bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a heterogenous activated B cell compartment arising early after antigen exposure preceding long-lived memory B cell formation
Authors: Fernandez Blanco L , Kuijper LH , Kummer LYL , Verstegen NJM , Bos A , Claireaux M , Duurland MC , Jorritsma T , Steenhuis M , Kerster G , Garcia Vallejo JJ , van Gils MJ , van Dam PJ , Stalmam EW , Wieske L , Boekel L , Wolbink GJ , Tas SW , Rispens T , Kuijpers TW , Eftimov F , ten Brinke A , van Ham SM 
Published: December 2024

AbstractOnce formed, plasma cells and memory B cells (MBCs) are difficult to eradicate, posing a problem in the context of unwanted antibody responses. Characterizing early B cell differentiation stages after antigen encounter is thus crucial to target and prevent unwanted antibody formation. Here, we unravelled in-depth antigen-specific B cell responses longitudinally after SARS-CoV-2 mRNA vaccination in healthy individuals using multiparameter spectral flow cytometry. The early antigen-specific B cell response was dominated by spike-specific IgG+CD27+CD71+activated B cells (ActBCs), previously assigned as germinal center-derived and DN2 extrafollicular B cells. Within the early IgG+ActBC compartment, six distinct clusters were identified with specific contraction dynamics, whereby some of these clusters were more closely related to pre-ASCs and others more to long-lived MBCs. Some of the highly contracting ActBC clusters expressed CD11c, a marker previously used to define atypical B cells. The transient presence of different ActBC clusters could also be observed in total B cells when gated in an antigen- independent manner. Our results thus delineate the early stages of the antigen-specific B cell response, with a further dissection of the CD71+ActBC compartment. Detection of ActBC clusters early after antigen encounter in total B cells opens avenues for future evaluation of their potential to serve as a proxy for antigen-reactive B cells in autoimmunity or other unwanted B cell responses.
Acoustic tumor paint for real-time imaging, surgical guidance and recurrence monitoring of brain tumors with ultrasound
Authors: Rabut Claire , Daghlian George H. , Barturen-Larrea Pierina , Li Hongyi Richard , Bruegge Ruth Vorder , Jones Rebecca M. , Malounda Dina , Pinton Gianmarco F. , Shapiro Mikhail G. 
Published: December 2024

ABSTRACTThe rapid growth, invasiveness, and resistance to treatment of glioblastoma multiforme (GBM) underscore the urgent need for improved diagnostics and therapies. Current surgical practice is limited by challenges with intraoperative imaging, while recurrence monitoring requires expensive magnetic resonance or nuclear imaging scans. Here we introduce “acoustic tumor paint”, an approach to labeling brain tumors for ultrasound imaging – a widely accessible imaging modality. We show that gas vesicles (GVs), natural air-filled protein nanostructures, preferentially accumulate in brain tumors following systemic administration in syngeneic and xenograft mouse models of GBM. This enables real-time tumor visualization during surgery and postoperative monitoring of recurrence. We characterize GV uptake and breakdown by tumors and their resident cells and support clinical translatability by documenting non-toxic repeated administration. We also demonstrate the potential for post-operative monitoring in humans by imaging GVs through a human skull and an FDA-approved skull prosthesis. Acoustic tumor paint has the potential to enhance diagnostic accuracy, improve surgical outcomes, make monitoring more accessible, and extend survival in GBM patients.
Differential expression of sex regulatory genes in gonads ofAstyanax mexicanussurface fish and cavefish
Authors: Webster Kaitlyn A. , Ponte Bethany , Vasquez-Gross Hans , Petereit Juli , Hutchinson John , Riddle Misty R. 
Published: December 2024

