bluuebunny/crossref_metadata_2025_split huggingface dataset:
TCR signaling via NFATc1 constrains IL-15-induced NK-like activation of human memory CD8+T cells
Authors: Lee Hoyoung , Kim So-Young , Kim Sang-Hoon , Yu Hosun , Jeong Seongju , Kim Kyung Hwan , Kim Chang Gon , Koh June-Young , Kim Hyung-Don , Han Ji Won , Park Su-Hyung , Eun Hyuk Soo , Shin Eui-Cheol 
Published: January 2025

SummaryHere we investigated the regulatory mechanisms of TCR-independent bystander activation and NK-like cytotoxicity of human memory CD8+T cells. We found that TCR signals suppressed characteristic features of IL-15-induced CD8+T-cell activation, including increased NKG2D expression and upregulation of genes related to NK cytotoxicity and IFN response. Moreover, ionomycin suppressed IL-15-induced bystander activation and NK-like cytotoxicity, indicating that Ca2+-calcineurin signaling is responsible for TCR-mediated suppression of IL-15-induced bystander activation. In detail, NFATc1 suppressed IL-15- induced bystander activation via binding to AP-1 that is necessary for the IL-15-induced upregulation of NK cytotoxicity-related genes. Consistent with these results, calcineurin inhibitors enhanced IL-15-induced NKG2D expression in the presence of TCR signals. Additionally, we defined genes upregulated by IL-15 and downregulated by concurrent TCR signals as an IL-15-induced bystander activation gene set, and found that this gene signature was upregulated in bystander CD8+T cells from patients with hepatitis A virus infection. This study paves the way for further investigation of bystander CD8+T-cell activation in various pathological conditions, and its regulation.Graphical abstract
A qualitative study of how maternal morbidities impact women’s quality of life during pregnancy and postpartum in five countries in sub-Saharan Africa and South Asia
Authors: Abdulai Martha , Adhikary Priyanka , Baumann Sasha G. , Ejaz Muslima , Priya Jenifer Oviya , Spelke M. Bridget , Akelo Victor , Asante Kwaku Poku , Berhane Bitanya M. , Bisht Shruti , Boamah-Kaali Ellen , Diaz-Guzman Gabriela , Cherian Anne George , Hoodbhoy Zahra , Kasaro Margaret P. , Khan Amna , Kuttamperoor Janae , Lall Dorothy , Manohari Gifta Priya , Mazumder Sarmila , McDonnell Karen , Mehrihajmir Mahya , Mutale Wilbroad , Mwebia Winnie K. , Nisar Imran , Ochola Kennedy , Otieno Peter , Ouma Gregory , Patel Piya , Phiri Winifreda , Sharma Neeraj , Smith Emily R. , Tawiah Charlotte , Vallone Natalie J. , Sylvetsky Allison C. 
Published: January 2025

ABSTRACTAimMaternal morbidities present a major burden to the health and well-being of childbearing women. However, their impacts on women’s quality of life (QoL) are not well understood. This work aims to describe the extent to which the morbidities women experience during pregnancy and postpartum affect their QoL and identify any protective or risk factors.MethodsThis qualitative study included pregnant and postpartum women in Kenya, Ghana, Zambia, Pakistan, and India. Data were collected between November 2023 and June 2024. Participants were selected via purposive sampling, with consideration of age, trimester, and time since delivery. A total of 23 focus group discussions with 118 pregnant and 88 late (≥6 months) postpartum participants and 48 in-depth interviews with early (≤6 weeks) postpartum participants were conducted using semi-structured guides developed by the research team. Data was analyzed using a collaborative inductive thematic approach.ResultsFour overarching themes were identified across pregnancy and the postpartum period: (1) physical and emotional challenges pose a barrier to daily activities; (2) lack of social support detracts from women’s QoL; (3) receipt of social support mitigates adverse impacts of pregnancy and postpartum challenges on QoL; and (4) economic challenges exacerbate declines in women’s QoL during pregnancy and postpartum.ConclusionsBodily discomfort and fatigue were near-universal experiences. Physical and emotional morbidities related to childbearing limited women’s ability to complete daily tasks and adversely impacted their perceived QoL. Social and financial support from the baby’s father, family and/or in-laws, community members, and healthcare providers are important to mitigate the impacts of pregnancy and postpartum challenges on women’s health and well-being.
Attractive Targeted Sugar Baits for malaria control in western Kenya (ATSB-Kenya) – Effect of ATSBs on epidemiologic and entomologic indicators: a Phase III, open-label, cluster-randomised, controlled trial
Authors: Ogwang Caroline , Samuels Aaron M , McDermott Daniel P , Kamau Alice , Lesosky Maia , Obiet Kizito , Janssen Julia M , Odongo Wycliffe , Gimnig John E , Gutman Julie R , Schultz Jonathan S , Towett Oliver , Seda Brian , Chepkirui Mercy , Muchoki Margaret , Omondi Seline , Kosgei Jackline , Polo Brian , Aduwo Frank , Otieno Kephas , Donnelly Martin J , Kariuki Simon , Ochomo Eric , Kuile Feiko ter , Staedke Sarah G 
Published: January 2025

