bluuebunny/crossref_metadata_2025 huggingface dataset:
Antenatal care attendance, intermittent preventive treatment in pregnancy and knowledge on malaria: A cross sectional study in a government and a private district Hospitals
Authors: Ahiabor Charity , Courtin David , Anyan William , Mama Atikatou , Frempong Naa Adjeley , Kusi Kwadwo A. , Ofori Michael F. , Adu Bright , Lawson Bernard W. , Anang Abraham K. , Ndam Nicaise T.
Published: May 2023

Ghana has made significant strides in maternal healthcare under the National Health Insurance Scheme, but more effort is required to achieve the Sustainable Development Goal 3.1 target of <70 deaths/100,000 live births from the current 308 deaths/100,000. This study sought to investigate knowledge about ANC, ANC attendance, knowledge about malaria and IPTp among pregnant women, visiting a government Hospital in Mafi-Adidome (a rural community) and a private Hospital in Battor-Dugame (a rural-urban community) in the Volta region (a high malaria endemic area in Ghana).

A total of 1295 consenting pregnant women participated in the study. Information on sociodemographic characteristics, knowledge about ANC, IPTp and knowledge about malaria were collected by questionnaire. Chi-square tests were used to compare proportions of variables across the two study sites.

Higher proportion (70.8%) of participants accessing Battor Catholic Hospital showed adequate knowledge about ANC than 38.1% in Adidome Government Hospital (X2(7) =105.11; p<0.001). Also, higher numbers (46.6%) in Battor Catholic Hospital showed adequate knowledge on the timing for IPTp administration than 21.1% in Adidome Government Hospital (X2(2) =83.37; p<0.001). Although knowledge about malaria was generally low (0–33.3%) at both health centres, high proportions of participants (>80%) possess and use mosquito bed nets for malaria prevention. A lower proportion (46.6%) of participants in Battor Catholic Hospital made the WHO recommended 4-7 visits compared to 50.2% participants in Adidome Government Hospital. Age, marital status, employment and education influenced utilization of antenatal and delivery services. More sensitization on the importance of ANC and hospital delivery is needed in the study areas.
Perceptions about male circumcision among HIV vaccine efficacy trial participants in Soweto, South Africa: a qualitative study
Authors: Sibiya Mbalenhle , Laher Fatima , Mulaudzi Mamakiri , Makhale Lerato M. , Salami Taibat , Hornschuh Stefanie , Tieu Hong-Van , Dietrich Janan J.
Published: May 2023

Male circumcision has both health benefits and significance to some cultures. We sought to understand perceptions about male circumcision as part of the HIV prevention toolkit among participants enrolled in a preventive HIV vaccine efficacy trial in South Africa. We conducted a qualitative study with 28 people aged 18-35 years old who self-reported that they were not living with HIV, provided informed consent, and who were participating in the HVTN 702 vaccine efficacy trial in Soweto. Using a semi-structured guide, we facilitated four focus group discussions (FGDs) stratified by age, gender, and sexual orientation. FGDs were audio-recorded, transcribed verbatim, translated into English, and thematically analysed. Four main themes emerged. (1) Everyone had accurate knowledge about what male circumcision is, and some participants stated that it partially reduces acquisition of HIV and sexually transmitted infections. (2) There was an emerging distrust of cultural circumcision because of perceived lack of transparency and adverse events. (3) There was a perception that circumcision boosted masculinity. (4) The choice to circumcise was influenced by parents, family, and female partners. In conclusion, the study found that young South African HIV vaccine trial participants accurately understand the HIV prevention benefits of male circumcision, but uptake decisions are embedded within a context that is informed by culture, sexuality and masculinity norms and values.
Defining and emulating target trials of the effects of postexposure vaccination using observational data
Authors: Boyer Christopher , Lipsitch Marc
Published: May 2023

Postexposure vaccination has the potential to prevent or modify the course of clinical disease among those exposed to a pathogen. However, due to logistical constraints, postexposure vaccine trials have been difficult to implement in practice. In place of trials, investigators have used observational data to estimate the effectiveness or optimal timing window for postexposure vaccines, but the relationship between these analyses and those that would be conducted in a trial is often unclear. Here, we define several possible target trials for postexposure vaccination and show how, under certain conditions, they can be emulated using observational data. We emphasize the importance of the incubation period and the timing of vaccination in trial design and emulation. As an example, we specify a protocol for postexposure vaccination against mpox and provide a step-by-step description of how to emulate it using data from a healthcare database or contact tracing program. We further illustrate some of the benefits of the target trial approach through simulation.
COVID-19 risk variant associations with chromatin remodelling, DNA maintenance and surfactant genes are infection dependent in the lung
Authors: Jaros Rachel K. , Golovina Evgeniia , O’Sullivan Justin M.
Published: May 2023

