bluuebunny/crossref_metadata_2025 huggingface dataset:
An assessment of the state of conservation planning in Europe
Authors: Jung Martin , Alagador Diogo , Chapman Melissa , Hermoso Virgilio , Kujala Heini , O'Connor Louise , Schinegger Rafaela , Verburg Peter H. , Visconti Piero
Published: April 2024

Expanding and managing current habitat and species protection measures is at the heart of the European biodiversity strategy. A structured approach is needed to gain insights into such issues is systematic conservation planning, which uses techniques from decision theory to identify places and actions that contribute most effectively to policy objectives given a set of constraints. Yet culturally and historically determined European landscapes make the implementation of any conservation plans challenging, requiring an analysis of synergies and trade-offs before implementation. In this work, we review the scientific literature for evidence of previous conservation planning approaches, highlighting recent advances and success stories. We find that the conceptual characteristics of European conservation planning studies likely reduced their potential in contributing to better-informed decisions. We outline pathways towards improving the uptake of decision theory and multi-criteria conservation planning at various scales, particularly highlighting the need for (a) open data and intuitive tools, (b) the integration of biodiversity-focused conservation planning with multiple objectives, (c) accounting of dynamic ecological processes and functions, and (d) better facilitation of entry-points and co-design practices of conservation planning scenarios with stakeholders. By adopting and improving these practices, European conservation planning might become more actionable and adaptable towards implementable policy outcomes.

This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
The importance of regeneration processes on forest biodiversity in old-growth forests in the Pacific Northwest
Authors: Luu Hoang , Ris Lambers Janneke Hille , Lutz James A. , Metz Margaret , Snell Rebecca S.
Published: April 2024

Forest diversity is the outcome of multiple species-specific processes and tolerances, from regeneration, growth, competition and mortality of trees. Predicting diversity thus requires a comprehensive understanding of those processes. Regeneration processes have traditionally been overlooked, due to high stochasticity and assumptions that recruitment is not limiting for forests. Thus, we investigated the importance of seed production and seedling survival on forest diversity in the Pacific Northwest (PNW) using a forest gap model (ForClim). Equations for regeneration processes were fit to empirical data and added into the model, followed by simulations where regeneration processes and parameter values varied. Adding regeneration processes into ForClim improved the simulation of species composition, compared to Forest Inventory Analysis data. We also found that seed production was not as important as seedling survival, and the time it took for seedlings to grow into saplings was a critical recruitment parameter for accurately capturing tree species diversity in PNW forest stands. However, our simulations considered historical climate only. Due to the sensitivity of seed production and seedling survival to weather, future climate change may alter seed production or seedling survival and future climate change simulations should include these regeneration processes to predict future forest dynamics in the PNW.

This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
Using ancient sedimentary DNA to forecast ecosystem trajectories under climate change
Authors: Alsos Inger Greve , Boussange Victor , Rijal Dilli Prasad , Beaulieu Marieke , Brown Antony Gavin , Herzschuh Ulrike , Svenning Jens-Christian , Pellissier Loïc
Published: April 2024

Ecosystem response to climate change is complex. In order to forecast ecosystem dynamics, we need high-quality data on changes in past species abundance that can inform process-based models. Sedimentary ancient DNA (
sed
aDNA) has revolutionised our ability to document past ecosystems' dynamics. It provides time series of increased taxonomic resolution compared to microfossils (pollen, spores), and can often give species-level information, especially for past vascular plant and mammal abundances. Time series are much richer in information than contemporary spatial distribution information, which have been traditionally used to train models for predicting biodiversity and ecosystem responses to climate change. Here, we outline the potential contribution of
sed
aDNA to forecast ecosystem changes. We showcase how species-level time series may allow quantification of the effect of biotic interactions in ecosystem dynamics, and be used to estimate dispersal rates when a dense network of sites is available. By combining palaeo-time series, process-based models, and inverse modelling, we can recover the biotic and abiotic processes underlying ecosystem dynamics, which are traditionally very challenging to characterise. Dynamic models informed by
sed
aDNA can further be used to extrapolate beyond current dynamics and provide robust forecasts of ecosystem responses to future climate change.

This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
Towards a novel biosphere in 2300: rapid and extensive global and biome-wide climatic novelty in the Anthropocene
Authors: Ordonez Alejandro , Riede Felix , Normand Signe , Svenning Jens-Christian
Published: April 2024

Recent climate change has effectively rewound the climate clock by approximately 120 000 years and is expected to reverse this clock a further 50 Myr by 2100. We aimed to answer two essential questions to better understand the changes in ecosystems worldwide owing to predicted climate change. Firstly, we identify the locations and time frames where novel ecosystems could emerge owing to climate change. Secondly, we aim to determine the extent to which biomes, in their current distribution, will experience an increase in climate-driven ecological novelty. To answer these questions, we analysed three perspectives on how climate changes could result in novel ecosystems in the near term (2100), medium (2200) and long term (2300). These perspectives included identifying areas where climate change could result in new climatic combinations, climate isoclines moving faster than species migration capacity and current environmental patterns being disaggregated. Using these metrics, we determined when and where novel ecosystems could emerge. Our analysis shows that unless rapid mitigation measures are taken, the coverage of novel ecosystems could be over 50% of the land surface by 2100 under all change scenarios. By 2300, the coverage of novel ecosystems could be above 80% of the land surface. At the biome scale, these changes could mean that over 50% of locations could shift towards novel ecosystems, with the majority seeing these changes in the next few decades. Our research shows that the impact of climate change on ecosystems is complex and varied, requiring global action to mitigate and adapt to these changes. This article is part of the theme issue ‘Biodiversity dynamics and stewardship in a transforming biosphere’.

