bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling forest dynamics using integral projection models (IPMs) and repeat LiDAR
Authors: Rosen Alice , Battison Robin , Hernández Christina M. , Spacey Oliver , McLean Jessie , Prober Suzanne , Gascoigne Samuel , McMahon Sean , Jucker Tommaso , Salguero-Gómez Roberto
Published: January 2025

Estimating the life histories and population dynamics of trees is important for predicting how forests respond to climate change and disturbances. To do so, ecologist often use stage-structured population models, which explicitly account for individual heterogeneity. However, the data needed to parameterise these models is typically constrained by time- and labour-intensive field methods.

Despite growing access to remote sensing imagery that could potentially ‘satiate’ these data-hungry population models, these data remain underutilised in population ecology. Here, we demonstrate a pipeline that integrates repeat-LiDAR data with a type of structured demographic model (Integral Projection Model, IPM) to examine forest-wide dynamics in response to environmental drivers. Using Australia’s Great Western Woodlands as a case study, we model the survival and growth of ∼40,000 eucalypt trees over a decade to estimate their life expectancy and characterise multiple stages of growth (height growth and crown expansion).

Our results indicate distinct responses of small trees (where vital rates are predicted by height) and large trees (which invested predominantly in expanding crown area) to proxies for competition and soil moisture (local canopy density and topographic wetness index, respectively). Parameterising structured population models using LiDAR data therefore offers a step-change in perspective towards more ecologically meaningful forest dynamics.

To broaden the application of this pipeline, we highlight three priorities: (1) Application to more complex systems such as mixed species stands and dense, multilayered canopies); (2) Incorporating complete life histories, including reproduction and early life stages; and (3) Using in long-term or comparative studies through improved availability of high-quality, comparable, repeat-LiDAR surveys. By combining remote sensing data with detailed insights from field- based studies, this pipeline represents a scalable framework for guiding forest management and conservation decisions.
Regulatory Analysis of Root Architectural and Anatomical Adaptation to Nitrate and Ammonium inBrachypodium distachyon
Authors: Rouina Hamid , Singh Dilkaran , Arlt Christopher , Malekian Babak , Schreiber Lukas , Stich Benjamin , Marshall-Colon Amy
Published: January 2025

Root system architecture plays an important role in nitrate and ammonium uptake, the two primary nitrogen (N) forms essential for plant growth. Plants deploy different strategies to optimize the N uptake by roots, based on a complicated regulatory network that controls root phenotype and physiology. Here, we studied the response of root architecture to varying N applications in the model speciesBrachypodium distachyon. Using a combination of phenotypic and transcriptomic analyses, we examined how different forms and concentrations of ammonium and nitrate affect root growth, biomass allocation, and N uptake. N concentrations significantly influence root traits such as root length, root hair development, and aerenchyma formation in response to nitrate and ammonium. Plants grown in ammonium conditions had thin but highly branched roots, whereas nitrate application resulted in shorter, thicker roots with denser root hair at higher nitrate concentrations. Furthermore, using advanced co-expression network analysis, we identified an Atypical Aspartic Protease (APs) gene encoding an aspartyl protease family protein and a phosphoenolpyruvate carboxylase 1 (PEPC1) gene in brachypodium, which potentially control the root architectural and anatomical adaptions to different N form. APs expression showed a positive correlation with total root length and lateral root development, along with a negative correlation with root hair density. In contrast, PEPC1 exhibited positive correlations with cortex, stele, root cross-sectional areas, and root hair density, while showing a negative correlation with total root length. These genes likely play an important role in the transcriptional regulatory networks involved in these adaptive responses, which highlight the complex interplay between root morphology, nitrogen metabolism, and environmental nutrient conditions.
Detailed tandem repeat allele profiling in 1,027 long-read genomes reveals genome-wide patterns of pathogenicity
Authors: Danzi Matt C. , Xu Isaac R. L. , Fazal Sarah , Dolzhenko Egor , Pellerin David , Weisburd Ben , Reuter Chloe , Sampson Jacinda , Folland Chiara , Wheeler Matthew , O’Donnell-Luria Anne , Wuchty Stefan , Ravenscroft Gianina , Eberle Michael A. ,   All of Us Research Program Long Read Working Group, Zuchner Stephan
Published: January 2025

Tandem repeats are a highly polymorphic class of genomic variation that play causal roles in rare diseases but are notoriously difficult to sequence using short-read techniques1,2. Most previous studies profiling tandem repeats genome-wide have reduced the description of each locus to the singular value of the length of the entire repetitive locus3,4. Here we introduce a comprehensive database of 3.6 billion tandem repeat allele sequences from over one thousand individuals using HiFi long-read sequencing. We show that the previously identified pathogenic loci are among the most variable tandem repeat loci in the genome, when incorporating nucleotide resolution sequence content to measure the longest pure motif segment. More broadly, we introduce a novel measure, ‘tandem repeat constraint’, that assists in distinguishing potentially pathogenic from benign loci. Our approach of measuring variation as ‘the length of the longest pure segment’ successfully prioritizes pathogenic repeats within their previously published linkage regions. We also present evidence for two novel pathogenic repeat expansion candidates. In summary, this analysis significantly clarifies the potential for short tandem repeat pathogenicity at over 1.7 million tandem repeat loci and will aid the identification of disease-causing repeat expansions.
Understanding detection probability in a low-density population to inform optimal eDNA sampling for freshwater mussels
Authors: Rodgers Torrey W , Mock Karen E
Published: January 2025