During viral infection the structure of host chromatin is modified. It is generally assumed that these chromatin modifications will affect variant-gene mapping, and therefore gene expression. What is not clear is how limitations imposed by host germline risk affect the expression changes that occur with infection induced chromatin remodelling. Critically, this lack of information extends to how germline variants associated with severe SARS-CoV-2 impact on tissue-specific gene expression changes in response to infection-induced chromatin conformation changes. Here we combined temporal chromatin conformation data from SARS-CoV-2 stimulated cells with a lung spatial-eQTL gene expression analysis to contextualise the functional effects and contributions of germline risk on the severe phenotypes observed in SARS-CoV-2. We identify changes in lung-specific SARS-CoV-2 risk variant-gene mapping across the infection time course. Our results provide evidence for infection-induced chromatin remodelling that impacts the regulation of genes associated with the severity of SARS-CoV-2 infection. The gene targets we identified are functionally involved in host chromatin modifications and maintenance and the expression of these genes is amplified by SARS-CoV-2-induced epigenetic remodelling. The effect of this remodelling includes transcriptional changes to gene targets such asSMARCA4, NCOR1, DNMT1, DNMT3a, DAXX, andPIAS4, all critical components of epigenetic control mechanisms and SARS-CoV-2 antiviral activity, along with several genes involved in surfactant metabolism. We show how severe-phenotype-associated eQTLs form and break in an infection time-course-dependent manner that mimics positive feedback loops connecting germline variation with the process of viral infection and replication. Our results provide a novel bridge between existing COVID-19 epigenetic research and demonstrate the critical role of epigenomics in understanding SARS-CoV-2-risk-associated gene regulation in the lung.
Single-cell RNA analysis reveals the cell atlas of human intracranial aneurysm and rupture-related inflammation features
Authors: Ji Hang , Li Yue , Sun Haogeng , Chen Ruiqi , Zhou Ran , Xiao Anqi , Yang Yongbo , Wang Rong , You Chao , Liu Yi
Published: May 2023

Background

Intracranial aneurysms (IA) is a common condition and may ultimately result in life-threatening hemorrhagic strokes. A precise understanding of the cellular and gene expression perturbations in human IA tissue may enlighten additional therapeutics for unruptured IA.

Methods

A total of 21,332 qualified cells were obtained from four cell-sparse ruptured and unruptured human IA tissues. Detailed cell atlas and dynamics, gene expression perturbations, and inflammation features were thoroughly investigated using multiple machine learning-based algorithms.

Results

Endothelial cells, smooth muscle cells (SMCs), fibroblasts and, for the first time, pericytes have been identified in human IA tissue. A significant proportion of immune cells are also identified, with the number of monocyte/macrophages and neutrophils being notably higher in ruptured IA. By leveraging external datasets, macrophages characterized by transcriptional activation of NF-κB and HIVEP2 is most strongly associated with IA rupture. Interestingly, the recruitment and activation of macrophages and their functional characteristics in terms of TNFα and chemokine production remain consistent between unruptured and ruptured IA.

Conclusions

This study provides insights into the pathophysiology and molecular underpinnings of the IA wall and may motivate novel therapeutic options for unruptured IA.
Neuronal damage and inflammatory biomarkers are associated with the affective and chronic fatigue-like symptoms due to end-stage renal disease
Authors: Al-Hakeim Hussein Kadhem , Al-Raheem Twaij Basim Abd , Al-Naqeeb Tabarek Hadi , Moustafa Shatha Rouf , Maes Michael
Published: May 2023

Background

Many biochemical, immunological, and neuropsychiatric changes are associated with end-stage renal disease (ESRD). Neuronal damage biomarkers such as glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), S100 calcium-binding protein B (S100B), ionized calcium-binding adaptor molecule-1 (IBA1), and myelin basic protein (MBP) are among the less-studied biomarkers of ESRD.

Aim

We examined the associations between these neuro-axis biomarkers, inflammatory biomarkers, e.g., C-reactive protein (CRP), interleukin (IL-6), IL-10, and zinc, copper, and neuropsychiatric symptoms due to ERSD.

Methods

ELISA techniques were used to measure serum levels of neuronal damage biomarkers in 70 ESRD patients, and 46 healthy controls.

Results

ESRD patients have higher scores of depression, anxiety, fatigue, and physiosomatic symptoms than healthy controls. Aberrations in kidney function tests and the number of dialysis interventions are associated with the severity of depression, anxiety, fibro-fatigue and physiosomatic symptoms, peripheral inflammation, nestin, and NFL. Serum levels of neuronal damage biomarkers (NFL, MBP, and nestin), CRP, and interleukin (IL)-10 are elevated, and serum zinc is decreased in ESRD patients as compared with controls. The neuronal damage biomarkers NFL, nestin, S100B and MBP are associated with the severity of one or more neuropsychiatric symptom domains. Around 50% of the variance in the neuropsychiatric symptoms is explained by NFL, nestin, S00B, copper, and an inflammatory index.

Conclusions

The severity of renal dysfunction and/or the number of dialysis interventions may induce peripheral inflammation and, consequently, neurotoxicity to intermediate filament proteins, astrocytes, and the blood-brain barrier, leading to the neuropsychiatric symptoms of ESRD.
A time-resolved meta-analysis of consensus gene expression profiles during human T-cell activation
Authors: Rade Michael , Böhlen Sebastian , Neuhaus Vanessa , Löffler Dennis , Blumert Conny , Köhl Ulrike , Dehmel Susann , Sewald Katherina , Reiche Kristin
Published: May 2023

Background

The coordinated transcriptional regulation of activated T-cells is based on the complex dynamic behavior of signaling networks. Given an external stimulus, T-cell gene expression is characterized by impulse and sustained patterns over the course. Here, we analyzed the temporal pattern of activation across different T-cell populations to develop consensus gene signatures for T-cell activation.