AbstractBackgroundAstyanax mexicanusis a single species of fish that consists of river-dwelling (surface) and cave-dwelling morphotypes. Little is known about how sexual determination, differentiation or reproduction have evolved in the surface morphs or cavefish, though divergence in reproductive strategy is expected as the latter have adapted to the novel cave environment. Evolution of the gonad transcriptome may underlie the differences in gamete morphology, fertility, and fecundity previously reported between morphotypes.ResultsWe compared the ovary and testis transcriptome of surface fish and cavefish at juvenile and adult stages. We found that samples clustered by developmental stage, sex, and morphotype identity. Several key genes that are typically associated with the female gonad in other vertebrates showed a reversal in sexual dimorphism or were not differentially expressed between sexes inA. mexicanus. In contrast, while gene expression typically associated with male gonads was largely conserved and consistent with vertebrate testicular expression profiles. Transcriptional and physiological differences between surface fish and cavefish morphotypes were observed in gonads from both sexes. Cavefish ovaries exhibited unique upregulation of neuron development and differentiation genes, and extensive innervation of the ovarian epithelium, while cavefish testes showed increased expression of angiogenesis regulating genes, and greater vasculature density compared to surface fish testes.ConclusionsThese results reveal significant gene expression differences betweenA. mexicanussurface fish and cavefish morphotypes that may have functional consequences in gonad morphogenesis and fertility. Our findings provide a foundation for investigating the evolution of sex regulatory pathways and reproductive strategies in animals adapting to new and challenging environments in which nutrient availability, temperature, and mate selection are suboptimal.
Cryogenic light microscopy with Ångstrom precision deciphers structural conformations of PIEZO1
Authors: Mazal Hisham , Schambony Alexandra , Sandoghdar Vahid 
Published: December 2024

AbstractDespite the impressive progress in molecular biochemistry and biophysics, many questions regarding the conformational states of large (transmembrane) protein complexes persist. In the case of the PIEZO protein, investigations by cryogenic electron microscopy (Cryo-EM) and atomic force microscopy (AFM) have established a symmetric trimer structure with three long-bladed domains in a propeller-like configuration. A transition of PIEZO protein from curved to flat conformation is hypothesized to actuate closed and open channels for the flow of ions. However, conclusive high-resolution data on the molecular organization of PIEZO in its native form are lacking. To address this shortcoming, we exploit single-particle cryogenic light microscopy (spCryo-LM) to decipher the conformational states of the mouse PIEZO1 protein (mPIEZO1) in the cell membrane. Here, we implement a high-vacuum cryogenic shuttle to transfer shock-frozen unroofed cell membranes in and out of a cryostat for super-resolution microscopy at liquid helium temperature. By localizing fluorescent labels placed at the extremities of the three blades with Ångstrom precision, we ascertain three configurations of the protein with radii of 6, 12, and 20 nm as projected onto the membrane plane. Our data suggest that in the smallest configuration, the blades form a nano-dome structure that is more strongly curved than previously observed and predicted by AlphaFold-3. In the largest conformation, we believe the structure must fully unbend in an anticlockwise manner to form a flat extended state. We attribute the 12 nm conformation, the most frequently occupied state, to an intermediate state and discuss our results in the context of the findings from other groups. Combination of spCryo-LM and Cryo-EM measurements together within situphotothermal stimulation promises to provide quantitative insight into the interplay between structure and function of PIEZO and other biomolecular complexes in their native environments.
The antiangiogenic peptide VIAN-c4551 inhibits lung melanoma metastasis in mice by reducing pulmonary vascular permeability
Authors: Perez Alma Lorena , Zamora Magdalena , Bahena Manuel , Williams Regina Aramburo , Adán-Castro Elva , Bertsch Thomas , Triebel Jakob , de la Escalera Gonzalo Martinez , Robles Juan Pablo , Clapp Carmen 
Published: December 2024

