bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary signet ring cell carcinoma of the appendix presenting as gangrenous appendicitis with peritonitis: A case report
Authors: Liu Kuang-Ting , Chang Yueh-Ching , Lin Yu-Chieh , Chang Junn-Liang
Published: October 2024

Introduction and clinical importance:

Primary signet ring cell carcinoma (SRCC) of the appendix is an exceedingly rare malignancy with a non-specific clinical manifestations, and it often masquerades as acute appendicitis. Case presentation

A 76-year-old man presented with acute abdominal pain and peritonitis. Abdominal computed tomography revealed relative acute appendicitis with peritonitis, and emergency laparoscopic partial cecectomy with appendectomy revealed gangrenous appendicitis with perforation. A histopathological examination revealed a primary appendiceal signet ring cell carcinoma (PASRCC).

Clinical discussion:

This case highlights the importance of considering appendiceal malignancies in the differential diagnosis of acute appendicitis. SRCC is a histological variant commonly associated with multiple malignancies of the gastrointestinal tract, particularly gastric and colorectal cancers.

Conclusion:

PASRCC is a rare malignancy presenting with symptoms indistinguishable from those of acute appendicitis. Clinicians should maintain a high index of suspicion for appendiceal malignancy, particularly in older patients with atypical clinical presentations. Early recognition, accurate diagnosis by histopathological and immunohistochemical examinations, and appropriate management are essential for optimizing the outcomes in these patients.
Breast reconstruction using the superficial circumflex iliac artery superficial branch perforator (SCISP) flap
Authors: Schwaiger Karl , Scharfetter Sandra , Russe Elisabeth , Köninger Fabian , Pumberger Peter , Wechselberger Gottfried
Published: October 2024

The deep inferior epigastric perforator (DIEP) flap is the gold standard for autologous breast reconstruction. One downside is its risk of postsurgical herniation and bulging due to the opening of the rectus fascia and intramuscular dissection of the rectus abdominis muscle. Additionally this part of the surgery is very time consuming. While the superficial inferior epigastric artery perforator (SIEA) flap has been thoroughly described for total autologous breast reconstruction, the use of the superficial circumflex iliac artery perforator flap in this field is limited. This series introduces the use of an extended superficial circumflex iliac artery (SCIA) perforator flap nourished solely by perforators of the superficial branch of the SCIA- artery for total autologous breast reconstruction.

Superficial preparation over the abdominal wall was performed without incising the rectus fascia, dissecting the superficial branch of the SCIA and its accompanying veins and the superficial inferior epigastric vein for additional venous drainage.

Four patients underwent successful autologous breast reconstruction with this extended SCIP (superficial circumflex iliac artery perforator)-flap-variation. The term superficial circumflex iliac artery superficial branch perforator (SCISP) flap was introduced to standardize the surgical technique for using only perforators of the superficial branch of the SCIA as free flaps.

The SCISP flap is safe and viable for total autologous breast reconstruction, particularly for women with small to medium sized breasts and with superficial dominance of the abdominal vascular system.
Frequency-dependence may moderate fitness costs linked to reduced bird song complexity
Authors: Appleby Daniel , Langmore Naomi , Heinsohn Robert , Crates Ross
Published: October 2024

Animal cultures can undergo rapid changes associated with innovations, revolutions or population decline. Where a rapid shift results in reduced complexity of cultural behaviours, it may have fitness consequences for individuals. Here, we report a dramatic shift in the dominant song type of critically endangered wild regent honeyeaters
Anthochaera phrygia
. Between 2015 and 2019, most males in the Blue Mountains sang a typical regent honeyeater song (typical Blue Mountains song), but 5%–10% sang an abbreviated version of the song with half the number of syllables (the clipped Blue Mountains song), which was associated with lower pairing success. Since 2020, the proportion of males singing the clipped Blue Mountains song has increased to 50%–75% each year. The likelihood of successful pairing in these males showed a significant concomitant increase, suggesting that the fitness costs associated with the abbreviated song decreased as it became the dominant song type. Our results suggest that the fitness consequences of loss of song complexity in declining and fragmented populations may be ameliorated by frequency-dependent shifts in song type preference.
Season-specific genetic variation underlies early-life migration in a partially migratory bird
Authors: Fortuna Rita , Acker Paul , Ugland Cassandra R. , Burthe Sarah J. , Harris Michael P. , Newell Mark A. , Gunn Carrie , Morley Timothy I. , Haaland Thomas R. , Swann Robert L. , Wanless Sarah , Daunt Francis , Reid Jane M.
Published: October 2024

Eco-evolutionary responses to environmentally induced selection fundamentally depend on magnitudes of genetic variation underlying traits that facilitate population persistence. Additive genetic variances and associated heritabilities can vary across environmental conditions, especially for labile phenotypic traits expressed through early life. However, short-term seasonal dynamics of genetic variances are rarely quantified in wild populations, precluding inference on eco-evolutionary outcomes in seasonally dynamic systems. This limitation applies to seasonal migration versus residence, constituting one key trait where rapid microevolution could rescue partially migratory populations from changing seasonal environments. We fitted novel quantitative genetic ‘capture–recapture animal models’ to multi-generational pedigree and year-round resighting data from 11 cohorts of European shags (
Gulosus aristotelis
), to estimate season-specific additive genetic variances in liabilities to migrate, and in resulting expression of migration, in juveniles’ first autumn and winter. We demonstrate non-negligible genetic variation underlying early-life migration, with twice as large additive genetic variances and heritabilities in autumn than winter. Since early-life survival selection on migration typically occurs in winter, highest genetic variation and strongest selection are seasonally desynchronized. Our results reveal complex within- and among-year dynamics of early-life genetic and phenotypic variation, demonstrating that adequate inference of eco-evolutionary outcomes requires quantifying microevolutionary potential on appropriate scales and seasonal timeframes.
Universal versus taxon-specific drivers of helminth prevalence and intensity of infection
Authors: Martins Paulo Mateus , Poulin Robert
Published: October 2024