Methods

We applied a meta-analysis of anti-CD3/CD28 induced CD4+ T-cell activation kinetics of publicly available transcriptomewide time series using a random effects model. We used non-negative matrix factorization, an unsupervised deconvolution method, to infer changes in biological patterns over time. For verification and to further map a wider variety of the T-cell landscape, we performed a time series of transcriptome-wide RNA sequencing on activated blood T-cells. Lastly, we matched the identified consensus biomarker signatures to single-cell RNA sequencing (scRNA-Seq) data of autologous anti-CD19 chimeric antigen receptor (CAR) T-cells from 24 patients with large B cell lymphoma (LBCL) to characterize activation status of the cell product before infusion.

Results

We identified time-resolved gene expression profiles comprising 521 genes of up to 10 disjunct time points during activation and different polarization conditions. The gene signatures include central transcriptional regulators of T-cell activation, representing successive waves as well as sustained patterns of induction. They cover early, intermediate, and late response expression rates across multiple T-cell populations, thus defining consensus biomarker signatures for T-cell activation. Intermediate and late response activation signatures in CAR T-cell infusion products were correlated to immune effector cell-associated neurotoxicity syndrome.

Conclusion

In conclusion, we describe temporally resolved gene expression patterns across T-cell populations. These biomarker signatures are a valuable source for e.g., monitoring transcriptional changes during T-cell activation with a reasonable number of genes, annotating T-cell states in single-cell transcriptome studies or assessing dysregulated functions of human T-cell immunity.
Single-cell Mayo Map (scMayoMap): an easy-to-use tool for cell type annotation in single-cell RNA-sequencing data analysis
Authors: Yang Lu , Ng Yan Er , Sun Haipeng , Li Ying , Chini Lucas C.S. , LeBrasseur Nathan K. , Chen Jun , Zhang Xu
Published: May 2023

Single-cell RNA-sequencing (scRNA-seq) has become a widely used tool for both basic and translational biomedical research. In scRNA-seq data analysis, cell type annotation is an essential but challenging step. In the past few years, several annotation tools have been developed. These methods require either labeled training/reference datasets, which are not always available, or a list of predefined cell subset markers, which are subject to biases. Thus, a user-friendly and precise annotation tool is still critically needed. We curated a comprehensive cell marker database namedscMayoMapDatabaseand developed a companion R packagescMayoMap, an easy-to-use single cell annotation tool, to provide fast and accurate cell type annotation. The effectiveness ofscMayoMapwas demonstrated in 48 independent scRNA-seq datasets across different platforms and tissues.scMayoMapperforms better than the currently available annotation tools on all the datasets tested. Additionally, thescMayoMapDatabasecan be integrated with other tools and further improve their performance.scMayoMapandscMayoMapDatabasewill help investigators to define the cell types in their scRNA-seq data in a streamlined and user-friendly way.
Scalable Mesenchymal Stem Cells Enrichment from Bone Marrow Aspirate using Deterministic Lateral Displacement (DLD) Microfluidics Sorting
Authors: Kwan Zen Nicholas Tan , Kwek Kerwin Zeming , Leng Teo Kim , Loberas Mavis , Lee Jialing , Goh Chin Ren , Yang Da Hou , Oh Steve , Hoi Po James Hui , Cool Simon M. , Hou Han Wei , Han Jongyoon
Published: May 2023

The growing interest in regenerative medicine has opened new avenues for novel cell therapies using stem cells. Bone Marrow Aspirate (BMA) is an important source of stromal mesenchymal stem cells (MSCs). Conventional MSC harvesting from BMA relies on archaic centrifugation methods, often leading to poor yield due to osmotic stress, high centrifugation force, convoluted workflow, and long experimental time (∼ 2 – 3 hours). To address these issues, we have developed a scalable microfluidic technology based on Deterministic Lateral Displacement (DLD) for MSC isolation. This passive, label-free cell sorting method capitalizes on the morphological differences between MSCs and blood cells (leukocytes and RBCs) for effective separation using an inverted L-shaped pillar array. To improve throughput, we developed a novel portable multiplexed DLD system that can process 2.5 mL of raw BMA in 20 ± 5 minutes, achieving a 2-fold increase in MSC recovery compared to centrifugation methods. Taken together, we envision the developed DLD platform will enable fast and efficient isolation of MSCs from BMA for effective downstream cell therapy in clinical settings.
Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model
Authors: Bjørnstad Ole Vidhammer , Carrasco Manuel , Finne Kenneth , Winge Ingeborg , Askeland Cecilie , Arnes Jarle B. , Knutsvik Gøril , Kleftogiannis Dimitrios , Paulo Joao A. , Akslen Lars A. , Vethe Heidrun
Published: May 2023