AbstractIntroductionCancer cells drive the increase in vascular permeability mediating tumor cell extravasation and metastatic seeding. VIAN-c4551, an antiangiogenic peptide analog of vasoinhibin, inhibits the growth and vascularization of melanoma tumors in mice. Because VIAN-c4551 is a potent inhibitor of vascular permeability, we evaluated whether its antitumor action extended to a reduction in metastasis generation.MethodsCirculating levels of vascular endothelial growth factor (VEGF), lung vascular permeability, melanoma cell extravasation, and melanoma pulmonary nodules were assessed in C57BL/6J mice intravenously inoculated with murine melanoma B16-F10 cells after acute treatment with VIAN-c4551. VEGF levels, transendothelial electrical resistance, and transendothelial migration in cocultures of B16-F10 cells and endothelial cell monolayers supported the findings.ResultsB16-F10 cells increased circulating VEGF levels and elevated lung vascular permeability 2 hours after inoculation. VIAN-c4551 prevented enhanced vascular permeability and reduced melanoma cell extravasation after 2 hours and the number and size of macroscopic and microscopic melanoma tumors in lungs after 17 days. In vitro, VIAN-c4551 suppressed the B16-F10 cell-induced and VEGF mediated increase in endothelial cell monolayer permeability and the transendothelial migration of B16-F10 cells.ConclusionsThese findings support the inhibition of distant vascular permeability for the prevention of tumor metastasis and unveil the anti-vascular permeability factor VIAN-c4551 as a potential therapeutic drug able to prevent metastasis generation by lowering the extravasation of melanoma cells.
AuroraB-kinase methylation by SETD6 regulates cytokinesis and protects cells from chromosomal instability
Authors: Feldman Michal , Chopra Anand , Nachmias Dikla , Biggar Kyle K. , Sevilla Daniel , Elia Natalie , Levy Dan 
Published: December 2024

ABSTRACTSETD6 is a non-histone lysine methylatransferase, previously shown to participate in several housekeeping signaling pathways such as the NFkB pathway, Wnt signaling pathway, mitosis and more. In the current study we show evidence that SETD6 methylation is involved in the regulation of cytokinesis - the final process that divides cell contents into two daughter cells. SETD6 depleted HeLa cells presented high levels of chromatin bridges and actin patches, which are commonly observed following chromosomal segregation errors. In a proteomic screen we identified Aurora-B as a novel SETD6 substrate. Aurora-B kinase is an essential regulator of cytokinesis, known to actively delay cytokinesis as a response to the presence of chromatin in the midzone. We found that SETD6 binds and methylates Aurora-B on two adjacent lysine residues. Upon replication stress, Aurora-B methylation by SETD6 increases but is abolished when the two lysine methylation targets are substituted. In addition, replication stress led to a high tendency of SETD6 depleted cells to multinucleate, a major chromosomal-instability (CIN) phenotype. We detected a significant reduction in the Aurora-B kinase activity during cytokinesis in SETD6 knockout cells upon replication stress, which could be the mechanism underlying the accumulation of CIN phenotypes in these cells. CIN is a hallmark of cancer and is associated with tumor cell malignancy. Our findings suggest that Aurora-B methylation by SETD6 carries meaningful implications on tumorigenic cellular pathways.
Construction, Deployment, and Usage of the Human Reference Atlas Knowledge Graph for Linked Open Data
Authors: Bueckle Andreas , Herr Bruce W. , Hardi Josef , Quardokus Ellen M. , Musen Mark A. , Börner Katy 
Published: December 2024

AbstractThe Human Reference Atlas (HRA) for the healthy, adult body is being developed by a team of international, interdisciplinary experts across 20+ consortia. It provides standard terminologies and data structures for describing specimens, biological structures, and spatial positions of experimental datasets and ontology-linked reference anatomical structures (AS), cell types (CT), and biomarkers (B). We introduce the HRA Knowledge Graph (KG) as central data resource for HRA v2.2, supporting cross-scale, biological queries to Resource Description Framework graphs using SPARQL. In February 2025, the HRA KG covered 71 organs with 5,800 AS, 2,268 CT, 2,531 B; it had 10,064,033 nodes, 171,250,177 edges, and a size of 125.84 GB. The HRA KG comprises 13 types of Digital Objects (DOs) using the Common Coordinate Framework Ontology to standardize core concepts and relationships across DOs. We (1) provide data and code for HRA KG construction; (2) detail HRA KG deployment by Linked Open Data principles; and (3) illustrate HRA KG usage via application programming interfaces, user interfaces, data products. A companion website is athttps://cns-iu.github.io/hra-kg-supporting-information.
The colon is an extra-pancreatic source of glucagon: demonstration in a mouse model of pancreatectomy
Authors: Jarry Anne-Charlotte , Le Beyec Johanne , Bado André , Gautier Jean-François , Riveline Jean-Pierre , Blondeau Bertrand , Guillemain Ghislaine , Le Gall Maude 
Published: December 2024

