bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virological characteristics of SARS-CoV-2 Omicron BA.5.2.48
Authors: Wang Wenqi , Jin Qiushi , Liu Ruixue , Zeng Wentao , Zhu Pengfei , Li Tingting , Wang Tiecheng , Xiang Haiyang , Zhang Hang , Chen Qin , Gao Yun , Lai Yana , Yan Fang , Xia Xianzhu , Li Jianmin , Wang Xuefeng , Gao Yuwei 
Published: March 2024

AbstractWith the prevalence of sequentially-emerged sublineages including BA.1, BA.2 and BA.5, SARS-CoV-2 Omicron infection has transformed into a regional epidemic disease. As a sublineage of BA.5, the BA.5.2.48 outbreak and evolved into multi-subvariants in China without clearly established virological characteristics, especially the pathogenicity. Though reduced airborne transmission and pathogenicity of former Omicron sublineages have been revealed in animal models, the virological characteristics of BA.5.2.48 was unidentified. Here, we evaluated the in vitro and in vivo virological characteristics of two isolates of the prevalent BA.5.2.48 subvariant, DY.2 and DY.1.1 (a subvariant of DY.1). DY.2 replicates more efficiently than DY.1.1 in HelahACE2+cells and Calu-3 cells. The A570S mutation (of DY.1) in a normal BA.5 spike protein (DY.2) leads to a 20% improvement in the hACE2 binding affinity, which is slightly reduced by a further K147E mutation (of DY.1.1). Compared to the normal BA.5 spike, the double-mutated protein demonstrates efficient cleavage and reduced fusogenicity. BA.5.2.48 demonstrated enhanced airborne transmission capacity in hamsters than BA.2. The pathogenicity of BA.5.2.48 is greater than BA.2, as revealed in K18-hACE2 rodents. Under immune selection pressure, DY.1.1 shows stronger fitness than DY.2 in hamster turbinates. Thus the outbreaking prevalent BA.5.2.48 multisubvariants exhibites divergent virological features.ImportanceOmicron continues to circulate and evolves novel sublineages with indistinguishable pathogenicity and transmission. Therefore humanized Omicron-sensitive animal models must be applied to evaluate the virological characteritics and antiviral therapeutics. By using multiple models including the Omicron-lethal H11-K18-hACE2 rodents, BA.5.2.48 revealed higher pathogenicity in the novel H11-K18-hACE2 rodent models than the previously epidemic BA.2, and thus the models are more adapted to Omicron studies. Moreover, the regional outbreaking of BA.5.2.48 promotes the multidirectional evolution of its subvariants, gaining either enhanced pathogenicity or a fitness in upper airways which is associated with higher transmission, highlighting the importance of surveillance and virological studies on regionally endemic sublineages which represents the short-run evolutionary direction of Omicron.
Chitin synthase targeting antifungal agents for Mucormycosis (Black fungus disease) caused byRhizopus delemar- Anin-silicostudy
Authors: George Abhilash J , Nair Achuthsankar S , Vijayalakshmio B 
Published: March 2024

ABSTRACTMucormycosis, a severe fungal infection caused byMucoralesfungi, particularlyRhizopus delemar, has prompted the development of new and more potent antifungal drugs due to the emergence of drug-resistant strains. Currently used drugs are known to be toxic to human cells also, which is a major drawback in their administration. Antifungal drugs commercially under use and their structurally modified analogues along with 30 plants reported with antifungal activity from IMPPAT database, totalling 229 compounds, were screened against the best modelled structure of Chitin Synthase, a key target enzyme ofRhizopus delemarbyin-silicomolecular docking studies. Computerized methods to assess absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles was employed to further filter key lead drug candidates from among the docked ligands that could act as potential antifungal medications. Modified structures of Posaconazole, Nikkomycin and Isavuconazole were found to give better docking results than compared to the original drugs, though they failed to comply with ADMET parameters. Among the phytochemicals, 1-nonacosanol displayed binding affinity (highest LibDock score) greater than the synthetic drugs and their derivatives, though it too failed to comply with ADMET parameters. The phytochemical Dihydrocapsaicin was found to be the best compound that satisfied all the parameters such as ADMET, TOPKAT, Lipinski’s and Veber’s rule along with good binding affinity. All in all, this novel study paves a way to investigate the interaction of Chitin Synthase inhibitors at molecular level to achieve an alternative solution with less toxic effects to treat Mucormycosis.
Anthropometric-related percentile curves for muscle size and strength of lower limb muscles of typically developing children
Authors: Vandekerckhove Ines , Hanssen Britta , Peeters Nicky , Dewit Tijl , Beukelaer Nathalie De , Van den Hauwe Marleen , Waele Liesbeth De , Campenhout Anja Van , Groote Friedl De , Desloovere Kaat 
Published: March 2024