Environmental DNA (eDNA) offers a sensitive tool for detecting aquatic species, including those at low population densities. However, effective use of eDNA in conservation and monitoring efforts requires an understanding of detection probabilities and optimal replication effort necessary to minimize false negatives. This study assessed the probability of detecting Anodonta nuttalliana, a native freshwater mussel, in two Utah populations with contrasting densities (medium and low). We conducted traditional visual sampling alongside highly replicated eDNA sampling at both sites. In the medium-density population, eDNA provided high detection probabilities with minimal replication. However, in the low-density population, substantially greater replication was needed to achieve similar detection probabilities. Despite the increased eDNA replication effort needed to detect the low-density population, eDNA outperformed traditional visual sampling, which failed to detect live mussels at the low-density site. Our findings highlight the critical balance between sampling effort and detection success, offering guidance for optimizing eDNA sampling strategies in monitoring efforts, especially for species which occur at low densities.
Is early initiated physical rehabilitation exercise superior to no physical rehabilitation exercise following total hip arthroplasty? A systematic review and narrative synthesis
Authors: Madsen Merete Nørgaard , Mikkelsen Lone Ramer , Christiansen David Høyrup , Østergaard Helle Kvistgaard , Bandholm Thomas
Published: January 2025

Background

Physical rehabilitation exercise (PRE) is commonly prescribed in the early stage after total hip arthroplasty (THA). However, systematic reviews investigating the effectiveness of PRE have reported diverse results, and often included trials using PRE in both groups or initiated at a later stage after surgery, which does not reflect clinical practice. Therefore, the study objective was to investigate whether early initiated PRE following THA was superior to no PRE in terms of improving function, reducing pain and increasing quality of life at end of intervention and 12 months after surgery.

Methods

A systematic review of randomized controlled trials (RCT) was conducted. Included studies were RCTs comparing PRE initiated within 3 months after primary THA due to osteoarthritis with no PRE. MEDLINE, Embase, Cinahl, Cochrane and Pedro were searched for published articles, while Scopus, Web of Science, ClinicalTrials.govand WHO International Clinical Trials Registry Platform were searched for conference papers and pre-registered trials. Study methodology was assessed by Cochrane Risk of Bias 2 (RoB2) tool and overall quality of evidence by the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). Incomplete outcome data and heterogeneity among studies precluded meta-analysis. Thus, data synthesis using vote counting was applied and tested by the binomial probability test. The results were narratively presented in text and tabular form distributed on pain, patient-reported function and performance-based function.

Results

A total of 10742 references were screened. Three trials (two published papers and one conference abstract) with a total of 151 participants were included in the narrative synthesis. Only outcomes at end of treatment (ranging from 3-18 weeks after surgery) were available. The observed direction of effect favored PRE in the single study reporting patient-reported function, in both studies reporting pain and in two out of three studies reporting performance-based function. However, the testing did not show significant evidence of effect of PRE. Overall, a high risk of bias was present, and quality of evidence was very low.

Discussion

Limited and very low quality of evidence showed no clear benefits or harms of PRE. Hence, no conclusions on superiority of PRE to no PRE can be drawn. High quality randomized controlled trials are needed to determine the effectiveness of using PRE early after THA.

Other

Registration: PROSPERO, CRD42020203574
Perspectives on Cervical Cancer Prevention Strategies and a Combination Treatment for Cervical Precancer in South African Women Living with HIV and Male Partners
Authors: Teodoro Nicholas S. , Ngcobo Nkosinathi , Jean-Baptiste Milenka , Mulongo Masangu , Milford Cecilia , Beksinska Malgorzata , Burgess Jaqueline , Luvuno Sibusisiwe , Nkoana Jermina , Mayisela Nonkululeko , Rahangdale Lisa , Chibwesha Carla J.
Published: January 2025

Introduction

Cervical cancer remains the second most common cancer among women worldwide, with 85% of cases occurring in low-and middle-income countries (LMIC). Women living with HIV (WLWH) are at a particularly high risk of developing for high-grade cervical intraepithelial neoplasia (CIN2/3) and cervical cancer, and the standard surgical treatment is far less effective in this population. Thus, research on medical therapies and combination treatment options remain a priority. In preparation for a clinical trial involving adjuvant intravaginal 5-fluorouracil (5FU) cream following surgical treatment for CIN2/3, we explored the acceptability of our proposed intervention among WLWH and male partners.

Methods

We conducted qualitative interviews with WLWH and male partners in Johannesburg, South Africa between April 2022 and September 2022. We invited WLWH to participate in semi-structured focus group discussions (FGDs), while male partners were invited to participate in semi-structured in-depth interviews (IDIs). The analysis utilized a rapid, deductive approach in which quotations were identified and categorized into relevant domains: factors affecting cervical cancer screening, the initiation of 5FU vaginal cream, and adherence to 5FU.

