bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of cathelicidins in neutrophil biology
Authors: Yoon Grace , Puentes Rodrigo , Tran Jacquelyn , Multani Anmol , Cobo Eduardo R
Published: May 2024

Despite their relatively short lifespan, neutrophils are tasked with counteracting pathogens through various functions, including phagocytosis, production of reactive oxygen species, neutrophil extracellular traps (NETs), and host defense peptides. Regarding the latter, small cationic cathelicidins present a conundrum in neutrophil function. Although primarily recognized as microbicides with an ability to provoke pores in microbial cell walls, the ability of cathelicidin to modulate key neutrophil functions is also of great importance, including the release of chemoattractants, cytokines, and reactive oxygen species, plus prolonging neutrophil lifespan. Cumulative evidence indicates a less recognized role of cathelicidin as an “immunomodulator”; however, this term is not always explicit, and its relevance in neutrophil responses during infection and inflammation is seldom discussed. This review compiles and discusses studies of how neutrophils use cathelicidin to respond to infections, while also acknowledging immunomodulatory aspects of cathelicidin through potential crosstalk between sources of the peptide.
Sleeping but not defenceless: seed dormancy and protection
Authors: Hubert Benjamin , Leprince Olivier , Buitink Julia
Published: May 2024

To ensure their vital role in disseminating the species, dormant seeds have developed adaptive strategies to protect themselves against pathogens and predators. This is orchestrated through the synthesis of an array of constitutive defences that are put in place in a developmentally regulated manner, which are the focus of this review. We summarize the defence activity and the nature of the molecules coming from the exudate of imbibing seeds that leak into their vicinity, also referred to as the spermosphere. As a second layer of protection, the dual role of the seed coat will be discussed; as a physical barrier and a multi-layered reservoir of defence compounds that are synthesized during seed development. Since imbibed dormant seeds can persist in the soil for extensive periods, we address the question of whether during this time a constitutively regulated defence programme is switched on to provide further protection, via the well-defined pathogenesis-related (PR) protein family. In addition, we review the hormonal and signalling pathways that might be involved in the interplay between dormancy and defence and point out questions that need further attention.
NiS ultrafine nanorod with translational and rotational symmetry
Authors: Kang Jianxin , Hu Qi , Zhang Ruixuan , Gao Ang , Huang Zhongning , Su Ziming , Pei Ke , Zhang Qinghua , Liu Li-Min , Che Renchao , Gu Lin , Guo Er-Jia , Guo Lin
Published: May 2024

Anisotropy is a significant and prevalent characteristic of materials, conferring orientation-dependent properties, meaning that the creation of original symmetry enables key functionality that is not found in nature. Even with the advancements in atomic machining, synthesis of separated symmetry in different directions within a single structure remains an extraordinary challenge. Here, we successfully fabricate NiS ultrafine nanorods with separated symmetry along two directions. The atomic structure of the nanorod exhibits rotational symmetry in the radial direction, while its axial direction is characterized by divergent translational symmetry, surpassing the conventional crystalline structures known to date. It does not fit the traditional description of the space group and the point group in three dimensions, so we define it as a new structure in which translational symmetry and rotational symmetry are separated. Further corroborating the atomic symmetric separation in the electronic structure, we observed the combination of stripe and vortex magnetic domains in a single nanorod with different directions, in accordance with the atomic structure. The manipulation of nanostructure at the atomic level introduces a novel approach to regulate new properties finely, leading to the proposal of new nanotechnology mechanisms.
Distinct features of ANCA-associated hypertrophic pachymeningitis compared with other etiologies: findings from a study of 74 patients
Authors: Martín-Nares Eduardo , Romero-Sánchez Griselda , Cortez-Domínguez Edwin Ulises , Cano-Cruz Lilian Guadalupe , Hinojosa-Azaola Andrea
Published: May 2024

Objectives

We aimed to characterize the clinical and radiological features, and outcomes, of a large cohort of hypertrophic pachymeningitis (HP) patients from a single centre.

Methods

We conducted a retrospective study at a tertiary referral centre, encompassing patients diagnosed with HP between 2003 and 2022. The diagnosis of HP relied on the identification of thickening of the dura mater via MRI of the brain or spine.

Results

We included 74 patients, with a mean age of 43.6 ± 14.2 years, of whom 37 (50%) were male. Among the 74, 32 (43.2%) had an immune-mediated origin, including 21 with granulomatosis with polyangiitis (GPA) (predominantly PR3-ANCA positive), four with SLE, three with IgG4-related disease, three with idiopathic HP, and one with RA. Non-immune-mediated HP accounted for 45 cases (56.8%). Within this category, 21 (28.4%) were infectious cases, with 14 having Mycobacterium tuberculosis infection (TB-HP), and 21 (28.4%) having malignancy-associated HP. The clinical and MRI characteristics exhibited variations among the four etiological groups. Hypoglycorrhachia was primarily observed in infectious HP and malignancy-associated HP. Immune-mediated HP was associated with a peripheral pattern of contrast enhancement and the Eiffel-by-night sign. MRI features strongly indicative of TB-HP included leptomeningeal involvement, brain parenchymal lesions, and arterial stroke. MPO-ANCA GPA was associated with a higher prevalence of spinal HP.

