a homodimerization-dependent mechanism by which Ubx regulates splicing. Notably, this mechanism enables the decoupling of Ubx-DNA and -RNA binding activity in splicing. We identify a critical residue for Ubx-RNA binding and demonstrate the essential role of Ubx-RNA binding ability for its homeotic functions. Overall, we uncover a unique mechanism for Ubx-mediated splicing and underscore the critical contribution of synergistic DNA/RNA binding for its morphogenetic functions. These findings advance our understanding of co-transcriptional regulation and highlight the significance of TF-DNA/RNA synergistic function in shaping gene regulatory networks in living organisms.

Graphical abstract

Highlights

Ubx homodimerization enables decoupling of DNA- and RNA-dependent splicing regulation

The homeodomain K58 amino acid is critical for Ubx-RNA binding ability

Ubx-RNA binding ability is essential for splicing regulation

Dual DNA/RNA binding activities shape Ubx homeotic functions
Ethylene Modulates the Phenylpropanoid Pathway by EnhancingVvMYB14Expression via the ERF5-Melatonin-ERF104 Pathway in Grape Seeds
Authors: Gao Shiwei , Wang Fei , Wang Shengnan , Lan Shuxia , Xu Yujiao , Lyu Xinning , Kang Hui , Yao Yuxin
Published: September 2024

Ethylene plays a crucial role in regulating polyphenol metabolism, however the underlying mechanism remains largely unknown. This work demonstrated that ethylene release occurred earlier than melatonin during seed ripening. Ethylene treatment increased theVvASMTexpression and melatonin content.VvERF5was elucidated to bind to the ERE element in theVvASMTpromoter.VvERF5overexpression increased ASMT expression and melatonin content while its suppression generated the opposite results in grape seeds, calli and/or Arabidopsis seeds. Using the promoter ofVvMYB14, which was strongly induced by melatonin, a melatonin responsive element (MTRE) was identified.VvERF104was revealed not only to be strongly induced by melatonin but to bind to the MTRE of theVvMYB14.VvERF104overexpression and suppression largely increased and decreased the MYB14 expression, respectively, in grape seeds, calli and/or Arabidopsis seeds.VvMYB14overexpression widely modified the expression of genes in phenylpropanoid pathway and phenolic compound content in grape seeds. DAP-seq revealed that the MEME-1 motif was the most likely binding sites ofVvMYB14.VvPAL,VvC4HandVvCHSwere verified to be the target genes ofVvMYB14. Additionally, the roles ofVvERF5,VvASMTandVvERF104in mediating ethylene-induced changes in phenylpropanoid pathway were elucidated using their suppressing seeds. Collectively, ethylene increased theVvMYB14expression via the pathway of ERF5-melatonin-ERF104 and thereby modified phenylpropanoid pathway.
Screening of histone mutants reveals a domain within the N-terminal tail of histone H3 that regulates the Tup1-independent repressive role of Cyc8 at the activeFLO1
Authors: Singh Ranu , Tomar Raghuvir Singh
Published: September 2024

Yeast flocculation relies on cell surface flocculin proteins encoded by theFLO1gene. The expression ofFLO1is antagonistically regulated by the Tup1-Cyc8 and the Swi-Snf complexes. The Post translational modifications of core histones regulate the transcription of Tup1-Cyc8-regulated genes. However, the mechanisms by which the physical presence of tail residues regulateFLO1transcription process and flocculation is yet to be completely understood. Through screening we have identified a new region within the N-terminal tail of histone H3 regulating the transcription ofFLO1andFLO5. One of the histone H3 N-terminal truncation mutants H3Δ(17–24) showed higherFLO1expression compared to wild-type H3. Results revealed that in absence of 17-24 stretch the occupancy of Cyc8 decreases from the upstream regions ofFLO1. Additionally, analysis suggests that Hda1 is required for the Cyc8-mediated repression ofFLO1. Altogether we demonstrate that 17–24 stretch is essential for the Tup1 independent binding of Cyc8 at the promoters assisted by Hda1, leading to the strong repression ofFLO1transcription. In the absence of the 17–24 stretch, Cyc8 cannot bind, resulting in uncontrolled transcription ofFLO1.
A novelUNC93B1gain-of-function mutation leads to TLR7 and TLR8 hyperactivation and systemic lupus erythematosus
Authors: Han Xu , Wang Ruoran , Ozen Seza , Wang Qintao , Dong Wei , Zeng Yi , Xu Ouyuan , Şener Seher , Guo Li , Gu Ying , Yang Huanming , Yu Xiaomin , Tao Panfeng , Zhou Qing
Published: September 2024