Results

We conducted 9 FGDs comprising 48 WLWH and 18 IDIs with male partners. The mean age of participants was 43 years, and the majority (75%) had completed secondary education. Most women (75%) had also undergone Pap smear screening and 50% had a prior abnormal Pap smear. Qualitative analysis revealed that education on HPV and cervical cancer, prior experience with the health system, and social perceptions/stigma influenced cervical cancer screening uptake and were important factors in the initiation of and adherence to 5FU. Men’s knowledge about cervical cancer was extremely limited. Overall, participants’ perceptions of the proposed trial intervention were positive, with most participants expressing confidence that women would be able to use and adhere to the intravaginal 5FU cream. Concerns raised included possible effects of 5FU on fertility, contraceptive requirements, and the recommendation for brief periods of abstinence following cream use to prevent partner side effects.

Conclusions

Although participants had some cervical cancer knowledge, misperceptions about HPV and cervical cancer were common and prevented follow-up for abnormal Pap results. Participants emphasized the need for thorough counseling about 5FU, citing this as integral for uptake. Utilizing stakeholder input to design the clinical trial is necessary to promote acceptability and adherence to the trial intervention.
The emergence and persistence of inequalities in adolescent mental health: the Resilience, Ethnicity and AdolesCent Mental Health (REACH) cohorts
Authors: Knowles Gemma , Gayer-Anderson Charlotte , Davis Samantha , Stanyon Daniel , Ofori Aisha , Blakey Rachel , Richards Thai-sha , Hashi Adna , Clement-Gbede Karima Shyan , Kitisu Jonas , Tettey Niiokani , Lowis Katie , Turner Alice , Dorn Lynsey , Putzgruber Esther , Pinfold Vanessa , Harding Seeromanie , Bhui Kamaldeep , Morgan Craig
Published: January 2025

Background

Mental health problems are not distributed equally in society. Our understanding of when social inequalities in mental health emerge is limited. We sought to examine inequalities in trajectories of mental distress in diverse, representative cohorts of adolescents in inner-London.

Methods

We analysed longitudinal data from our cohort study of adolescent mental health, REACH (n=4663; 51% girls, 29% free school meals [FSM], 85% minoritised ethnic groups). We used latent growth curve models to estimate trajectories of mental distress (total, internalising, and externalising scores from the self-report Strengths and Difficulties Questionnaire) from age 11-16 years, overall and by gender, FSM, ethnic group, and their intersections.

Results

We found strong evidence of differences in trajectories of mental distress by gender and FSM. Higher mean internalising scores in girls (vs. boys) were evident at age 11-12 and this inequality widened year-on-year (difference in mean intercepts: 0.74 [95% CI 0.52, 0.96]; slopes: 0.50 [0.39, 0.61]). Higher mean levels of distress among those receiving FSM (vs. not) were evident at age 11-12 years (e.g., difference in intercepts, general distress: 0.79 [0.19, 1.39]), and this difference, though modest, persisted through adolescence. By ethnic group and intersecting identities, the picture was more complex and mixed. Broadly, Black African youth generally reported better mental health trajectories vs. their peers; Black Caribbean and Mixed Black-and-White youth shared similar trajectories, differing somewhat from Black African; and by age 16, internalising distress was highest among lower-income White British girls.

Conclusions

In diverse inner-cities, adolescence is an important period in the emergence and persistence of some of the inequalities in mental health reported in adults; others are more nuanced.
Locally induced traveling waves generate globally observable traveling waves
Authors: Petras Kirsten , Grabot Laetitia , Dugué Laura
Published: January 2025

Cortical traveling waves have been proposed as a fundamental mechanism for neural communication and computation. Methodological uncertainties currently limit the interpretability of non-invasive, extracranial traveling wave data, sparking debates about their cortical origin. Studies using EEG or MEG typically report waves that cover large portions of the sensor array which are often interpreted as reflecting long range cortical waves. Meanwhile, invasive, intracranial recordings in humans and animals routinely find both local, mesoscopic waves and large scale, macroscopic waves in cortex. Whether the global sensor-array waves found with EEG/MEG necessarily correspond to macroscopic cortical waves or whether they are merely projections of local dynamics remains unclear. In this study, we made use of the well-established retinotopic organization of early visual cortex to generate traveling waves with known properties in human participants (N=19, m/f) via targeted visual stimulation, while simultaneously recording MEG and EEG. The inducer stimuli were designed to elicit waves whose traveling direction in mesoscopic retinotopic visual areas depends on stimulus direction, while leaving macroscopic activation patterns along the visual hierarchy largely unchanged. We observed that the preferred direction of traveling waves across the sensor array was influenced by that of the visual stimulus, but only at the stimulation frequency. Comparison between single-trial and trial-averaged responses further showed considerable temporal variation in traveling wave patterns across trials. Our results highlight that under tight experimental control, non-invasive, extracranial recordings can recover mesoscopic traveling wave activity, thus making them viable tools for the investigation of spatially constrained wave dynamics.

