bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal-invasive 3D laser printing of microimplantsin organismo
Authors: Afting Cassian , Mainik Philipp , Vazquez-Martel Clara , Abele Tobias , Kaul Verena , Göpfrich Kerstin , Lemke Steffen , Blasco Eva , Wittbrodt Joachim 
Published: January 2024

AbstractMulti-photon 3D laser printing has gathered much attention in recent years as a means of manufacturing biocompatible scaffolds that can modify and guide cellular behaviorin vitro. However,in vivotissue engineering efforts have been limited so far to the implantation of beforehand 3D printed biocompatible scaffolds andin vivobioprinting of tissue constructs from bioinks containing cells, biomolecules, and printable hydrogel formulations. Thus, a comprehensive 3D laser printing platform forin vivoandin situmanufacturing of microimplants raised from synthetic polymer-based inks is currently missing.Here we present a platform for minimal-invasive manufacturing of microimplants directly in the organism by one-photon photopolymerization and multi-photon 3D laser printing. Employing a commercially available elastomeric ink giving rise to biocompatible synthetic polymer-based microimplants, we demonstrate first applicational examples of biological responses toin situprinted microimplants in the teleost fishOryzias latipesand in embryos of the fruit flyDrosophila melanogaster. This provides a framework for future studies addressing the suitability of inks forin vivo3D manufacturing. Our platform bears great potential for the direct engineering of the intricate microarchitectures in a variety of tissues in model organisms and beyond.
First-in-classTransactivator-Free, Doxycycline-inducible IL-18-engineered CAR-T cells for relapsed/refractory B-cell lymphomas
Authors: Justicia-Lirio Pedro , Tristán-Manzano María , Maldonado-Pérez Noelia , Barbero-Jiménez Carmen , Cortijo-Gutiérrez Marina , Pavlovic Kristina , Molina-Estevez Francisco J , Muñoz Pilar , Hinckley-Boned Ana , Griñán-Lison Carmen , Navarro-Marchal Saúl A , Muñoz-Ballester Julia , González-Sierra Pedro A , Herrera Concha , Marchal Juan A , Martín Francisco 
Published: January 2024

AbstractBackgroundDespite their success treating type B cancers, Chimeric Antigen Receptor (CAR) T cells still showed limited efficacy in certain lymphomas and solid tumors. Reinforcing conventional CAR-T cells to release cytokines can improve their efficacy but also increase safety concerns. Several strategies have been developed to regulate their secretion using minimal promoters that are controlled by chimeric proteins harboring transactivators. However, these chimeric proteins can disrupt the normal physiology of target cells.MethodsCo-transduction with CAR19 and Lent-On-Plus-IL-18 LVs allowed for generating constitutive CAR/Dox-inducible IL-18 CAR-T cells that respond to ultra-low doses of doxycycline (iTRUCK19.18). iTRUCK19.18 were evaluated against an aggressive Burkitt lymphoma modelin vitroandin vivo, against primary B-cell tumors and against a CD19-engineered pancreatic tumor model. Patient-derived iTRUCK19.18 cells were also generated.ResultsiTRUCK19.18 controlled IL-18 release through a dual mechanism dependent on doxycycline and T cell activation, thereby enhancing the safety profile. IL-18 release increased the activation state/proinflammatory profile of T cells in a doxycycline-dependent manner without altering cellular fitness, which was translated into an increased CAR-T cell antitumor activity against aggressive hematologic and solid tumor models. In a clinically relevant context, we generated patient-derived iTRUCK19.18 cells able to significantly increase elimination of primary B cells tumors under doxycycline. Furthermore, IL-18-releasing iTRUCK19.18 polarized pro-tumoral M2 macrophages towards an antitumoral phenotype (M1), suggesting the ability to modulate the tumor microenvironment.ConclusionWe have generated the first transactivator-free inducible TRUCKs from healthy donors and B-cell neoplasms patients. iTRUCK19-18 exhibit dual safety control mechanisms for IL-18 secretion and improved antitumoral activity against type-B neoplasms. Inducible IL-18 secretion not only enhanced T cell potency but could also change the tumor microenvironment to a more antitumoral state.
Microalgal biofilm induces larval settlement in the model marine wormPlatynereis dumerilii
Authors: Hird Cameron , Jékely Gáspár , Williams Elizabeth A. 
Published: January 2024