Conclusios

Within our cohort, GPA and Mycobacterium tuberculosis emerged as the predominant causes of HP. We identified significant disparities in clinical and radiological features among the various etiologies, which could have implications for diagnosis.
International Experience of Implementing Cognitive Remediation for People With Psychotic Disorders
Authors: Dark Frances L , Amado Isabelle , Erlich Matthew D , Ikezawa Satoru
Published: May 2024

Background

Cognitive remediation (CR) is an effective therapy for the cognitive impact of mental illness, especially schizophrenia. Global efforts are being made to implement CR into routine mental health services with the aim of improving functional outcomes for the population of people recovering from mental illness. Implementation and dissemination of CR in heterogeneous settings require knowledge gleaned from formal implementation research and pragmatic experiential learning. This article describes cross-cultural approaches to CR implementation, focusing on initiatives in France, the United States, Australia, and Japan.

Method

Key leaders in the implementation of CR in France, the United States, Australia, and Japan were asked to describe the implementation and dissemination process in their settings with respect to the categories of context, implementation, outcomes, facilitators, and barriers.

Results

All 4 sites noted the role of collaboration to leverage the implementation of CR into mental health rehabilitation services. In France, high-level, government organizational backing enhanced the dissemination of CR. Academic and clinical service partnerships in the United States facilitated the dissemination of programs. The advocacy from service users, families, and carers can aid implementation. The support from international experts in the field can assist in initiating programs but maintenance and dissemination require ongoing training and supervision of staff.

Conclusions

CR is an effective intervention for the cognitive impact of schizophrenia. Programs can be implemented in diverse settings globally. Adaptations of CR centering upon the core components of effective CR therapy enhance outcomes and enable programs to integrate into diverse settings.
SEC: A core hub during cell fate alteration
Authors: Zhang Zhijing , Xu Jingyi , Liu Jiqiang , Wang Jiaqiang , Lei Lei
Published: May 2024

Pol II pause release is a rate‐limiting step in gene transcription, influencing various cell fate alterations. Numerous proteins orchestrate Pol II pause release, thereby playing pivotal roles in the intricate process of cellular fate modulation. Super elongation complex (SEC), a large assembly comprising diverse protein components, has garnered attention due to its emerging significance in orchestrating physiological and pathological cellular identity changes by regulating the transcription of crucial genes. Consequently, SEC emerges as a noteworthy functional complex capable of modulating cell fate alterations. Therefore, a comprehensive review is warranted to systematically summarize the core roles of SEC in different types of cell fate alterations. This review focuses on elucidating the current understanding of the structural and functional basis of SEC. Additionally, we discuss the intricate regulatory mechanisms governing SEC in various models of cell fate alteration, encompassing both physiological and pathological contexts. Furthermore, leveraging the existing knowledge of SEC, we propose some insightful directions for future research, aiming to enhance our mechanistic and functional comprehension of SEC within the diverse landscape of cell fate alterations.
Morbidly Obese Patients Have Similar Clinical Outcomes and Recovery Kinetics After Minimally Invasive Decompression
Authors: Shahi Pratyush , Subramanian Tejas , Singh Sumedha , Araghi Kasra , Asada Tomoyuki , Korsun Maximilian , Singh Nishtha , Tuma Olivia , Simon Chad , Vaishnav Avani , Mai Eric , Zhang Joshua , Kwas Cole , Allen Myles , Kim Eric , Heuer Annika , Sheha Evan , Dowdell James , Qureshi Sheeraz , Iyer Sravisht
Published: May 2024

Study Design.

Retrospective cohort.

Objective.

To study the impact of class 2/3 obesity (body mass index, BMI ≥35) on outcomes following minimally invasive decompression.

Summary of Background Data.

No previous study has analyzed the impact of class 2/3 obesity on outcomes following minimally invasive decompression.

Materials and Methods.

Patients who underwent primary minimally invasive decompression were divided into four cohorts based on their BMI: normal (BMI: 18.5–<25), overweight (25–<30), class 1 obesity (30–<35), and class 2/3 obesity (BMI ≥35). Outcome measures were: 1) intraoperative variables: operative time, estimated blood loss (EBL); 2) patient-reported outcome measures (PROMs) (Oswestry disability index, ODI; visual analog scale, VAS back and leg; 12-Item Short Form Survey Physical Component Score, SF-12 PCS); 3) global rating change (GRC), minimal clinically important difference (MCID), and patient acceptable symptom state (PASS) achievement rates; 4) return to activities; and 5) complication and reoperation rates.

Results.

Totally, 838 patients were included (226 normal, 357 overweight, 179 class 1 obesity, and 76 class 2/3 obesity). Class 1 and 2/3 obesity groups had significantly greater operative times compared with the other groups. Class 2/3 obesity group had worse ODI, VAS back and SF-12 PCS preoperatively, worse ODI, VAS back, VAS leg and SF-12 PCS at below six months, and worse ODI and SF-12 PCS at above six months. However, they had significant improvement in all PROMs at both postoperative timepoints and the magnitude of improvement was similar to other groups. No significant differences were found in MCID and PASS achievement rates, likelihood of betterment on the GRC scale, return to activities, and complication/reoperation rates.