SummaryGlucagon is considered as a pancreas-specific hormone. However, an extra-pancreatic source of glucagon, which secretion is inappropriately induced by oral glucose, has been suspected for years in patients with diabetes. In a mouse model of subtotal pancreatectomy, we recapitulated the abnormal secretion of glucagon in response to oral glucose observed in pancreatectomised patients and excluded the remaining pancreas as the source of glucagon. We showed that the colon can produce and secrete glucagon. Subtotal pancreatectomy resulted in an increased expression of PCSK2 protease in the colon that favors the maturation of proglucagon into glucagon over other glucagon-related peptides normally produced by enteroendocrine cells. These results identify a mechanism that could contribute to abnormal glucagon production and poor glycemic control in pancreatectomized diabetic subjects. Moreover, our findings may pave the road to new therapeutic strategies to counteract poor glucose control for patients with diabetes.
Sexual Failure Decreases Sweet Taste Perception in MaleDrosophilavia Dopaminergic Signaling
Authors: Wang Gaohang , Qi Wei , Huang Rui , Wang Liming 
Published: December 2024

AbstractSweet taste perception, a critical aspect of the initiation of feeding behavior, is primarily regulated by an animal’s internal metabolic state. However, non-metabolic factors, such as motivational and emotional states, can also influence peripheral sensory processing and hence feeding behavior. While mating experience is known to induce motivational and emotional changes, its broader impact on other innate behaviors such as feeding remains largely uncharacterized. In this study, we demonstrated that mating failure of male fruit flies suppressed sweet taste perception via dopamine signaling in specific neural circuitry. Upon repetitive failure in courtship, male flies exhibited a sustained yet reversible decline of sweet taste perception, as measured by the proboscis extension reflex (PER) towards sweet tastants as well as the neuronal activity of sweet-sensing Gr5a+neurons in the proboscis. Mechanistically, we identified a small group of dopaminergic neurons projecting to the subesophageal zone (SEZ) and innervating with Gr5a+neurons as the key modulator. Repetitive sexual failure decreased the activity of these dopaminergic neurons and in turn suppressed Gr5a+neurons via Dop1R1 and Dop2R receptors. Our findings revealed a critical role for dopaminergic signaling in integrating reproductive experience with appetitive sensory processing, providing new insights into the complex interactions between different innate behaviors and the role of brain’s reward systems in regulating internal motivational and emotional states.
Evaluation of Three Diets Based on Dry, Live, and Wet Feeds for Optimal Growth of Discus Fish (Symphysodonp.) Under Controlled Conditions in Florencia, Caquetá, Colombia
Authors: Navarro-Morales Alejandro , Cháux Jenniffer Tatiana Díaz , Castañeda Helman Castañeda , Ruiz-Valderrama Diego Huseth , Valencia Alexander Velasquez 
Published: December 2024

AbstractThis study evaluated the effect of three diets, wet (PAP), live (DAP) and commercial feed (COC), on the growth of juvenile discus fish (Symphysodonsp), under controlled environmental conditions in the Colombian Amazon. The PAP diet was made with animal protein and Amazonian fruits. The DAP diet consisted of the provision of live food (Moina macrocopa); Both diets were mixed in equal parts with the concentrate to be supplied to the fish. In the COC diet, only the commercial feed was supplied. The daily supply of each diet corresponded to 6% of the average body weight of the juveniles, adjusting the quantity in each measurement. Each treatment had four repetitions (aquarium), with a density of 0.32 individuals per liter for a total of 192 discus fish. The growth of the juveniles was monitored by taking morphometry every nine days for 63 days. The morphometric variables presented differences between the diets, the highest values were recorded in PAP and DAP. The morphometric variables such as total length and weight were positively associated with nutritional contents such as proteins, lipids and carbohydrates present in DAP and PAP. These components influenced the growth of the fish and were related to the feed conversion factor. It is suggested that fish fed with DAP and PAP continued to grow thanks to the biological and enzymatic stimuli provided by these foods, unlike the COC feeding with the lower growth reported. These results demonstrate that the combination of live foods prepared according to the habits and nutritional requirements of the species with concentrates promote the growth of the fish, promoting optimal development and general well-being of the discus fish during growth under controlled conditions.
Probing a scalar singlet-triplet extension of the standard model via vector boson fusion at a muon collider
Authors: Bandyopadhyay Priyotosh , Parashar Snehashis 
Published: December 2024

