bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases
Authors: Rolin Camille , Zimmer Jacques , Seguin-Devaux Carole 
Published: May 2024

AbstractBy binding to multiple antigens simultaneously, multispecific antibodies are expected to substantially improve both the activity and long-term efficacy of antibody-based immunotherapy. Immune cell engagers, a subclass of antibody-based constructs, consist of engineered structures designed to bridge immune effector cells to their target, thereby redirecting the immune response toward the tumor cells or infected cells. The increasing number of recent clinical trials evaluating immune cell engagers reflects the important role of these molecules in new therapeutic approaches for cancer and infections. In this review, we discuss how different immune cell types (T and natural killer lymphocytes, as well as myeloid cells) can be bound by immune cell engagers in immunotherapy for cancer and infectious diseases. Furthermore, we explore the preclinical and clinical advancements of these constructs, and we discuss the challenges in translating the current knowledge from cancer to the virology field. Finally, we speculate on the promising future directions that immune cell engagers may take in cancer treatment and antiviral therapy.
Environment modulates protein heterogeneity through transcriptional and translational stop codon readthrough
Authors: Romero Romero Maria Luisa , Poehls Jonas , Kirilenko Anastasiia , Richter Doris , Jumel Tobias , Shevchenko Anna , Toth-Petroczy Agnes 
Published: May 2024

AbstractStop codon readthrough events give rise to longer proteins, which may alter the protein’s function, thereby generating short-lasting phenotypic variability from a single gene. In order to systematically assess the frequency and origin of stop codon readthrough events, we designed a library of reporters. We introduced premature stop codons into mScarlet, which enabled high-throughput quantification of protein synthesis termination errors in E. coli using fluorescent microscopy. We found that under stress conditions, stop codon readthrough may occur at rates as high as 80%, depending on the nucleotide context, suggesting that evolution frequently samples stop codon readthrough events. The analysis of selected reporters by mass spectrometry and RNA-seq showed that not only translation but also transcription errors contribute to stop codon readthrough. The RNA polymerase was more likely to misincorporate a nucleotide at premature stop codons. Proteome-wide detection of stop codon readthrough by mass spectrometry revealed that temperature regulated the expression of cryptic sequences generated by stop codon readthrough in E. coli. Overall, our findings suggest that the environment affects the accuracy of protein production, which increases protein heterogeneity when the organisms need to adapt to new conditions.
Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes
Authors: Keener Rebecca , Chhetri Surya B. , Connelly Carla J. , Taub Margaret A. , Conomos Matthew P. , Weinstock Joshua , Ni Bohan , Strober Benjamin , Aslibekyan Stella , Auer Paul L. , Barwick Lucas , Becker Lewis C. , Blangero John , Bleecker Eugene R. , Brody Jennifer A. , Cade Brian E. , Celedon Juan C. , Chang Yi-Cheng , Cupples L. Adrienne , Custer Brian , Freedman Barry I. , Gladwin Mark T. , Heckbert Susan R. , Hou Lifang , Irvin Marguerite R. , Isasi Carmen R. , Johnsen Jill M. , Kenny Eimear E. , Kooperberg Charles , Minster Ryan L. , Naseri Take , Viali Satupa’itea , Nekhai Sergei , Pankratz Nathan , Peyser Patricia A. , Taylor Kent D. , Telen Marilyn J. , Wu Baojun , Yanek Lisa R. , Yang Ivana V. , Albert Christine , Arnett Donna K. , Ashley-Koch Allison E. , Barnes Kathleen C. , Bis Joshua C. , Blackwell Thomas W. , Boerwinkle Eric , Burchard Esteban G. , Carson April P. , Chen Zhanghua , Chen Yii-Der Ida , Darbar Dawood , de Andrade Mariza , Ellinor Patrick T. , Fornage Myriam , Gelb Bruce D. , Gilliland Frank D. , He Jiang , Islam Talat , Kaab Stefan , Kardia Sharon L. R. , Kelly Shannon , Konkle Barbara A. , Kumar Rajesh , Loos Ruth J. F. , Martinez Fernando D. , McGarvey Stephen T. , Meyers Deborah A. , Mitchell Braxton D. , Montgomery Courtney G. , North Kari E. , Palmer Nicholette D. , Peralta Juan M. , Raby Benjamin A. , Redline Susan , Rich Stephen S. , Roden Dan , Rotter Jerome I. , Ruczinski Ingo , Schwartz David , Sciurba Frank , Shoemaker M. Benjamin , Silverman Edwin K. , Sinner Moritz F. , Smith Nicholas L. , Smith Albert V. , Tiwari Hemant K. , Vasan Ramachandran S. , Weiss Scott T. , Williams L. Keoki , Zhang Yingze , Ziv Elad , Raffield Laura M. , Reiner Alexander P. ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,   TOPMed Hematology and Hemostasis Working Group,   TOPMed Structural Variation Working Group, Arvanitis Marios , Greider Carol W. , Mathias Rasika A. , Battle Alexis 
Published: May 2024