This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
Global indicators of the environmental impacts of invasive alien species and their information adequacy
Authors: Henriksen Marie V. , Arlé Eduardo , Pili Arman , Clarke David A. , García-Berthou Emili , Groom Quentin , Lenzner Bernd , Meyer Carsten , Seebens Hanno , Tingley Reid , Winter Marten , McGeoch Melodie A.
Published: April 2024

Monitoring the extent to which invasive alien species (IAS) negatively impact the environment is crucial for understanding and mitigating biological invasions. Indeed, such information is vital for achieving Target 6 of the Kunming–Montreal Global Biodiversity Framework. However, to-date indicators for tracking the environmental impacts of IAS have been either lacking or insufficient. Capitalizing on advances in data availability and impact assessment protocols, we developed environmental impact indicators to track realized and potential impacts of IAS. We also developed an information status indicator to assess the adequacy of the data underlying the impact indicators. We used data on 75 naturalized amphibians from 82 countries to demonstrate the indicators at a global scale. The information status indicator shows variation in the reliability of the data and highlights areas where absence of impact should be interpreted with caution. Impact indicators show that growth in potential impacts are dominated by predatory species, while potential impacts from both predation and disease transmission are distributed worldwide. Using open access data, the indicators are reproducible and adaptable across scales and taxa and can be used to assess global trends and distributions of IAS, assisting authorities in prioritizing control efforts and identifying areas at risk of future invasions.

This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
Future changes in society and climate may strongly shape wild large-herbivore faunas across Europe
Authors: Davoli Marco , Svenning Jens-Christian
Published: April 2024

Restoring wild communities of large herbivores is critical for the conservation of biodiverse ecosystems, but environmental changes in the twenty-first century could drastically affect the availability of habitats. We projected future habitat dynamics for 18 wild large herbivores in Europe and the relative future potential patterns of species richness and assemblage mean body weight considering four alternative scenarios of socioeconomic development in human society and greenhouse gas emissions (SSP1–RCP2.6, SSP2–RCP4.5, SSP3–RCP7.0, SSP5–RCP8.5). Under SSP1–RCP2.6, corresponding to a transition towards sustainable development, we found stable habitat suitability for most species and overall stable assemblage mean body weight compared to the present, with an average increase in species richness (in 2100: 3.03 ± 1.55 compared to today′s 2.25 ± 1.31 species/area). The other scenarios are generally unfavourable for the conservation of wild large herbivores, although under the SSP5–RCP8.5 scenario there would be increase in species richness and assemblage mean body weight in some southern regions (e.g. + 62.86 kg mean body weight in Balkans/Greece). Our results suggest that a shift towards a sustainable socioeconomic development would overall provide the best prospect of our maintaining or even increasing the diversity of wild herbivore assemblages in Europe, thereby promoting trophic complexity and the potential to restore functioning and self-regulating ecosystems.

This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
Predicting the responses of European grassland communities to climate and land cover change
Authors: Liu Chang , Van Meerbeek Koenraad
Published: April 2024

European grasslands are among the most species-rich ecosystems on small spatial scales. However, human-induced activities like land use and climate change pose significant threats to this diversity. To explore how climate and land cover change will affect biodiversity and community composition in grassland ecosystems, we conducted joint species distribution models (SDMs) on the extensive vegetation-plot database sPlotOpen to project distributions of 1178 grassland species across Europe under current conditions and three future scenarios. We further compared model accuracy and computational efficiency between joint SDMs (JSDMs) and stacked SDMs, especially for rare species. Our results show that: (i) grassland communities in the mountain ranges are expected to suffer high rates of species loss, while those in western, northern and eastern Europe will experience substantial turnover; (ii) scaling anomalies were observed in the predicted species richness, reflecting regional differences in the dominant drivers of assembly processes; (iii) JSDMs did not outperform stacked SDMs in predictive power but demonstrated superior efficiency in model fitting and predicting; and (iv) incorporating co-occurrence datasets improved the model performance in predicting the distribution of rare species.

This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
Soil properties constrain forest understory plant distributions along an elevation gradient
Authors: Ni Ming , Vellend Mark
Published: April 2024

Projections of spatial biodiversity dynamics under climate warming are often based on models including only climate variables, and when non-climatic factors (e.g. soil) are included, data are often at much coarser spatial resolutions than those experienced by plants. Field studies along elevation gradients permit the gathering of detailed soil data, while still covering a wide climatic gradient. Here, an intensive field survey of four spring forest herbs along an elevation gradient showed that soil properties had substantial impacts on the occurrence/abundance of all species, and that soil effects were more pronounced at higher elevations. For
Trillium erectum
and
Claytonia caroliniana
, very infrequent occurrences at high elevation were strongly associated with rare microsites with high pH or nutrients. In a seven-year transplant experiment with
T. erectum
, we found that individuals grew to much smaller sizes at high than low elevation, suggesting that environmental factors rather than dispersal limitation constrain the species' upper range limit, despite substantial warming in recent decades. Our study demonstrates that soil factors interact strongly with climate to determine plant range limits along climatic gradients. Unsuitable soils for plants at high elevations or latitudes may represent an important constraint on future plant migration and biodiversity change.