AbstractAimsTo establish anthropometric-related percentile curves for muscle size and strength in a cohort of typically developing (TD) children and to demonstrate their use through applications in children with cerebral palsy (CP) and Duchenne muscular dystrophy (DMD).MethodsLower limb muscle size and strength were assessed in a large cross-sectional cohort of TD children with 3D freehand ultrasound (four muscles, n=154, male/female=82/72, age range: 0y7mo-17y10mo) and fixed dynamometry (seven muscle groups, n=153, male/female=108/45, age range: 4y6mo-16y1mo), respectively. Generalized additive models for location, scale and shape were used to estimate anthropometric-related, i.e. body mass and height, TD percentile curves and to convert outcomes of individual patients with CP and DMD into z-scores.ResultsMuscle size and strength, as well as their inter-subject variation, increased with increasing anthropometric values. Individual patients exhibited negative z-scores, indicating muscle size and strength deficits in reference to TD peers.InterpretationThe established anthropometric-related percentile curves for muscle size and strength in a cohort of TD children can successfully be used to express patient outcomes in reference to TD. This facilitates the interpretation of muscle size and weakness in children with a motor disability and allows for the evaluation of the disease progression and treatment impact during growth.
A high-resolution haplotype pangenome uncovers somatic hybridization, recombination and intercontinental migration in oat crown rust
Authors: Henningsen Eva C. , Lewis David , Nazareno Eric , Huang Yung-Fen , Steffenson Brian J. , Boesen Brendan , Kianian Shahryar F. , Stone Eric , Dodds Peter N. , Sperschneider Jana , Figueroa Melania 
Published: March 2024

AbstractBasidiomycetes like rust fungi have complex reproductive cycles and dikaryotic life stages which influence their population structure and evolution.Puccinia coronataf. sp.avenae(Pca), the causal agent of oat crown rust, is a pathogen of global economic importance. To investigate the genetic diversity of the species, as well as the role of mating type system and nuclear exchange (somatic hybridization) in host adaptation ofPcawe acquired whole genome sequencing data of Taiwanese and Australian isolates, adding to existing data for USA and South African populations. An atlas of 30 chromosome-level, fully-phased nuclear haplotypes from six USA isolates and nine Australian isolates was generated to capture the genomic composition of key oat crown rust lineages. This study provides evidence of nuclear exchange and recombination of haplotypes in both the USA and AustralianPcapopulations as mechanisms for the introduction of genetic diversity. The limitations of assuming clonal evolutionary history from virulence phenotyping is demonstrated by the detection of either sexual or cryptic genetic recombination in thePcaAustralian population. Overall, the characterization of intercontinental migration ofPcaat the haplotype level provides further impetus for molecular monitoring of rust pathogen populations on a global scale.
What We (Don’t) Know about Parrot Welfare: A Systematic Literature Review
Authors: Piseddu Andrea , van Zeeland Yvonne R. A. , Rault Jean-Loup 
Published: March 2024