Two key epidemiological parameters, prevalence and mean intensity of infection, together capture the abundance of macroparasite populations, the strength of density-dependent effects they experience, their potential impact on host population dynamics and the selective pressures they exert on their hosts. Yet, the drivers of the extensive variation observed in prevalence and mean intensity of infection, even among related parasite taxa infecting related hosts, remain mostly unknown. We performed phylogenetically grounded Bayesian modelling across hundreds of amphibian populations to test the effects of various predictors of prevalence and intensity of infection by six families of helminth parasites. We focused on the potential effects of key host traits and environmental factors pertinent to focal host populations, i.e. the local diversity of the amphibian community and local climatic variables. Our analyses revealed several important determinants of prevalence or intensity of infection in various parasite families, but none applying to all families. Our study uncovered no universal driver of parasite infection levels, even among parasite taxa from the same phylum, or with similar life cycles and transmission modes. Although local variables not considered here may have effects extending across taxa, our findings suggest the need for a taxon-specific approach in any attempt to predict disease dynamics and impacts in the face of environmental and climatic changes.
Parental care reduces parasite-induced mortality in a coral reef fish
Authors: Grutter Alexandra S. , Blomberg Simone P. , Duong Berilin , Fargher Bronwyn E. , Feeney William E. , McCormick Mark I. , Nicholson Matthew D. , Sikkel Paul C. , Warner Robert R. , Kuris Armand M.
Published: October 2024

Settlement patterns of juvenile fish shape coral reef communities. During the recruitment process, predation rates are extremely high. However, the role that parental care plays in reducing mortality, especially by cryptic natural enemies such as parasites, remains largely unstudied. We investigated whether parental care in the spiny chromis damselfish (
Acanthochromis polyacanthus
) protects juveniles from parasite-induced mortality by gnathiid isopods (
Gnathia aureamaculosa
). Using laboratory experiments, we found that survival of recently hatched juveniles when exposed to gnathiids was higher when parents were present (77%) than when parents were absent (25%). Investigation of their faeces in the field and laboratory indicates that adults consume gnathiids. Together, our data suggest that parental care plays a key role in reducing parasite-induced mortality of juvenile spiny chromis via parental consumption of gnathiids. This highlights the overlooked role of parasites as a source of high mortality in juvenile coral reef fishes and the composition of coral reef fish communities.
Selective colonization of microplastics, wood and glass by antimicrobial-resistant and pathogenic bacteria
Authors: Stevenson Emily M. , Rushby-Jones Owen , Buckling Angus , Cole Matthew , Lindeque Penelope K. , Murray Aimee K.
Published: October 2024

Graphical abstract

Summary of key findings. Polystyrene and wood were selectively colonized by antimicrobial-resistant (AMR) bacteria, while bio-beads selected for potential Escherichia coli pathogens and surface weathering did not significantly influence AMR colonization. Created in BioRender. Stevenson, E. (2024) BioRender.com/r90g504
Effects of Home-Based EEG Neurofeedback Training as a Non-Pharmacological Intervention for Parkinson’s Disease
Authors: Cooke Andrew , Hindle John , Lawrence Catherine , Bellomo Eduardo , Pritchard Aaron W. , MacLeod Catherine A. , Martin-Forbes Pam , Jones Sally , Bracewell Martyn , Linden David E. J. , Mehler David M. A.
Published: October 2024

Aberrant movement-related cortical activity has been linked to impaired motor function in Parkinson’s disease (PD). Dopaminergic drug treatment can restore these, but dosages and long-term treatment are limited by adverse side-effects. This experiment reports the first study of home-based electroencephalographic (EEG) neurofeedback training as a non-pharmacological candidate treatment for PD. Sixteen people with PD received six home visits comprising symptomology self-reports, a standardised motor assessment, and a precision handgrip force production task while EEG was recorded (visits 1, 2 and 6); and 3 × 1-hr EEG neurofeedback training sessions to reduce EEG high-alpha power before initiating handgrip movements (visits 3 to 5). Participants successfully learned to self-regulate movement-related alpha rhythms, and this appeared to expedite the initiation of precision movements. There was no evidence of wider symptomology reduction. Interviews indicated that the intervention was well-received. We conclude that home-based neurofeedback for people with PD is feasible and warrants further research.
Detection of Nanoliter-Scale Cortical Perivascular Spaces Using Heavily T2-weighted MRI at 7T
Authors: Saib Gael , Demir Zeynep H. , Taylor Paul A. , Lalith Talagala S. , Koretsky Alan P.
Published: October 2024

Background

There is increasing interest in high-contrast cerebrospinal fluid (CSF) MRI to image perivascular spaces (PVSs). Dilated PVSs, associated with aging, dementia, and various other conditions, have been commonly detected within the white matter, basal ganglia, and midbrain. 7T MRI has enabled the early detection of smaller PVSs due to very high contrast and resolution. However, to date, PVSs in the cerebral cortex has received limited attention, despite that the identification of early changes in the cortical PVS could give valuable insight into neurological conditions.

