julilili42/papers huggingface dataset:
Emergence of multiple collective motility modes in a physical model of cell chains
2025-01-30

Collective cell migration underpins key (patho)physiological processes, ranging from embryonic development to wound healing and cancer metastasis. While notable progress has been made in elucidating mechanisms that drive collective cell motility, the classification remains incomplete. In this study, we focus on the migration patterns of small cell chains, specifically cohesive pairs of cells migrating after each other on flat surfaces. Experiments with Dictyostelium discoideum (Dd) cells, which typically display amoeboid motility, revealed two distinct motility modes in cell pairs: the individual contributor (IC) mode, where each cell generates its own traction force dipole, and the supracellular (S) mode, characterized by a single dipole. Intriguingly, the IC mode dominates in Dd pairs, but the S mode prevails in Madin-Darby canine kidney (MDCK) cell doublets, which typically undergo mesenchymal motility. This observation highlights an apparent discrepancy in emergent motility modes between cell types. To uncover the physical mechanisms driving these diverse motility modes, we developed a two-dimensional biophysical model incorporating mechanochemical details such as cell-cell adhesion, combined with membrane-cortex contractility, and cell-matrix adhesion. Our model could recapitulate many experimental observations; the IC mode emerged naturally in amoeboid doublets when both cells exerted similar traction stresses, while the S mode dominated with “stronger” leaders that essentially pull on trailers. In contrast, in our simulations, mesenchymal MDCK-like pairs largely migrated in supracellular arrangement (S mode), with traction stress patterns representative of a rear-drive system with a “pushy” trailer, rather than a front-drive system. Our findings also showed that increasing cell-matrix adhesion predisposes amoeboid cell chains to act autonomously (IC mode), but the chain’s motility mode was largely insensitive to changes in cell-cell adhesion parameters. Contrary to amoebas, MDCK-like cell chains showed a bias towards S mode when increasing cell-matrix adhesion and a preference on IC mode when increasing cell-cell adhesion. Extending the model to longer cell chains, we showcase the model’s applicability across scales, providing a foundation for exploring collective migratory behavior in other contexts.
Quantitative Enhancement of Arsenate Immobilization Induced by Vacancy Defects on Various Exposed Lattice Facets of Hematite
2025-01-31

Defects are common features in hematite that arise from deviations from the perfect mineral crystal structure. Vacancy defects have been shown to significantly enhance arsenate (As) immobilization by hematite. However, the contributions from vacancy defects on different exposed facets of hematite have not been fully quantified. In this study, hematite samples with various morphologies were pretreated with sodium borohydride (NaBH<sub>4</sub>) to generate oxygen vacancy defects (OVDs), analyzed quantitatively using extended X-ray absorption fine structure (EXAFS) and thermogravimetric analysis (TG). Batch experiments revealed that the OVDs on different exposed facets showed significant variations in improving arsenate adsorption, i.e., the quantitative enhancement of arsenate adsorption amount per unit OVD concentration (Δ<i>Q</i><sub>m</sub>/<i>C</i><sub>defect</sub>) followed the sequence of (110) facet (80.05 μmol/mmol<sub>def</sub>) > (001) facet (31.85 μmol/mmol<sub>def</sub>) > (012) facet (13.14 μmol/mmol<sub>def</sub>). The underlying mechanism by which OVDs affect arsenate adsorption across different exposed facets of hematite was studied. The results reveal that the tremendous improvement of arsenate adsorption caused by OVDs on the (110) facet compared to (001) and (012) facets was attributed to their stronger bonding strength of As to under-coordinated Fe atoms, thus significantly promoting the immobilization of arsenate. The findings of this study enhance our ability to precisely understand the migration and fate of As while also aiding in the design of highly efficient iron mineral materials for mitigating As pollution.
Cysteine-Directed Isobaric Labeling Combined with GeLC-FAIMS-MS for Quantitative Top-Down Proteomics
2025-01-31