This article is part of the theme issue ‘Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere’.
Distinct genomic and immunologic tumor evolution in germlineTP53-driven breast cancers
Authors: Boruah Nabamita , Hoyos David , Moses Renyta , Hausler Ryan , Desai Heena , Le Anh N , Good Madeline , Kelly Gregory , Raghavakaimal Ashvathi , Tayeb Maliha , Narasimhamurthy Mohana , Doucette Abigail , Gabriel Peter , Feldman Michael J. , Park Jinae , Lopez de Rodas Miguel , Schalper Kurt A. , Goldfarb Shari B. , Nayak Anupma , Levine Arnold J. , Greenbaum Benjamin D. , Maxwell Kara N.
Published: April 2024

Pathogenic germlineTP53alterations cause Li-Fraumeni Syndrome (LFS), and breast cancer is the most common cancer in LFS females. We performed first of its kind multimodal analysis of LFS breast cancer (LFS-BC) compared to sporadic premenopausal BC. Nearly all LFS-BC underwent biallelic loss ofTP53with no recurrent oncogenic variants exceptERBB2(HER2) amplification. Compared to sporadic BC,in situand invasive LFS-BC exhibited a high burden of short amplified aneuploid segments (SAAS). Pro-apoptotic p53 target genesBAXandTP53I3failed to be up-regulated in LFS-BC as was seen in sporadic BC compared to normal breast tissue. LFS-BC had lower CD8+ T-cell infiltration compared to sporadic BC yet higher levels of proliferating cytotoxic T-cells. Within LFS-BC, progression fromin situto invasive BC was marked by an increase in chromosomal instability with a decrease in proliferating cytotoxic T-cells. Our study uncovers critical events in mutant p53-driven tumorigenesis in breast tissue.
Pseudomonas aeruginosasurface motility and invasion into competing communities enhances interspecies antagonism
Authors: Sánchez-Peña Andrea , Winans James B. , Nadell Carey D. , Limoli Dominique H.
Published: April 2024

Chronic polymicrobial infections involvingPseudomonas aeruginosaandStaphylococcus aureusare prevalent, difficult to eradicate, and associated with poor health outcomes. Therefore, understanding interactions between these pathogens is important to inform improved treatment development. We previously demonstrated thatP. aeruginosais attracted toS. aureususing type IV pili-mediated chemotaxis, but the impact of attraction onS. aureusgrowth and physiology remained unknown. Using live single-cell confocal imaging to visualize microcolony structure, spatial organization, and survival ofS. aureusduring coculture, we found that interspecies chemotaxis providesP. aeruginosaa competitive advantage by promoting invasion into and disruption ofS. aureusmicrocolonies. This behavior rendersS. aureussusceptible toP. aeruginosaantimicrobials. Conversely, in the absence of type IV pilus motility,P. aeruginosacells exhibit reduced invasion ofS. aureuscolonies. Instead,P. aeruginosabuilds a cellular barrier adjacent toS. aureusand secretes diffusible, bacteriostatic antimicrobials like 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO) into theS. aureuscolonies.P. aeruginosareduced invasion leads to the formation of denser and thickerS. aureuscolonies with significantly increased HQNO-mediated lactic acid fermentation, a physiological change that could complicate the effective treatment of infections. Finally, we show thatP. aeruginosamotility modifications of spatial structure enhance competition againstS. aureus. Overall, these studies build on our understanding of howP. aeruginosatype IV pili-mediated interspecies chemotaxis mediates polymicrobial interactions, highlighting the importance of spatial positioning in mixed-species communities.
Glenn circulation causes early and progressive shunting in a surgical model of pulmonary arteriovenous malformations
Authors: Wan Tina , Rousseau Henry , Mattern Carol , Tabor Madeline , Hodges Matthew R. , Ramchandran Ramani , Spearman Andrew D.
Published: April 2024

Background

Pulmonary arteriovenous malformations (PAVMs) universally develop in patients with single ventricle congenital heart disease (CHD). Single ventricle PAVMs have been recognized for over 50 years, yet they are poorly understood, and we lack any medical therapies. To improve our understanding of single ventricle PAVM initiation and progression, we developed a surgical rat model of Glenn circulation and characterized PAVM physiology over multiple time points.

Methods

Using adult rats, we performed a left thoracotomy and end-to-end anastomosis of the left superior vena cava to the left pulmonary artery (unilateral Glenn), or sham surgical control. To assess for PAVM physiology in the left lung, we quantified intrapulmonary shunting using two independent methods (bubble echocardiography and fluorescent microsphere injection) at 2 weeks, 2 months, and 6 months. Additionally, we performed arterial blood gas measurements to assess oxygenation and plethysmography to assess ventilation.