Tumor neurogenesis, a process by which new nerves invade tumors, is a growing area of interest in cancer research. Nerve presence has been linked to aggressive features of various solid tumors, including breast and prostate cancer. A recent study suggested that the tumor microenvironment may influence cancer progression through recruitment of neural progenitor cells from the central nervous system. However, the presence of neural progenitors in human breast tumors has not been reported. Here, we investigate the presence of Doublecortin (DCX) and Neurofilament-Light (NFL) co-expressing (DCX+/NFL+) cells in patient breast cancer tissue using Imaging Mass Cytometry. To map the interaction between breast cancer cells and neural progenitor cells further, we created anin vitromodel mimicking breast cancer innervation, and characterized using mass spectrometry-based proteomics on the two cell types as they co- evolved in co-culture. Our results indicate stromal presence of DCX+/NFL+ cells in breast tumor tissue from a cohort of 107 patient cases, and that neural interaction contribute to drive a more aggressive breast cancer phenotype in our co-culture models. Our results support that neural involvement plays an active role in breast cancer and warrants further studies on the interaction between nervous system and breast cancer progression.
A multiscale theory for spreading and migration of adhesion-reinforced mesenchymal cells
Authors: Shu Wenya , Kaplan C. Nadir
Published: May 2023

We present a chemomechanical whole-cell theory for the spreading and migration dynamics of mesenchymal cells that can actively reinforce their adhesion to an underlying viscoelastic substrate as a function of its stiffness. Our multiscale model couples the adhesion reinforcement effect at the subcellular scale with the nonlinear mechanics of the nucleus-cytoskeletal network complex at the cellular scale to explain the concurrent monotonic area-stiffness and non-monotonic speed-stiffness relationships observed in experiments: We consider that large cell spreading on stiff substrates flattens the nucleus, increasing the viscous drag force on it. The resulting force balance dictates a reduction in the migration speed on stiff substrates. We also reproduce the experimental influence of the substrate viscosity on the cell spreading area and migration speed by elucidating how the viscosity may either maintain adhesion reinforcement or prevent it depending on the substrate stiffness. Additionally, our model captures the experimental directed migration behavior of the adhesion-reinforced cells along a stiffness gradient, known as durotaxis, as well as up or down a viscosity gradient (viscotaxis or anti-viscotaxis), the cell moving towards an optimal viscosity in either case. Overall, our theory explains the intertwined mechanics of the cell spreading, migration speed and direction in the presence of the molecular adhesion reinforcement mechanism.
Multi temporal multispectral UAV remote sensing allows for yield assessment across European wheat varieties already in tillering stage
Authors: Camenzind Moritz , Yu Kang
Published: May 2023

High throughput field phenotyping techniques employing multispectral cameras allow to extract a variety of variables and features to predict yield and yield related traits, but little is known about which types of multispectral features may allow to forecast yield potential in the early growth phase. In this study, we hypothesized that the best features for predicting yield in an early stage might be different from the best predictors for the late growth stages. Based on a variety testing trial of 19 European wheat varieties in 2021, multispectral images were taken on 19 dates ranging from tillering to harvest by an unmanned aerial vehicle measuring reflectance in five bands, including visible bands, Red-edge and the near-infrared (NIR). Orthomosaic images were created, and then the single band reflectances, vegetation indices (VI) and texture features (TF) based on a gray level correlation matrix (GLCM) were extracted. We evaluated the performance of these three types of features for yield prediction and classification at different growth stages by, i) using features on each of the measurement dates, ii) smoothing features across the 19 dates, and iii) combining features across the directly adjacent dates, in combination with the random forest models. Our results showed that, for most features, measurements at the flowering stage showed the best performance and the Red reflectance was able to predict yield with a RMSE of 47.4 g m-2(R2= 0.63), the best VI was NDRE predicting yield with a RMSE of 47.9 g m-2(R2= 0.63), the best TF was contrast predicting yield with a RMSE of 57.2 g m-2(R2= 0.46) at the booting stage. Combining dates improved yield prediction in all dates and made the prediction errors more stable across dates. Rather than the Red-edge band, visible bands especially the Red band enabled to distinguish between the high- and low-yielding varieties already in the tillering stage, with a total accuracy of 76.7%. The study confirms our hypothesis and further implies that, in the early stages, the visible bands may be more effective than Red-edge bands in assessing the yield potential in a range of testing varieties.
Impacts of global food supply on biodiversity via land use and climate change
Authors: Boakes Elizabeth H , Dalin Carole , Etard Adrienne , Newbold Tim
Published: May 2023

Land-use change is currently the greatest driver of biodiversity change, with climate change predicted to match or surpass its impacts by mid-century. The global food system is a key driver of both these anthropogenic pressures, thus the development of sustainable food systems will be critical to halting and reversing biodiversity loss. Previous studies of the biodiversity footprint of food tend to focus on land use alone. We use the multi-regional input-output model EXIOBASE to estimate the impacts of biodiversity embedded within the global food system. We build on prior analyses, calculating the impacts of both agricultural land-use and greenhouse gas (GHG) emission footprints for the same two metrics of biodiversity: local species richness and rarity-weighted species richness. Our biodiversity models capture regional variation in the sensitivity of biodiversity both to land-use differences and to climate change. We find that the footprint of land area does not capture the biodiversity impact embedded within trade that is provided by our metric of land-driven species richness change, and that our metric of rarity-weighted richness places a greater emphasis on the biodiversity costs in Central and South America. We find that methane emissions are responsible for 70% of the overall GHG-driven biodiversity footprint and that, in several regions, emissions from a single year’s food production cause biodiversity loss equivalent to 2% or more of that region’s total historic land use. The measures we present are simple to calculate and could be incorporated into decision making and environmental impact assessments by governments and businesses.
Rediversification Following Ecotype Isolation Reveals Hidden Adaptive Potential
Authors: Ascensao Joao A , Denk Jonas , Lok Kristen , Yu QinQin , Wetmore Kelly M , Hallatschek Oskar
Published: May 2023