The quantification of proteoforms, i.e., all molecular forms in which proteins can be present, by top-down proteomics provides essential insights into biological processes at the molecular level. Isobaric labeling-based quantification strategies are suitable for multidimensional separation strategies and allow for multiplexing of the samples. Here, we investigated cysteine-directed isobaric labeling by iodoTMT in combination with a gel- and gas-phase fractionation (GeLC-FAIMS-MS) for in-depth quantitative proteoform analysis. We optimized the acquisition workflow (i.e., the FAIMS compensation voltages, isolation windows, acquisition strategy, and fragmentation method) using a two-proteome mix to increase the number of quantified proteoforms and reduce ratio compression. Additionally, we implemented a mass feature-based quantification strategy in the widely used deconvolution algorithm FLASHDeconv, which improves and facilitates data analysis. The optimized iodoTMT GeLC-FAIMS-MS workflow was applied to quantitatively analyze the proteome of <i>Escherichia coli</i> grown under glucose or acetate as the sole carbon source, resulting in the identification of 726 differentially abundant proteoforms.
Lignin and Peptide Promote the Abundance and Activity of Arsenic Methylation Microbes in Paddy Soils
2025-01-31

Rice physiological straighthead disease is induced by microbially mediated arsenic methylation and usually regionally distributed in paddy soils. However, the biogeochemical mechanism underlying the geographic distribution of microbial communities harboring methylating genes (<i>arsM</i>) remains unclear. Herein, we revealed significant (<i>p</i> = 0.001) differences in the <i>arsM</i> communities in different regions of Chinese paddy soils at the continental scale. Moreover, a positive correlation between the diversity of <i>arsM</i> communities and the chemodiversity of soil dissolved organic matter (DOM) was revealed. Among the different DOM components, lignin- and peptide-like DOM are the most important DOM components impacting the abundance and diversity of <i>arsM</i> communities. Metatranscriptomic analyses of 18 selected paddy soil samples revealed that the expression of the <i>arsM</i> gene increased with increasing soil lignin and peptide contents. Compared with the control, the addition of lignin and peptide significantly (<i>p</i> < 0.05) increased the methylated As concentration in the incubated paddy soils. Communities harboring <i>arsM</i> genes belonging to the phyla <i>Chloroflexota</i>, <i>Verrucomicrobiota</i>, <i>Deltaproteobacteria</i>, <i>Thermodesulfobacteriota</i>, and <i>Ignavibacteriota</i> mostly dominated in paddy soils with relatively high lignin and peptide contents. This study highlights the correlation between the diversity of DOM and <i>arsM</i> communities in paddy soils and provides mechanistic information for soil arsenic contamination control and sustainable rice production.
Discontinuation of immune checkpoint inhibitors for reasons other than disease progression and the impact on relapse and survival of advanced melanoma patients. A systematic review and meta-analysis
2025-01-31

Background Despite durable responses achieved with Immune Checkpoint Inhibitors (ICIs), data about optimal duration of treatment, especially in the context of adverse events, remain scarce. Objective To systematically review the evidence concerning the impact of treatment discontinuation with ICIs for reasons other than progressive disease (PD) on relapse rates and survival of melanoma patients. Methods A systematic literature search was conducted in three electronic databases until July 2024. Studies referring to melanoma patients who ceased ICIs electively (i.e. due to complete response (CR), protocol completion or patient/physician’s wish) or due to treatment-limiting toxicities (TLTs) were selected. Relapse rates (RRs) post cessation, time to PD, rechallenge and disease control rate (DCR) after 2 nd course were the main outcomes. Random-effects models were preferred, and subgroup and sensitivity analyses were conducted to investigate possible sources of heterogeneity. Results 38 and 35 studies were included in qualitative and quantitative synthesis, respectively. From 2542 patients discontinued treatment with ICIs electively or due to TLTs, 495 experienced progression [number of studies (n)=34, RR 20.9%, 95%CI 17.1 – 24.7%, I 2 85%) and higher rates were detected in patients with TLTs compared to elective discontinuation. Mean time to PD was 14.26 months (n=18, mean time 14.26, 95%CI 11.54 – 16.98, I 2 93%) and was numerically higher in patients who ceased for CR compared to patients with TLTs. Treatment duration before cessation was not associated with risk and time to relapse, while mucosal melanomas and non-CR as BOR during treatment led to increased risk for relapse and shorter time to PD compared to other histologic subtypes or CR. Rechallenge with ICI resulted in 57.3% DCR and 28.6% pooled CR rates (n=22, CR rate 28.6%, 95%CI 17.1 – 40.2, I 2 68%). Heterogeneity among studies was high, but subgroup analysis based on type of ICI used (anti-CTL4 and anti-PD1 inhibitor or anti-PD1 monotherapy) and type of study (RCTs or observational studies), along with sensitivity analyses did not reveal significant alterations in results. Conclusion Discontinuation of ICIs in patients without progression is possible. Outcomes to rechallenge with ICIs may differ depending on the reason for discontinuation, but remains a considerable option. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD42024547792.
Paper and Pencil Design of Color-Pure Organic Emitters: The Curious Case of Xanthene Dyes
2025-01-31