Dysfunctions in nucleic acid-sensing Toll-like receptors (TLRs) disrupt nucleic acid tolerance, leading to systemic lupus erythematosus (SLE). Here, we report a novel homozygous gain-of-function p.R95L mutation in the TLR chaperone protein UNC93B1 in an SLE patient. Bulk and single-cell transcriptional analysis of the patient’s peripheral blood mononuclear cells (PBMCs) revealed significantly elevated inflammation in T cells and myeloid cells due to enhanced dendritic cells function. TheUNC93B1R95L mutation leads to hyperactivation of TLR7/8, but not TLR3/9, upon stimulation with specific agonistsin vitro. TransgenicUnc93b1R95L/R95Lmice develop inflammatory and autoimmune phenotypes, and the upregulation of inflammatory signaling differs among organs, with a specific contribution of malfunctioned T cells and B cells. In human and mouse cell lines, theUNC93B1R95L mutation promotes TLR7/8 signaling by enhancing its binding to ssRNA, without affecting TLR7/8 translocation. Overall, our results elucidate the pathology of organs and the immunological profiles of immune cell populations in the development of SLE caused by theUNC93B1R95L mutation through the TLR7/8 axis.
The association between malnutrition and cognitive development in infancy as manifest in EEG functional connectivity and power spectral density
Authors: Hartjen Berit , Kakon Shahria , Rahman Navin , Greaves Garrett , Xie Wanze , Tofail Fahmida , Haque Rashidul , Nelson Charles A.
Published: September 2024

Malnutrition, particularly undernutrition, is a critical global health challenge, contributing to nearly half of all deaths among children under 5 and severely impacting physical and mental health, along with neural and cognitive development. Prior research by Xie et al. (2019a) linked growth faltering to altered EEG functional connectivity (FC) at 36 months and poorer cognitive outcomes at 48 months; however, no associations were found at 6 months for EEG measures or at 27 months for cognitive outcomes. Our study investigates these relationships in a sample of 12-month-old infants in Dhaka, Bangladesh, using various growth measurements (height/length-for-age, weight-for-age, weight-for-height/length, head-circumference-for-age, and mid-upper-arm-circumference-for-age z-scores) as indicators of nutritional status. Brain development was assessed through EEG, focusing on power spectral density (PSD) and FC, while cognitive development was evaluated with the Bayley Scales of Infant and Toddler Development, Fourth Edition. Our findings reveal that, at 12 months, growth faltering, indicative of undernutrition, was associated with reduced PSD, while initial correlations with increased FC did not remain significant after false discovery rate (FDR) correction. PSD was further positively linked to cognitive development, but associations with FC were not significant post-correction. Notably, EEG PSD in the theta and alpha bands mediated the relationship between malnutrition and behavioral outcomes. These results underscore the early impact of malnutrition on brain development, highlighting the importance of PSD in understanding neural development in this context. Our study emphasizes the need for early intervention and continuous monitoring to mitigate the adverse effects of malnutrition on infant brain and cognitive development.

RESEARCH HIGHLIGHTS

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EEG power spectral density (PSD) in the theta and alpha frequency bands at 12 months sheds light on undernutrition’s impact on cognitive development.

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Better nutritional health, indicated by higher height/length-for-age (HAZ), leads to increased theta and alpha PSD, contributing to better cognitive outcomes.