In this article, we investigate the Y=0 SU(2) scalar triplet and Z2-odd scalar singlet extension of the standard model (SM). Here, the triplet charged Higgs boson decays to ZW±, breaking the custodial symmetry at the tree level, proportional to the triplet vacuum expectation value, while the singlet provides the dark matter (DM) relic. The triplet neutral Higgs boson (T0) can decay fully invisibly owing to the triplet-singlet portal coupling λst. The other SM Higgs portal couplings λht,λhs are constrained by the Higgs boson to diphoton observations, and the dark matter relic and direct searches as well as invisible Higgs decay bounds, respectively. For a cleaner signature, we indulge in a futuristic multi-TeV muon collider (MuC) to probe both the triplet scalars (T±,T0) via vector boson fusion with forward muon tagging, at the center-of-mass energies of 3 and 10 TeV. The analysis is comprised of a traditional cut-based approach and a boosted decision tree (BDT) classifier, where the latter is more effective for lower energies. With large missing energy contributions to the final states from combinations of DM mass and λst, the 3 TeV MuC is projected to probe triplet scalar masses of 450 GeV with the BDT classifier. The 10 TeV MuC can pinpoint the custodial symmetry breaking T±→ZW±→3-lepton decay up to 800 GeV of triplet scalar mass from cut-based analysis, with λst as low as 1.5 being adequate.

Published by the American Physical Society
2024
Combined x-ray diffraction, electrical resistivity, and
ab initio
study of
(TMTTF)2PF6
under pressure: Implications for the unified phase diagram
Authors: Itoi Miho , Yoshimi Kazuyoshi , Ma Hanming , Misawa Takahiro , Tsumuraya Takao , Bhoi Dilip , Komatsu Tokutaro , Mori Hatsumi , Uwatoko Yoshiya , Seo Hitoshi 
Published: December 2024

We present a combined experimental and theoretical study on the quasi-one-dimensional organic conductor (TMTTF)2PF6, and elucidate the variation of its physical properties under pressure. We fully resolve the crystal structure by single crystal x-ray diffraction measurements using a diamond anvil cell up to 8 GPa, and based on the structural data, we perform first-principles density-functional theory calculations and derive the extended Hubbard-type Hamiltonians. Furthermore, we compare the behavior of the resistivity measured up to 3 GPa using a BeCu clamp-type cell and the ground state properties of the obtained model numerically calculated by the many-variable variational Monte Carlo method. Our main findings are as follows: (i) The crystal was rapidly compressed up to about 3 GPa where the volume drops to 80% and gradually varies down to 70% at 8 GPa. The transfer integrals increase following such behavior whereas the screened Coulomb interactions decrease, resulting in a drastic reduction of correlation effect. (ii) The degree of dimerization in the intrachain transfer integrals, as the result of the decrease in structural dimerization together with the change in the intermolecular configuration, almost disappears above 4 GPa; the interchain transfer integrals also show characteristic variations under pressure. (iii) The results of identifying the characteristic temperatures in the resistivity and the charge and spin orderings in the calculations show an overall agreement: The charge ordering sensitively becomes unstable above 1 GPa, while the spin ordering survives up to higher pressures. These results shed light on the similarities and differences between applying external pressure and substituting the chemical species (chemical pressure).

Published by the American Physical Society
2024