AbstractGenome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.
Immune features are associated with response to neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer
Authors: Beckabir Wolfgang , Zhou Mi , Lee Jin Seok , Vensko Steven P. , Woodcock Mark G. , Wang Hsing-Hui , Wobker Sara E. , Atassi Gatphan , Wilkinson Alec D. , Fowler Kenneth , Flick Leah M. , Damrauer Jeffrey S. , Harrison Michael R. , McKinnon Karen P. , Rose Tracy L. , Milowsky Matthew I. , Serody Jonathan S. , Kim William Y. , Vincent Benjamin G. 
Published: May 2024

AbstractNeoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC). Immune checkpoint inhibition (ICI) alone, and ICI in combination with chemotherapy, have demonstrated promising pathologic response (<pT2) in the neoadjuvant setting. In LCCC1520 (NCT02690558), a phase 2 single-arm trial of neoadjuvant chemo-immunotherapy (gemcitabine and cisplatin plus pembrolizumab; NAC-ICI) for MIBC, 22/39 patients responded (pathologic downstaging as primary outcome), as previously described. Here, we report post-hoc correlative analyses. Treatment was associated with changes in tumor mutational profile, immune gene signatures, and RNA subtype switching. Clinical response was associated with an increase in plasma IL-9 from pre-treatment to initiation of cycle 2 of therapy. Tumors harbored diverse predicted antigen landscapes that change across treatment and are associated with APOBEC, tobacco, and other etiologies. Higher pre-treatment tumor PD-L1 and TIGIT RNA expression were associated with complete response. IL-8 signature and Stroma-rich subtype were associated with improved response to NAC-ICI versus neoadjuvant ICI (ABACUS trial, NCT02662309). Plasma IL-9 represents a potential predictive biomarker of NAC-ICI response, while tumor IL-8 signature and stroma-rich subtype represent potential predictive biomarkers of response benefit of NAC-ICI over neoadjuvant ICI. Future efforts must include additional independent biomarker discovery and validation, ultimately to improve the selection of patients for ICI-related treatments.
Multispecies deep learning using citizen science data produces more informative plant community models
Authors: Brun Philipp , Karger Dirk N. , Zurell Damaris , Descombes Patrice , de Witte Lucienne C. , de Lutio Riccardo , Wegner Jan Dirk , Zimmermann Niklaus E. 
Published: May 2024

AbstractIn the age of big data, scientific progress is fundamentally limited by our capacity to extract critical information. Here, we map fine-grained spatiotemporal distributions for thousands of species, using deep neural networks (DNNs) and ubiquitous citizen science data. Based on 6.7 M observations, we jointly model the distributions of 2477 plant species and species aggregates across Switzerland with an ensemble of DNNs built with different cost functions. We find that, compared to commonly-used approaches, multispecies DNNs predict species distributions and especially community composition more accurately. Moreover, their design allows investigation of understudied aspects of ecology. Including seasonal variations of observation probability explicitly allows approximating flowering phenology; reweighting predictions to mirror cover-abundance allows mapping potentially canopy-dominant tree species nationwide; and projecting DNNs into the future allows assessing how distributions, phenology, and dominance may change. Given their skill and their versatility, multispecies DNNs can refine our understanding of the distribution of plants and well-sampled taxa in general.
An inorganic-blended p-type semiconductor with robust electrical and mechanical properties
Authors: Meng You , Wang Weijun , Fan Rong , Lai Zhengxun , Wang Wei , Li Dengji , Li Xiaocui , Quan Quan , Xie Pengshan , Chen Dong , Shao He , Li Bowen , Wu Zenghui , Yang Zhe , Yip SenPo , Wong Chun-Yuen , Lu Yang , Ho Johnny C. 
Published: May 2024