Conclusions.

Class 2/3 obese patients have worse PROMs preoperatively and postoperatively. However, they show similar improvement in PROMs, MCID and PASS achievement rates, likelihood of betterment, recovery kinetics, and complication/reoperation rates as other BMI groups following minimally invasive decompression.
Craniofacial Fracture with Superior Orbital Fissure Syndrome Resulting in Pupil-sparing Oculomotor Nerve Palsy
Authors: Taniguchi Hiroshi , Nishioka Hiroshi , Kuriyama Erika , Inoue Yoshikazu , Okumoto Takayuki
Published: May 2024

Superior orbital fissure syndrome (SOFS) is a rare complication of craniofacial fracture, caused by damage to cranial nerves Ⅲ, Ⅳ, Ⅴ, and Ⅵ, which typically is associated with ophthalmoplegia, blepharoptosis, pupil dilatation and fixation, and upper eyelid and forehead hypesthesia. However, we here describe a very unusual case of craniofacial fracture with SOFS in the absence of pupil symptoms, involving a patient who was injured when he fell while riding his bicycle. Upon medical examination, we observed mild blepharoptosis and ophthalmoplegia of the right eye without pupillary symptoms. Computed tomography (CT) revealed basal skull and zygomatic fractures. After the patient had been treated conservatively for his skull base fracture, facial bone reduction was performed at our hospital. Because ophthalmoplegia and blepharoptosis remained after the surgery, we checked the preoperative CT images again and discovered stenosis of the superior orbital fissure. Postoperative CT revealed a widening of the superior orbital fissure after the facial bone reduction, and therefore, the patient was given steroid treatment without additional surgery. At 6 months postoperatively, the cranial nerves had completely recovered. Our finding emphasizes that, in contrast to common theory, trauma-induced SOFS can result in pupil-sparing oculomotor nerve palsy.
An Exaggeration? Reality?
Authors: Sarman Abdullah , Tuncay Suat
Published: May 2024

Artificial intelligence (AI) represents a system endowed with the ability to derive meaningful inferences from a diverse array of datasets. Rooted in the advancements of machine learning models, AI has spawned various transformative technologies such as deep learning, natural language processing, computer vision, and robotics. This technological evolution is poised to witness a broadened spectrum of applications across diverse domains, with a particular focus on revolutionizing healthcare services. Noteworthy among these innovations is OpenAI's creation, ChatGPT, which stands out for its profound capabilities in intricate analysis, primarily facilitated through extensive language modeling. In the realm of healthcare, AI applications, including ChatGPT, have showcased promising outcomes, especially in the domain of neonatal nursing. Areas such as pain assessment, feeding processes, and patient status determination have witnessed substantial enhancements through the integration of AI technologies. However, it is crucial to approach the deployment of such applications with a judicious mindset. The accuracy of the underlying data must undergo rigorous validation, and any results lacking a solid foundation in scientific insights should be approached with skepticism. The paramount consideration remains patient safety, necessitating that AI applications, like ChatGPT, undergo thorough scrutiny through controlled and evidence-based studies. Only through such meticulous evaluation can the transformative potential of AI be harnessed responsibly, ensuring its alignment with the highest standards of healthcare practice.
Measuring Physical Activity in Children Who Do Not Walk and With Cerebral Palsy: An Exploratory Case Series
Authors: Toomer-Mensah Nia , O’Neil Margaret , Blacutt Miguel , Quinn Lori
Published: May 2024

Aim:

The purpose of this case series was to describe physical activity (PA) amount and intensity in the home and school environment. Accelerometers and heart rate (HR) monitors are reliable and valid measures of PA in children with cerebral palsy (CP) who can walk. There is limited research on PA measures in children with CP who cannot walk.

Methods:

Three 9-year-old boys with CP, Gross Motor Function Classification System levels IV and V, participated in a 1-week measurement period wearing waist- and wrist-worn triaxial accelerometers to measure PA counts and a wrist-worn HR monitor to measure PA intensity. PA intensity was calculated using an estimated HR max. Accelerometer counts were reported. Parents and school staff completed activity and eating journals.

Results:

Six days of PA and HR data were analyzed. Two participants spent more time in moderate/vigorous PA intensity during school compared to at home. Activities with greatest PA intensity included oral eating, communication, and social engagement. Higher activity counts were recorded from the wrist compared with the waist accelerometers. PA and eating journal adherence were high in both settings.