Microbial communities play a critical role in ecological processes, and their diversity is key to their functioning. However, little is known about if communities can regenerate ecological diversity following species removal or extinction, and how the rediversified communities would compare to the original ones. Here we show that simple two-ecotype communities from theE. coliLong Term Evolution Experiment (LTEE) consistently rediversified into two ecotypes following the isolation of one of the ecotypes, coexisting via negative frequency-dependent selection. Communities separated by more than 30,000 generations of evolutionary time rediversify in similar ways. The rediversified ecotype appears to share a number of growth traits with the ecotype it replaces. However, the rediversified community is also different compared to the original community in ways relevant to the mechanism of ecotype coexistence, for example in stationary phase response and survival. We found substantial variation in the transcriptional states between the two original ecotypes, whereas the differences within the rediversified community were comparatively smaller, but with unique patterns of differential expression. Our results suggest that evolution may leave room for alternative diversification processes even in a maximally reduced community of only two strains. We hypothesize that the presence of alternative evolutionary pathways may be even more pronounced in communities of many species, highlighting an important role for perturbations, such as species removal, in evolving ecological communities.
The glucocorticoid dexamethasone impairs the expression of anti-viral mediators in activated macrophages by inhibiting both expression and function of interferon β
Authors: O’Neil John D , Bolimowska Oliwia O , Clayton Sally A , Tang Tina , Daley Kalbinder K , Lara-Reyna Samuel , Warner Jordan , Martin Claire S , Mahida Rahul Y , Hardy Rowan S , Arthur J Simon C , Clark Andrew R
Published: May 2023

Glucocorticoids potently inhibit expression of many inflammatory mediators, and have been very widely used to treat both acute and chronic inflammatory diseases for more than seventy years. However, they can have several unwanted effects, amongst which immunosuppression is one of the most common. Here we investigated effects of the synthetic glucocorticoid dexamethasone on the responses of primary mouse bone marrow-derived macrophages to the pro-inflammatory agonist lipopolysaccharide (LPS). At the mRNA level, dexamethasone inhibited the LPS-induced expression of more than 100 genes that are involved in cell-intrinsic defence against viral pathogens. Expression of most of the corresponding proteins was also reduced by dexamethasone. This antiviral disarmament occurred at two distinct levels. First, dexamethasone strongly and dose-dependently inhibited the expression of the type I interferon IFNβ by LPS-activated macrophages. IFNβ mediates an autocrine positive feedback loop in LPS-treated macrophages, promoting the expression of antiviral genes and other interferon-stimulated genes. Hence reduction of IFNβ expression contributes to impaired expression of antiviral genes. Dexamethasone also acted downstream of IFNβ to inhibit expression of a subset of interferon-regulated genes. We tested a number of hypotheses based on previous publications, but found that no single mechanism could account for more than a small fraction of the broad suppressive impact of dexamethasone on macrophage type I interferon signaling, underlining the complexity of this pathway. Preliminary experiments indicated that dexamethasone exerted similar inhibitory effects on primary human monocyte-derived or alveolar macrophages.
Cancer associated fibroblast subtypes modulate the tumor-immune microenvironment and are associated with skin cancer malignancy
Authors: Forsthuber Agnes , Aschenbrenner Bertram , Korosec Ana , Jacob Tina , Annusver Karl , Krajic Natalia , Kholodniuk Daria , Frech Sophie , Zhu Shaohua , Purkhauser Kim , Lipp Katharina , Werner Franziska , Nguyen Vy , Griss Johannes , Bauer Wolfgang , Soler Cardona Ana , Weber Benedikt , Weninger Wolfgang , Gesslbauer Bernhard , Staud Clement , Nedomansky Jakob , Radtke Christine , Wagner Stephan N. , Petzelbauer Peter , Kasper Maria , Lichtenberger Beate M.
Published: May 2023

Cancer-associated fibroblasts (CAFs) play a key role in cancer progression and treatment outcome. This study dissects the yet unresolved intra-tumoral variety of CAFs in three skin cancer types — Basal Cell Carcinoma, Squamous Cell Carcinoma, and Melanoma — at molecular and spatial single-cell resolution. By integral analysis of the fibroblasts with the tumor microenvironment, including epithelial, mesenchymal, and immune cells, we characterize three distinct CAF subtypes: myofibroblast-like RGS5+ CAFs, matrix CAFs (mCAFs), and immunomodulatory CAFs (iCAFs). Notably, large cohort tissue analysis reveals marked shifts in CAF subtype patterns with increasing malignancy. Two CAF types exhibit immunomodulatory capabilities via distinct mechanisms. mCAFs synthesize extracellular matrix and have the ability to ensheath tumor nests, potentially limiting T cell invasion in low-grade tumors. In contrast, iCAFs are enriched in late-stage tumors, especially infiltrative BCC and high-grade melanoma, and express unexpectedly high mRNA and protein levels of cytokines and chemokines, pointing to their integral role in immune cell recruitment and activation. This finding is further supported by our observation that in vitro exposure of primary healthy fibroblasts to skin cancer cell secretomes induces an iCAF-like phenotype with immunomodulatory functions. Thus, targeting CAF variants, particularly the immunomodulatory iCAF subtype, holds promise for improved efficacy of immunotherapy in skin cancers.
Connexin 43 mediated collective cell migration is independent of Golgi orientation
Authors: Sharma Madhav , Mukherjee Suvam , Shaw Archana Kumari , Mondal Anushka , Behera Amrutamaya , Das Jibitesh , Bose Abhishek , Sinha Bidisha , Das Sarma Jayasri
Published: May 2023

