bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractCheckpoint 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

AbstractPurposeChoroidal 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.MethodsWe 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.ResultsWe 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).ConclusionsBoth 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

AbstractIntroductionMucus 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 analysisWe 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 DisseminationThe 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 studyUtilization 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

AbstractGenomic 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 StatementPrevailing 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

AbstractProteins 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

AbstractRegulation 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

AbstractOyster 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

AbstractThe 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

AbstractSocial 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

AbstractIn-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.
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

ABSTRACTBreast 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

AbstractIf 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.