AbstractAttractive targeted sugar baits (ATSBs) are a novel malaria control tool designed to target mosquitoes outdoors. We conducted a cluster-randomised trial to evaluate the impact of ATSBs on malaria indicators in Kenya. Seventy clusters (>100 households/cluster) in Siaya county were randomly assigned (1:1) to intervention or control. Pyrethroid-only long-lasting insecticidal nets were distributed to all clusters, aiming for universal coverage. Two ATSBs containing dinotefuran were hung outside household structures in intervention clusters. ATSBs were monitored every two months and replaced every six months over two years. Three consecutive cohorts of randomly selected children (1-<15 years) were enrolled, aiming to accrue 1,260 person-years over two years of follow-up. Incidence of clinical malaria (fever with a positive malaria test) was the primary outcome. A multilevel Poisson regression model was applied, with clusters as a random intercept and study arm as a fixed effect. Secondary outcomes were malaria prevalence in community residents (≥1 month), and parity of mosquitos captured through human landing catches. In March 2022, ATSBs were delivered to 33,180 of 33,419 (99.3%) household structures in intervention clusters. Overall, 268,268 ATSBs were deployed over two years. Of 2,962 cohort children enrolled (intervention=1,497; control=1,465), 2,869 (96.9%) were included in the primary analysis (intervention=1,461; control=1,408), contributing 1,445 person-years of follow-up. Malaria incidence was 1.32 episodes per person-years in the intervention arm versus 1.20 in the control (unadjusted incidence rate ratio 1.11; 95% CI: 0.75-1.65; p=0.598). Of 7,488 community residents surveyed(intervention=3,760; control=3,728), 1,474 (39.2%) intervention and 1,461 (39.2%) control participants tested positive for malaria (unadjusted odds ratio [OR] 0.98; 95% CI: 0.60-1.59; p=0.93). Of 6,457 female anopheles mosquitoes collected (intervention=4,058; control=2,399), 3,579 (88.2%) intervention and 1,973 (82.2%) control mosquitoes were parous (OR 1.34; 95% CI: 0.91-1.99; p=0.14). In Kenya, we found no evidence that ATSBs reduced clinical malaria incidence, malaria prevalence, or vector parity.Trial registrationClinicaltrials.gov (NCT05219565), 22 January 2022;https://clinicaltrials.gov/study/NCT05219565
Arrow heads at Obi-Rakhmat (Uzbekistan) 80 ka ago
Authors: Plisson Hugues , Kharevich Alëna V. , Kharevich Vladimir M. , Chistiakov Pavel V. , Zotkina Lydia V. , Baumann Malvina , Pubert Eric , Kolobova Ksenya A. , Krivoshapkin Andrei I. 
Published: January 2025