Results

We identified pathologic intrapulmonary shunting by bubble echocardiography as early as 2 weeks post-Glenn surgery, and shunting continued chronically at 2- and 6-months post-Glenn. Shunting also progressed over time, demonstrated by increased shunting of 10µm microspheres at 6 months. Shunting was accompanied by mildly decreased arterial oxygenation, but there were no differences in ventilation as quantified by plethysmography.

Conclusions

Our surgical animal model of unilateral Glenn circulation re-creates the clinical condition of single ventricle PAVMs with early and progressive intrapulmonary shunting. This model is poised to characterize single ventricle PAVM pathophysiology and lead to mechanistic and therapeutic discovery.

Graphic Abstract
Assessing the Impact of use of HIV self-testing on the incidence of HIV Infection in Nigeria: a systematic review and meta-analysis
Authors: Eleje George Uchenna , Emmanuel Godwin Omokhagbo , Akinsolu Folahanmi Tomiwa , Foláyan Morẹ́nikẹ́ Oluwátóyìn
Published: April 2024

Background

Human immunodeficiency virus (HIV) self-testing tool is a widely adopted tool in Nigeria. However, there is little known about its impact in reducing HIV infection rates in Nigeria. This review aims to assess the impact of the use of HIV self-testing on the incidence of HIV infections in the country.

Methods

This was a systematic review and meta-analysis. Studies conducted in Nigeria on HIV self- testing with or without comparison to other HIV tests were included. The primary outcomes considered were the detection rate of new HIV cases and the acceptability (uptake) rate for HIV self-testing. Secondary outcomes were the usability rate, repeat testing rate, willingness rate, awareness rate, incidence of social harm, and incidence of high-risk behaviour. Electronic databases (PubMed/Medline, Web of Science, Scopus, CINAHL, and Cochrane Library) and Google Scholar were searched for relevant studies. Searches were conducted till December 2, 2023. Pooled estimates were calculated using a random-effects model with the DerSimonian Laird method. Heterogeneity was analyzed using the I2test, and risk of bias was assessed with the Hoy and colleagues’ scale. Meta-analysis was conducted where possible. The protocol was registered with PROSPERO (CRD42023479752).

Results

Eight studies, encompassing 7,556 participants, met the inclusion criteria. The overall risk of bias for the included studies was adjudged low. The detection rate of HIV self-testing for new HIV cases was 25.78% (95% CI: 0.90-50.66, I2:100.0), acceptability (uptake) rate was 56.92% (95% CI: 26.54-87.30, I2:100.0), and repeat testing rate was 20.10% (95% CI: -11.44-51.65, I2:100.0). Usability rate, willingness rate, awareness rate, and incidence of high-risk behaviour were reported in one study respectively, with no information on the incidence of social harm. Sensitivity analysis was done, and subgroup analyses could not be estimated due to insufficient data.

Conclusions

The use of HIV self-testing test kits in Nigeria showed a high detection rate of new HIV cases, moderate acceptability, but low repeat testing rates. However, the evidence is limited. Larger, higher-quality studies are essential to explore the broader impact of HIV self-testing on reducing HIV incidence in Nigeria.
Evaluation of Cataract Surgery as a Cause of Astigmatism among Patients Undergoing Phacoemulsification and Extracapsular Cataract Extraction at KCMC Hospital
Authors: Malakibungu Suzo Ambindwile , Makupa Andrew , Makupa William
Published: April 2024

Background

Despite the advance of cataract surgery astigmatism still occur after cataract surgery due to several reasons these include the preparation and closure of the surgical wound, the choice of suture material, and both intraoperative and postoperative manipulations in Phacoemulsification and Extracapsular cataract Etraction.

Objectives

To evaluate cataract surgery as cause of astigmatisms among patients undergoing phacoemulsification and extracapsular cataract extraction at eye department in KCMC hospital from Sept 2022 to April 2023

Methods

It is a clinic-based, prospective cohort study. Keratometric values and demographic data were collected for eligible patients who had undergone phacoemulsification and Extracapsular Cataract Extraction using a non-contact Auto Refkeratometer BARK-80.

Results

A total of 215 patients were recruited for the study. There were 129 (60%) females and 86 (40%) males. The mean age was 67.481 (SD 10.79years). A total 110 patients had undergone phacoemulsification and 105 had undergone Extracapsular Cataract Extraction (ECCE). 189 (87.91%), had a magnitude greater or equal (≥) to 0.5 post OP astigmatism. The mean corneal astigmatism among all patients undergone ECCE were 2.29D (SD 1.41 D) and all undergone PHACO were 0.95D (SD 0.79 D). The mean astigmatism among patients who had cataract surgery done by specialist were 1.19D (SD 0.09 D) and 2.41D (SD 0.16 D) were done by residents There was no astigmatism in 7 patients (3.26%), with-the-rule (WTR) in 68 patients (31.63%), against-the-rule (ATR) in 112 patients (52.09%) and oblique astigmatism (OA) in 28 patients (13.02%). The tendency of a gradual change from with the rule (WTR) to against the rule (ATR) astigmatism was noted as the age advanced.