Purpose

To determine if PVSs can be detected within the cerebral cortex in healthy participants by using heavily T2-weighted MRI at 7T.

Materials and Methods

A T2-weighted TSE sequence was optimized to detect CSF with high resolution and contrast at 7T while reducing the contribution from surrounding tissues. A semi-automated processing pipeline was used to extract PVSs and analyze their density in the whole brain including the cerebral cortex.

Results

A total of 17 healthy volunteers were scanned at 7T (10 Males and 7 Females, aged 40±14 years). The optimized 3D-TSE sequence (0.125 mm3volume, 0.5 mm isotropic resolution, 500 ms TE, 2.4 s TR and 10 min scan time) enabled a CNR of approximatively 180:1 after denoising, with a CSF volume detection limit of about 5 nL per voxel. At this sensitivity, average PVS density was found to be about 4.0% in white matter, 2.7% in deep gray matter and 1.3% in the cortex. Highest cortical PVS density was found to be in the insular cortex. Four characteristic classes of PVS morphology within the cortex or passing through the cortex were identified.

Conclusion

High-resolution CSF imaging using optimized 3D-TSE MRI at 7T allows nanoliter scale volume detection of cortical PVSs in healthy individuals. This lays the groundwork for exploring cortical PVSs and their potential for use in diagnosis or prognosis of neurological diseases.
Chikungunya Virus VLP Vaccine: Phase 3 Trial in Adolescents and Adults
Authors: Richardson Jason S. , Anderson Deborah M. , Mendy Jason , Tindale Lauren C. , Muhammad Sufia , Loreth Tobi , Tredo Sarah Royalty , Warfield Kelly L. , Ramanathan Roshan , Caso Jorge T. , Jenkins Victoria A. , Ajiboye Patrick , Bedell Lisa ,   the EBSI-CV-317-004 Study Group
Published: October 2024

1

Background

Chikungunya disease is a growing global public health concern. Chikungunya virus (CHIKV) virus-like particle (VLP) vaccine is a single dose, pre-filled syringe for intramuscular injection.

Methods

A pivotal phase 3 randomized, double-blind, placebo-controlled trial was conducted in healthy adolescents and adults 12-64 years of age. Participants received either CHIKV VLP vaccine or placebo on Day 1. Immunogenicity objectives assessed CHIKV serum neutralizing antibody (SNA) titers (NT80) at selected timepoints. Safety was assessed through Day 183 postvaccination.

Results

A total of 2790 participants received CHIKV VLP vaccine and 464 received placebo (n=3454). Coprimary endpoints were met including 1) immunologic superiority to placebo and 2) geometric mean titer at Day 22. Results demonstrated that CHIKV VLP vaccine induced a protective seroresponse (SNA NT80≥100; considered the presumptive seroprotective antibody response), in 97% of individuals at Day 15 (2 weeks), in 98% of individuals at Day 22, and in 86% of individuals at Day 183 (6 months). CHIKV VLP vaccine demonstrated a favorable safety profile. The majority of adverse events were self-limited and grade 1 or 2 in severity. The most common adverse events were injection site pain, fatigue, headache, and myalgia.

Conclusions

CHIKV VLP vaccine induces a rapid and robust immune response by Day 15 that lasts through Day 183 postvaccination. These findings support the potential for this vaccine to protect individuals 12-64 years of age from disease caused by CHIKV. (Funded by Emergent BioSolutions Inc. and Bavarian Nordic A/S [as successor in interest to Emergent BioSolutions Inc.];ClinicalTrials.govnumber,NCT05072080).
A novel DNA methylation-based surrogate biomarker for chronic systemic inflammation (InfLaMeS): results from the Health and Retirement Study
Authors: Meier Helen C.S. , Klopack Eric T. , Farnia Mateo P. , Hernandez Belinda , Mitchell Colter , Faul Jessica D. , McCrory Cathal , Kenny Rose Anne , Crimmins Eileen M.
Published: October 2024

Chronic low-grade systemic inflammation is a risk factor for chronic diseases and mortality and is an important biomarker in health research. DNA methylation (DNAm) surrogate biomarkers are valuable exposure, risk factor and health outcome predictors in studies where the measures cannot be measured directly and often perform as well or better than direct measure. We generated a DNAm surrogate biomarker for chronic, systemic inflammation from a systemic inflammation latent variable of seven inflammatory markers and evaluated its performance relative to measured inflammatory biomarkers in predicting several age-associated outcomes of interest, including mortality, activities of daily living and multimorbidity in the Health and Retirement Study (HRS). The DNAm surrogate, Inflammation Latent Variable Methylation Surrogate (InfLaMeS), correlated with seven individual inflammation markers (r= −0.2-0.6) and performed as well or better to the systemic inflammation latent variable measure when predicting multimorbidity, disability, and 4-year mortality in HRS. Findings were validated in an external cohort, The Irish Longitudinal Study of Ageing. These results suggest that InfLaMeS provides a robust alternative to measured blood-chemistry measures of inflammation with broad applicability in instances where values of inflammatory markers are not measured but DNAm data is available.
Association Between Angiotensin Receptor-Neprilysin Inhibitor Use and Clinical Outcomes in Concurrent Heart Failure with Reduced Ejection Fraction and End-Stage Renal Disease
Authors: Jung Mi-Hyang , Cho Dong-Hyuk , Choi Jimi , Kim Mi-Na , Lee Chan Joo , Son Jung-Woo , Youn Jong-Chan , Yoo Byung-Su
Published: October 2024