Conclusion:

The findings provide preliminary data to evaluate PA amount and intensity in children with CP who have little walking ability. It is important to consider PA levels in daily activity for youth with CP when designing plans of care.
EZH2-driven immune evasion defines high-risk pediatric AML with t(16;21) FUS::ERG gene fusion
Authors: Buteyn Nathaniel J , Burke Connor G , Sartori Vincent J , Deering-Gardner Eve , DeBruine Zachary J , Kamarudin Dahlya , Chandler Darrell P , Monovich Alexander C , Perez Monika W , Yi Joanna S , Ries Rhonda E , Alonzo Todd A , Ryan Russell JH , Meshinchi Soheil , Triche Timothy J
Published: May 2024

Despite decades of research, acute myeloid leukemia (AML) remains a remarkably lethal malignancy. While pediatric AML (pAML) carries a more favorable prognosis than adult AML, the past 25 years of large clinical trials have produced few improvements in pAML survival. Nowhere is this more evident than in patients carrying a t(16;21)(p11;q22) translocation, which yields theFUS::ERGfusion transcript. Patients withFUS::ERG-positive AML are often primary refractory, and most responders quickly relapse. In COG clinical trials, allogeneic stem cell transplantation was of no benefit toFUS::ERGpAML patients; 100% of transplanted patients succumbed to their disease. Expression of major histocompatibility complex (MHC) class I & II and costimulatory molecules is absent at diagnosis inFUS::ERGAML, mirroring the epigenetic mechanism of post-transplant relapse seen in adult AML and its associated dismal outcomes. Here we show that this class-defining immune-repressive phenotype is driven by overexpression of theEZH2histone lysine methyltransferasein vitroand in multiple clinical cohorts. We show that treatment with the FDA-approved EZH2 inhibitor tazemetostat along with IFN-γ reverses this phenotype, re-establishes MHC presentation, and severely impairs the viability ofFUS::ERGAML cells. EZH2 inhibitors may thus provide the first targeted therapeutic option for patients with this high-risk subtype of pAML, with particular benefit as a bridge to successful allogeneic stem cell transplantation.

STATEMENT OF SIGNIFICANCE

FUS::ERGpAML patients have dismal outcomes. Here we show a ubiquitous immune-evasive phenotype, defined by elevated EZH2 levels and loss of MHC class I and II receptors, present in these patients at diagnosis. Treatment with the EZH2 inhibitor tazemetostat and IFN-γ reverses this phenotype in patient-derived cell lines.
Immunopipe: A comprehensive and flexible scRNA-seq and scTCR-seq data analysis pipeline
Authors: Wang Panwen , Yu Yue , Dong Haidong , Zhang Shuwen , Sun Zhifu , Zeng Hu , Mondello Patrizia , Kocher Jean-Pierre A. , Wang Junwen , Asmann Yan W. , Lin Yi , Li Ying
Published: May 2024

Single-cell sequencing technologies provide us with information at the level of individual cells. The combination of single-cell RNA-seq and single-cell TCR-seq profiling enables the exploration of cell heterogeneity and T-cell receptor repertoires simultaneously. The integration of both types of data can play a crucial role in enhancing our understanding of T-cell-mediated immunity and, in turn, facilitate the advancement of immunotherapy. Here, we present immunopipe, a comprehensive and flexible pipeline to perform integrated analysis of scRNA-seq and scTCR-seq data. In addition to the command line tool, we provide a user-friendly web interface for pipeline configuration and execution monitoring, benefiting researchers without extensive programming experience. With its comprehensive functionality and ease of use, immunopipe empowers researchers to uncover valuable insights from scRNA-seq and scTCR-seq data, ultimately advancing the understanding of immune responses and immunotherapy development.
The immune cell dynamics in the peripheral blood of cHL patients receiving anti-PD1 treatment
Authors: Cristaldi Vanessa , Terzi di Bergamo Lodovico , Patruno Lucrezia , Kallikourdis Marinos , Cassanmagnago Giada Andrea , Corrado Francesco , Calabretta Eleonora , Condoluci Adalgisa , di Trani Martina , Rahal Daoud , Basso Gianluca , Peano Clelia , Graudenzi Alex , Antoniotti Marco , Rossi Davide , Carlo-Stella Carmelo
Published: May 2024

Checkpoint blockade therapy (CBT) involving anti-PD1 antibodies represents the standard approach for cHL patients who do not respond to second-line therapy. Nonetheless, only 20% of relapsed/refractory (R/R) cHL patients treated with CBT achieve complete remission. In this study, we extensively examined the immune dynamics in eight R/R cHL patients treated with CBT, consisting of four complete responders (CR) and four experiencing disease progression (PD), by single cell analysis of peripheral blood mononuclear cells (PBMCs). Our unique approach encompassed longitudinal analysis with three time points, providing a comprehensive understanding of the evolving immune responses during anti-PD1 therapy. Through gene expression profiling, we identified a stable and distinctive KLRG1+/ FOS+/JUN+/GZMA+/CD8+ T cell phenotype in patients achieving complete responses. This specific CD8+ T cell subset exhibited sustained activation, underscoring its potential pivotal role in mounting an effective immune response against cHL. Furthermore, T cell receptor (TCR) analysis revealed that in responder patients there is clonal expansion between TCR clonotypes specifically in the KLRG1+/FOS+/JUN+/GZMA+/CD8+ T cell subset. Our longitudinal study offers unique insights into the complex immune dynamics of multiply relapsed/highly pre-treated cHL patients undergoing anti-PD1 therapy.
Corneal neuropathy in central serous chorioretinopathy
Authors: Bourges Jean-Louis , Leclercq Bastien , Behar-Cohen Françine
Published: May 2024

Purpose

Choroidal sympathetic innervation is impaired in central serous chorioretinopathy (CSCR) (1), throughout mineralocorticoid receptor.(2) We hypothesize that the CSCR condition modifies the entire eyeball innervation system. Corneal nerve shape is easily observed by in vivo confocal microscopy (IVCM).(3) We explored corneal nerves morphology in 2 groups of patients with CSCR and without (CTRL), using vivo confocal microscopy.