Conclusion

The present study reveals the magnitude of astigmatism is higher in patients underwent Extra Capsular Cataract Extraction than Phacoemulsification in eye department at KCMC hospital and pre-existing astigmatism is a cause of surgical induced astigmatism if pre- operative astigmatism correction is not taken into consideration.
Spatiotemporal transcriptomic profiling reveals the dynamic immunological landscape of alveolar echinococcosis
Authors: Ou Zhihua , Li Li , Ren Peidi , Zhou Ting-Ting , He Fan , Chen Jialing , Cai Huimin , Han Xiumin , Wu Yao-Dong , Li Jiandong , Li Xiu-Rong , Tan Qiming , Li Wenhui , Chen Qi , Zhang Nian-Zhang , He Xiuju , Chen Wei-Gang , Zhao Yanping , Sun Jiwen , Zhang Qian , Wu Yan-Tao , Liang Yingan , You Jie , Hu Guohai , Tian Xue-Qi , Liao Sha , Fu Bao-Quan , Chen Ao , Cai Xue-Peng , Yang Huanming , Wang Jian , Jin Xin , Xu Xun , Jia Wan-Zhong , Li Junhua , Yan Hong-Bin
Published: April 2024

Alveolar echinococcosis (AE) is caused by the invasive growth of the metacestodes ofEchinococcus multilocularis(E. multilocularis). The early diagnosis, management, and treatment of AE remains challenging. Herein, we integrated bulk RNA-seq, scRNA-seq, and ST technologies to reveal the immune characteristics both spatially and chronologically inE. multilocularisinfected mouse liver. An unprecedented high-resolution spatial atlas of theE. multilocularisinfection foci was obtained, revealing the pivotal role of neutrophils,Spp1+monocyte-derived macrophages (MoMFs), and fibroblasts in AE progression. We observed continuous recruitment of neutrophils and macrophages into the infected tissues, indicating prolonged immune stimulation by the growing metacestodes. However, their spatial distribution patterns and functions changed during the infection cause. At the early infection stage,Il1bhineutrophils aggregated in the lesion displayed the highest pattern-recognition receptor activity and may kill the metacestodes through NETosis, but their death in the infection foci might also trigger immune suppression. Meanwhile,Spp1+MoMFs attached to the protoscoleces to clear the infection. At the late infection stage, the neutrophils failed to infiltrate into the lesion although their continuous recruitment into the infected liver. Even though theSpp1+MoMFs enclosing the microcysts ofE. multilocularismay retain their pathogen-killing ability, they may also promote fibrosis and angiogenesis through interaction with fibroblasts. The pro- and anti-inflammatory phenotype balance of these immune cells may be associated with the transition of parasite control strategy from “active killing” to “negative segregation” by the host. Our findings identify key molecular traits involved in AE development, which may benefit the treatment of echinococcosis.
Compromised actin dynamics underlie the orofacial cleft in Baraitser-Winter Cerebrofrontofacial Syndrome with a variant inACTB
Authors: Tsujimoto Takayuki , Ou Yushi , Suzuki Makoto , Murata Yuka , Inubushi Toshihiro , Nagata Miho , Ishihara Yasuki , Yonei Ayumi , Miyashita Yohei , Asano Yoshihiro , Sakai Norio , Sakata Yasushi , Ogino Hajime , Yamashiro Takashi , Kurosaka Hiroshi
Published: April 2024

Craniofacial anomalies encompassing the orofacial cleft are associated with >30% of systemic congenital malformations. Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF) is a rare genetic disorder attributed to variants in the actin beta (ACTB) or actin gamma genes that are correlated with a range of craniofacial abnormalities, including cleft lip and/or palate. The underlying pathological mechanism of BWCFF remains elusive, and it is necessary to investigate the etiology of orofacial clefts in BWCFF.

In this study, we identified a missense variant (c.1043C>T: p.S348L) in theACTBgene from a patient with BWCFF and concomitant cleft lip and palate. Furthermore, we performed functional assessments of this variant using various disease models such as the MDCK cell line andXenopus laevis. These models revealed a compromised capacity of mutated ACTB to localize at the epithelial junction, consequently affecting the behavior of epithelial cells. Additionally, we made the noteworthy discovery that mutated ACTB exhibited an impaired ability to bind PROFILIN1, a critical factor in actin polymerization. This defective ability may contribute to the molecular etiology of aberrant epithelial cell adhesion and migration, resulting in orofacial cleft formation in BWCFF.

Author Summary

Advances in clinical sequencing have rapidly elucidated the genetic basis of rare diseases affecting multiple organs. In this study, we investigate the role of a variant in theACTBgene, which is fundamental to cell structure, in causing orofacial clefts in the Baraitser-Winter Cerebrofrontofacial Syndrome (BWCFF), known for its distinctive facial anomalies. Using epithelial cell lines and frog embryo models, we investigated the effects of theACTBgene alteration on cellular functions. Our results indicate that this genetic change disrupts the normal adhesion and movement of epithelial cells, processes that are critical for facial development. This research underscores the importance of theACTBgene in shaping the face and suggests new directions for future research, potentially informing the diagnosis and treatment of BWCFF and related conditions.
Automated live-cell single-molecule tracking in enteroid monolayers reveals transcription factor dynamics probing lineage-determining function
Authors: Walther Nike , Anantakrishnan Sathvik , Dailey Gina M. , Tjian Robert , Darzacq Xavier
Published: April 2024