Significant statement

Non-invasively obtained time-resolved neuroimaging data is often thought to primarily reflect neural dynamics on the largest spatial scales. In the context of cortical traveling waves, this assumption can lead to a misinterpretation of spatio-temporal patterns observed in the sensor array. We here show that it is in principle possible that the global sensor array data is dominated by spatially constrained, local cortical traveling wave activity. Our findings crucially inform the ongoing discussion about the origin of traveling waves observed in surface recordings.
Improved synapsis dynamics accompany meiotic stability in Arabidopsis arenosa autotetraploids
Authors: Gonzalo Adrian , Nayak Aditya , Bomblies Kirsten
Published: January 2025

During meiosis, the correct pairing, synapsis, and recombination of homologous chromosome pairs is critical for fertility of sexual eukaryotes. These processes are challenged in polyploids, which possess additional copies of each chromosome. Polyploidy thus provides a unique context to study how evolution can modify meiotic programs in response to challenges. We previously observed that in Arabidopsis arenosa newly formed (neo-)polyploids, synapsis defects precede chromosomes associating in aberrant multivalent and univalent configurations. Here we study synapsis dynamics in genotypes with varying levels of meiotic stability to ask whether efficient synaptic progression is a key component of evolving stable tetraploid meiosis. We develop a method to quantify synapsis dynamics using the progression of foci of the pro-crossover factor HEI10 as a reference. HEI10 initially appears at many small loci before accumulating only at crossover sites. In diploids, this transition begins while there is still significant asynapsis, which quickly declines as HEI10 accumulation to fewer foci progresses. In neo-tetraploids, suboptimal elongation of synaptic initiation sites, and perhaps defective pairing, precedes synapsis stalling before the onset of HEI10 accumulation. In established tetraploids, HEI10 accumulation begins only when asynapsis is minimal, suggesting an enhanced HEI10/synapsis co-dynamic (even compared to diploids). Hybrids generated by crossing neo- and established tetraploids exhibit intermediate phenotypes. We find the extent of asynapsis correlates positively with crossover numbers, as well as a higher frequency of multivalents and univalent, which can disturb chromosome segregation. Our work supports the hypothesis that improving the efficiency of synapsis is important for evolving polyploid meiotic stability.
Intestinal stem cell renewal controlled by capillary morphogenesis gene 2 following injury
Authors: Bracq Lucie , Chuat Audrey , Kunz Béatrice , Burri Olivier , Guiet Romain , van der Goot F. Gisou
Published: January 2025

Patients with the rare genetic disorder Hyaline Fibromatosis Syndrome (HFS) often succumb before 18 months of age due to severe diarrhea and protein-losing enteropathy. As HFS is caused by loss-of-function mutations in the gene encoding capillary morphogenesis gene 2 (CMG2), also known as Anthrax Toxin Receptor 2, these symptoms highlight a critical yet unclear role for CMG2 in the gut. Here, we demonstrate that CMG2 knockout mice exhibit normal colon morphology and no signs of inflammation until the chemical induction of colitis. In these conditions, the colons of knockout mice do not regenerate despite previously experiencing similarly severe colitis, due to an inability to replenish their intestinal stem cell pool. Specifically, CMG2 knockout impairs the transition from fetal-like to Lgr5+ adult stem cells, which is associated with a defect in ß-catenin nuclear translocation. Our findings suggest that CMG2 functions as a context-specific modulator of Wnt signaling, essential for replenishing the pool of intestinal stem cells following injury. This study provides new insights into the molecular mechanisms underlying protein-losing enteropathy in HFS and offers a broader understanding of fetal-like regenerative responses.

GRAPHICAL ABSTRACT
Pollen morphology, deep learning, phylogenetics, and the evolution of environmental adaptations inPodocarpus
Authors: Adaimé Marc-Élie , Urban Michael A. , Kong Shu , Jaramillo Carlos , Punyasena Surangi W.
Published: January 2025

Podocarpuspollen morphology is shaped by both phylogenetic history and the environment. We analyzed the relationship between pollen traits quantified using deep learning and environmental factors within a comparative phylogenetic framework.

We investigated the influence of mean annual temperature, annual precipitation, altitude, and solar radiation in driving morphological change. We used trait-environment regression models to infer the temperature tolerances of 31 NeotropicalPodocarpiditesfossils. Ancestral state reconstructions were applied to thePodocarpusphylogeny with and without the inclusion of fossils.

Our results show that temperature and solar radiation influence pollen morphology, with thermal stress driving an increase in pollen size and higher UV-B radiation selecting for thicker corpus walls. Fossil temperature tolerances inferred from trait-environment models aligned with paleotemperature estimates from global paleoclimate models. Incorporating fossils into ancestral state reconstructions revealed that early ancestralPodocarpuslineages were likely adapted to warm climates, with cool-temperature tolerance evolving independently in high-latitude and high-altitude species.

Our results highlight the importance of deep learning-derived features in advancing our understanding of plant environmental adaptations over evolutionary timescales. Deep learning allows us to quantify subtle interspecific differences in pollen morphology and link these traits to environmental preferences through statistical and phylogenetic analyses.
Mitigating Proinflammatory SASP and DAMP with Urolithin A: A Novel Senomorphic Strategy
Authors: Barkovskaya Anna , Brauning Ashley , Chamoli Manish , Rane Anand , Andersen Julie K , Sharma Amit
Published: January 2025