ABSTRACTA free-swimming larval stage features in many marine invertebrate life cycles. To transition to a seafloor-dwelling juvenile stage, larvae need to settle out of the plankton, guided by specific environmental cues that lead them to an ideal habitat for their future life on the seafloor. Although the marine annelidPlatynereis dumeriliihas been cultured in research labs since the 1950s and has a free-swimming larval stage, specific environmental cues that induce settlement in this nereid worm are yet to be identified. Here we demonstrate that microalgal biofilm is a key settlement cue forP. dumeriliilarvae, inducing earlier onset of settlement, and enhancing subsequent juvenile growth as a primary food source. We tested the settlement response ofP. dumeriliito 40 different strains of microalgae, predominantly diatom species, finding thatP. dumeriliihave species-specific preferences in their choice of settlement substrate. The most effective diatom species for inducingP. dumeriliilarval settlement were benthic pennate species includingGrammatophora marina,Achnanthes brevipes, andNitzschia ovalis. The identification of specific environmental cues forP. dumeriliisettlement enables a link between its ecology and the sensory and nervous system signalling that regulate larval behaviour and development. Incorporation of diatoms intoP. dumeriliiculture practices will improve the husbandry of this marine invertebrate model.
Large-Scale COI Gene Data Analysis for the Development of a Gel-Based Multiplex PCR Test Capable of Identifying Biting Midge Vector Species and Haplotypes (Diptera: Ceratopogonidae) of theCulicoidessubgenusAvaritiaFox, 1955
Authors: Dähn Oliver , Werner Doreen , Mathieu Bruno , Kampen Helge 
Published: January 2024

AbstractThe emergence of culicoid-transmitted bluetongue and Schmallenberg viruses in several European countries demonstrated the ability of indigenous biting midge species to transmit pathogens. Entomologic research programmes identified members of the Obsoletus Group (CulicoidessubgenusAvaritia) as keyplayers in disease epidemiology in Europe. However, morphological identification of potential vectors to species level is challenging due to the existence of isomorphic species. PCR tests developed to facilitate genetic species determination have been dismantled by the discovery of new genetic variants (haplotypes) ofC. obsoletussensu stricto (s.s.), forming distinct clades. In this study, 4,422 GenBank entries of the mitochondrial cytochrome c oxidase subunit I (COI) gene of subgenusAvaritiamembers of the genusCulicoideswere analyzed to develop a conventional multiplex PCR, capable of detecting all vector species and recently described clades of the western Palaearctic in this subgenus. Numerous GenBank entries incorrectly assigned to a species were identified, analyzed and reassigned. The results suggest that the three clades ofC. obsoletusrepresent independent species, whereasC. montanusshould rather be regarded as a genetic variant ofC. obsoletuss.s.. Based on these findings, specific primers were designed and validated with DNA material from field-caught biting midges which achieved very high diagnostic sensitivity (100%) when compared to an established reference PCR (82.6%). Hence, the newly developed multiplex PCR represents the first molecular tool which enables both the identification of accepted species and of the three clades ofC. obsoletuss.s. and could provide new insights into the ecology of the latter.
Selective Regulation of a Defined Subset of Inflammatory and Immunoregulatory Genes by an NF-κB p50-IκBζ Pathway
Authors: Daly Allison E. , Yeh George , Soltero Sofia , Smale Stephen T. 
Published: January 2024

SUMMARYThe five NF-κB family members and three nuclear IκB proteins play important biological roles, but the mechanisms by which distinct NF-κB and IκB proteins contribute to selective gene transcription remain poorly understood, especially at a genome-scale level. Using nascent transcript RNA-seq, we observed considerable overlap between p50-dependent and IκBζ-dependent genes in Toll-like receptor 4 (TLR4)-activated macrophages. Key immunoregulatory genes, includingIl6,Il1b,Nos2,Lcn2,andBatf,are among the p50-IκBζ co-dependent genes. IκBζ bound genomic sites occupied by NF-κB dimers at earlier time points. However, p50-IκBζ co-dependence does not coincide with preferential binding of either p50 or IκBζ, as both proteins and RelA co-occupy thousands of genomic sites. A common feature of p50-IκBζ co-dependent genes is a nearby p50/RelA/IκBζ co-bound site exhibiting p50-dependent binding of both RelA and IκBζ. This result and others suggest that IκBζ may act in concert with RelA:p50 heterodimers. Notably, the IκBζ-dependent and p50-IκBζ-co-dependent genes comprise a high percentage of genes that exhibit the greatest differential expression between TLR4-stimulated and tumor necrosis factor receptor (TNFR)-stimulated macrophages. Thus, our genome-centric analysis reveals a defined p50-IκBζ pathway that selectively activates a set of key immunoregulatory genes and serves as an important contributor to the differential TNFR and TLR4 responses.
3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression
Authors: Mortenson Katelyn L. , Dawes Courtney , Wilson Emily R. , Patchen Nathan E. , Johnson Hailey E. , Gertz Jason , Bailey Swneke D. , Liu Yang , Varley Katherine E. , Zhang Xiaoyang 
Published: January 2024