Lineage transcription factors (TFs) provide one regulatory level of differentiation crucial for the generation and maintenance of healthy tissues. To probe TF function by measuring their dynamics during adult intestinal homeostasis, we established HILO-illumination-based live-cell single-molecule tracking (SMT) in mouse small intestinal enteroid monolayers recapitulating tissue differentiation hierarchiesin vitro. To increase the throughput, capture cellular features, and correlate morphological characteristics with diffusion parameters, we developed an automated imaging and analysis pipeline, broadly applicable to 2D culture systems. Studying two absorptive lineage-determining TFs, we find an expression level-independent contrasting diffusive behavior: While Hes1, key determinant of absorptive lineage commitment, displays a large cell-to-cell variability and an average fraction of DNA-bound molecules of ∼32%, Hnf4g, conferring enterocyte identity, exhibits more uniform dynamics and a bound fraction of ∼56%. Our results suggest that TF diffusive behavior can indicate the progression of differentiation and modulate earlyversuslate differentiation within a lineage.

Highlights

- Automated live-cell single-molecule tracking records hundreds of cells in enteroid monolayers

- Cellular diffusion clustering and morphological feature correlation reveals subpopulations

- Transcription factor dynamics regulate differentiation independent of expression level

- Hes1 and Hnf4g display contrasting dynamics assisting earlyvs.late absorptive differentiation
Microgliosis driven by palmitate exposure alters energy metabolism and extracellular vesicles release that impact behavior and systemic metabolism
Authors: De Paula Gabriela C. , Aldana Blanca , Battistella Roberta , Calle Rosalia Fernández , Bjure Andreas , Lundgaard Iben , Deierborg Tomas , Duarte João M. N.
Published: April 2024

Dietary patterns that include an excess of foods rich in saturated fat are associated with brain dysfunction. Although microgliosis has been proposed to play a key role in the development of brain dysfunction in diet-induced obesity (DIO), neuroinflammation with cytokine over-expression is often not always observed. Thus, mechanisms by which microglia contribute to brain impairment in DIO are uncertain. Using the BV2 cell model, we investigated the gliosis profile of microglia exposed to palmitate (200 µmol/L), a saturated fatty acid abundant in high-fat diet and in the brain of obese individuals. We observed that microglia respond to a 24-hour palmitate exposure with increased proliferation, and with a metabolic network rearrangement that favors energy production from glycolysis rather than oxidative metabolism, despite stimulated mitochondria biogenesis. In addition, while palmitate did not induce increased cytokine expression, it modified the protein cargo of released extracellular vesicles (EVs). When administered intra-cerebroventricularly to mice, EVs from palmitate-exposed microgliain vitroled to memory impairment, depression-like behavior, and glucose intolerance, when compared to mice receiving EVs from vehicle-treated microglia. We conclude that microglia exposed to palmitate can mediate brain dysfunction through the cargo of shed EVs.
Enabling Electric Field Model of Microscopically Realistic Brain
Authors: Qi Zhen , Noetscher Gregory M. , Miles Alton , Weise Konstantin , Knösche Thomas R. , Cadman Cameron R. , Potashinsky Alina R. , Liu Kelu , Wartman William A. , Nunez Ponasso Guillermo , Bikson Marom , Lu Hanbing , Deng Zhi-De , Nummenmaa Aapo R. , Makaroff Sergey N.
Published: April 2024

Modeling brain stimulation at the microscopic scale may reveal new paradigms for various stimulation modalities. We present the largest map to date of extracellular electric field distributions within a layer L2/L3 mouse primary visual cortex brain sample. This was enabled by the automated analysis of serial section electron microscopy images with improved handling of image defects, covering a volume of 250 × 140 × 90 μm3. The map was obtained by applying a uniform brain stimulation electric field at three different polarizations and accurately computing microscopic field perturbations using the boundary element fast multipole method.

We used the map to identify the effect of microscopic field perturbations on the activation thresholds of individual neurons. Previous relevant studies modeled a macroscopically homogeneous cortical volume. Our result shows that the microscopic field perturbations – an ‘electric field spatial noise’ with a mean value of zero – only modestly influence the macroscopically predicted stimulation field strengths necessary for neuronal activation. The thresholds do not change by more than 10% on average. Under the stated limitations and assumptions of our method, this result justifies the conventional theory of “invisible” neurons embedded in a macroscopic brain model for transcranial magnetic and transcranial electrical stimulation.

However, our result is solely sample-specific and largely neglects the effect of the microcapillary network. Furthermore, we only considered the uniform impressed field and a single- pulse stimulation time course.

Significance statement

This study is arguably the first attempt to model brain stimulation at the microscopic scale, enabled by automated analysis of modern scanning electron microscopy images of the brain. It concentrates on modeling microscopic perturbations of the extracellular electric field caused by the physical cell structure and is applicable to any type of brain stimulation.