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Initial correlations between undernutrition, increased EEG functional connectivity (FC), and poorer cognitive outcomes did not remain significant after FDR correction.

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Findings highlight the critical role of nutritional interventions in early childhood to support optimal neural and cognitive development.
Characterizing the Longitudinal Impact of Backward Locomotor Treadmill Training on Walking and Balance Outcomes in Chronic Stroke Survivors: A Randomized Single Center Clinical Trial
Authors: Awosika Oluwole O. , Drury Colin , Garver Amanda , Boyne Pierce , Sucharew Heidi J. , Wasik Emily , Bhattacharya Amit , Dunning Kari , Khatri Pooja , Kissela Brett M.
Published: September 2024

Background and Purpose

Walking and balance impairments after stroke are a global health concern, causing significant morbidity and mortality. However, effective strategies for achieving meaningful recovery in the chronic stages are limited. Backward locomotor treadmill training (BLTT) is a novel walking rehabilitation protocol that is safe, feasible, and likely beneficial in stroke survivors; however, its efficacy has not been tested. This single-center, randomized, assessor-blind clinical trial aims to test the preliminary efficacy of BLTT compared to forward locomotor treadmill training (FLTT) on walking speed, symmetry, and postural stability.

Methods

Forty stroke survivors [BLTT (N=19), FLTT (N=21); mean age= 56.3 ± 8.6 years; 53% Female; 30% Non-Hispanic Black] with mild-moderate walking impairment were enrolled. Participants underwent nine 30-minute BLTT or FLTT sessions over three weeks. The primary outcome was the mean change in the 10-meter walk test (10 MWT) at 24 hours post-training (24 hr POST). Secondary outcome measures were changes in spatiotemporal walking symmetry and postural stability during quiet standing at 24 hr POST. Retention was explored at Days 30- and 90 POST.

Results

We report clinically meaningful (≥ 0.16 m/s) improvements in overground walking speed at 24 hr POST, with retention up to Day 90 POST with BLTT and FLTT. However, contrary to our working hypothesis, no between-group differences in walking speed were observed. Nonetheless, we found that BLTT resulted in offline improvements in spatial symmetry and retention of subcomponents of the modified clinical test of sensory interaction on balance (mCTSIB), including the testing of proprio-vestibular integration up to Day 30 POST.

Conclusion

Among chronic stroke patients with mild-moderate walking impairment, BLTT and FLTT both resulted in long-lasting and clinically meaningful improvement in walking speed. However, preliminary findings suggest that BLTT may better comprehensively target walking asymmetry and sensory systems processing and integration.
The beginnings of light-dependent nuclear relocation in land plants
Authors: Iwabuchi Kosei , Yagi Hiroki , Moriya Kenta C. , Komatsu Aino , Sakai Yuuki , Shimada Tomoo , Nishihama Ryuichi , Kohchi Takayuki , Harada Akiko , Watanabe Yo-hei , Ueda Haruko , Hara-Nishimura Ikuko
Published: September 2024

The terrestrialization of plants was accompanied by exposure to several environmental stresses. Adaptation to these stresses required numerous changes at the cellular and molecular level. One such adaptation in the leaves ofArabidopsis thalianais the movement of cell nuclei to avoid UV damage. In the dark, the nuclei locate to the bottom walls of leaf cells to distance genetic material from external stresses, but in response to intense blue light (an indication of the presence of UV), they move to the side walls to escape UV-induced DNA damage1. The movement is driven by the photoreceptor phototropin and the actin cytoskeleton2. However, how this protective mechanism evolved in land plants remains unclear. Here, we show that in the liverwortMarchantia polymorpha, nuclei show a similar, but less stable movement in response to intense blue light. In the dark,M. polymorphapositioned nuclei on the upper walls of epidermal cells in young thalli, but in response to intense blue light, the nuclei immediately moved to the side walls, similar toA. thaliana. However, the movement was transient and the nuclei returned to the upper walls through both the actin and microtubule cytoskeletons.