The quest for color-pure emitters for multicolor bioimaging as well as for ultrahigh definition organic light-emitting diodes demands facile design concepts to avoid tedious synthetic or computational trial-and-error procedures. We have recently presented a simple recipe to construct color-pure blue emitters, which combines basic resonance structure and frontier molecular orbital treatments; this recipe applies to multiresonant type emitters and allows to enlarge the chemical space toward novel structural motifs. In the current work, we show that such fundamental considerations further apply to the structurally entirely different family of xanthene dyes. Opposite to the related polymethine dye family with small bond length alternation (BLA) in the ground and in the excited state (S<sub>0</sub>, S<sub>1</sub>), however, xanthene dyes display large BLA in S<sub>0</sub> and in S<sub>1</sub>, so that the overall change in BLA, Δ<sub>BL</sub>, is small. This gives equally rise to color-pure emission; the underlying reasons for this curious behavior are carved out in the current study. This generalization of the recipe in fact constitutes the desired "paper and pencil" design strategy, spanning now the whole visible range.
Multimetallic Half-Sandwich Complexes of the Rare-Earth Metals
2025-01-31

Multimetallic half-sandwich complexes of the paramagnetic lanthanides gadolinium, terbium, dysprosium, holmium, and erbium as well as of diamagnetic yttrium are readily accessible via AlMe<sub>4</sub>/halogenido exchange reactions of Cp*Ln(AlMe<sub>4</sub>)<sub>2</sub> with the mild halogenido transfer reagents Me<sub>3</sub>SiI and Me<sub>3</sub>GeX (Cp* = C<sub>5</sub>Me<sub>5</sub>; X = Br, Cl). Depending on the rare-earth-metal center and halogenido ion size, complexes with distinct structural motifs and nuclearities are obtained, including dimeric compounds [Cp*Ln(AlMe<sub>4</sub>)(μ<sub>2</sub>-Cl)]<sub>2</sub> for the smaller metal centers Ln = Ho, Er, iodido-bridged tetranuclear rings [Cp*Ln(μ<sub>2</sub>-I)<sub>2</sub>]<sub>4</sub> (Ln = Y, Tb, Dy, Ho, Er), and a heterobimetallic tetramethylaluminato-bridged gadolinium cluster [Cp*<sub>4</sub>Gd<sub>4</sub>I<sub>7</sub>(AlMe<sub>4</sub>)]<sub>2</sub>. The tetranuclear dysprosium complex [Cp*Dy(μ<sub>2</sub>-I)<sub>2</sub>]<sub>4</sub> shows single-molecule magnet (SMM) behavior in zero applied field with an effective energy barrier of 164(10) cm<sup>-1</sup>.
COVID-19 facial covering during outdoor recreation reflects historical disease prevalence and culture above and beyond governmental measures – A study in 53 countries
2025-01-31

The COVID-19 pandemic severely influenced human behavior due to governmental restrictions. In addition to administrative restrictions, other factors, like historical disease prevalence and culture might impact on recent behavior. The parasite stress theory of values and sociality predicts an influence of historical diseases on human culture and may be of important influence on current human behavioral responses towards the pandemic. To address the influence on behavior, we studied mask use in outdoor recreationists (N = 4863) from 53 cultures. Studying outdoor recreationists is advantageous because people have at least some choices over their mask use, and it is less strictly controlled. We hypothesize that pathogen prevalence and cultural values of a society predict mask usage above and beyond the simplistic explanation of the strength of the governmental pandemic-related restrictions. Our results indicate that societal variables, especially individualism, contribute to the mask use during leisure activities, with people from more individualistic societies reporting lesser mask usage. Further, historic pathogen prevalence has a significant influence on mask use, even when controlling for the stringency measures of the government, HDI and population density. Zoonotic disease richness, however, did not receive significance. A mediation model showed that historical pathogen prevalence had an indirect effect on mask use, via the two pathways collectivism-individualism and governmental regulations. The total effect size of pathogen prevalence on mask use was 0.61, and with 0.24 as direct, and 0.37 indirect effects. Our data fit into the parasite stress theory of values and sociality. Our results provide evidence that the governmental decisions and restrictions themselves are influenced by the historical pathogens.
TotalSegmentator MRI: Robust Sequence-independent Segmentation of Multiple Anatomic Structures in MRI
2025-02-01