Background

Although angiotensin receptor-neprilysin inhibitor (ARNI) therapy has been shown to improve outcomes in heart failure with reduced ejection fraction (HFrEF), its benefits in patients with end-stage renal disease (ESRD) on dialysis remain uncertain. This study investigated the clinical outcomes of ARNI compared to renin-angiotensin system (RAS) blockers in HFrEF patients with concomitant ESRD on dialysis.

Methods

Using the Korean National Health Insurance Service database, we identified individuals with HFrEF and ESRD on dialysis who were prescribed either ARNI or RAS blockers between 2017 and 2021. After applying inverse probability of treatment weighting, we compared 2,104 patients on ARNI with 2,191 on RAS blockers. The primary endpoint was a composite of all-cause mortality and any hospitalization over 2 years.

Results

Baseline characteristics were balanced between the groups. ARNI use was associated with a significantly lower risk of the primary endpoint (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75–0.97) compared to RAS blockers. Additionally, ARNI was associated with a lower risk of all-cause mortality (HR 0.68, 95% CI 0.54–0.86) and any hospitalization (HR 0.86, 95% CI 0.75–0.98). Subgroup analyses demonstrated consistent associations between ARNI use and reduced risk across all subgroups (age, sex, comorbidities, and medications). Good adherence to ARNI was associated with a lower risk of the primary outcome, whereas non-adherence showed no such benefit.

Conclusion

In a real-world population with HFrEF and ESRD on dialysis, ARNI use was associated with a lower risk of all-cause mortality and hospitalization compared to RAS blockers, particularly in those with good adherence to therapy.

Abstract Figure

Graphical Abstract. Association between Angiotensin Receptor-Neprilysin Inhibitor Use and Clinical Outcomes in Patients with Concurrent Heart Failure with Reduced Ejection Fraction and End-Stage Renal Disease on Dialysis

In this real-world study of patients with heart failure with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD) on dialysis, the use of angiotensin receptor-neprilysin inhibitor (ARNI) was associated with a significant reduction in the risk of all-cause mortality and any hospitalization compared to renin-angiotensin system (RAS) blockers. These benefits were particularly evident in patients who adhered well to their medication.
CytoLNCpred - A computational method for predicting cytoplasm associated long-coding RNAs in 15 cell-lines
Authors: Choudhury Shubham , Mehta Naman Kumar , Raghava Gajendra P. S.
Published: October 2024

The function of long non-coding RNA (lncRNA) is largely determined by its specific location within a cell. Previous methods have used noisy datasets, including mRNA transcripts in tools intended for lncRNAs, and excluded lncRNAs lacking significant differential localization between the cytoplasm and nucleus. In order to overcome these shortcomings, a method has been developed for predicting cytoplasm-associated lncRNAs in 15 human cell-lines, identifying which lncRNAs are more abundant in the cytoplasm compared to the nucleus. All models in this study were trained using five-fold cross validation and tested on an independent dataset. Initially, we developed machine and deep learning based models using traditional features like composition and correlation. Using composition and correlation based features, machine learning algorithms achieved an average AUC of 0.7049 and 0.7089, respectively for 15 cell-lines. Secondly, we developed machine based models developed using embedding features obtained from the large language model DNABERT-2. The average AUC for all the cell-lines achieved by this approach was 0.6604. Subsequently, we also fine-tuned DNABERT-2 on our training dataset and evaluated the fine-tuned DNABERT-2 model on the independent dataset. The fine-tuned DNABERT-2 model achieved an average AUC of 0.6336. Correlation-based features combined with ML algorithms outperform LLM-based models, in the case of predicting differential lncRNA localization. These cell-line specific models as well as web-based service are available to the public from our web server (https://webs.iiitd.edu.in/raghava/cytolncpred/) .

HIGHLIGHTS

Prediction of cytoplasm-associated lncRNAs in 15 human cell lines

Machine learning using composition and correlation features

DNABERT-2 embeddings for lncRNA localization prediction

Correlation-based models outperform LLM-based models

Web server and models available for public use

AUTHOR’S BIOGRAPHY

Shubham Choudhury is currently working as Ph.D. in Computational Biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.

Naman Kumar Mehta is currently working as Ph.D. in Computational Biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.