UnlikeA. thaliana,M. polymorpharesponded to prolonged (> 1 day) exposure to low light by moving nuclei from the upper to the side walls through both the actin and microtubule cytoskeletons and two photoreceptors (phototropin and phytochrome). However, no light-dependent nuclear relocation was observed in charophyte algae, suggesting that light-dependent nuclear relocation was initially established in the common ancestor of land plants as a result of terrestrialization and then diverged during land plant evolution.
Integrative Molecular Dynamics Simulations Untangle Cross-Linking Data to Unveil Mitochondrial Protein Distributions
Authors: Schuhmann Fabian , Akkaya Kerem Can , Puchkov Dmytro , Lehmann Martin , Liu Fan , Pezeshkian Weria
Published: September 2024

Cross-linking mass spectrometry (XL-MS) enables the mapping of protein-protein interactions on the cellular level. When applied to all compartments of mitochondria, the sheer number of cross-links and connections can be over-whelming, rendering simple cluster analyses convoluted and uninformative. To address this limitation, we integrate the XL-MS data, 3D electron microscopy data, and localization annotations with a supra coarse-grained molecular dynamics simulation to sort all data, making clusters more accessible and interpretable. In the context of mitochondria, this method, through a total of 6.9 milliseconds of simulations, successfully identifies known, suggests unknown protein clusters, and reveals the distribution of inner mitochondrial membrane proteins allowing a more precise localization within compartments. Our integrative approach suggests, that two so-far ambigiously placed proteins FAM162A and TMEM126A are localized in the cristae, which is validated through super resolution microscopy. Together, this demonstrates the strong potential of the presented approach.Entry for the Table of Contents

The approach combines cross-linking mass spectrometry, electron microscopy, and coarse-grained molecular dynamics simulations to map protein-protein interactions in mitochondria. This integration makes complex data clusters accessible, revealing protein distributions and localizations. Notably, it allows the localization of FAM162A and TMEM126A through super-resolution microscopy, showcasing the synergy of experimental and computational methods.
Mutations in legume symbiosis genes create a complex selective landscape for natural genetic variation in rhizobia during multi-strain inoculations
Authors: Guha Sohini , Bledsoe Regina B. , Sutherland Jeremy , Epstein Brendan , Fry Gwendolyn M. , Young Nevin D. , Tiffin Peter , Burghardt Liana T.
Published: September 2024

In the mutualism between leguminous plants and rhizobia bacteria, rhizobia live inside root nodules, creating the potential for host genes to shape the rhizobial selective environment. Single-strain screens have identified many host genes influencing symbiosis. However, it’s unknown whether these genes influence which rhizobial strains colonize and thrive inside nodules during multi-strain inoculations. In this study, we inoculated 18Medicago truncatulasymbiotic mutants (including mutations that alter NCR peptide production, plant defence, and nodule number regulation) with a mixture of 86Sinorhizobium melilotistrains. In multi-strain inoculations, most mutations led to reduced host benefits but widely varying effects on host investment and rhizobial benefit (i.e., strain relative fitness), revealing widespread host gene by strain fitness interactions. Genome-wide association studies identify genetic variants on rhizobial replicons pSymA and pSymB as important in mediating strain fitness responses to host mutations. While most top variants only affected rhizobial fitness when one host gene was disrupted, we identified ten variant groups with pervasive effects across six or more host mutations. These variants occurred primarily on pSymA, the symbiotic replicon, and includefixLand a few metabolic genes. In contrast to the limited-effect variants, variants with pervasive positive effects in mutants tended to adversely affect strain fitness in wild-type hosts. Our results reveal how host symbiosis genes perturb the selective landscape and symbiotic outcomes for rhizobia and set the stage for improving rhizobial inoculants and breeding legume hosts better adapted for multi-strain environments.
Apparent timescaling of fossil diversification rates is caused by sampling bias
Authors: Reijenga Bouwe R. , Close Roger A.
Published: September 2024