AbstractWhen they are occasionally found in Middle Palaeolithic Neanderthal settlements, lithic weapons heads are large and do not differ in size, shaping or type from those used for activities other than hunting, such as plant gathering or butchery. The presence in a same assemblage of various types of armatures, some of which are microlithic and designed for this purpose, has only been documented in Modern Humans sites.Recent studies show that light projectile points, which were to become the structuring element of Upper Palaeolithic lithic industries, were already present in its formative stages. However, they remain marginal in debates regarding the Middle to Upper Paleolithic transition.We present here the first results of a search for weapon heads in the oldest layers of the Obi-Rakhmat rock shelter, at around 80 ka. This site, located in the western foothills of the Tian Shan Mountains, northeastern Uzbekistan, has yielded a blade-based lithic industry which is forming part of the continuity of the Levantine Early Middle Paleolithic but with several innovative traits. The assemblage is based on a systematic blade production (regular thick narrow blades from unipolar and bipolar sub-prismatic and narrow-faced cores, thin and wide blades from flat-faced Levallois-like cores) along with shorter pieces from convergent or centripetal Levallois cores, and bladelets from burin-cores and other small cores.Three types of projectile armature are identified from their impact marks: retouched points, bladelets and raw micropoints which were so far unseen due to their fragmentary state. The micropoints are too narrow for having been fitted to anything other than arrow shafts. They are similar to the armatures described in a pioneer settlement by Sapiens in the Rhône Valley, France, 25,000 years later.
Repurposing Metal-Based Therapeutics for Human Metapneumovirus (HMPV): An Integrative Computational Approach
Authors: Dubey Amit , Kumar Manish , Tufail Aisha , Dwivedi Vivek Dhar 
Published: January 2025

AbstractHuman metapneumovirus (HMPV) poses a significant global health challenge, with limited therapeutic options available. This study employs a comprehensive computational framework to repurpose metal-based drugs as potential HMPV inhibitors. A library of compounds was systematically evaluated using virtual screening, high-precision molecular docking, molecular dynamics (MD) simulations, density functional theory (DFT) calculations, molecular electrostatic potential (MESP) mapping, and pharmacophore modeling. Key candidates, including Auranofin, Silver Sulfadiazine, and Gallium Nitrate, demonstrated high binding affinities (ΔGbinding: -68.5 to -62.7 kcal/mol) and favorable stability metrics (RMSD: 2.1–2.4 Å). ADME-toxicity (ADMET) profiling highlighted Auranofin’s robust bioavailability (80%) and extended half-life (8.5 hours), while Ribavirin and Favipiravir emerged as safe controls with minimal toxicity. Quantum chemical analyses reinforced the compounds’ electronic stability and reactivity. This integrative study provides a promising avenue for repurposing existing therapeutics, bridging computational insights with translational potential to combat HMPV.
Strategies for resolving cellular phylogenies from sequential lineage tracing data
Authors: Mulberry Nicola , Stadler Tanja 
Published: January 2025

AbstractA combination of recent advancements in molecular recording devices and sequencing technologies has made it possible to generate lineage tracing data on the order of thousands of cells. Dynamic lineage recorders are able to generate random, heritable mutations which accumulate continuously on the timescale of developmental processes; this genetic information is then recovered using single-cell RNA sequencing. These data have the potential to hold rich phylogenetic information due to the irreversible nature of the editing process, a key feature of the employed CRISPR-based systems that deviates from traditional assumptions about molecular mutation processes, and recent technologies have furthermore made it possible for mutations to be acquired sequentially. Understanding the information content of these recorders remains an open area of investigation. Here, we model a sequentially-edited recording system and analyse the experimental conditions over which exact phylogenetic reconstruction occurs with high probability. We find, using simulation and theory, explicit parameter regimes over which simple and efficient distance-based reconstruction methods can accurately resolve the cellular phylogeny. We furthermore illustrate how our theoretical results could be used to help inform experimental design.HighlightsUncovering cellular phylogenies is a key goal in developmental biology.State-of-the-art lineage tracing tools generate genetic sequences with irreversible and ordered mutations which can be recovered at the single-cell resolution.We analyze these experimental systems and assess when accurate reconstruction of the cellular phylogeny is possible.
DNA-free CRISPR Genome Editing in Raspberry (Rubus idaeus) through RNP-mediated Protoplast Transfection and Comparison of Indel Analysis Techniques
Authors: Creeth Ryan , Thompson Andrew , Kevei Zoltan 
Published: January 2025