Data availability statement

Post-processed cell CAD models (383, stl format), microcapillary CAD models (34, stl format), post-processed neuron morphologies (267, swc format), extracellular electric field and potential distributions at different polarizations (267x3, MATLAB format), *.ses projects files for biophysical modeling with Neuron software (267x2, Neuron format), and computed neuron activating thresholds at different conditions (267x8, Excel tables, without the sample polarization correction from Section 2.8) are made available online throughBossDB, a volumetric open-source database for 3D and 4D neuroscience data.
Bacttle: a microbiology educational board game for lay public and schools
Authors: Miguel Trabajo Tania , Dorcey Eavan , van der Meer Jan Roelof
Published: April 2024

1.

Inspired by the positive impact of serious games on science understanding and motivated by personal interests in scientiﬁc outreach, we developed ‘Bacttle’, an easy-to-play microbiology board game with adaptive difficulty, targeting any player from 7 years old onward. Bacttle addresses both the lay public and teachers for use in classrooms as a way of introducing microbiology concepts.

The layout of the game and its mechanism are the result of multiple rounds of trial, feedback and re-design. The ﬁnal version consists of a deck of cards, a 3D-printed board and tokens (with a paper-based alternative), with all digital content open source. Players in Bacttle take on the character of a bacterial species. The aim for each species is to proliferate under the environmental conditions of the board and the interactions with the board and with other players, which vary as the play evolves. Players start with a given number of lives that will increase or decrease based on the traits they play for different environmental scenarios. Such bacterial traits come in the form of cards that can be deployed strategically.

In order to assess the impact of the game on microbiological knowledge, we scored differences in the understanding of general concepts before and after playing the game. We assessed a total of 169 visitors at two different university open day science fairs. Players were asked to ﬁll a brief survey before and after the game with questions targeting conceptual advances. Results show that Bacttle increases general microbiology knowledge on players as young as 5 years old, and with the highest impact on those who have noa priorimicrobiology comprehension.
Hexokinase 2 expression in apical enterocytes correlates with inflammation severity in patients with inflammatory bowel disease
Authors: Weber-Stiehl Saskia , Taubenheim Jan , Järke Lea , Röcken Christoph , Schreiber Stefan , Aden Konrad , Kaleta Christoph , Rosenstiel Philip , Sommer Felix
Published: April 2024

Background

Inflammation is characterized by a metabolic switch promoting glycolysis and lactate production. Hexokinases (HK) catalyze the first reaction of glycolysis and inhibition of epithelial HK2 protected from colitis in mice. HK2 expression has been described as elevated in patients with intestinal inflammation, however there is conflicting data from few cohorts especially with severely inflamed individuals, thus systematic studies linking disease activity with HK2 levels are needed.

Methods

We examined the relationship between HK2 expression and inflammation severity using bulk transcriptome data derived from the mucosa of thoroughly phenotyped patients suffering from intestinal inflammation of two independent cohorts. Analyzing publicly available single cell RNA sequencing data and performing immunofluorescence on colonic biopsies of unrelated patients with intestinal inflammation confirmed the RNA-based findings on cellular and protein level.

Results

HK2 expression gradually increased from mild to intermediate inflammation, yet strongly declined at high inflammation scores. Expression of epithelial marker genes also declined at high inflammation scores, whereas that of candidate immune marker genes increased, indicating a cellular remodeling of the mucosa during inflammation with an infiltration of HK2-negative immune cells and a loss of the apical epithelium – the main site of HK2 expression. Normalizing for the enterocyte loss clearly identified epithelial HK2 expression as gradually increasing with disease activity and remaining elevated at high inflammation scores. HK2 protein expression was mostly restricted to brush border enterocytes and these cells along with HK2 levels vanished with increasing disease severity.

Conclusions

Our findings clearly define dysregulated epithelial HK2 expression as an indicator of disease activity in intestinal inflammation and suggest targeted HK2-inhibition as a potential therapeutic avenue.
Comparative metagenomic profiling of seed-borne microbiomes in a landrace and a hybrid maize variety
Authors: Henaut-Jacobs Sarah , Cyríaco Beatriz Elisa Barcelos , Pedrosa-Silva Francisnei , Olivares Fabio Lopes , Venancio Thiago Motta
Published: April 2024

The plant seed-borne microbiome comprises microorganisms vertically inherited from the mother plant. This microbiome is often linked to early-life protection and seedling growth promotion. Here, we compare the seed-borne bacteriomes of a commercial hybrid and a landrace maize variety. The landrace variety displays a more diverse seed-borne microbiome, featuring a variety of taxa across samples. In contrast, the microbiome of the hybrid variety is less diverse and more uniform across samples. Although both microbiomes lack a functional nitrogen fixation apparatus, we found a remarkably distinct presence of genes associated with phytohormone production and phosphate solubilization, particularly in the landrace variety. In addition, we recovered 18 metagenome-assembled genomes (MAGs), including four from potentially novel species. Collectively, our results allow a better understanding of the contrasting diversity between maize varieties and open important perspectives for designing synthetic microbial communities for agroecosystems.
The interplay of recombination landscape, a transposable element and population history in European populations ofChironomus riparius
Authors: Pettrich Laura C. , King Robert , Field Linda M. , Waldvogel Ann-Marie
Published: April 2024