AbstractParrots are popular companion animals but show prevalent and at times severe welfare issues. Nonetheless, there are no scientific tools available to assess parrot welfare. The aim of this systematic review was to identify valid and feasible outcome measures that could be used as welfare indicators for companion parrots. From 1848 peer-reviewed studies retrieved, 98 met our inclusion and exclusion criteria (e.g. experimental studies, captive parrots). For each outcome collected, validity was assessed based on the statistical significance reported by the authors, as other validity parameters were rarely available for evaluation. Feasibility was assigned by considering the need for specific instruments, veterinary-level expertise or handling the parrot. A total of 1512 outcomes were evaluated, of which 572 had a significant p-value and were considered feasible. These included changes in behaviour (e.g. activity level, social interactions, exploration), body measurements (e.g. body weight, plumage condition) and abnormal behaviours, amongst others. However, a high risk of bias undermined the internal validity of these outcomes. Moreover, a strong taxonomic bias, a predominance of studies on parrots in laboratories, and an underrepresentation of companion parrots jeopardized their external validity. These results provide a promising starting point for validating a set of welfare indicators in parrots.
Intrinsically disordered RNA-binding motifs cooperate to catalyze RNA folding and drive phase separation
Authors: Niedner-Boblenz Annika , Monecke Thomas , Hennig Janosch , Klostermann Melina , Hofweber Mario , Davydova Elena , Gerber André P. , Anosova Irina , Mayer Wieland , Müller Marisa , Heym Roland Gerhard , Janowski Robert , Paillart Jean-Christophe , Dormann Dorothee , Zarnack Kathi , Sattler Michael , Niessing Dierk 
Published: March 2024

AbstractRNA-binding proteins are essential for gene regulation and the spatial organization of cells. Here, we report that the yeast ribosome biogenesis factor Loc1p is an intrinsically disordered RNA-binding protein with eight repeatingpositively charged,unstructurednucleic acid binding (PUN) motifs. While a single of these previously undefined motifs stabilizes folded RNAs, multiple copies strongly cooperate to catalyze RNA folding. In the presence of RNA, these multivalent PUN motifs drive phase separation. Proteome-wide searches in pro-and eukaryotes for proteins with similar arrays of PUN motifs reveal a strong enrichment in RNA-mediated processes and DNA remodeling. Thus, PUN motifs are potentially involved in a large variety of RNA-and DNA-related processes by concentrating them in membrane-less organelles. The general function and wide distribution of PUN motifs across species suggests that in an ancient “RNA world” PUN-like motifs may have supported the correct folding of early ribozymes.
Identification of stress specific autophagy regulators from tandem CRISPR screens
Authors: Losier Truc T. , Rousseaux Maxime W.C. , Russell Ryan C. 
Published: March 2024

AbstractAutophagy is a conserved degradative process that promotes cellular homeostasis under stress conditions. Under nutrient starvation autophagy is largely non-selective, promoting the indiscriminate breakdown of cytosolic components. Conversely, selective autophagy is responsible for the specific turnover of damaged organelles including endoplasmic reticula, lysosomes, mitochondria, and peroxisomes. The mechanisms of selective autophagy are best understood through the activity of cargo-specific receptors called autophagy receptors, which facilitate the engulfment of the targeted cargo within autophagosomes, leading to subsequent degradation. We hypothesized that selective autophagy may be regulated by distinct upstream signaling from starvation induced autophagy, providing an additional layer of regulatory control to targeted autophagic degradation. To comprehensively address this question we conducted kinome-wide CRISPR screens to identify distinct signaling pathways responsible for the regulation of basal autophagy, starvation-induced autophagy, and two types of selective autophagy, ER-phagy and pexophagy. These parallel screens identified established and novel autophagy shared regulators under these conditions, as well as kinases specifically required for ER-phagy or pexophagy. More specifically, CDK11A and NME3 were further characterized to be selective ER-phagy regulators. Meanwhile, PAN3 and CDC42BPG were identified as activator or inhibitor of pexophagy, respectively. Collectively, these datasets provide the first comparative description of the kinase signaling specificity, separating regulation of selective autophagy and bulk autophagy.HighlightsParallel pooled kinome genetic knockout screens reveal known and novel regulators of autophagy under basal conditions, nutrient starvation, ER stress, and peroxisomal stressSelective ER and peroxisomal autophagy both have unique activators and inhibitors that distinguish them from bulk autophagyCDK11A and NME3 specifically induce and inhibit ER-phagy, respectivelyPAN3 and CDC42BPG specifically induce and inhibit pexophagy, respectively
Tangled genetic relationships within theFusobacteriumgenus
Authors: Molteni Cristian , Forni Diego , Cagliani Rachele , Sironi Manuela 
Published: March 2024