AbstractProtoplast-based systems have been utilised in a wide variety of plant species to enable genome editing without chromosomal introgression of foreign DNA into plant genomes. This allows elite cultivars to be edited without further genetic segregation, preserving their unique genetic composition and their regulatory status as non-transgenic. This can be achieved by DNA-free genome editing in protoplasts, followed by regeneration. However, protoplast isolation presents a barrier to the development of advanced breeding technologies in raspberry and no protocol has been published for DNA-free genome editing in the species. Pre-assembled ribonucleoprotein complexes (RNPs) do not require cellular processing and the commercial availability of Cas9 proteins and synthetic guide RNAs has streamlined genome editing protocols. This study presents a novel high-yielding protoplast isolation protocol from raspberry stem cultures and RNP-mediated transfection of protoplast with CRISPR-Cas9. Targeted mutagenesis of the phytoene desaturase gene at two intragenic loci resulted in an editing efficiency of 19%, though estimated efficiency varied depending on the indel analysis technique. Only amplicon sequencing was sensitive enough to confirm genome editing in a low efficiency sample. To our knowledge, this study constitutes the first use of DNA-free genome editing in raspberry. This protocol provides a valuable platform for understanding gene function and facilitates the development of precision breeding in this important soft fruit crop.
Antibacterial, antibiofilm and anti-quorum sensing activities of 1,2,3,5-tetrazine derivatives linked to a benzothiazole moiety
Authors: Dzoyem Jean Paul , Tsemeugne Joseph , Pone Kamdem Boniface , Foyou Meupiap Rostand , Kuate Boris Arnaud , Mkounga Pierre , Fekam Boyom Fabrice , McGaw Lyndy Joy 
Published: January 2025

AbstractA series of known tetrazine derivatives, containing benzothiazole scaffold, were prepared during the coupling reactions of selected diazotized 2-aminobenzo[d]thiazole derivatives with p-acetaminophen. The as-prepared compounds were characterized based on NMR and MS spectrometry. The antibacterial and anti-biofilm activities of the synthesized compounds were evaluated by microdilution method, whereas the anti-quorum sensing effect was carried out using assay for the inhibition of violacein formation. As a result, compounds4a, 4band4crevealed minimum inhibitory concentrations and minimum bactericidal concentrations ranging from 8 to 128 µg/mL and from 32 to 256 µg/mL, respectively. Compounds4a(52-86.5%),4b(57.7-79.4%) and4c(59.9-80.3%) prevented biofilm formation in all the four bacteria tested with percentages of inhibition more than 50%. The concentrations of4a, 4band4cthat inhibited 50% of violacein production were found to be 62.71, 28.56 and 107.45 µg/mL, respectively, thus attesting that these compounds possess anti-quorum sensing activity. Noteworthy, our previous investigation attested that these compounds are non-cytotoxic on the human mammalian cells Vero.This novel contribution demonstrates the antibacterial, antibiofilm and anti-quorum sensing activities of tetrazine-based benzothiazoles, which might be prospected as scaffolds for the discovery of efficient antibiotics with decreased risk of microbial drug resistance.
Q-score as a reliability measure for protein, nucleic acid, and small molecule atomic coordinate models derived from 3DEM density maps
Authors: Pintilie Grigore , Shao Chenghua , Wang Zhe , Hudson Brian P. , Flatt Justin W. , Schmid Michael F. , Morris Kyle , Burley Stephen K. , Chiu Wah 
Published: January 2025

AbstractAtomic coordinate models are important in the interpretation of 3D maps produced with cryoEM and sub-tomogram averaging in cryoET, or more generically, 3D electron microscopy (3DEM). In addition to visual inspection of such maps and models, quantitative metrics convey the reliability of the atomic coordinates, in particular how well the model is supported by the experimentally determined 3DEM map. A recently introduced metric, Q-score, was shown to correlate well with the reported resolution of the map for well-fitted models. Here we present new statistical analyses of Q-scores based on its application to ∼10,000 maps and models archived in EMDB and PDB. Further we introduce two new metrics based on Q-score: Q-relative-all and Q-relative-resolution to compare a map and model to all entries in the EMDB and those with similar resolution respectively. We also explore through illustrative examples of proteins, nucleic acids, and small molecules how Q-scores can indicate whether the atomic coordinates are well-fitted to 3DEM maps and whether some parts of a map may be poorly resolved due to factors such as molecular flexibility, radiation damage, and/or conformational heterogeneity. Lastly, we show examples of how Q-scores can effectively be converted to atomic B-factors. These analyses provide a basis for how Q-scores can be interpreted effectively to evaluate 3DEM maps and atomic coordinate models prior to publication and archiving.SynopsisQ-scores are calculated each atom in models fitted to 3DEM (3D electron microscopy) maps. They measure how well the model fits the map, and also reflect the quality of the map as they correlate to resolution. Here we develop a statistical model for Q-scores applied to many maps and models in the EMDB (Electron Microscopy Database) and PDB (Protein Data Bank) respectively, and show how it can be used to assess the reliability of entire models as well as their subcomponents.
APE1 active site residue Asn174 stabilizes the AP-site and is essential for catalysis
Authors: DeHart Kaitlin M. , Hoitsma Nicole M. , Thompson Spencer H. , Borin Veniamin A. , Agarwal Pratul K. , Freudenthal Bret D. 
Published: January 2025