TotalSegmentator MRI is an open-source, user-friendly tool that provides automatic, robust sequence-independent segmentations of major anatomic structures on MRI scans; the ready-to-use online tool is available at https://totalsegmentator.com .
Adiponectin reduces immune checkpoint inhibitor-induced inflammation without blocking anti-tumor immunity
2025-02-01

Immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitors (ICIs) cause morbidity and necessitate cessation of treatment. Comparing irAE treatments, we find that anti-tumor immunity is preserved in mice after extracorporeal photopheresis (ECP) but reduced with glucocorticosteroids, TNFα blockade, and α4β7-integrin inhibition. Local adiponectin production elicits a tissue-specific effect by reducing pro-inflammatory T cell frequencies in the colon while sparing tumor-specific T cell development. A prospective phase-1b/2 trial (EudraCT-No.2021-002073-26) with 14 patients reveals low ECP-related toxicity. Overall response rate for all irAEs is 92% (95% confidence interval [CI]: 63.97%-99.81%); colitis-specific complete remission rate is 100% (95% CI: 63.06%-100%). Glucocorticosteroid dosages could be reduced for all patients after ECP therapy. The ECP-adiponectin axis reduces intestinal tissue-resident memory T cell activation and CD4<sup>+</sup>IFN-γ<sup>+</sup> T cells in patients with ICI-induced colitis without evidence of loss of anti-tumor immunity. In conclusion, we identify adiponectin as an immunomodulatory molecule that controls ICI-induced irAEs without blocking anti-tumor immunity.
Recombinase polymerase amplification technology for point-of-care diagnosis of neglected tropical diseases
2025-02-01

Recombinase Polymerase Amplification (RPA) technology significantly advances the diagnostics of neglected tropical diseases (NTDs), providing rapid, isothermal, and minimally preparative testing ideally suited for under-resourced countries. This review critically assesses the current applications, limitations, and potential of RPA for detecting a broad spectrum of NTD pathogens, including viruses, bacteria, helminths, and fungi. The ability of RPA to operate under constant temperature conditions without the need for complex thermal cycling facilitates rapid pathogen detection within minutes, enhancing its utility for decentralized point-of-care testing in remote and underserved regions. RPA, however, faces limitations, including the labor-intensive and costly validation of primer design, especially for multiplex assays, and a susceptibility to nonspecific amplification. These challenges highlight the need for continuous refinement to ensure reliable and consistent performance across diverse environmental conditions. Despite these constraints, the scalability of RPA assays and their compatibility with portable detection platforms make them well-suited for deployment in field settings without access to traditional laboratory infrastructure. This review emphasizes the transformative potential of RPA in NTD diagnostics, enhancing accessibility, precision, and timeliness of interventions, ultimately contributing to improved global public health outcomes.
Eye saccades align optic flow with retinal specializations during object pursuit in freely moving ferrets
2025-02-01

During prey pursuit, how eye rotations, such as saccades, enable continuous tracking of erratically moving targets while enabling an animal to navigate through the environment is unknown. To better understand this, we measured head and eye rotations in freely running ferrets during pursuit behavior. By also tracking the target and all environmental features, we reconstructed the animal's visual fields and their relationship to retinal structures. In the reconstructed visual fields, the target position clustered on and around the high-acuity retinal area location, the area centralis, and surprisingly, this cluster was not significantly shifted by digital removal of either eye saccades, exclusively elicited when the ferrets made turns, or head rotations that were tightly synchronized with the saccades. Here, we show that, while the saccades did not fixate the moving target with the area centralis, they instead aligned the area centralis with the intended direction of travel. This also aligned the area centralis with features of the optic flow pattern, such as flow direction and focus of expansion, used for navigation by many species. While saccades initially rotated the eyes in the same direction as the head turn, saccades were followed by eye rotations countering the ongoing head rotation, which reduced image blur and limited information loss across the visual field during head turns. As we measured the same head and eye rotational relationship in freely moving tree shrews, rats, and mice, we suggest that these saccades and counter-rotations are a generalized mechanism enabling mammals to navigate complex environments during pursuit.
Cross‐Continental Shifts of Ecological Strategy in a Global Plant Invader
2025-02-01