ABSTRACTCancer genomes are composed of many complex structural alterations on chromosomes and extrachromosomal DNA (ecDNA), making it difficult to identify non-coding enhancer regions that are hijacked to activate oncogene expression. Here, we describe a 3D genomics-based analysis called HAPI (Highly Active Promoter Interactions) to characterize enhancer hijacking. HAPI analysis of HiChIP data from 34 cancer cell lines identified enhancer hijacking events that activate both known and potentially novel oncogenes such asMYC, CCND1,ETV1,CRKL, andID4. Furthermore, we found enhancer hijacking among multiple oncogenes from different chromosomes, often includingMYC, on the same complex amplicons such as ecDNA. We characterized aMYC-ERBB2chimeric ecDNA, in whichERBB2heavily hijacksMYC’s enhancers. Notably, CRISPRi of theMYCpromoter led to increased interaction ofERBB2withMYCenhancers and elevatedERBB2expression. Our HAPI analysis tool provides a robust strategy to detect enhancer hijacking and reveals novel insights into oncogene activation.
Efficacy of Transposition of Plicated Medial Rectus Muscles in the Treatment of A- or V- Pattern Exotropia (An Egyptian Comparative Study)
Authors: El-aidy Lamiaa A. , Ibrahim Yasser M. , Elmarakby Mohamed A. , Ghali Manar A. 
Published: January 2024

AbstractObjectiveTo report effectiveness of bimedial plication and vertical transposition for correction of exotropia associated with A- or V-pattern and compare it with bimedial resection and vertical transposition.Methods and analysisWe retrospectively reviewed the results of surgery of patients who underwent bimedial plication (group I) versus bimedial resection (group II) with vertical offset to correct both exotropia and pattern deviation not secondary to oblique overaction in the period between January 2021 and January 2023. Results of both groups were compared. Success was considered when pattern deviation was ≤ 8 prism diopters PD and horizontal deviation was within 10 PD of orthophoria at 6 months postoperatively.ResultsThe mean preoperative angle of exotropia in PD was 40.6 ± 7.2 in group I and 41.1 ± 7.5 in group II (p=.8). At 6 months postoperatively, they achieved angle of 4.6 ± 4.1 and 2.5 ± 4.5 PD respectively (no significant difference between both groups; p=.19). The mean preoperative pattern deviation was 21.3 ± 3.7 PD in group I and 21.6 ± 4.4 in group II. Postoperative pattern collapse was 16.7 ± 5.6 and 16.6 ± 4.1 respectively. The percentage of success in pattern collapse was 90.6% in group I and 84.4% in group II (no significant difference between both groups; p=.71).ConclusionVertical transposition with plication of medial recti is a safe, effective, and rapid technique for correction of cases of A- or V- pattern exotropia not associated with oblique overaction. Results were not significantly different from resection/vertical transposition.What is already known in this topic?A- or V-pattern exotropia without significant inferior oblique overaction can be treated by vertical transposition of the horizontal recti after ordinary recession or resection.Some studies reported muscle plication and transposition as an alternative technique to resection and transposition. Plication allow preservation of ciliary circulation and lowering the incidence of muscle loss.What this study adds?In this retrospective study, we concluded that medial rectus plication and transposition is an effective alternative technique to medial rectus resection and transposition in treatment of A- or V- pattern exotropia without significant inferior oblique overaction (No significant difference between both techniques).What this study might affect research, practice or policy?Vertical Transposition of plicated medial recti is a new promising technique which should be considered in managing cases of A- or V-pattern exotropia without significant inferior oblique overaction.
Development, validation and clinical utility of Short-term AdVerse-effects of Electroconvulsive therapy (SAVE) Checklist
Authors: Uppinkudru Chithra , Pathak Harsh , Raj Kumar K , Bridgit S , Bagali Kiran , Pantoji Makarand , Ezhumalai Nathiya , Parlikar Rujuta , Shah Vyoma , Balachander Srinivas , Sreeraj Vanteemar S , Mehta Urvakhsh Meherwan , Sinha Preeti , Arumugham Shyam Sundar , Venkatasubramanian Ganesan , Thirthalli Jagadisha 
Published: January 2024