AbstractFusobacteria have been associated to different diseases, including colorectal cancer (CRC), but knowledge of which taxonomic groups contribute to specific conditions is incomplete. We analyzed the genetic diversity and relationships within theFusobacteriumgenus. We report recent and ancestral recombination in core genes, indicating that fusobacteria have mosaic genomes and emphasizing that taxonomic demarcation should not rely on single genes/gene regions. Across databases, we found ample evidence of species miss-classification and of undescribed species, which are both expected to complicate disease association. By focusing on a lineage that includesF. periodonticum/pseudoperiodonticumandF. nucleatum, we show that genomes belong to four modern populations, but most known species/subspecies emerged from individual ancestral populations. Of these, theF. periodonticum/pseudoperiodonticumpopulation experienced the lowest drift and displays the highest genetic diversity, in line with the less specialized distribution of these bacteria in oral sites. A highly drifted ancestral population instead contributed genetic ancestry to a new species, which includes genomes classified within theF. nucleatum animalisdiversity in a recent CRC study. Thus, evidence herein calls for a re-analysis ofF. nucleatum animalisfeatures associated to CRC. More generally, our data inform future molecular profiling approaches to investigate the epidemiology ofFusobacterium-associated diseases.
The structure of the R2T complex reveals a different architecture of the related HSP90 co-chaperones R2T and R2TP
Authors: Palacios-Abella Alberto , López-Perrote Andrés , Boskovic Jasminka , Fonseca Sandra , Úrbez Cristina , Rubio Vicente , Llorca Oscar , Alabadí David 
Published: March 2024

ABSTRACTHeat shock protein 90 (HSP90) is a molecular chaperone that contributes to the maturation and activation of substrates in multiple cellular pathways. Its activity is supported by various co-chaperones. One of these is R2TP, a complex of RuvBL1-RuvBL2-RPAP3-PIH1D1 in humans, which is involved in the assembly of various multiprotein complexes, including mTORC1 and Box C/D and Box H/ACA snoRNPs. Structural analyses have shown that the complex is organized around a heterohexameric ring of the ATPases RuvBL1-RuvBL2 in both yeast and humans. In addition, several R2TP-like co-chaperones have been identified in humans, such as R2T, which lacks PIH1D1, but these are less well characterized. In seed plants, there are no PIH1D1 orthologs. Here, we have identified the R2T complex ofArabidopsisand determined its cryoEM structure. R2T associates with the prefoldin-like complexin vivoand is located in the cytosolic and nuclear compartments. R2T is organized as a dodecamer of AtRuvBL1-AtRuvBL2a that forms two rings, with one AtRPAP3 anchored to each ring. AtRPAP3 has no effect on the ATPase activity of AtRuvBL1-AtRuvBL2a and binds with a different stoichiometry than that described for human R2TP. We show the interaction of AtRPAP3 with AtRuvBL2a and AtHSP90in vivoand describe the residues involved. Taken together, our results show that AtRPAP3 recruits AtRuvBL1-AtRuvBL2a and AtHSP90 via a mechanism that is also conserved in other eukaryotes, but that R2T and R2TP co-chaperone complexes have distinct structures that also suggest differences in their functions and mechanisms.
Unlocking Precision Gene Therapy: Harnessing AAV Tropism with Nanobody Swapping at Capsid Hotspots
Authors: Hoffmann Mareike D. , Gallant Joseph P. , LeBeau Aaron M. , Schmidt Daniel 
Published: March 2024