Gajendra P. S. Raghava is currently working as Professor and Head of Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India
Cell tracking with accurate error prediction
Authors: Betjes Max A. , Tans Sander J. , van Zon Jeroen S.
Published: October 2024

Cell tracking is an indispensable tool for studying development by time-lapse imaging. However, existing cell trackers cannot assign confidence to predicted tracks, which prohibits fully automated analysis without manual curation. We present a fundamental advance: an algorithm that combines neural networks with statistical physics to determine cell tracks with error probabilities for each step in the track. From these we can obtain error probabilities for any tracking feature, from cell cycles to lineage trees, that function like p-values in data interpretation. Our method greatly speeds up tracking analysis by limiting manual curation to rare low-confidence tracking steps. Importantly, it also enables fully-automated analysis by retaining only high-confidence track segments, which we demonstrate by analyzing cell cycles and differentiation events at scale, for thousands of cells in multiple intestinal organoids. Our approach brings cell dynamics-based organoid screening within reach, and enables transparent reporting of cell tracking results and associated scientific claims.
Manipulation of thebrown glume and internode 1gene leads to alterations in lignified tissue coloration, lignification, and pathogen resistance in wheat
Authors: Hua Lei , Song Rui , Hao Xiaohua , Zhang Jing , Liu Yanna , Luo Jing , Ren Xiaopeng , Li Hongna , Wang Guiping , Rehman Shams ur , Wu Jiajie , Fu Daolin , Dong Yuxiu , Wang Xiaodong , Zhang Chaozhong , Chen Shisheng
Published: October 2024

Lignin is a crucial component of the cell wall, providing mechanical support and protection against biotic and abiotic stresses. However, little is known about wheat lignin-related mutants and their roles in pathogen defense. In this study, we identified an ethyl methanesulfonate (EMS)-derivedAegilops tauschiimutant namedbrown glume and internode 1(bgi1), which exhibits reddish-brown pigmentation in various tissues, including internodes, spikes, and glumes. Using map-based cloning and single nucleotide polymorphism (SNP) analysis, we identifiedAET6Gv20438400(BGI1) as the leading candidate gene, encoding the TaCAD1 protein. The mutation occurred in the splice acceptor site of the first intron, resulting in a premature stop codon inBGI1. We validated the function ofBGI1using loss-of-function EMS and gene editing knockout mutants, both of which displayed reddish-brown pigmentation in lignified tissues.BGI1knockout mutants exhibited reduced lignin content and shearing force relative to wild type, whileBGI1overexpression transgenic plants showed increased lignin content and enhanced disease resistance against common root rot andFusariumcrown rot. We confirmed that BGI1 exhibits CAD activity bothin vitroandin vivo, playing an important role in lignin biosynthesis.BGI1was highly expressed in the stem and spike and localized in the cytoplasm. Transcriptome analysis revealed the regulatory networks associated withBGI1. Finally, we demonstrated that BGI1 interacts with TaPYL-1D, potentially involved in the abscisic acid signaling pathway. The identification and functional characterization ofBGI1significantly advance our understanding of CAD proteins in lignin biosynthesis and plant defense against pathogen infection in wheat.
A Rab-Kinesin12-Fused kinase module couples vesicle delivery and phragmoplast remodelling during cytokinesis inArabidopsis
Authors: Elliott Liam , Kalde Monika , Yamada Moé , Hála Michal , Smertenko Andrei , Rozier Frédérique , Evry James , Irani Niloufer , Jaillais Yvon , Hussey Patrick J , Žárský Viktor , Moore Ian , Kirchhelle Charlotte
Published: October 2024

Cytokinesis is a key process in the development of multicellular organisms, through both formative and proliferative divisions. In land plants, successful cytokinesis requires precise targeting of Golgi-derived vesicles to the future division plane by the phragmoplast, a cytoskeletal structure that undergoes continuous remodelling. Endomembrane trafficking and phragmoplast remodelling are tightly coupled, indicating the existence of active crosstalk. However, although many molecular regulators of membrane trafficking and cytoskeletal organisation are known, it remains poorly understood how these processes are co-ordinated. Here, we describe a regulatory module consisting of the membrane-associated GTPase RAB-A2a, cytoskeleton-associated Class II Kinesin-12s, and the Fused kinase orthologue TIO. We provide evidence that the interaction between these molecules at the midzone is essential for cytokinesis inArabidopsisthrough simultaneously targeting vesicles to the midzone and coupling phragmoplast remodelling to vesicle delivery.
Evolution and theft: loss of state transitions in Bryopsidales macroalgae and photosynthetic sea slugs
Authors: Havurinne Vesa , Rivoallan Axelle , Mattila Heta , Tyystjärvi Esa , Cartaxana Paulo , Cruz Sónia
Published: October 2024

Green macroalgae within the order Bryopsidales lack the fundamental photoprotective mechanisms of green algae, the xanthophyll cycle and energy-dependent dissipation of excess light. Here, by measuring chlorophyll fluorescence at 77K after specific light treatments, we show that Bryopsidales algae also lack state transitions, another ubiquitous photoprotection mechanism present in other green algae. Certain Sacoglossa sea slugs can feed on Ulvophyceae algae, including some Bryopsidales, and steal chloroplasts –kleptoplasts– that remain functional inside the animal cells for months without the support of the algal nucleus. Our data reveal that the state transition capacity is not retained in the kleptoplasts of the sea slugs, and we provide evidence that the loss is caused by structural changes during their incorporation by the animals. This enforced chloroplast sphericity was observed in all studied kleptoplastic associations, and we propose that it is a fundamental property supporting long-term retention of kleptoplasts in photosynthetic sea slugs.
Investigating Honey Bee Pollen Foraging Patterns Across a Season Using DNA Metabarcoding
Authors: Larsen Sydney N. , Steffen Joshua G. , Briggs Heather M.
Published: October 2024