ABSTRACT Aim Plant invasions are a global problem that requires studying plants and their environmental associations across native and introduced ranges. Location 2000 km transects in China, Europe and North America. Time Period June 2019–July 2020. Major Taxa Studied Japanese knotweed ( Reynoutria japonica ). Methods We surveyed 150 populations of Japanese knotweed, a noxious invader of the temperate zone, along 2000 km transects in native China and the introduced ranges of Europe and North America. Results We found that larger plants and denser populations in the introduced ranges were associated with shifts in leaf economy and chemical defences. Introduced knotweed populations had higher SLA but reduced leaf chlorophyll, lignin, C:N ratio and leaf toughness along with altered leaf tannins, flavonoids and alkaloids. We found three distinct multivariate knotweed phenotypes primarily in the introduced ranges, and two multivariate knotweed phenotypes mainly in native populations. Main Conclusions Decreased herbivore and pathogen impacts in introduced populations and changes in environmental associations indicate that enemy release and novel habitat conditions might have driven the emergence of novel ecological strategies in this global plant invader.
Tree Diversity Increases Carbon Stocks and Fluxes Above—But Not Belowground in a Tropical Forest Experiment
2025-02-01

ABSTRACT International commitments advocate large‐scale forest restoration as a nature‐based solution to climate change mitigation through carbon (C) sequestration. Mounting evidence suggests that mixed compared to monospecific planted forests may sequester more C, exhibit lower susceptibility to climate extremes and offer a broader range of ecosystem services. However, experimental studies comprehensively examining the control of tree diversity on multiple C stocks and fluxes above‐ and belowground are lacking. To address this gap, we leverage data from the Sardinilla experiment in Panama, the oldest tropical tree diversity experiment, which features a gradient of one‐, two‐, three‐ and five‐species mixtures of native tree species. Over 16 years, we measured multiple above‐ and belowground C stocks and fluxes, ranging from tree aboveground C, over leaf litter C production, to soil organic carbon (SOC). We show that tree diversity significantly increased aboveground C stocks and fluxes, with a 57% higher gain in aboveground tree C in five‐species mixtures compared to monocultures (35.7 ± 1.8 vs. 22.8 ± 3.4 Mg C ha −1 ) 16 years after planting. In contrast, we observed a net reduction in SOC (on average −11.2 ± 1.1 Mg C ha −1 across diversity levels) and no significant difference in SOC 3 stocks (the predominantly tree‐derived, i.e., C 3 plant‐derived SOC fraction) between five‐species mixtures and monocultures (13.0 ± 0.9 vs. 15.1 ± 1.3 Mg C ha −1 ). Positive tree diversity effects persisted despite repeated climate extremes and strengthened over time for aboveground tree growth. Structural equation models showed that higher tree growth in mixtures enhanced leaf litter and coarse woody debris C fluxes to the soil, resulting in a tightly linked C cycle aboveground. However, we did not observe significant links between above‐ and belowground C stocks and fluxes. Our study elucidates the mechanisms through which higher tree diversity bolsters the climate mitigation potential of tropical forest restoration. Restoration schemes should prioritize mixed over monospecific planted forests.
Standard Protocols for Characterising Primary and In Vitro‐Generated Human Hepatocytes
2025-02-01

ABSTRACT Hepatocyte‐like cells (HLCs) derived from pluripotent stem cells (PSCs) or direct reprogramming are an unlimited source of human hepatocytes for biomedical applications. HLCs are used to model human diseases, develop precise drugs and establish groundbreaking regenerative cell‐based therapies. Primary human hepatocytes are the gold standard for studying human liver biology and pathology. However, their widespread use is limited by their rapid dedifferentiation in vitro, reliance on transplant‐rejected donor organs, poor scalability and significant batch‐to‐batch variations. Therefore, high‐quality ‘off‐the‐shelf’ HLCs are needed to overcome those limitations. Basic stepwise differentiation protocols have been developed to generate HLCs from PSCs. To evaluate the quality of the in vitro generated products, HLCs have been phenotyped using various methods. This review discusses various biological assays and methods available for the robust evaluation of HLC quality, emphasising the importance of using 24‐h cultured primary human hepatocytes (PHHs) as a reference standard for comparison.