AbstractInorganic semiconductors typically have limited p-type behavior due to the scarcity of holes and the localized valence band maximum, hindering the progress of complementary devices and circuits. In this work, we propose an inorganic blending strategy to activate the hole-transporting character in an inorganic semiconductor compound, namely tellurium-selenium-oxygen (TeSeO). By rationally combining intrinsic p-type semimetal, semiconductor, and wide-bandgap semiconductor into a single compound, the TeSeO system displays tunable bandgaps ranging from 0.7 to 2.2 eV. Wafer-scale ultrathin TeSeO films, which can be deposited at room temperature, display high hole field-effect mobility of 48.5 cm2/(Vs) and robust hole transport properties, facilitated by Te-Te (Se) portions and O-Te-O portions, respectively. The nanosphere lithography process is employed to create nanopatterned honeycomb TeSeO broadband photodetectors, demonstrating a high responsibility of 603 A/W, an ultrafast response of 5 μs, and superior mechanical flexibility. The p-type TeSeO system is highly adaptable, scalable, and reliable, which can address emerging technological needs that current semiconductor solutions may not fulfill.
Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies
Authors: Wu Meng-Han , Valenca-Pereira Felipe , Cendali Francesca , Giddings Emily L. , Pham-Danis Catherine , Yarnell Michael C. , Novak Amanda J. , Brunetti Tonya M. , Thompson Scott B. , Henao-Mejia Jorge , Flavell Richard A. , D’Alessandro Angelo , Kohler M. Eric , Rincon Mercedes 
Published: May 2024

AbstractMitochondrial respiration is essential for the survival and function of T cells used in adoptive cellular therapies. However, strategies that specifically enhance mitochondrial respiration to promote T cell function remain limited. Here, we investigate methylation-controlled J protein (MCJ), an endogenous negative regulator of mitochondrial complex I expressed in CD8 cells, as a target for improving the efficacy of adoptive T cell therapies. We demonstrate that MCJ inhibits mitochondrial respiration in murine CD8+ CAR-T cells and that deletion of MCJ increases their in vitro and in vivo efficacy against murine B cell leukaemia. Similarly, MCJ deletion in ovalbumin (OVA)-specific CD8+ T cells also increases their efficacy against established OVA-expressing melanoma tumors in vivo. Furthermore, we show for the first time that MCJ is expressed in human CD8 cells and that the level of MCJ expression correlates with the functional activity of CD8+ CAR-T cells. Silencing MCJ expression in human CD8 CAR-T cells increases their mitochondrial metabolism and enhances their anti-tumor activity. Thus, targeting MCJ may represent a potential therapeutic strategy to increase mitochondrial metabolism and improve the efficacy of adoptive T cell therapies.
Highly porous metal-organic framework liquids and glasses via a solvent-assisted linker exchange strategy of ZIF-8
Authors: Xue Wen-Long , Kolodzeiski Pascal , Aucharova Hanna , Vasa Suresh , Koutsianos Athanasios , Pallach Roman , Song Jianbo , Frentzel-Beyme Louis , Linser Rasmus , Henke Sebastian 
Published: May 2024

AbstractBy combining the porosity of crystalline metal-organic frameworks (MOFs) with the unique processability of the liquid state, melt-quenched MOF glasses offer exciting opportunities for molecular separation. However, progress in this field is limited by two factors. Firstly, only very few MOFs melt at elevated temperatures and transform into stable glasses upon cooling the corresponding MOF liquid. Secondly, the MOF glasses obtained thus far feature only very small porosities and very small pore sizes. Here, we demonstrate solvent-assisted linker exchange (SALE) as a versatile method to prepare highly porous melt-quenched MOF glasses from the canonical ZIF-8. Two additional organic linkers are incorporated into the non-meltable ZIF-8, yielding high-entropy, linker-exchanged ZIF-8 derivatives undergoing crystal-to-liquid-to-glass phase transitions by thermal treatment. The ZIF-8 glasses demonstrate specific pore volumes of about 0.2 cm3g–1, adsorb large amounts of technologically relevant C3 and C4 hydrocarbons, and feature high kinetic sorption selectivities for the separation of propylene from propane.
H2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours
Authors: Dibitetto Diego , Liptay Martin , Vivalda Francesca , Dogan Hülya , Gogola Ewa , González Fernández Martín , Duarte Alexandra , Schmid Jonas A. , Decollogny Morgane , Francica Paola , Przetocka Sara , Durant Stephen T. , Forment Josep V. , Klebic Ismar , Siffert Myriam , de Bruijn Roebi , Kousholt Arne N. , Marti Nicole A. , Dettwiler Martina , Sørensen Claus S. , Tille Jean-Christophe , Undurraga Manuela , Labidi-Galy Intidhar , Lopes Massimo , Sartori Alessandro A. , Jonkers Jos , Rottenberg Sven 
Published: May 2024