Methods

We quantified choroid thickness in both groups by OCT-EDI mode (Spectralis; Heidelberg). Patients were free from corneal disease. We explored the central, mid-peripheral, paralimbal and limbal corneal areas of patients with and without CSCR by IVCM (HRT3; Heidelberg). We proceeded with the multilayer module of acquisition and analyzed systematically the subepithelial area (SE), Bowman’s layer (BL), anterior (AS)/intermediate (IS)/deep stroma (DS) (Depth<50µm/50≤D<150µm/D≥150µm respectively), and endothelium. We semi-quantified as absent (0), rare (1) or common (2) by scoring the morphological corneal nerves abnormalities in both groups.

Results

We compared 15 CSCR to 11 age-matched CTRL. While abnormalities were detected sparsely (n=3; in SE, BL and A), 8 CTRL showed normal corneal nerve networks. All CSCR but one displayed nerve abnormalities. Nerve abnormalities were considered as normal, moderate, or severe in respectively 8, 3 and none CRTL versus 1, 3 and 12 CSCR. Nerves alterations were noticeably analogous to each other in all layers for CSCR. More subnormal nerve patterns were observed compared to CTRL in the 5 explored layers (p≤ 0.001).

Conclusions

Both thin nerve network and subepithelial plexus are altered in cornea of CSCR patients compared to CTRL, mainly across anterior layers and along straight nerve ramifications crossing the mid stroma of cornea. Nerve fiber abnormalities seems to develop in the cornea of CSCR patients in the absence of clinical corneopathy, and could serve as an early marker for the disease.
Airway Mucus Plugs in Community-Living Adults: A Study Protocol
Authors: Abdalla Maya , Elalami Rim , Cho Michael H , O’Connor George T , Rice Mary , Horowitz Michael , Akhoundi Neda , Yen Andrew , Kalhan Ravi , Diaz Alejandro A.
Published: May 2024

Introduction

Mucus pathology plays a critical role in airway diseases like chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). Up to 32% of community-living persons report clinical manifestations of mucus pathology (e.g., cough and sputum production). However, airway mucus pathology has not been systematically studied in community-living individuals. In this study, we will use an objective, reproducible assessment of mucus pathology on chest computed tomography (CT) scans from community-living individuals participating in the Coronary Artery Risk Development in Young Adults (CARDIA) and Framingham Heart Study (FHS) cohorts.

Methods and analysis

We will determine the clinical relevance of CT-based mucus plugs and modifiable and genetic risk and protective factors associated with this process. We will evaluate the associations of mucus plugs with lung function, respiratory symptoms, and chronic bronchitis and examine whether 5-yr. persistent CT-based mucus plugs are associated with the decline in FEV1and future COPD. Also, we will assess whether modifiable factors, including air pollution and marijuana smoking are associated with increased odds of CT-based mucus plugs and whether cardiorespiratory fitness is related in an opposing manner. Finally, we will determine genetic resilience/susceptibility to mucus pathology. We will use CT data from the FHS and CARDIA cohorts and genome-wide sequencing data from the TOPMed initiative to identify common and rare variants associated with CT-based mucus plugging.

Ethics and Dissemination

The Mass General Brigham Institutional Review Board approved the study. Findings will be disseminated through peer-reviewed journals and at professional conferences.

Strengths and limitations of this study

Utilization of data from two well-characterized large community-based US cohorts.

Use of chest CT scans to identify and quantify mucus plugs, providing a more objective and reproducible measure of airway pathology.

Use of whole-genome sequencing to identify common and rare genetic variants associated with mucus pathology.

Only the inclusion of participants self-identified as non-Hispanic white and non-Hispanic black.

A limitation of retrospective study design using prospectively collected data.
Fitness consequences of structural variation inferred from a House Finch pangenome
Authors: Fang Bohao , Edwards Scott V.
Published: May 2024

Genomic structural variants (SVs) play a crucial role in adaptive evolution, yet their average fitness effects and characterization with pangenome tools are understudied in wild animal populations. We constructed a pangenome for House Finches, a model for studies of host-pathogen coevolution, using long-read sequence data on 16 individuals (32de novo-assembled haplotypes) and one outgroup. We identified 643,207 SVs larger than 50 base pairs, mostly (60%) involving repetitive elements, with reduced SV diversity in the eastern US as a result of its introduction by humans. The distribution of fitness effects of genome-wide SVs was estimated using maximum likelihood approaches and showed SVs in both coding and non-coding regions to be on average more deleterious than smaller indels or single nucleotide polymorphisms. The reference-free pangenome facilitated discovery of a 10-million-year-old, 11-megabase-long pericentric inversion on chromosome 1. We found that the genotype frequencies of the inversion, estimated from 135 birds widely sampled geographically and temporally, increased steadily over the 25 years since House Finches were first exposed to the bacterial pathogenMycoplasma gallispecticumand showed signatures of balancing selection, capturing genes related to immunity and telomerase activity. We also observed shorter telomeres in populations with a greater number of years exposure toMycoplasma. Our study illustrates the utility of applying pangenome methods to wild animal populations, helps estimate fitness effects of genome-wide SVs, and advances our understanding of adaptive evolution through structural variation.