Senescent cells are known to contribute to aging and age-related diseases. One key way they influence aging is by secreting senescence-associated secretory phenotype (SASP) factors along with several damage-associated molecular pattern (DAMP) molecules. Consequently, inhibiting SASP and DAMP signaling (senomorphics) has emerged as a therapeutic strategy. Urolithin A (UA), a gut-derived metabolite produced from ellagitannins and ellagic acid found in berries, nuts, and pomegranates, has demonstrated potent anti-inflammatory properties and protective effects against aging and age-related conditions in experimental models. Here we demonstrate that UA lowers the expression and release of pro-inflammatory SASP and DAMP factors at least in part, on the downregulation of cytosolic DNA release and subsequent decrease in cGAS-STING signaling.
β1 Integrin–FAK–Piezo1 signalling axis drivesin-situstiffening mediated ECM remodelling and invasion of 3D breast epithelium
Authors: Sakthivel Kabilan , Kotowska Anna , Portner Ellen Juel , Merry Catherine , Nordenfelt Pontus , Simonsen Adam Cohen , Wright Amanda J. , Swaminathan Vinay
Published: January 2025

Stiffening of tissue is a hallmark of cancer progression, driving invasive phenotypes through complex interactions between cells and their extracellular matrix (ECM). However, the mechanisms linking mechanical cues to ECM remodelling and invasion remain incompletely understood. Here, using anin-situstiffening model that allows for modulation of ECM stiffness around fully formed normal mammary acini embedded in their native ECM microenvironment, we identify critical steps in basement membrane (BM) and stromal ECM remodelling during invasion and discover the molecular mechanisms driving this process. We find that stiffening of the ECM around normal mammary acini results in rapid loss and degradation of laminin (LN) and upregulation of the fibronectin (FN) secretion around the acini. This priming phase is followed by the onset of invasion which requires localized upregulation of LN production and ECM remodelling. Mechanistically, ECM production and remodelling as well as invasion is mediated by β1 integrin–FAK signalling, which activates mechanosensitive ion channels (MSCs). Further, we identify Piezo1 as the MSC downstream of β1 integrin–FAK that drives BM disruption and stromal ECM remodelling. Taken together, our results identify the mechanisms by which stiffness can trigger invasive phenotypes from normal tissues.
SDS-22 stabilizes the PP1 catalytic subunits GSP-1/-2 contributing to polarity establishment inC. elegansembryos
Authors: Li Yi , Calvi Ida , Gotta Monica
Published: January 2025

In many cells, cell polarity depends on the asymmetric distribution of the conserved PAR proteins, maintained by a balanced activity between kinases and phosphatases. TheC. elegansone-cell embryo is polarized along the anterior-posterior axis, with the atypical protein kinase C PKC-3 enriched in the anterior, and the ring finger protein PAR-2 in the posterior. PAR-2 localization is regulated by PKC-3 and the PP1 phosphatases GSP-1/-2. Here, we find that, like GSP-2 depletion, depletion of the conserved PP1 interactor SDS-22 results in the rescue of the polarity defects of apkc-3temperature-sensitive mutant. Consistent with the rescue, SDS-22 depletion or mutation results in reduced GSP-1/-2 protein levels and activity. The decreased levels of GSP-1/-2 can be rescued by reducing proteasomal activity. Our data suggest that SDS-22 regulates polarity not by directly regulating the localization or activity of GSP-1/-2, but by protecting these PP1 catalytic subunits from proteasome-mediated degradation, supporting recent data in human cells showing the SDS22 is required to stabilize nascent PP1.
Disentangling the evolutionary history of terrestrial planarians through phylogenomics
Authors: Benítez-Álvarez Lisandra , Escudero Nuria , Salces-Ortiz Judit , Rojo Iñaki , Fernández-Álvarez Fernando Ángel , Mateos Eduardo , Carbayo Fernando , Fernández Rosa
Published: January 2025

Triclads (Platyhelminthes, Tricladida) are found in marine, freshwater, and terrestrial habitats worldwide except Antarctica. Terrestrial planarians are grouped into the family Geoplanidae, which is subdivided into the subfamilies Geoplaninae, Bipaliinae, Rhynchodeminae, and Microplaninae. Some of these subfamilies result from taxonomic rearrangements based on molecular phylogenies inferred from a few molecular markers. However, the diagnosis of Rhynchodeminae was not aligned with the morphology of all its representatives. While the subfamilies are recovered as monophyletic in recent molecular phylogenies, robust hypotheses regarding the relationships between them remain unknown. In this study, we employ for the first time a phylogenomic framework to investigate the evolutionary relationships among the subfamilies, starting by obtaining the first transcriptomes for 15 species of terrestrial planarians. A total of 16 different datasets, comprising nearly two thousand single-copy genes inferred from transcriptomic data, were analyzed using various phylogenetic inference methods. We recovered, for the first time, a well-supported topology of phylogenetic relationships among Geoplanidae subfamilies, positioning Bipaliinae and Microplaninae as a clade sister to Rhynchodeminae + Geoplaninae. Internal relationships within the genusMicroplanawere not supported in our analyses. The subfamily Rhynchodeminae, represented in our phylogeny by species from the tribes Rhynchodemini and Caenoplanini, is re-diagnosed to align with previous taxonomic rearrangements. This study not only represents a significant step forward in the phylogenetic resolution of Geoplanidae but also provides important insights into the broader evolutionary dynamics shaping land planarian diversity.

Highlights

First transcriptomes of multiple terrestrial planarians sequenced.

First molecular phylogeny of terrestrial planarians at subfamily level based on transcriptomic data.

Highly supported topology for phylogenetic interrelationship among terrestrial planarians subfamilies.