AbstractApurinic/Apyrimidinic (AP)-sites are common and highly mutagenic DNA lesions that can arise spontaneously or as intermediates during Base Excision Repair (BER). The enzyme apurinic/apyrimidinic endonuclease 1 (APE1) initiates repair of AP-sites by cleaving the DNA backbone at the AP-site via its endonuclease activity. Here, we investigated the functional role of the APE1 active site residue N174 that contacts the AP-site during catalysis. We analyzed the effects of three rationally designed APE1 mutations that alter the hydrogen bonding potential, size, and charge of N174: N174A, N174D, and N174Q. We found impaired catalysis of the APE1N174Aand APE1N174Dmutants due to disruption of hydrogen bonding and electrostatic interactions between residue 174 and the AP-site. In comparison, the APE1N174Qmutant was less impaired due to retaining similar hydrogen bonding and electrostatic characteristics as N174 in wild-type APE1. Structures and computational simulations further revealed that the AP-site was destabilized within the active sites of the APE1N174Aand APE1N174Dmutants due to loss of hydrogen bonding between residue 174 and the AP-site. Cumulatively, we show that N174 stabilizes the AP-site within the APE1 active site through hydrogen bonding and electrostatic interactions to enable effective catalysis. These findings highlight the importance of N174 in APE1’s function and provide new insights into the molecular mechanism by which APE1 processes AP-sites during DNA repair.
‘Munger’ black raspberry: Insights into its role as a virus indicator for Rubus species
Authors: Sierra-Mejia Andrea , Tzanetakis Ioannis E. 
Published: January 2025

ABSTRACT‘Munger’ black raspberry (Rubus occidentalis) has been a preferred indicator forRubusviruses. The working hypothesis behind the ‘Munger’ elevated susceptibility to viruses is its ability to sustain elevated virus titers; however, no research has yet explored this concept. To address this, we utilized an infectious clone of blackberry chlorotic ringspot virus to study the differences in virus expression between twoRubusspecies:R. occidentalis(‘Munger’) andR. L. subgenus RubusWatson (blackberry, ‘Natchez’). Our data demonstrate that virus accumulation in ‘Munger’ is over 47,300 times higher compared to ‘Natchez,’ enhancing our understanding of virus-host dynamics and providing valuable insights into why ‘Munger’ is a preferred indicator species for virus detection inRubusspp.
Quorum sensing mediates morphology and motility transitions in the model archaeonHaloferax volcanii
Authors: Chatterjee Priyanka , Consoli Caroline E. , Schiller Heather , Winter Kiersten K. , McCallum Monica E. , Schulze Stefan , Pohlschroder Mechthild 
Published: January 2025

AbstractQuorum sensing (QS) is a mechanism of intercellular communication that enables microbes to alter gene expression and adapt to the environment. This cell-cell signaling is necessary for intra- and interspecies behaviors such as virulence and biofilm formation. While QS has been extensively studied in bacteria, little is known about cell-cell communication in archaea. Here we established an archaeal model system to study QS. We showed that forHaloferax volcanii, the transition from motile rods to non-motile disks is dependent on a possibly novel, secreted small molecule present in cell-free conditioned medium (CM). Moreover, we determined that this putative QS molecule fails to induce the morphology transition in mutants lacking the regulatory factors, DdfA and CirA. Using quantitative proteomics of wild-type cells, we detected significant differential abundances of 236 proteins in the presence of CM. Conversely, in the ΔddfAmutant, addition of CM resulted in only 110 proteins of significant differential abundances. These results confirm that DdfA is involved in CM-dependent regulation. CirA, along with other proteins involved in morphology and swimming motility transitions, is among the proteins regulated by DdfA. These discoveries significantly advance our understanding of microbial communication within archaeal species.