Significance Statement

Prevailing genomic research on adaptive and neutral evolution has focused primarily on single nucleotide polymorphisms (SNPs). However, structural variation (SV) plays a critical role in animal adaptive evolution, often directly underlying fitness-relevant traits, although their average effects on fitness are less well understood. Our study constructs a pangenome for the House Finch using long-read sequencing, capturing the full spectrum of genomic diversity without use of a reference genome. In addition to detecting over half a million SVs, we also document a large inversion that shows evidence of contributing to disease resistance. Our use of long-read sequencing and pangenomic approaches in a wild bird population presents a compelling approach to understanding the complexities of molecular ecology and adaptive evolution.

Graphical abstract
An atlas of protein-protein associations of human tissues prioritizes candidate disease genes
Authors: Laman Trip Diederik S , van Oostrum Marc , Memon Danish , Frommelt Fabian , Baptista Delora , Panneerselvam Kalpana , Bradley Glyn , Licata Luana , Hermjakob Henning , Orchard Sandra , Trynka Gosia , McDonagh Ellen , Fossati Andrea , Aebersold Ruedi , Gstaiger Matthias , Wollscheid Bernd , Beltrao Pedro
Published: May 2024

Proteins that interact together participate in the same cellular process and influence the same organismal traits. Despite the progress in mapping protein-protein interactions we lack knowledge of how they differ between tissues. Due to coordinated (post)transcriptional control, protein complex members have highly correlated abundances that are predictive of functional association. Here, we have compiled 7873 proteomic samples measuring protein levels in 11 human tissues and use these to define an atlas with tissue-specific protein associations. This method recapitulates known protein complexes and the larger structural organization of the cell. Interactions of stable protein complexes are well preserved across tissues, while signaling and metabolic interactions show larger variation. Further, we find that less than 18% of differences between tissues are estimated to be due to differences in gene expression while cell-type specific cellular structures, such as synaptic components, represent a significant driver of differences between tissues. We further supported the brain protein association network through co-fractionation experiments in synaptosomes, curation of brain derived pull-down data and AlphaFold2 models. Together these results illustrate how this brain specific protein interaction network can functionally prioritize candidate genes within loci linked to brain disorders.
Analysis of developmental gene expression using smFISH andin silicostaging ofC. elegansembryos
Authors: Breimann Laura , Bahry Ella , Zouinkhi Marwan , Kolyvanov Klim , Street Lena Annika , Preibisch Stephan , Ercan Sevinç
Published: May 2024

Regulation of transcription during embryogenesis is key to development and differentiation. To study transcript expression throughoutCaenorhabditis elegansembryogenesis at single-molecule resolution, we developed a high-throughput single-molecule fluorescence in situ hybridization (smFISH) method that relies on computational methods to developmentally stage embryos and quantify individual mRNA molecules in single embryos. We applied our system tosdc-2, a zygotically transcribed gene essential for hermaphrodite development and dosage compensation. We found thatsdc-2is rapidly activated during early embryogenesis by increasing both the number of mRNAs produced per transcription site and the frequency of sites engaged in transcription. Knockdown ofsdc-2anddpy-27, a subunit of the dosage compensation complex (DCC), increased the number of active transcription sites for the X chromosomal genedpy-23but not the autosomal genemdh-1, suggesting that the DCC reduces the frequency ofdpy-23transcription. The temporal resolution fromin silicostaging of embryos showed that the deletion of a single DCC recruitment element near thedpy-23gene causes higherdpy-23mRNA expression after the start of dosage compensation, which could not be resolved using mRNAseq from mixed-stage embryos. In summary, we have established a computational approach to quantify temporal regulation of transcription throughoutC. elegansembryogenesis and demonstrated its potential to provide new insights into developmental gene regulation.
Combinatorial characterization of bacterial taxa-driven differences in the microbiome of oyster reefs
Authors: Cyphert Erika L. , Nand Sanjiev , Franco Gabriela , Hajkowski Michael , Soto Luzmaria , Lee Danica Marvi , Ferner Matt , Zabin Chela , Blumenthal Jeffrey , Deck Anna , Boyer Katharyn , Burrus Kai , Hernandez Christopher J , Anand Archana
Published: May 2024