AbstractElectroconvulsive therapy (ECT) is one of the most effective treatments in psychiatry. However, it has many cognitive and non-cognitive adverse effects (AEs). There are lacunae in the systematic literature on non-cognitive AEs that need a standard, comprehensive and specific clinical tool to evaluate this. Hence, a checklist of short-term AEs of ECT (SAVE) with a 2-phase assessment was developed. Content validation was done using 15 experts’ ratings and predefined content validity ratio and index (CVR and CVI) in a two-stage modified Delphi method. The checklist had a good CVR and CVI with a final tool of 39 items. The tool was sensitive and identified the non-cognitive AEs after ECT. Cardiovascular and musculoskeletal systems displayed the highest incidence. Many participants exhibited delayed recovery in orientation, gait, and stance, highlighting a necessity for meticulous monitoring. SAVE is the first standardised tool to assess short-term ECT-related AEs systematically. This checklist identified a clinically significant incidence of AEs that would otherwise remain unnoticed. Its regular use may enhance the safety of ECT and patient comfort by supporting early identification and intervention for AEs. However, given the transient nature of AEs, further studies are needed to determine their predictive validity for long-term consequences.
Optimisation of surfactin yield inBacillususing active learning and high-throughput mass spectrometry
Authors: Albornoz Ricardo Valencia , Oyarzún Diego , Burgess Karl 
Published: January 2024

AbstractIntegration of machine learning and high throughput measurements are essential to drive the next generation of the design-build-test-learn (DBTL) cycle in synthetic biology. Here, we report the use of active learning in combination with metabolomics for optimising production of surfactin, a complex lipopeptide resulting from a non-ribosomal assembly pathway. We designed a media optimisation algorithm that iteratively learns the yield landscape and steers the media composition toward maximal production. The algorithm led to a 160% yield increase after three DBTL runs as compared to an M9 baseline. Metabolomics data helped to elucidate the underpinning biochemistry for yield improvement and revealed Pareto-like trade-offs in production of other lipopeptides from related pathways. We found positive associations between organic acids and surfactin, suggesting a key role of central carbon metabolism, as well as system-wide anisotropies in how metabolism reacts to shifts in carbon and nitrogen levels. Our framework offers a novel data-driven approach to improve yield of biological products with complex synthesis pathways that are not amenable to traditional yield optimisation strategies.Graphical abstract
Food web structure mediate positive and negative effects of diversity on ecosystem functioning in a large floodplain river
Authors: Borzone Mas Dalmiro , Scarabotti Pablo A. , Alvarenga Patricio , Vaschetto Pablo A , Arim Matias 
Published: January 2024

AbstractResearch programs on Biodiversity-Ecosystem Functioning (BEF) and Food Web Structure (FWS) have contributed to understanding the impact of biodiversity on the functioning and architecture of ecosystems, but the interconnectedness between these components was seldom attended until recently. Several theoretical hypotheses predict an interconnection between BEF and FWS but were poorly and independently evaluated. We estimated 63 sink food webs of predatory fish in the Paraná River, covering a large gradient of community richness. We evaluated available hypotheses and their interrelationship through path analyses. A well-supported causal structure was identified, supporting that species richness directly increased standing biomass, modularity, and intermodular connection, whereas decreased interaction strength, connectance, and nestedness. A direct positive effect of modularity and connectance on biomass indicates that FWS can determine the BEF. Richness promotes biomass directly and through the increase in modularity but can also decrease biomass due to the decay in connectance, with similar positive and negative effects of richness on biomass. In this sense, the relationship between diversity and ecosystem functioning cannot be blind to FWS. Environmental homogenization and reduction in functional diversity may undermine the conditions for modular food webs, switching positive BEF to negative ones with potential cascading effects in the whole ecosystem.
Joint signatures of morphological and microstructural inter-individual variation in the Alzheimer’s spectrum
Authors: Bussy Aurélie , Patel Raihaan , Parent Olivier , Salaciak Alyssa , Bedford Saashi A. , Farzin Sarah , Tullo Stephanie , Picard Cynthia , Villeneuve Sylvia , Poirier Judes , Breitner John CS , Devenyi Gabriel A. ,   PREVENT-AD Research Group, Tardif Christine L. , Chakravarty M. Mallar 
Published: January 2024