The western honey bee, orApis mellifera, is a vital pollinator, essential for both ecosystems and agriculture worldwide. As human influences on these bees become more pronounced, understanding their pollen foraging behavior is increasingly important. Pollen provides crucial nutrients forA. melliferasuch as protein and lipids that are necessary for hive health and prosperity. Pollen DNA metabarcoding allows for the longitudinal analysis of the floral sources of corbicular (bee-collected) pollen. In this study we employ the use of metabarcoding and Oxford Nanopore Sequencing technology to analyze the floral composition of pollen samples collected on a weekly basis from two closely related hives. In total, we identified 74 distinct plant taxa (at the genus level) between the two hives. Although both hives had equivalent values of taxonomic richness and diversity, the majority of taxa identified were unique to the individual hives. This indicates a large degree of variation in pollen foraging despite the hives’ relative proximity. In addition to this interhive analysis, we also analyzed changes in pollen origin of a single hive across the course of five months. We identified 59 distinct plant taxa within samples from this hive whose presence and relative abundance differ drastically on a weekly basis with no taxa being present in all samples across the observed time period. In addition, even though there was a median of 8 to 9 taxa detected in each sample, each sample was composed primarily of 1 to 2 taxa indicating a degree of foraging preference that changes on a regular basis. Further quantitative and qualitative comparisons completed in this study demonstrate the degree of variation in pollen foraging patterns both throughout the season and between hives.
Identification and Targeting of Regulators of SARS-CoV-2-Host Interactions in the Airway Epithelium
Authors: Dirvin Brooke , Noh Heeju , Tomassoni Lorenzo , Cao Danting , Zhou Yizhuo , Ke Xiangyi , Qian Jun , Jangra Sonia , Schotsaert Michael , García-Sastre Adolfo , Karan Charles , Califano Andrea , Cardoso Wellington V.
Published: October 2024

Although the impact of SARS-CoV-2 in the lung has been extensively studied, the molecular regulators and targets of the host-cell programs hijacked by the virus in distinct human airway epithelial cell populations remain poorly understood. This is in part ascribed to the use of nonprimary cell systems, overreliance on single-cell gene expression profiling that does not ultimately reflect protein activity, and bias toward the downstream effects rather than their mechanistic determinants. Here we address these issues by network-based analysis of single cell transcriptomic profiles of pathophysiologically relevant human adult basal, ciliated and secretory cells to identify master regulator (MR) protein modules controlling their SARS-CoV-2-mediated reprogramming. This uncovered chromatin remodeling, endosomal sorting, ubiquitin pathways, as well as proviral factors identified by CRISPR analyses as components of the host response collectively or selectively activated in these cells. Large-scale perturbation assays, using a clinically relevant drug library, identified 11 drugs able to invert the entire MR signature activated by SARS-CoV-2 in these cell types. Leveraging MR analysis and perturbational profiles of human primary cells represents a novel mechanism-based approach and resource that can be directly generalized to interrogate signatures of other airway conditions for drug prioritization.
hu.MAP3.0: Atlas of human protein complexes by integration of > 25,000 proteomic experiments
Authors: Fischer Samantha N. , Claussen Erin R. , Kourtis Savvas , Sdelci Sara , Orchard Sandra , Hermjakob Henning , Kustatscher Georg , Drew Kevin
Published: October 2024

Macromolecular protein complexes carry out most functions in the cell including essential functions required for cell survival. Unfortunately, we lack the subunit composition for all human protein complexes. To address this gap we integrated >25,000 mass spectrometry experiments using a machine learning approach to identify > 15,000 human protein complexes. We show our map of protein complexes is highly accurate and more comprehensive than previous maps, placing ∼75% of human proteins into their physical contexts. We globally characterize our complexes using protein co-variation data (ProteomeHD.2) and identify co-varying complexes suggesting common functional associations. Our map also generates testable functional hypotheses for 472 uncharacterized proteins which we support using AlphaFold modeling.

Additionally, we use AlphaFold modeling to identify 511 mutually exclusive protein pairs in hu.MAP3.0 complexes suggesting complexes serve different functional roles depending on their subunit composition. We identify expression as the primary way cells and organisms relieve the conflict of mutually exclusive subunits. Finally, we import our complexes to EMBL-EBI’s Complex Portal (https://www.ebi.ac.uk/complexportal/home) as well as provide complexes through our hu.MAP3.0 web interface (https://humap3.proteincomplexes.org/). We expect our resource to be highly impactful to the broader research community.
Rapid onset fibrotic remodeling and ventricular dysfunction induced by phenylephrine involve targeted reprogramming of myocyte and fibroblast transcriptomes
Authors: Kimball Todd H. , Gromova Tatiana , Gehred Natalie D. , Chapski Douglas J. , Wang Ke , Vaseghi Marmar , Fischer Matthew A. , Lefer David J. , Vondriska Thomas M.
Published: October 2024

Catecholamine dysregulation is a common feature of multiple acute and chronic cardiac conditions, including heart failure. To investigate the role of altered α-adrenergic stimulation on cardiac function, we developed a short-term exposure model, administering phenylephrine subcutaneously to mice for one week. Compared to vehicle-injected controls, phenylephrine-treated animals exhibited increased ejection fraction, decreased chamber size, diastolic dysfunction and ventricular hypertrophy in the absence of hypertension. Remarkably, these animals developed extensive fibrotic remodeling of the tissue that plateaued at 24 hours and myocyte hypertrophy localized to regions of fibrotic deposition after 3 days of treatment. Transcriptome analyses of purified myocyte and fibroblast populations from these hearts revealed an unexpected role for myocytes in the production of extracellular matrix. Comparison with other models of cardiac stress, including pressure overload hypertrophy and cytokine activation of fibroblasts, identified stimulus-specific transcriptional circuits associated with cardiac pathology. Given the rapid, robust fibrotic response that preceded myocyte hypertrophy, intercellular communication analyses were conducted to investigate fibroblast to myocyte signaling, identifying potential crosstalk between these cells. These studies thoroughly describe and phenotypically characterize a new model of short-term catecholamine stress and provide an atlas of transcriptional remodeling in myocytes and fibroblasts.