Unclear interrelationships between species from the genusMicroplana.

The subfamily Rhynchodeminae is re-diagnosed at the morphological level.
Metabolic tagging reveals surface-associated lipoproteins in mycobacteria
Authors: Parkin Lia A. , Maceren Julian P. , Palande Aseem , Previti Mary L. , Seeliger Jessica C.
Published: January 2025

Mycobacteria such as the causative agent of tuberculosis,Mycobacterium tuberculosis, encode over 100 bioinformatically predicted lipoproteins. Despite the importance of these post-translationally modified proteins for mycobacterial survival, many remain experimentally unconfirmed. Here we characterized metabolic incorporation of diverse fatty acid analogues as a facile method of adding chemical groups that enable downstream applications such as detection, crosslinking and enrichment, of not only lipid-modified proteins, but also their protein interactors. Having shown that incorporation is an active process dependent on the lipoprotein biosynthesis pathway, we discovered that lipid-modified proteins are also located at the mycobacterial cell surface. These data counter the commonly held assumption that mycobacteria do not move lipoproteins across the cell envelope and thus have implications for uncovering a novel transport pathway and the roles of lipoproteins at the interface with the host environment. Our findings and the tools we developed will enable the further study of pathways related to lipoprotein function and metabolism in mycobacteria and other bacteria in which lipoproteins remain poorly understood.
Specificity Protein 1 is essential for the limb trajectory of ephrin-mediated spinal motor axons
Authors: Liao Pinwen , Chang Ming-Yuan , Yang Wen-Bin , Lin Keefer , Li Yi-Chao , Chuang Jian-Ying , Wu Yi-Hsin , Kania Artur , Chang Wen-Chang , Hsu Tsung-I , Kao Tzu-Jen
Published: January 2025

The precise organization of neural circuits requires highly specific axon guidance, facilitated by cell-surface guidance receptors on axonal growth cones that help neurons reach their target destinations. Despite a limited repertoire of known guidance receptors and ligands, neural systems achieve complex axonal networks, suggesting that additional regulatory mechanisms exist. One proposed strategy is the co-expression of ligands and their receptors on the same axons, allowing modulation of receptor responsiveness to guidance cues. To investigate this mechanism, we studied the spinal lateral motor column (LMC) motor neurons, which make a binary axon pathfinding decision toward limb targets. We hypothesized that specificity protein 1 (Sp1), a transcription factor, regulates ephrin expression in LMC neurons, thereby modulating receptor functions viacis-attenuation to ensure accurate axonal pathfinding. Our results show that Sp1 is indeed expressed in LMC neurons during critical axonal extension periods. Manipulating Sp1 activity disrupted LMC axon trajectory selection, and RNA-Seq analysis indicated that Sp1 regulates genes associated with axon guidance, including ephrins. We found that Sp1 knockdown affected ephrin/Ephcis-binding andtrans-signaling, highlighting Sp1’s role in controlling axonal projections through ephrin gene regulation. Additionally, coactivators p300 and CBP are essential for Sp1’s regulatory function. These findings identify Sp1 as a key transcription factor in LMC neurons, essential for ephrin expression and ephrin/Eph-mediated axon guidance, providing insights into the molecular mechanisms of neural circuit formation.
The zinc-finger protein POGZ associates with Polycomb repressive complex 1 to regulate bone morphogenetic protein signaling during neuronal differentiation
Authors: Chavez Jessenia , Wolf Trevor , Geng Zhuangzhuang , Tai Yen Teng , Bright Kathleen , Stafford James , Gao Zhonghua
Published: January 2025

Polycomb Repressive Complex 1 (PRC1) is a family of epigenetic regulators critical for mammalian development. Elucidating PRC1 composition and function across cell types and developmental stages is key to understanding the epigenetic regulation of cell fate determination. In this study, we discovered POGZ, a prominent Autism Spectrum Disorder (ASD) risk factor, as a novel component of PRC1.6, forming the PRC1.6-POGZ complex. Functional assays revealed that POGZ elicits transcriptional repression that is dependent on RING1B expression. Analysis of publicly available ChIP-Seq data showed that POGZ highly colocalizes with RING1B and HP1γ, two PRC1.6 components, at genes involved in multiple aspects of transcriptional regulation in the embryonic mouse cortex. AlthoughPogzknockout (KO) does not compromise stem cell pluripotency,Pogzablation in neuronal progenitor cells (NPCs) led to widespread transcriptomic dysregulation with failed activation of key neuronal genes. Finally, we demonstrated that PRC1.6-POGZ regulates neuronal differentiation by repressing the bone morphogenetic protein (BMP) signaling pathway. These findings reveal a mechanism by which PRC1 and POGZ coordinate transcriptional regulation during neuronal differentiation, which offers insights into how disruptions in this pathway may contribute to neurodevelopmental disorders such as ASD.
Nucleotide-resolution Mapping of RNA N6-Methyladenosine (m6A) modifications and comprehensive analysis of global polyadenylation events in mRNA 3’ end processing in malaria pathogenPlasmodium falciparum
Authors: Catacalos-Goad Cassandra , Chakrabarti Manohar , Salem Doaa Hassan , Camporeale Carli , Somalraju Sahiti , Tegowski Matthew , Singh Ruchi , Reid Robert W. , Janies Daniel A. , Meyer Kate D. , Janga Sarath Chandra , Hunt Arthur G. , Chakrabarti Kausik
Published: January 2025