Cell migration is vital for multiple physiological functions and is involved in the metastatic dissemination of tumour cells in various cancers. For effective directional migration, cells often reorient their secretory traffic towards the leading edge by reorienting the Golgi apparatus. However, conflicting results on the positioning of the Golgi relative to the migrating cell raise questions about its regulation. Herein, we address the role of gap junction protein Connexin 43, which connects cells allowing the direct exchange of molecules and also controls the distribution of microtubules. We utilized HeLa WT (wild-type cells lacking Connexin 43) and HeLa 43 cells (stably expressing Connexin 43). We found that functional Connexin 43 channels affected Golgi morphology and reduced the ability of reorientation of Golgi (towards the leading edge) during cell migration. Although Connexin 43 also reduced migration velocity, the front displayed enhanced coherence in movement, implying an augmented collective nature of migration compared to HeLa WT cells lacking the cell-cell connectivity evidenced in HeLa 43. The increase in vimentin and basal actin in HeLa 43 shows that Connexin 43 expression alters the cytoskeleton. Non-invasive measurement of basal membrane height fluctuations revealed that HeLa 43 had a lower membrane tension and a more uniform intra- and inter-cellular distribution than HeLa WT, similar to their coherence in migration. We, therefore, propose that the reduced Golgi reorientation in HeLa 43 might be linked to lesser dependence on directed secretory trafficking, which is believed to be required to buffer the increasing tension caused by migration.
Long term trend and short-term dynamics of a willow grouse population
Authors: Willebrand Tomas , Kleiven Eivind Flittie , Willebrand Maria Hörnell , Brittas Rolf
Published: May 2023

Willow ptarmiganLagopus lagopusand rock ptarmiganLagopus mutus,are abundant in Arctic and tundra regions, but negative trends in their distribution have recently been reported. Rapid climate change has been identified as the cause of this decline. Willow ptarmigan is adapted to harsh winter conditions, and winters with less snow could increase vulnerability when the ground is snow-free. In this study, we used a hierarchical state-space model to analyze 139 km line transects in mid-Sweden over 46 years. We assessed long-term trends in the adult population and estimated the effects of breeding success and climate on short-term changes. Contrary to our expectations, the adult population did not exhibit a negative trend. Breeding success was significantly positive for adult population change, but late spring had a significant negative effect on population change. The number of snow-free days in spring and autumn increased during the study; however, neither variable had a negative effect on adult population change. The adult willow ptarmigan followed a pattern of a stationary population under the influence of both stochastic and density-dependent factors, and changes in adults showed a negative density dependence. Our study area is in the southern range of the tundra, and we suggest that the stable dynamics of the adult population can be explained by a diverse predator assemblage that makes it impossible for the population to escape a top-down regulation.
Supporting diamond open access journals. Interest and feasibility of direct funding mechanisms
Authors: Dufour Quentin , Pontille David , Torny Didier
Published: May 2023

More and more academics and governements consider that the open access model based on Article Processing Charges (APC) is problematic, not only due to the inequalities it generates and reinforces, but also because it has become unsustainable and even opposed to open access values. They consider that scientific publishing based on a model where both authors and readers do not pay – the so-called Diamond, or non-APC model – should be developed and supported. However, beyond the display of such a support on an international scale, the landscape of Diamond journals is rather in the form of loosely connected archipelagos, and not systematically funded. This article explores the practical conditions to implement a direct funding mechanism to such journals, that is reccurent money provided by a funder to support the publication process. Following several recommendations from institutional actors in the open access world, we consider the hypothesis that such a funding would be fostered by research funding organizations (RFOs), which have been essential to the expansion of the APC model, and now show interest in supporting other models. Based on a questionnaire survey sent to more thant 1000 Diamond Open Access journals, this article analyzes their financial needs, as well as their capacity to interact with funders. It is structured around four issues regarding the implementation of a direct funding model : Do Diamond journals really make use of money, and to what end ? Do they need additional money? Are they able to engage monetary transactions? Are they able to meet RFOs’ visibility requirements? We show that a majority of OA Diamond journals could make use of a direct funding mechanism with certain adjustments. We conclude on the challenges that such a financial stream would spur.
HiPhase: Jointly phasing small and structural variants from HiFi sequencing
Authors: Holt James M. , Saunders Christopher T. , Rowell William J. , Kronenberg Zev , Wenger Aaron M. , Eberle Michael
Published: May 2023

Background

In diploid organisms, phasing is the problem of assigning the heterozygous variants to one of two haplotypes. Reads from PacBio HiFi sequencing provide long, accurate observations that can be used as the basis for both calling and phasing variants. HiFi reads also excel at calling larger classes of variation such as structural variants. However, current phasing tools typically only phase small variants, leaving larger structural variants unphased.