ABSTRACTAdeno-associated virus has been remarkably successful in the clinic, but its broad tropism is a practical limitation of precision gene therapy. A promising path to engineer AAV tropism is the addition of binding domains to the AAV capsid that recognize cell surface markers present on a targeted cell type. We have recently identified two previously unexplored capsid regions near the 2-fold valley and 5-fold pore of the AAV capsid that are amenable to insertion of larger protein domains including nanobodies. Here, we demonstrate that these hotspots facilitate AAV tropism switching through simple nanobody replacement without extensive optimization in both VP1 and VP2. We demonstrate highly specific targeting of human cancer cells expressing fibroblast activating protein (FAP). Our data suggest that engineering VP2 is the preferred path for maintaining both virus production yield and infectivity. Our study shows that nanobody swapping at multiple capsid location is a viable strategy for nanobody-directed cell-specific AAV targeting.
Donor side effects experienced under minimal controlled ovarian stimulation (COS) with in vitro maturation (IVM) versus conventional COS forin vitrofertilization (IVF) treatment
Authors: Marchante Maria , Barrachina Ferran , Piechota Sabrina , Fernandez-González Marta , Giovannini Alexa , Smith Trozalla , Kats Simone , Paulsen Bruna , González Eva , Calvente Virginia , Silvan Ana , Abittan Baruch , Klein Joshua , Klatsky Peter , Ordonez Daniel , Kramme Christian C. 
Published: March 2024

ABSTRACTObjectiveTo evaluate how minimal controlled ovarian stimulation (COS) for in vitro maturation (IVM) affects subjects’ oocyte retrieval experiences compared to conventional COS, considering side effectsDesignRetrospective Survey StudySettingClinical in vitro fertilization (IVF) treatment centers in Spain and the United States.SubjectsData were collected from subjects undergoing minimal COS (n=110; 600-800 IU FSH) for IVM and conventional COS for egg donation (n=48; 2000-3000 IU FSH) from April 2022 to November 2023. In the same period, a pairwise comparison of subjects (n=13) undergoing both minimal COS for IVM and conventional COS for oocyte cryopreservation was conducted.Intervention/ExposureMinimal and conventional controlled ovarian stimulation.Main Outcome MeasuresThe most common side effects suffered during ovarian stimulation and after OPU, satisfaction level, and the likelihood of recommending or repeating minimal or conventional COS. Statistical analysis included Mann Whitney, Wilcoxon, Chi-square, and McNemar tests, with a significance level set at p<0.05.ResultsDuring minimal COS, most subjects did not experience breast swelling (86%), pelvic or abdominal pain (76%), nausea or vomiting (96%), and bleeding (96%). After oocyte pick-up, the majority (75%) reported no pelvic or abdominal pain. The most common side effect was abdominal swelling (52%). Compared to conventional COS cycles, minimal COS subjects reported significantly less post-retrieval pain, with 33% experiencing no pain (vs. 6%; p=0.0011) and with a reduced severe level of pain (5% vs.19%; p=0.0097), leading to fewer subjects requiring pain medication (25% vs. 54%; p=0.0003). Additionally, 85% of women were very satisfied with minimal stimulation and would recommend or repeat the treatment. In the comparison in which each donor underwent both minimal and conventional COS treatments, women indicated more side effects with the conventional stimulation, presenting a significantly overall higher level of pain (p=0.0078).ConclusionReducing the hormonal dose for ovarian stimulation has a beneficial effect on subjects, suggesting the combination of minimal COS with IVM techniques is a well-tolerated alternative for women who cannot or do not wish to undergo conventional controlled ovarian hyperstimulation.
Nonlocal effects on the shock-augmented ignition scheme of laser inertial fusion
Authors: Yuan W. Q. , Zhao Z. H. , Zhu S. P. , He X. T. , Qiao B. 
Published: March 2024

Shock-augmented ignition (SAI) has recently been proposed as a viable approach to optimize the shock ignition scheme of laser fusion, which may substantially reduce laser power and intensity requirements and, as a result, greatly inhibit the growth of laser-plasma instabilities. However, the nonlocal thermal transport effect, which is believed to play a significant role in shock ignition, has not been considered in evaluation of the SAI scheme yet. Here, by self-consistently including modeling of the space-time-dependent nonlocal thermal transport into the radiation hydrodynamic simulations, we revisit the whole implosion and ignition dynamics of SAI numerically and theoretically. We find that, due to the nonlocal effect, on the one hand, the time-delay window between the igniter spike and the compression pulse in the drive laser for achieving high-gain fusion is much broadened from about 0.45 to 0.7 ns, relaxing the difficulty of laser pulse shaping; on the other hand, both the coast time and the fusion burn duration are significantly reduced by, respectively, 0.22 ns and 47 ps, in favor of increasing the hot-spot pressure around the stagnation stage.

Published by the American Physical Society
2024