Graphical Abstract
Pan-Prediction of MHC-II Restricted Epitopes Across Species via an Alphafold-based Quantification Scheme
Authors: Wang Suqiu , Kong Lingming , Hu Dongmei , Zheng Liangzhen , Fei Caiyi , Du Liubao , Tang Ziche , Wang Sheng , Xu Shi , Yang Hanchun , Zhang Nianzhi
Published: October 2024

Predicting MHC-II restricted epitopes across species used to be challenging, but Alphafold (AF) may provide a structure-based pan-prediction solution. In this study, we established the new tool AF-pred with a clear standard for quantitative prediction results. Compared to the sequence-based tools heavily trained with human ligandome, AF-pred does not show advantage in predicting the binding patterns of human HLA-II but has far better performance in predicting binding patterns of other animals’ MHC-II. Using recently resolved bat MHC-II structures, we analyzed AF-pred’s prediction capability, logic and limitation. In addition, we also explored the impact of AF algorithm iterations on the prediction of MHC-II restricted epitopes. The results demonstrated that AF-pred is capable of cross-species prediction of MHC-II restricted epitopes and is conducive to the development of novel veterinary vaccines.
Rare variants and survival of patients with idiopathic pulmonary fibrosis
Authors: Alonso-Gonzalez Aitana , Jáspez David , Lorenzo-Salazar José M. , Ma Shwu-Fan , Strickland Emma , Mychaleckyj Josyf , Kim John S. , Huang Yong , Adegunsoye Ayodeji , Oldham Justin M. , Steward Iain , Molyneaux Philip L. , Maher Toby M. , Wain Louise V. , Allen Richard J. , Jenkins R. Gisli , Kropski Jonathan A. , Yaspan Brian , Blackwell Timothy S. , Zhang David , Garcia Christine Kim , Martinez Fernando J. , Noth Imre , Flores Carlos
Published: October 2024

Background

The clinical course of idiopathic pulmonary fibrosis (IPF) is highly variable and unpredictable, with multiple genetic variants influencing IPF outcomes. Notably, rare pathogenic variants in telomere-related genes are associated with poorer clinical outcomes in these patients. Here we assessed whether rare qualifying variants (QVs) in monogenic adult-onset pulmonary fibrosis (PF) genes are associated with IPF survival. Using polygenic risk scores (PRS), we also evaluated the influence of common IPF risk variants in individuals carrying these QVs.

Methods

We identified QVs in telomere and non-telomere genes linked to monogenic PF forms using whole-genome sequences (WGS) from 888 Pulmonary Fibrosis Foundation Patient Registry (PFFPR) individuals. We also derived a PRS for IPF (PRS-IPF) from 19 previously published common sentinel IPF variants. Using regression models, we then examined the mutual relationships of QVs and PRS-IPF and their association with survival. Validation of results was sought in WGS from an independent IPF study (PROFILE, n=472), and results from the two cohorts were meta-analyzed.

Results

Carriers of QVs in monogenic adult-onset PF genes, representing nearly 1 out of 6 IPF patients, were associated with lower PRS-IPF (Odds Ratio [OR]: 1.79; 95% Confidence Interval [CI]: 1.15-2.81; p=0.010) and shorter survival (Hazard Ratio [HR]: 1.53; 95% CI: 1.12-2.10; p=7.3×10-3). Notably, carriers of pathogenic variants at telomere genes showed the strongest association with survival (HR: 1.76; 95% CI: 1.13-2.76; p=0.013). The meta-analysis of the results showed a consistent direction of effect across both cohorts.

Conclusions

We revealed the opposite effects of QVs and PRS-IPF on IPF survival. Thus, a distinct IPF molecular subtype might be defined by QVs in monogenic adult-onset PF genes. Assessing the carrier status for QVs and modelling PRS-IPF promises to further contribute to predicting disease progression among IPF patients.
Long-term clinical and patient reported outcomes of an enhanced monofocal intraocular lens
Authors: Latz Catharina , Licht Annika , Ponto Katharina A. , Menzel-Severing Johannes , Piñero David P. , Mirshahi Alireza
Published: October 2024

Purpose

To evaluate long-term clinical and patient-reported outcomes (PROMs) following the implantation of an enhanced monofocal intraocular lens (IOL).

Methods

This ambispective non-comparative single-centre study involved 41 patients (ages 48-84) who underwent bilateral cataract surgery with the Tecnis Eyhance IOL (model ICB00, Johnson & Johnson Vision). Distance and intermediate visual acuities, refraction, and PROMs were assessed 18 months or more after surgery. Spectacle independence was evaluated using the PRSIQ questionnaire, with patients self-reporting on visual quality, difficulties in performing specific tasks and perception of photic phenomena at distance and intermediate vision.