Oyster reefs are invaluable ecosystems that provide a wide array of critical ecosystem services, including water filtration, coastal protection, and habitat provision for various marine species. However, these essential habitats face escalating threats from climate change and anthropogenic stressors. To combat these challenges, numerous oyster restoration initiatives have been undertaken, representing a global effort to preserve and restore these vital ecosystems. A significant, yet poorly understood, component of oyster reefs is the microbial communities. These communities account for a substantial proportion of marine reefs and are pivotal in driving key biogeochemical processes. Particularly, the environmental microbiome plays a crucial role in supporting the health and resilience of oyster populations. In our study, we sought to shed light on the microbiome within oyster reef ecosystems by characterizing the abundance, and diversity of microorganisms in the soil, biofilm, and oysters in 4 sites using a combinatorial approach to identify differentially abundant microbes by sample type and by sampling location. Our investigation revealed distinct microbial taxa in oysters, sediment and biofilm. The maximum Shannon Index indicated a slightly increased diversity in Heron’s Head (5.47), followed by Brickyard park (5.35), Dunphy Park (5.17) and Point Pinole (4.85). This is likely to be driven by significantly higher oyster mortality observed at Point Pinole during routine monitoring and restoration efforts. InterestinglyRuminococcus, Streptococcus, Staphylococcus, Prevotella, Porphyromonas, Parvimonas, Neisseria, Lactococcus, Haemophilus, Fusobacterium, Dorea, Clostridium, Campylobacter, Bacteroides, andAkkermansiawere positively associated with the biofilm. Yet we have limited understanding of their beneficial and/or detrimental implications to oyster growth and survival. By unraveling the intricate relationships in microbial composition across an oyster reef, our study contributes to advancing the knowledge needed to support effective oyster reef conservation and restoration efforts.
Development of shell field populations in gastropods
Authors: Phuangphong Supanat , Yoshikawa Hiroki , Kojima Yune , Wada Hiroshi , Morino Yoshiaki
Published: May 2024

The embryonic shell field of mollusks first appears during gastrulation of the dorsal ectoderm and subsequently develops into the shell-secreting mantle in adult animals. Although several lines of evidence have revealed that this shell field lineage is exclusively derived from the second quartet (2q) of the 16-cell embryos, it is generally believed that the establishment of the shell field fate would be accomplished only after receiving inductive signals from the invaginated endoderm. Despite being accepted as a comprehensive model for molluskan shell field specification, the validity of this induction hypothesis remains questionable owing to the lack of clear experimental evidence and contradictory results. Here, we attempted to re-investigate the inductive role of the endoderm in shell field fate establishment in the limpetNipponacmea fuscoviridisby experimentally disrupting cell-cell contacts between cell lineages after the 16-cell stage. First, we characterized the shell field cell population by performing two-colorin situhybridization. We characterized at least three cell populations in the developing shell field. Using single-cell transcriptome analysis, we identified several specific effector genes for each population, as well as transcription factor genes. Differentiation of each shell field population was inspected in 2q blastomeres isolated from other cells of the 16-cell embryos. Despite the absence of any interlineage interactions (including ectoderm-endoderm contacts), the expression of marker genes for each shell field population was observed in the isolated 2q fragments. In addition, the expression of several shell field genes was detected in embryos in which cytokinesis was blocked at the 16-cell stage. We concluded that the early process of shell field differentiation in the 2q lineage occurs mostly independently of the interactions with other lineages.
Discrimination against non-nestmates functions to exclude socially parasitic conspecifics in an ant
Authors: Nakamura Takuma P. , Dobata Shigeto
Published: May 2024

Social animals utilise various communication methods to organise their societies. In social insects, nestmate discrimination plays a crucial role in regulating colony membership. Counter to this system, socially parasitic species employ diverse behavioural and chemical strategies to bypass their host’s detection. In this study, we tested whether such parasitic adaptations could be detected in the incipient stage of social parasitism that is observed as intraspecific phenomena in some social insects. The Japanese parthenogenetic antPristomyrmex punctatusharbours a genetically distinct cheater lineage which infiltrates and exploits host colonies. We found that intrusion of this intraspecific social parasite was defended by nestmate discrimination of host colonies without any behavioural strategies specialised in social parasitism. Most of the cheaters were eliminated through aggressions by host workers that are typically observed against non-nestmates, resulting in a low intrusion success rate for the cheaters (6.7%). This result contrasts with the expectation from interspecific social parasitism but rather resembles the intraspecific counterpart reported in Cape honeybees (Apis mellifera capensis), illustrating the role of nestmate discrimination against the intrusion of intraspecific social parasites.
Optimised in-solution enrichment of over a million ancient human SNPs
Authors: Davidson Roberta , Roca-Rada Xavier , Ravishankar Shyamsundar , Taufik Leonard , Haarkötter Christian , Collen Evelyn , Williams Matthew , Webb Peter , Irfan Mahmud M. , Djami Erlin Novita Idje , Purnomo Gludhug A. , Santos Cristina , Malgosa Assumpció , Manzanilla Linda R. , Silva Ana Maria , Tereso Sofia , Matos Vítor , Carvalho Pedro C. , Fernandes Teresa , Maurer Anne-France , Teixeira João C. , Tobler Raymond , Fehren-Schmitz Lars , Llamas Bastien
Published: May 2024