Plasmodium falciparumis an obligate human parasite of the phylum Apicomplexa and is the causative agent of the most lethal form of human malaria. Although N6-methyladenosine modification is thought to be one of the major post-transcriptional regulatory mechanisms for stage-specific gene expression in apicomplexan parasites, the precise base position of m6A in mRNAs or noncoding RNAs in these parasites remains unknown. Here, we report global nucleotide-resolution mapping of m6A residues inP. falciparumusing DART-seq technology, which quantitatively displayed a stage-specific, dynamic distribution pattern with enrichment near mRNA 3’ ends. In this process we identified 894, 788, and 1,762 m6A-modified genes in Ring, Trophozoite and Schizont stages respectively, with an average of 5-7 m6A sites per-transcript at the individual gene level. Notably, several genes involved in malaria pathophysiology, such as KAHRP, ETRAMPs, SERA and stress response genes, such as members of Heat Shock Protein (HSP) family are highly enriched in m6A and therefore could be regulated by this RNA modification. Since we observed preferential methylation at the 3’ ends ofP. falciparumtranscripts and because malaria polyadenylation specificity factor PfCPSF30 harbors an m6A reader ‘YTH’ domain, we reasoned that m6A might play an important role in 3’-end processing of malaria mRNAs. To investigate this, we used two complementary high-throughput RNA 3’-end mapping approaches, which provided an initial framework to explore potential roles of m6A in the regulation of alternative polyadenylation (APA) during malaria development in human hosts.
Rapid clinical diagnosis and treatment of common, undetected, and uncultivable bloodstream infections using metagenomic sequencing from routine blood cultures with Oxford Nanopore
Authors: Govender Kumeren N. , Eyre David W.
Published: January 2025

Metagenomic sequencing could potentially revolutionise clinical microbiology, including identifying pathogens and predicting antimicrobial resistance (AMR) in seriously unwell patients with bloodstream infections. We present a direct-from-blood culture sequencing method that delivers results rapidly and accurately. In 273 randomly-selected blood cultures (211 positive, 62 negative), we achieved 97% sensitivity and 94% specificity (improving to 100% accounting for plausible additional infections) for species identification compared to established diagnostic methods. We detected 18 additional infections—13 polymicrobial and 5 previously unidentifiable—and delivered findings in 3.5 hours, nearly a third of time taken by routine methods. For the top ten pathogens, our method produced AMR results 20 hours quicker, with 88% sensitivity and 93% specificity. ForStaphylococcus aureusandEscherichia coli, AMR prediction sensitivity was 100% and 91%, and specificity 99% and 94% respectively. These findings suggest the potential of integrating clinical metagenomics into standard diagnostics for faster and more comprehensive pathogen detection.
A Multi-pathogen Hospitalization Forecasting Model for the United States: An Optimized Geo-Hierarchical Ensemble Framework
Authors: Xu Shaochong , Du Hongru , Dong Ensheng , Wang Xianglong , Zhang Liyue , Gardner Lauren M.
Published: January 2025

Accurate forecasting of infectious diseases is crucial for timely public health response. Ensemble frameworks have shown promising outcomes in short-term forecasting of COVID-19, among other respiratory viruses, however, there is a need to further improve these frameworks. Here, we propose the Multi-Pathogen Optimized Geo-Hierarchical Ensemble Framework (MPOG-Ensemble), a novel forecasting machine learning framework to forecast state-level hospitalizations of influenza, COVID-19, and RSV in the U.S. This framework is multi-resolution: it integrates state, regionally-trained, and nationally-trained models through an ensemble layer and applies various optimization methods to parameterize the model weights and enhance overall predictive accuracy. This proposed framework builds on existing forecasting literature by 1) employing an ensemble of three spatially hierarchical models with state-level forecasts as the output; 2) incorporating four distinct weight optimization methods to generate the ensemble; 3) utilizing clustering methods to dynamically identify multi-state regions as a function of short-term and long-term hospitalization trends for the regionally-trained model; and 4) providing a generalized multi-pathogen framework to forecast the expected near-term hospitalizations from Influenza, RSV and COVID-19. Results demonstrate MPOG-Ensemble is a robust framework with relatively high performance. Extensive experimentation using historical multi-pathogen data highlights the predictive power of our framework compared to existing ensemble approaches. Its robust performance underscores the framework’s effectiveness and potential for improving and broadening infectious disease forecasting.
Potato Late Blight Control with a Botanical Product and Reduced Copper Applications
Authors: Musa Tomke , Kägi Andreas , Gütlin Haruna , Schnee Sylvain , Massana-Codina Josep , Sullam Karen E.
Published: January 2025