AbstractAlzheimer’s disease (AD) is primarily characterized by the accumulation of amyloid and tau pathologies. However, alterations in the detailed organization and composition of neural tissue also contribute to the disease’s early stages. Here, we sought to explore whether hippocampal and cortical microstructural changes, such as myelin alterations and inflammation-mediated increases in iron, could serve as indices of AD-related pathophysiology. In this study, we included 158 participants across the AD spectrum: from individuals without cognitive impairment, at high risk for AD, in the prodromal phase with mild cognitive impairment, and suffering from clinical dementia. We measured atrophy using structural magnetic resonance imaging (MRI) and estimated myelin and iron content using quantitative MRI (qMRI) metrics derived from T1 and T2* relaxation, times respectively. We integrated these contrasts to estimate a joint multivariate signature of tissue alterations across the cortex and hippocampus using non-negative matrix factorization. The relevance of these signatures to AD-spectrum measures of medical history, lifestyle, and cognition were further explored using partial least squares correlation. Our results reveal lower disease-related cortical thickness over large areas of the cortex while T2* provided specific variation across the brain (lower in dorsomedial and superior temporal areas, superior frontal cortex, and premotor cortex, and higher in the occipital lobe). Additionally, we observed longer T1 and T2* times in the hippocampus associated with specific lifestyle risk factors like past smoking, high blood pressure, high cholesterol levels, and higher anxiety. These patterns were significantly related to older age, associated with AD progression, being female, and being an APOE-□4 carrier. Taken together, our results suggest that qMRI metrics could serve as a valuable non-invasive tool for exploring the role of myelin and inflammation in AD-related pathophysiology and could be sensitive to modifiable risk factors related to lifestyle and medical history. Future studies may use these signatures to investigate their relationship in investigations related to lifestyle interventions or novel therapeutics.
The Increasing Authorship trend in Neuroscience: A scientometric analysis across 11 countries
Authors: Paul Ann , Segreti Mariella , Pani Pierpaolo , Brunamonti Emiliano , Genovesio Aldo 
Published: January 2024

AbstractPrevious studies have demonstrated an increasing trend of the number of authors across various fields over the years. This trend has been attributed to the necessity for larger collaborations and, at times, to ethical issues regarding authorship attribution. Our study focuses on the evolution of authorship trends in the field of Neuroscience. We conducted our analysis based on a dataset containing 576,647 neuroscience publications produced from 2000 to 2022, focusing on the publications within the Group of ten (G10) countries. Using a matrix-based methodology, we extracted and analyzed the average number of authors per country. Our findings reveal a consistent rise in authorship across all G10 countries over the past two decades. Italy emerged with the highest average number of authors, while the Netherlands stood out for experiencing the most significant increase, particularly in the last decade. The countries with the lowest number of authors per publication were the USA, UK, and Canada.
Spatial proteomics of ER tubules reveals CLMN, an ER-actin tether at focal adhesions that promotes cell migration
Authors: Merta Holly , Isogai Tadamoto , Paul Blessy , Danuser Gaudenz , Henne W Mike 
Published: January 2024

SummaryThe endoplasmic reticulum (ER) is structurally and functionally diverse, yet how its functions are organized within morphological subdomains is incompletely understood. Utilizing TurboID-based proximity labeling and CRISPR knock-in technologies, here we map the proteomic landscape of the human ER and nuclear envelope. Spatial proteomics reveals enrichments of proteins into ER tubules, sheets, and nuclear envelope. We uncover an ER-enriched actin-binding protein, Calmin (CLMN), and define it as an ER-actin tether that localizes to focal adhesions adjacent to ER tubules. CLMN depletion perturbs focal adhesion disassembly, actin dynamics, and cell movement. Mechanistically, CLMN-depleted cells also exhibit defects in calcium signaling near ER-actin interfaces, suggesting CLMN promotes calcium signaling near adhesions to facilitate their disassembly. Collectively, we map the sub-organelle proteome landscape of the ER, identify CLMN as an ER-actin tether, and describe a non-canonical mechanism by which ER tubules engage actin to regulate cell migration.