Negative scaling relationships between both speciation and extinction rates on the one hand, and the age or duration of organismal groups on the other, are pervasive, and recovered in both molecular phylogenetic and fossil time series. The agreement between molecular and fossil data hints at a universal cause, and potentially to incongruence between micro- and macroevolution. However, the existence of negative rate scaling in fossil time series has not undergone the same level of scrutiny as in molecular data. Here, we analyse the marine fossil record across the last ~538.8 Ma of the Phanerozoic to investigate the presence and strength of negative rate scaling. We find that negative rate scaling arises under commonly applied age range-based per-capita rates, which do not control for sampling bias, but are severely reduced or absent when metrics are used that do correct for sampling. We further show by simulation that even moderately-incomplete sampling of species occurrences through time may induce rate scaling. We thus conclude that there are no significant scaling relationships present in these fossil clades, and that any apparent trend is caused by sampling artefacts and taxonomic practices. If rate scaling in molecular phylogenies is genuine, the absence of such a relationship in the fossil record will provide a valuable benchmark and constraint on what processes can cause it.

Highlights

Studies have found that fossil and molecular diversification rates scale with time

Such rate scaling hints at a disconnect between micro- and macroevolution

These trends are absent from the fossil record when controlling for sampling biases

Rate scaling in general may be artefactual, or fossils could show distinct patterns
Inorganic polyphosphate and the stringent response coordinately control cell division and cell morphology inEscherichia coli
Authors: Hamm Christopher W. , Gray Michael J.
Published: September 2024

Bacteria encounter numerous stressors in their constantly changing environments and have evolved many methods to deal with stressors quickly and effectively. One well known and broadly conserved stress response in bacteria is the stringent response, mediated by the alarmone (p)ppGpp. (p)ppGpp is produced in response to amino acid starvation and other nutrient limitations and stresses and regulates both the activity of proteins and expression of genes.Escherichia colialso makes inorganic polyphosphate (polyP), an ancient molecule evolutionary conserved across most bacteria and other cells, in response to a variety of stress conditions, including amino acid starvation. PolyP can act as an energy and phosphate storage pool, metal chelator, regulatory signal, and chaperone, among other functions. Here we report thatE. colilacking both (p)ppGpp and polyP have a complex phenotype indicating previously unknown overlapping roles for (p)ppGpp and polyP in regulating cell division, cell morphology, and metabolism. Disruption of either (p)ppGpp or polyP synthesis led to formation of filamentous cells, but simultaneous disruption of both pathways resulted in cells with heterogenous cell morphologies, including highly branched cells, severely mislocalized Z-rings, and cells containing substantial void spaces. These mutants also failed to grow when nutrients were limited, even when amino acids were added. These results provide new insights into the relationship between polyP synthesis and the stringent response in bacteria and point towards their having a joint role in controlling metabolism, cell division, and cell growth.

IMPORTANCE

Cell division is a fundamental biological process, and the mechanisms that control it inEscherichia colihave been the subject of intense research scrutiny for many decades. Similarly, both the (p)ppGpp-dependent stringent response and inorganic polyphosphate (polyP) synthesis are well-studied, evolutionarily ancient, and widely conserved pathways in diverse bacteria. Our results indicate that these systems, normally studied as stress-response mechanisms, play a coordinated and novel role in regulating cell division, morphology, and metabolism even under non-stress conditions.
A Sex-specific Mendelian Randomization-Phenome-Wide Association Study of Body Mass Index
Authors: Jiesisibieke Zhu Liduzi , Chan Io Ieong , Ng Jack Chun Man , Schooling C Mary
Published: September 2024

Background

Trials of incretins are making it increasingly clear that body mass index (BMI) is linked to several diseases throughout life, but trials cannot provide a comprehensive assessment of the role of BMI in health-related attributes for men and women. To systematically investigate the role of BMI, we conducted a sex-specific Mendelian randomization-phenome-wide association study.