In-solution hybridisation enrichment of genetic markers is a method of choice in paleogenomic studies, where the DNA of interest is generally heavily fragmented and contaminated with environmental DNA, and where the retrieval of genetic data comparable between individuals is challenging. Here, we benchmarked the commercial “Twist Ancient DNA” reagent from Twist Biosciences using sequencing libraries from ancestrally diverse ancient human samples with low to high endogenous DNA content (0.1–44%). For each library, we tested one and two rounds of enrichment, and assessed performance compared to deep shotgun sequencing. We find that the “Twist Ancient DNA” assay provides robust enrichment of ∼1.2M target SNPs without introducing allelic bias that may interfere with downstream population genetics analyses. Additionally, we show that pooling up to 4 sequencing libraries and performing two rounds of enrichment is both reliable and cost-effective for libraries with less than 27% endogenous DNA content. Above 38% endogenous content, a maximum of one round of enrichment is recommended for cost-effectiveness and to preserve library complexity. In conclusion, we provide researchers in the field of human paleogenomics with a comprehensive understanding of the strengths and limitations of different sequencing and enrichment strategies, and our results offer practical guidance for optimising experimental protocols.
Uncovering multiscale structure in the variability of larval zebrafish navigation
Authors: Sridhar Gautam , Vergassola Massimo , Marques João C. , Orger Michael B. , Costa Antonio Carlos , Wyart Claire
Published: May 2024

Animals chain movements into long-lived motor strategies, resulting in variability that ultimately reflects the interplay between internal states and environmental cues. To reveal structure in such variability, we build models that bridges across time scales that enable a quantitative comparison of behavioral phenotypes among individuals. Applied to larval zebrafish exposed to diverse sensory cues, we uncover a hierarchy of long-lived motor strategies, dominated by changes in orientation distinguishing cruising and wandering strategies. Environmental cues induce preferences along these modes at the population level: while fish cruise in the light, they wander in response to aversive (dark) stimuli or in search for prey. Our method enables us to encode the behavioral dynamics of each individual fish in the transitions among coarse-grained motor strategies. By doing so, we uncover a hierarchical structure to the phenotypic variability that corresponds to exploration-exploitation trade-offs. Within a wide range of sensory cues, a major source of variation among fish is driven by prior and immediate exposure to prey that induces exploitation phenotypes. However, a large degree of variability is unexplained by environmental cues, pointing to hidden states that override the sensory context to induce contrasting exploration-exploitation phenotypes. Altogether, our approach extracts the timescales of motor strategies deployed during navigation, exposing undiscovered structure among individuals and pointing to internal states tuned by prior experience.
Inter-individual and inter-regional variability of breast milk antibody reactivity to bacterial lipopolysaccharides
Authors: Crone Lisa , Sobek Jens , Müller Nicole , Restin Tanja , Bassler Dirk , Paganini Daniela , Zimmermann Michael B. , Zarnovican Patricia , Routier Françoise H. , Romero-Uruñuela Tais , Izquierdo Luis , Hennet Thierry
Published: May 2024

Breast milk is a vital source of nutrients, prebiotics, and protective factors, including antibodies and antimicrobial proteins. Using bacterial lipopolysaccharide arrays, we investigated the reactivity and specificity of breast milk antibodies towards microbial antigens, comparing samples from rural Kenya and urban Switzerland. Results showed considerable variability in antibody reactivity both within and between these locations. Kenyan breast milk demonstrated broad reactivity to bacterial lipopolysaccharides, likely due to increased microbial exposure. Antibodies primarily recognized the O-antigens of lipopolysaccharides and showed strong binding to specific carbohydrate motifs. Notably, antibodies against specificEscherichia coliO-antigens showed cross-reactivity with parasitic pathogens likeLeishmania majorandPlasmodium falciparum, thus showing that antibodies reacting against lipopolysaccharide O-antigens can recognize a wide range of antigens beyond bacteria. The observed diversity in antigen recognition highlights the significance of breast milk in safeguarding infants from infections, particularly those prevalent in specific geographic regions. The findings also offer insights for potential immunobiotic strategies to augment natural antibody-mediated defense against diverse pathogens.
Matching sounds to shapes: Evidence of the Bouba-Kiki effect in naïve baby chicks
Authors: Loconsole Maria , Benavides-Varela Silvia , Regolin Lucia
Published: May 2024

If you hear the non-words ‘Kiki’ and ‘Bouba’, you may be more likely to associate them with a spiky and a round object, respectively, rather than the opposite. This is a case of sound-symbolism, known as the Bouba-Kiki effect. Studies on four-months infants suggest that this effect might constitute a predisposed perceptual mechanism. However, these studies suffered from the impossibility of ruling out a fast experience-driven origin of the effect resulting from infants’ speed of learning, their sensitivity to environmental regularities, and the large number of sound-symbolic associations to which they are precociously exposed when interacting with adults. To better describe its ontogeny and fill in this gap, we tested the Bouba-Kiki effect in domestic chicks (Gallus gallus). Being a precocial species, chicks can be tested on the very early days of life, allowing for a virtually total control of their experience before test. Three-day-old chicks (n=42) first learned to circumnavigate a panel to obtain a food reward. Then, they were presented with two identical panels, one depicting a spiky shape, and one depicting a round shape, while hearing either the sound ‘Bouba’ or ‘Kiki’. We recorded which panel chicks chose with either sound, in a total of 24 trials. Chicks preferred the panel with the spiky shape when hearing the ‘Kiki’ sound, and that with the round shape when hearing the ‘Bouba’ sound. Results from naïve baby chicks hint at a predisposed mechanism for matching the two dimensions of shape and sound that may be widespread across species.