Methods

We developed HiPhase, a tool that jointly phases SNVs, indels, and structural variants. The main benefits of HiPhase are 1) dual mode allele assignment for detecting structural variants, 2) a novel application of the A*-algorithm to phasing, and 3) logic allowing phase blocks to span breaks caused by alignment issues around reference gaps and homozygous deletions.

Results

In our assessment, HiPhase produced an average phase block NG50 of 493 kb with 933 switchflip errors and fully phased 95.2% of genes, improving over the current state of the art. Additionally, HiPhase jointly phases SNVs, indels, and structural variants and includes innate multi-threading, statistics gathering, and concurrent phased alignment output generation.

Availability

https://github.com/PacificBiosciences/HiPhase
K29-linked unanchored polyubiquitin chains disrupt ribosome biogenesis and direct ribosomal proteins to the Intranuclear Quality control compartment (INQ)
Authors: Suresh Harsha Garadi , Bonneil Eric , Albert Benjamin , Dominique Carine , Costanzo Michael , Pons Carles , David Masinas Myra Paz , Shuteriqi Ermira , Shore David , Henras Anthony K. , Thibault Pierre , Boone Charles , Andrews Brenda J
Published: May 2023

Ribosome assembly requires precise coordination between the production and assembly of ribosomal components. Mutations in ribosomal proteins that inhibit the assembly process or ribosome function are often associated with Ribosomopathies, some of which are linked to defects in proteostasis. In this study, we examine the interplay between several yeast proteostasis enzymes, including deubiquitylases (DUBs), Ubp2 and Ubp14, and E3 ligases, Ufd4 and Hul5, and we explore their roles in the regulation of the cellular levels of K29-linked unanchored polyubiquitin (polyUb) chains. Accumulating K29-linked unanchored polyUb chains associate with maturing ribosomes to disrupt their assembly, activate the Ribosome assembly stress response (RASTR), and lead to the sequestration of ribosomal proteins at the Intranuclear Quality control compartment (INQ). These findings reveal the physiological relevance of INQ and provide insights into mechanisms of cellular toxicity associated with Ribosomopathies.
Reverse Engineering DNA Origami Nanostructure Designs from Raw Scaffold and Staple Sequence Lists
Authors: Shirt-Ediss Ben , Connolly Jordan , Elezgaray Juan , Torelli Emanuela , Navarro Silvia Adriana , Bacardit Jaume , Krasnogor Natalio
Published: May 2023

Designs for scaffolded DNA origami nanostructures are commonly and minimally published as the list of DNA staple and scaffold sequences required. In nearly all cases, high-level editable design files (e.g. caDNAno) which generated the low-level sequences are not made available. This de facto ‘raw sequence’ exchange format allows published origami designs to be re-attempted in the laboratory by other groups, but effectively stops designs from being significantly modified or re-purposed for new future applications. To make the raw sequence exchange format more accessible to further design and engineering, in this work we propose the first algorithmic solution to the inverse problem of converting staple/scaffold sequences back to a ‘guide schematic’ resembling the original origami schematic. The guide schematic can be used to aid the manual re-input of an origami into a CAD tool like caDNAno, hence recovering a high-level editable design file. Creation of a guide schematic can also be used to double check that a list of staple strand sequences does not have errors and indeed does assemble into a desired origami nanostructure prior to costly laboratory experimentation. We tested our reverse algorithm on 36 diverse origami designs from the literature and found that 29 origamis (81%) had a good quality guide schematic recovered from raw sequences. Our software is made available athttps://revnano.readthedocs.io.
Deep immunological imprinting due to the ancestral spike in the current bivalent COVID-19 vaccine
Authors: Wang Qian , Guo Yicheng , Tam Anthony R. , Valdez Riccardo , Gordon Aubree , Liu Lihong , Ho David D.
Published: May 2023

With the aim of broadening immune responses against the evolving SARS-CoV-2 Omicron variants, bivalent COVID-19 mRNA vaccines that encode the ancestral and Omicron BA.5 spike proteins have been authorized for clinical use, supplanting the original monovalent counterpart in numerous countries. However, recent studies have demonstrated that administering either a monovalent or bivalent vaccine as a fourth vaccine dose results in similar neutralizing antibody titers against the latest Omicron subvariants, raising the possibility of immunological imprinting. Utilizing binding immunoassays, pseudotyped virus neutralization assays, and antigenic mapping, we investigated antibody responses from 72 participants who received three monovalent mRNA vaccine doses followed by either a bivalent or monovalent booster, or who experienced breakthrough infections with the BA.5 or BQ subvariant after vaccinations with an original monovalent vaccine. Compared to a monovalent booster, the bivalent booster did not yield noticeably higher binding titers to D614G, BA.5, and BQ.1.1 spike proteins, nor higher virus-neutralizing titers against SARS-CoV-2 variants including the predominant XBB.1.5 and the emergent XBB.1.16. However, sera from breakthrough infection cohorts neutralized Omicron subvariants significantly better. Multiple analyses of these results, including antigenic mapping, made clear that inclusion of the ancestral spike prevents the broadening of antibodies to the BA.5 component in the bivalent vaccine, thereby defeating its intended goal. Our findings suggest that the ancestral spike in the current bivalent COVID-19 vaccine is the cause of deep immunological imprinting. Its removal from future vaccine compositions is therefore strongly recommended.
Genome assembly and analysis ofLactuca virosa: implications for lettuce breeding
Authors: Xiong Wei , van Workum Dirk-Jan M. , Berke Lidija , Bakker Linda V. , Schijlen Elio , Becker Frank F.M. , van de Geest Henri , Peters Sander , Michelmore Richard , van Treuren Rob , Jeuken Marieke , Smit Sandra , Schranz M. Eric
Published: May 2023