Potato late blight (PLB), due to the pathogenic oomycete,Phytophthora infestans, can cause extensive economic damage, particularly in organic potato production. Copper is used to combat PLB, but its reduction as a plant protection product is an increasing priority in Europe. Alternative control strategies, including botanicals, are a potential avenue to reduce copper and control PLB. We investigated the application ofFrangula alnusbark, its pairing with a reduced copper application, and a reduced copper application alone in field and lab experiments. The effect of different dosages and preparations on efficacy, and the posited active ingredients were examined.Frangula alnustreatments decreased disease severity compared to the untreated control but showed differences in efficacy depending on dosage and disease pressure. No difference in disease severity between the full and reduced copper treatments was observed. Through in vitro and in planta experiments, we investigated whetherF. alnusdirectly or indirectly controlled PLB. A bacterium (Erwiniaspp.), originating from theF. alnusextract, colonized the media and accounted for most of the direct inhibition in vitro, but removing microorganisms through filtration had no effect on the extract’s efficacy in planta. It is unclear whether extract-associated microorganisms contributed to PLB control and would require additional experimentation to assess. The presence of measured anthraquinones likely contributed to the effect ofF. alnus. Yields from the field experiments within each year remained stable despite different treatments and dosages, suggesting that treatment effectiveness is intertwined with the timing of disease development and ambient environmental conditions.
Single-nuclei multiome ATAC and RNA sequencing reveals the molecular basis of thermal plasticity inDrosophila melanogasterembryos
Authors: O’Leary Thomas S. , Mikucki Emily E. , Tangwancharoen Sumaetee , Boyd Joseph R. , Frietze Seth , Helms Cahan Sara , Lockwood Brent L.
Published: January 2025

Embryogenesis is remarkably robust to temperature variability, yet there is limited understanding of the homeostatic mechanisms that offset thermal effects during early development. Here, we measured the thermal acclimation response of upper thermal limits and profiled chromatin state and the transcriptome ofD. melanogasterembryos (Bownes Stage 11) using single-nuclei multiome ATAC and RNA sequencing. We report that thermal acclimation, while preserving a common set of primordial cell types, rapidly shifted the upper thermal limit. Cool-acclimated embryos showed a homeostatic response characterized by increased chromatin accessibility at transcription factor binding motifs for the transcriptional activator Zelda, along with enhanced activity of gene regulatory networks in the primordial cell types including the foregut and hindgut, mesoderm, and peripheral nervous system. In addition, cool-acclimated embryos had higher expression of genes encoding ribosomal proteins and enzymes involved in oxidative phosphorylation. Despite the hypothesis that differential heat tolerance might be explained by differential expression of molecular chaperones, we did not observe widespread differences in the chromatin accessibility or expression of heat shock genes. Overall, our results suggest that environmental robustness to temperature during embryogenesis necessitates homeostatic gene expression responses that regulate the speed of development, potentially imposing metabolic costs that constrain upper thermal limits.
Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment
Authors: Aviles-Huerta Daniela , Rossella Del Pizzo , Kowar Alexander , Baig Ali Hyder , Palazzo Giuliana , Stepanova Ekaterina , Amaya Ramirez Cinthia Claudia , D’Agostino Sara , Ratto Edoardo , Pechincha Catarina , Siefert Nora , Engel Helena , Du Shangce , Cadenas-De-Miguel Silvia , Miao Beiping , Cruz Vilchez Victor , Müller-Decker Karin , Elia Ilaria , Sun Chong , Palm Wilhelm , Loayza-Puch Fabricio
Published: January 2025

Cancer cells, immune cells, and stromal cells within the tumor microenvironment (TME) collaboratively influence disease progression and therapeutic responses. The nutrient-limited conditions of the TME, particularly the scarcity of glucose, amino acids, and lipids, challenge cancer cell survival1–4. However, the metabolic constraints faced by immune and stromal cells in comparison to cancer cells, and how these limitations affect therapeutic outcomes, remain poorly understood. Here, we introduce Dual Ribosome Profiling (DualRP), a method that allows for simultaneous analysis of translation and identification of ribosome stalling, revealing amino acid shortages in different cell types within tumors. Using DualRP, we uncover that interactions between cancer cells and fibroblasts trigger an inflammatory response, mitigating amino acid limitations during glucose starvation. In immunocompetent mouse models, we observe that immune checkpoint blockade therapy induces serine and glycine restrictions specifically in T cells, but not in cancer cells. We further demonstrate that these amino acids are essential for optimal T cell function bothin vitroandin vivo, highlighting their critical role in effective immunotherapy. Our findings show that therapeutic interventions create distinct metabolic demands across different tumor cell types, with nutrient availability significantly influencing the success of immunotherapy. DualRP’s ability to explore cell type-specific metabolic vulnerabilities offers a promising tool for advancing our understanding of tumor biology and improving therapeutic strategies.
Low-power microstructured atomic oven for alkaline-earth-like elements
Authors: Pick J. , Voß J. , Hirt S. , Kruse J. , Leopold T. , Schwarz R. , Klempt C.
Published: January 2025

Alkaline-earth-like elements play pivotal roles in advanced quantum sensing technologies, notably optical clocks, with unprecedented precision achieved in recent years. Despite remarkable progress, current optical-lattice clocks still face challenges in meeting the demanding size, weight, and power consumption constraints essential for space applications. Conventional atom sources, such as ovens or dispensers, require substantial heating power, which makes up a significant fraction of the overall power consumption of the system. Addressing this challenge, we present a microstructured atomic oven based on fused silica, designed for miniaturization and low-power operation. We characterize the oven by loading a magneto-optical trap with Yb evaporated from the oven and demonstrate operation with a loading rate above 108atoms/s for heating powers below 250 mW.

Published by the American Physical Society
2025