Results

At 18 months or later, 100.0%, 73.2%, 100% and 79.5% of patients achieved a binocular uncorrected distance, uncorrected intermediate, corrected distance, and distance-corrected intermediate visual acuity of 0.20 logMAR or better, respectively. Less than 10% of patients reported photic phenomena. Mean visual quality scores were 1.68±0.72 for distance and 2.05±0.92 for intermediate vision (1=very good to 6=very poor). The dashboard was clearly visible while driving for 95.1% of patients, while 45.0% could perform screen work without glasses; an additional 40.0% could do so with enlarged fonts. Complete spectacle independence was reported by 87.8% for distance vision, and 53.7% for intermediate vision. At least moderately satisfied were 90.2% with distance vision, 87.8% with intermediate vision, and 51.2% with near vision.

Conclusions

The enhanced monofocal IOL ICB00 provides good long-term distance and intermediate visual quality, leading to considerable spectacle independence and patient satisfaction. Most patients required near vision correction.
Accurate Cell Abundance Quantification using Multi-positive and Unlabeled Self-learning
Authors: Lin Yating , Chen Xiaoqi , Lin Yuxiang , Xiao Xu , Huang Zhibin , Yang Wenxian , Yu Rongshan , Han Jiahuai
Published: October 2024

Quantifying the abundance of different cell types in pathological samples can help to uncover the correlations between cell composition and pathological conditions, offering deeper insights into the roles of different cell types in complex diseases. Conventional methods for cell abundance estimation often employ unsupervised clustering or supervised learning to identify cell types and estimate their proportions. However, these methods face challenges in accurately quantifying cell abundances, as clustering results could be unreliable and supervised methods may misclassify cell types not presented in the training data. We introduce CleverXMBD1(denoted as Clever) for quantifying cell abundance from complex samples using a multi-class classifier trained with a confidence-based multi-positive and unlabeled loss function. Our evaluations show that Clever consistently and substantially outperforms existing methods in quantifying cell type abundance across multiple single cell datasets derived from different modalities, including CyTOF and image mass cytometry.
Probabilistic Multiple Sequence Alignment using Spatial Transformations
Authors: García López Sebastián , Hauberg Søren , Boomsma Wouter
Published: October 2024

Abstract

Multiple Sequence Alignment (MSA) has long been a prominent and critical tool in bioinformatics and computational biology. Its importance lies in its ability to provide valuable insights into the relationships between sequences and the evolutionary pressure leading to amino acid preferences at particular sites in a protein. Despite the recent advances in protein language models, MSAs remain critical in many applications, e.g. for state-of-the-art prediction of 3D structure and protein variant effects. Sequence alignment is typically considered a deterministic preprocessing step, leading to a single static MSA. Especially for low-similarity sequences, parts of an alignment will be subject to substantial uncertainty, which is disregarded when processing a static MSA. Earlier, HMM-based approaches handled this uncertainty by considering the full posterior ensemble over alignments. In this paper, we explore whether a similar approach is feasible within a modern deep learning approach, where we move beyond the Markovian restrictions of earlier models. In particular, we consider whether we can learn the alignment process as distribution over spatial transformations, in combination with a deep latent variable model of protein sequences. A proof-of-concept implementation of this work is available athttps://github.com/deltadedirac/Explicit_Disentanglement_Molecules.
A global resource constrained model to predict metabolic flux dynamics in fluctuating environments
Authors: Yuan Huili , Bai Yang , Fu Xiongfei
Published: October 2024

Environmental changes often induce global variations on bacterial gene expression, frequently accompanied by alterations in growth rates. Integrating non-metabolic cellular processes, such as gene expression and macromolecule synthesis, with metabolic modeling remains a significant challenge in systems biology due to the lack of mechanistic representation of gene regulation. Here, we introduce a novel constraint-based modeling framework called dynamic Constrained Allocation Flux Balance Analysis (dCAFBA), which comprehensively integrates metabolism, cellular resource allocation, and gene regulation. We employ a quasi-steady-state assumption, positing that reaction fluxes achieve balance at each time step, adapting more rapidly than protein synthesis and growth dilution. This approach enables the prediction of reaction flux dynamics and protein allocation necessary to achieve cellular objectives, such as optimizing growth during various growth shifts (including carbon, amino acid, and transcriptional signal), without detailing molecular gene regulations. Our model offers a new method for interpreting proteome allocation and cellular metabolism in complex and transient environments, providing mechanistic insights valuable for metabolic engineering.
Characteristics of Vitelline Warbler songs and calls
Authors: Cummings Wyatt J. , Goodman David D. L. , Layne Craig D. , Singer Katherine I. , Whitney Thomas M.
Published: October 2024

The Vitelline Warbler (Setophaga vitellina) is an understudied species endemic to a few small islands in the western Caribbean. Little is known beyond its phylogenetic relationship to other New World warblers. We used island-wide surveys and bioacoustic recordings to investigate the distribution, vocalizations, and ecology ofS. vitellinaacross a significant portion of the species’ range on Little Cayman Island. We recorded 417 songs from 91 individuals and analyzed the length, frequency, and shape of various song components. We observed and characterized high variation in the composition and character of songs. We also describe the call of the species, document an association with gumbo limbo (Bursera simaruba) trees, and report interactions with other bird species. Improved knowledge of Vitelline Warblers has value for evaluating conservation threats to an island endemic and for understanding the evolution of vocalization behavior in Neotropical songbirds.