AbstractHistone H2AX plays a key role in DNA damage signalling in the surrounding regions of DNA double-strand breaks (DSBs). In response to DNA damage, H2AX becomes phosphorylated on serine residue 139 (known as γH2AX), resulting in the recruitment of the DNA repair effectors 53BP1 and BRCA1. Here, by studying resistance to poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2-deficient mammary tumours, we identify a function for γH2AX in orchestrating drug-induced replication fork degradation. Mechanistically, γH2AX-driven replication fork degradation is elicited by suppressing CtIP-mediated fork protection. As a result, H2AX loss restores replication fork stability and increases chemoresistance in BRCA1/2-deficient tumour cells without restoring homology-directed DNA repair, as highlighted by the lack of DNA damage-induced RAD51 foci. Furthermore, in the attempt to discover acquired genetic vulnerabilities, we find that ATM but not ATR inhibition overcomes PARP inhibitor (PARPi) resistance in H2AX-deficient tumours by interfering with CtIP-mediated fork protection. In summary, our results demonstrate a role for H2AX in replication fork biology in BRCA-deficient tumours and establish a function of H2AX separable from its classical role in DNA damage signalling and DSB repair.
Phylogenomics reveals the evolutionary origins of lichenization in chlorophyte algae
Authors: Puginier Camille , Libourel Cyril , Otte Juergen , Skaloud Pavel , Haon Mireille , Grisel Sacha , Petersen Malte , Berrin Jean-Guy , Delaux Pierre-Marc , Dal Grande Francesco , Keller Jean 
Published: May 2024

AbstractMutualistic symbioses have contributed to major transitions in the evolution of life. Here, we investigate the evolutionary history and the molecular innovations at the origin of lichens, which are a symbiosis established between fungi and green algae or cyanobacteria. We de novo sequence the genomes or transcriptomes of 12 lichen algal symbiont (LAS) and closely related non-symbiotic algae (NSA) to improve the genomic coverage of Chlorophyte algae. We then perform ancestral state reconstruction and comparative phylogenomics. We identify at least three independent gains of the ability to engage in the lichen symbiosis, one in Trebouxiophyceae and two in Ulvophyceae, confirming the convergent evolution of the lichen symbioses. A carbohydrate-active enzyme from the glycoside hydrolase 8 (GH8) family was identified as a top candidate for the molecular-mechanism underlying lichen symbiosis in Trebouxiophyceae. This GH8 was acquired in lichenizing Trebouxiophyceae by horizontal gene transfer, concomitantly with the ability to associate with lichens fungal symbionts (LFS) and is able to degrade polysaccharides found in the cell wall of LFS. These findings indicate that a combination of gene family expansion and horizontal gene transfer provided the basis for lichenization to evolve in chlorophyte algae.
High-power electrically pumped terahertz topological laser based on a surface metallic Dirac-vortex cavity
Authors: Liu Junhong , Xu Yunfei , Li Rusong , Sun Yongqiang , Xin Kaiyao , Zhang Jinchuan , Lu Quanyong , Zhuo Ning , Liu Junqi , Wang Lijun , Cheng Fengmin , Liu Shuman , Liu Fengqi , Zhai Shenqiang 
Published: May 2024

AbstractTopological lasers (TLs) have attracted widespread attention due to their mode robustness against perturbations or defects. Among them, electrically pumped TLs have gained extensive research interest due to their advantages of compact size and easy integration. Nevertheless, limited studies on electrically pumped TLs have been reported in the terahertz (THz) and telecom wavelength ranges with relatively low output powers, causing a wide gap between practical applications. Here, we introduce a surface metallic Dirac-vortex cavity (SMDC) design to solve the difficulty of increasing power for electrically pumped TLs in the THz spectral range. Due to the strong coupling between the SMDC and the active region, robust 2D topological defect lasing modes are obtained. More importantly, enough gain and large radiative efficiency provided by the SMDC bring in the increase of the output power to a maximum peak power of 150 mW which demonstrates the practical application potential of electrically pumped TLs.
Contractile injection systems facilitate sporogenic differentiation of Streptomyces davawensis through the action of a phage tapemeasure protein-related effector
Authors: Nagakubo Toshiki , Nishiyama Tatsuya , Yamamoto Tatsuya , Nomura Nobuhiko , Toyofuku Masanori 
Published: May 2024