Genome resolution is often constrained for non-model species. This can be challenging for population genomic studies as estimations are highly dependent on the quality of the reference genome. This is the case for population history inferences where accuracy relies on the correct detection of single-nucleotide polymorphisms (SNPs) and accurate recombination rates. Here, we utilize a novel long-read genome assembly ofChironomus ripariuswith high resolution at a chromosome-scale and reanalyse Illumina resequencing data of five European populations. With the model MSMC2, new population demographies were inferred and compared to an older study based on a fragmented genome. Assembly contiguity and completeness led to an increase in accuracy of past demography, suggesting the onset of divergence of an ancestral population between late Pleistocene and early Holocene. These estimates are additionally supported by paleotemperature data, which reveal significant climate shifts in Central Europe during these times. Recombination severely influences population history estimates. With the new reference genome, it was possible to resolve the recombination landscape on the genome-wide scale across different populations using the tool iSMC. Recombination and the dispersal of transposable elements (TEs) in the genome are suspected to influence each other. One TE, known asCla-element, is suspected to be involved in the divergence of the differentC. ripariuspopulations. As it seems to be highly dynamic in the genome, its potential impact on the recombination landscape was explored. No global pattern could be detected which demonstrated a higher resistance of the recombination landscape to the impact of repetitive elements on genome integrity.
Three's Company: Anthropogenic factors shape co-occurrence in a meso-carnivore community in a semi-arid shared landscape of western India
Authors: Ganguly Divyajyoti
Published: April 2024

1. Human modification of natural landscapes accelerates species extinctions, promotes biological invasions, coerce range shifts, and restructure biotic communities. Mammalian meso-carnivores, considered sentinels of human-use landscapes, may experience increased mortality through road collisions and interactions with free-ranging dogs. Yet they may also benefit through resource subsidisation and decreased competition with larger carnivores. Our understanding of meso-carnivore community structure in modified ecosystems remain severely limited. 2. We examined a meso-carnivore community comprising golden jackal Canis aureus, jungle cat Felis chaus, Indian fox Vulpes bengalensis and desert cat Felis lybica ornata in a semi-arid landscape of Kachchh, western India. First, we mapped their potential habitats and the extent of fragmentation as a measure of vulnerability. We then assessed spatial, temporal and fine-scale spatio-temporal co-occurrence and responses to anthropogenic influences in the meso-carnivore community. We used a combination of camera-trapping and indirect sign surveys within an occupancy modelling framework to generate insights on species space-use and interactions. 3. The most fragmented habitat, open savanna, was positively associated with the occurrence of golden jackal, Indian fox and desert cat. Golden jackal spatially co-occurred with jungle cat and Indian fox with desert cat. Indian fox and desert cat showed spatial avoidance of golden jackal and jungle cat. Meso-carnivores did not show any spatial responses to free-ranging dogs, but showed varied responses to human infrastructure, i.e., settlements, roads and wind turbines, generally co-occurring less with each other in areas with high anthropogenic influence. 4. Spatially co-occurring meso-carnivores also overlapped substantially in the temporal dimension. Golden jackal and jungle cat showed high temporal overlap with free-ranging dogs, while Indian fox and desert cat appeared to avoid them. Temporally overlapping species generally showed fine-scale spatio-temporal aggregation. 5. Our results reveal species-specific responses to anthropogenic factors in the meso-carnivore community, often increasing overlap across space and time in a resource restricted landscape. Future loss of native savanna habitats and an increasing human footprint can elicit competition driven loss of sensitive species leading to homogenization of the meso-carnivore community. Our findings highlight the importance of considering species-specific responses as well the complex interplay amongst species to conserve multi-carnivore systems across shared, resource-constrained landscapes.
Application of tissue-scale tension to avian epitheliain vivoto study multiscale mechanics and inter-germ layer coupling
Authors: Oikonomou Panagiotis , Calvary Lisa , Cirne Helena C. , Welch Andreas E. , Durel John F. , Powell Olivia , Kim Kwantae , Nerurkar Nandan L.
Published: April 2024

As cross-disciplinary approaches drawing from physics and mechanics have increasingly influenced our understanding of morphogenesis, the tools available to measure and perturb physical aspects of embryonic development have expanded as well. However, it remains a challenge to measure mechanical properties and apply exogenous tissue-scale forces in vivo, particularly for epithelia. Exploiting the size and accessibility of the developing chick embryo, here we describe a simple technique to quantitatively apply exogenous forces on the order of 1-100 N to the endodermal epithelium. To demonstrate the utility of this approach, we performed a series of proof-of-concept experiments that reveal fundamental and unexpected mechanical behaviors in the early chick embryo, including mechanotype heterogeneity among cells of the midgut endoderm, complex non-cell autonomous effects of actin disruption, and a high degree of mechanical coupling between the endoderm and adjacent paraxial mesoderm. To illustrate the broader utility of this method, we determined that forces on the order of 10 N are sufficient to unzip the neural tube during primary neurulation. Together, these findings provide basic insights into the mechanics of embryonic epithelia in vivo in the early avian embryo, and provide a useful tool for future investigations of how morphogenesis is influenced by mechanical factors.

Graphical Abstract

Summary Statement

A simple approach is devised to quantitatively apply tension to epithelia in vivo, and used to study endoderm mechanics in the deeloping chick embryo.