Lettuce (Lactuca sativaL.) is a leafy vegetable crop with ongoing breeding efforts related to quality, resilience, and innovative production systems. Genetic variation of important traits in close relatives is necessary to meet lettuce breeding goals.Lactuca virosa(2x=2n=18), a wild relative assigned to the tertiary lettuce gene pool, has a much larger genome (3.7 Gbp) thanLactuca sativa(2.5 Gbp). It has been used in interspecific crosses and is a donor to modern crisphead lettuce cultivars. Here, we present ade novoreference assembly ofL. virosawith high continuity and complete gene space. This assembly facilitated comparisons to the genome ofL. sativaand to that of the wild speciesL. saligna, a representative of the secondary lettuce gene pool. To assess the diversity in gene content, we classified the genes of the threeLactucaspecies as core, accessory and unique. In addition, we identified three interspecific chromosomal inversions compared toL. sativa, which each may cause recombination suppression and thus hamper future introgression breeding. Using three-way comparisons in both reference-based and reference-free manners, we show that the proliferation of long-terminal repeat elements has driven the genome expansion ofL. virosa. Further, we performed a genome-wide comparison of immune genes, nucleotide-binding leucine-rich repeat, and receptor-like kinases amongLactucaspp. and indicate the evolutionary patterns and mechanisms behind their expansions. These genome analyses greatly facilitate the understanding of genetic variation inL. virosa, which is beneficial for the breeding of improved lettuce varieties.
Is there a latitudinal diversity gradient for symbiotic microbes? A case study with sensitive partridge peas
Authors: Harrison Tia L. , Parshuram Zoe A. , Frederickson Megan E. , Stinchcombe John R.
Published: May 2023

Mutualism is more prevalent in the tropics than temperate zones and is therefore expected to play an important role in generating and maintaining high species richness found at lower latitudes. However, results on the impact of mutualism on latitudinal diversity gradients are mixed, and few empirical studies sample both temperate and tropical regions. We investigated whether a latitudinal diversity gradient exists in the symbiotic microbial community associated with the legumeChamaecrista nictitans. We sampled bacteria DNA from nodules and the surrounding soil of plant roots across a latitudinal gradient (38.64 °N to 8.68 °N). Using 16S rRNA sequence data, we identified many non-rhizobial species withinC. nictitansnodules that cannot form nodules or fix nitrogen. Species richness increased towards lower latitudes in the non-rhizobial portion of the nodule community but not in the rhizobial community. The microbe community in the soil did not predict the non-rhizobia community inside nodules, indicating that host selection is important for structuring non-rhizobia communities in nodules. We next factorially manipulated the presence of three non-rhizobia strains in greenhouse experiments and found that co-inoculations of non-rhizobia strains with rhizobia had a marginal effect on nodule number and no effect on plant growth. Our results suggest that these non-rhizobia bacteria are likely commensals – species that benefit from associating with a host but are neutral for host fitness. Overall, our study suggests that temperateC. nictitansplants are more selective in their associations with the non-rhizobia community, potentially due to differences in soil nitrogen across latitude.
GARSA: An integrative pipeline for genome wide association studies and polygenic risk score inference in admixed human populations
Authors: Rossi Fernando P. N. , Patané José S. L. , de Souza Vinicius , Neyra Jennifer M. , Rosa Rogério S. , Krieger Jose E. , Teixeira Samantha K.
Published: May 2023

Genome-wide association studies (GWAS) and polygenic risk scores (PRS) are multistep analytical tools to identify genetic variants and to assess their contribution to phenotypes/diseases. These analyses are evolving and becoming instrumental to understand the genetic architecture of complex phenotypes/diseases. Nevertheless, to date, there is no single solution incorporating all major steps related to those analyses combined with robust populational bias correction. Here, we describe a semi-automated pipeline unifying steps involved in GWAS and PRS including widely used software. Our pipeline handles quality control (QC), GWAS, and PRS steps, managing different types of input/output files. Furthermore, it includes robust bias correction steps, such as inference of kinship matrix with correction for population structure, use of principal component analysis (PCA) with detection and removal of outlier variant followed by re-projection of related individuals (if desired), generation of PCA figures that assist in setting the best number of principal components (PCs) for association analysis, availability of mixed models, use of recommended software for GWAS based on population size, and a Markov chain Monte Carlo (MCMC) method to estimate best set of PRS parameters. Finally, we tested GARSA pipeline in a family-based Brazilian admixed population and demonstrated that the corrections implemented indeed mitigate bias in downstream analysis. The pipeline can be implemented on personal or server-side environments.

Availability

The development version (open-source) is available inhttps://github.com/LGCM-OpenSource/GARSA

Contact

Fernando P. N. Rossi -fernando.rossi@hc.fm.usp.br; José S. L. Patané -jose.patane@hc.fm.usp.br

Supplementary information

Supplementary tutorial.