AbstractContractile injection systems (CISs) are prokaryotic phage tail-like nanostructures loading effector proteins that mediate various biological processes. Although CIS functions have been diversified through evolution and hold the great potential as protein delivery systems, the functional characterisation of CISs and their effectors is currently limited to a few CIS lineages. Here, we show that the CISs of Streptomyces davawensis belong to a unique group of bacterial CISs distributed across distant phyla and facilitate sporogenic differentiation of this bacterium. CIS loss results in decreases in extracellular DNA release, biomass accumulation, and spore formation in S. davawensis. CISs load an effector, which is a remote homolog of phage tapemeasure proteins, and its C-terminal domain has endonuclease activity responsible for the CIS-associated phenotypes. Our findings illustrate that CISs can contribute to the reproduction of bacteria through the action of the effector and suggest an evolutionary link between CIS effectors and viral cargos.
Profiling complex repeat expansions in RFC1 in Parkinson’s disease
Authors: Alvarez Jerez Pilar , Daida Kensuke , Miano-Burkhardt Abigail , Iwaki Hirotaka , Malik Laksh , Cogan Guillaume , Makarious Mary B. , Sullivan Roisin , Vandrovcova Jana , Ding Jinhui , Gibbs J. Raphael , Markham Androo , Nalls Mike A. , Kesharwani Rupesh K. , Sedlazeck Fritz J. , Casey Bradford , Hardy John , Houlden Henry , Blauwendraat Cornelis , Singleton Andrew B. , Billingsley Kimberley J. 
Published: May 2024

AbstractA biallelic (AAGGG) expansion in the poly(A) tail of an AluSx3 transposable element within the gene RFC1 is a frequent cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS), and more recently, has been reported as a rare cause of Parkinson’s disease (PD) in the Finnish population. Here, we investigate the prevalence of RFC1 (AAGGG) expansions in PD patients of non-Finnish European ancestry in 1609 individuals from the Parkinson’s Progression Markers Initiative study. We identified four PD patients carrying the biallelic RFC1 (AAGGG) expansion and did not identify any carriers in controls.
A negative feedback loop underlies the Warburg effect
Authors: Jaiswal Alok , Singh Raghvendra 
Published: May 2024

AbstractAerobic glycolysis, or the Warburg effect, is used by cancer cells for proliferation while producing lactate. Although lactate production has wide implications for cancer progression, it is not known how this effect increases cell proliferation and relates to oxidative phosphorylation. Here, we elucidate that a negative feedback loop (NFL) is responsible for the Warburg effect. Further, we show that aerobic glycolysis works as an amplifier of oxidative phosphorylation. On the other hand, quiescence is an important property of cancer stem cells. Based on the NFL, we show that both aerobic glycolysis and oxidative phosphorylation, playing a synergistic role, are required to achieve cell quiescence. Further, our results suggest that the cells in their hypoxic niche are highly proliferative yet close to attaining quiescence by increasing their NADH/NAD+ ratio through the severity of hypoxia. The findings of this study can help in a better understanding of the link among metabolism, cell cycle, carcinogenesis, and stemness.
BOLD: Blood-gas and Oximetry Linked Dataset
Authors: Matos João , Struja Tristan , Gallifant Jack , Nakayama Luis , Charpignon Marie-Laure , Liu Xiaoli , Economou-Zavlanos Nicoleta , S. Cardoso Jaime , Johnson Kimberly S. , Bhavsar Nrupen , Gichoya Judy , Celi Leo Anthony , Wong An-Kwok Ian 
Published: May 2024

AbstractPulse oximeters measure peripheral arterial oxygen saturation (SpO2) noninvasively, while the gold standard (SaO2) involves arterial blood gas measurement. There are known racial and ethnic disparities in their performance. BOLD is a dataset that aims to underscore the importance of addressing biases in pulse oximetry accuracy, which disproportionately affect darker-skinned patients. The dataset was created by harmonizing three Electronic Health Record databases (MIMIC-III, MIMIC-IV, eICU-CRD) comprising Intensive Care Unit stays of US patients. Paired SpO2 and SaO2 measurements were time-aligned and combined with various other sociodemographic and parameters to provide a detailed representation of each patient. BOLD includes 49,099 paired measurements, within a 5-minute window and with oxygen saturation levels between 70–100%. Minority racial and ethnic groups account for ~25% of the data – a proportion seldom achieved in previous studies. The codebase is publicly available. Given the prevalent use of pulse oximeters in the hospital and at home, we hope that BOLD will be leveraged to develop debiasing algorithms that can result in more equitable healthcare solutions.