Methods

We comprehensively examined the associations of genetically predicted BMI in women (n: 194,174) and men (n: 167,020) with health-related attributes from the UK Biobank with inverse variance weighting and sensitivity analysis.

Results

BMI impacted 232 of 776 traits considered in women and 204 of 681 traits in men, after adjusting for false discovery; differences by sex were found for 105 traits. BMI was more strongly positively associated with heart disease, heart failure and hypertensive heart disease in men than women. BMI was more strongly positively associated with apolipoprotein B (ApoB), diastolic blood pressure, neuroticism, arthritis and triglycerides in women than men.

Conclusion

Our study revealed that BMI might affect a wide range of health-related attributes and highlights notable sex differences in its impact, including opposite associations for certain attributes, such as ApoB and neuroticism. These findings emphasize the importance of maintaining a healthy BMI.

Funding

None
Building and validating a predictive model for stroke risk in Chinese community-dwelling patients with chronic obstructive pulmonary disease using machine learning methods
Authors: Chen Yong , Yu Yonglin , Yang Dongmei , Chen Xiaoju
Published: September 2024

Background

The occurrence of stroke in patients with chronic obstructive pulmonary disease (COPD) can have potentially devastating consequences; however, there is still a lack of predictive models that accurately predict the risk of stroke in community-based COPD patients in China. The aim of this study was to construct a novel predictive model that accurately predicts the predictive model for the risk of stroke in community-based COPD patients by applying a machine learning methodology within the Chinese community.

Methods

The clinical data of 809 Community COPD patients were analyzed by using the 2020 China Health and Retirement Longitudinal Study (CHARLS) database. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to analyze predictors. Multiple machine learning (ML) classification models are integrated to analyze and identify the optimal model, and Shapley Additive exPlanations (SHAP) interpretation was developed for personalized risk assessment.

Results

The following six variables:Heart_disease,Hyperlipidemia,Hypertension,ADL_score, Cesd_score and Parkinson are predictors of stroke in community-based COPD patients. Logistic classification model was the optimal model, test set area under curve (AUC) (95% confidence interval, CI):0.913 (0.835-0.992), accuracy: 0.823, sensitivity: 0.818, and specificity: 0.823.

Conclusions

The model constructed in this study has relatively reliable predictive performance, which helps clinical doctors identify high-risk populations of community COPD patients prone to stroke at an early stage.
Impact of the WHELD/Brief Psychosocial Therapy intervention on psychosis in people with dementia: A Cluster Randomized Trial
Authors: Ballard C , McDermid J , Mills K , Sweetnam A , Fossey J
Published: September 2024

Neuropsychiatric Symptoms (NPS), particularly psychosis, are common in dementia and can significantly impact patient outcomes, caregivers and disease trajectory. Psychosis, which includes hallucinations and delusions, occurs in up to 50% of people with dementia and has been linked with lower quality of life and faster cognitive decline. While best practice guidelines have highlighted the importance of non-pharmacological treatments for NPS, evidence-based non-pharmacological approaches are limited. This exploratory analysis of a cluster randomized control trial (RCT) from the WHELD programme compares the WHELD/Brief Psychosocial Therapy intervention with treatment as usual in a 9-month trial across 69 UK nursing homes (N=8477, 553 completed). The current report analyzed outcomes for the participants with dementia-related psychosis (N=163) participating in the trial. Whilst the WHELD/Brief Psychosocial Therapy intervention did not significantly reduce NPI psychosis score, it did significantly improve apathy (p=0.006), agitation (p=0.038) and quality of life (p=0.01) in participants with psychosis. In addition there was a non-significant numerical improvement in caregiver perceived disruptiveness. These findings suggest that whilst the WHELD/ Brief Psychosocial Therapy intervention does not directly alleviate psychosis in people with dementia, it does significantly improve related neuropsychiatric symptoms and quality of life, offering meaningful benefits to people with dementia experiencing distressing psychotic symptoms.