bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural human knockouts and Mendelian disorders: deep phenotyping in Italian isolates
Authors: Spedicati Beatrice , Cocca Massimiliano , Palmisano Roberto , Faletra Flavio , Barbieri Caterina , Francescatto Margherita , Mezzavilla Massimo , Morgan Anna , Pelliccione Giulia , Gasparini Paolo , Girotto Giorgia 
Published: March 2021

AbstractWhole genome sequencing (WGS) allows the identification of human knockouts (HKOs), individuals in whom loss of function (LoF) variants disrupt both alleles of a given gene. HKOs are a valuable model for understanding the consequences of genes function loss. Naturally occurring biallelic LoF variants tend to be significantly enriched in “genetic isolates,” making these populations specifically suited for HKO studies. In this work, a meticulous WGS data analysis combined with an in-depth phenotypic assessment of 947 individuals from three Italian genetic isolates led to the identification of ten biallelic LoF variants in ten OMIM genes associated with known autosomal recessive diseases. Notably, only a minority of the identified HKOs (C7, F12, and GPR68 genes) displayed the expected phenotype. For most of the genes, instead, (ACADSB, FANCL, GRK1, LGI4, MPO, PGAM2, and RP1L1), the carriers showed none or few of the signs and symptoms typically associated with the related diseases. Of particular interest is a case presenting with a FANCL biallelic LoF variant and a positive diepoxybutane test but lacking a full Fanconi anemia phenotypic spectrum. Identifying KO subjects displaying expected phenotypes suggests that the lack of correct genetic diagnoses may lead to inappropriate and delayed treatment. In contrast, the presence of HKOs with phenotypes deviating from the expected patterns underlines how LoF variants may be responsible for broader phenotypic spectra. Overall, these results highlight the importance of in-depth phenotypical characterization to understand the role of LoF variants and the advantage of studying these variants in genetic isolates.
Ground deformation reveals the scale-invariant conduit dynamics driving explosive basaltic eruptions
Authors: Ripepe M. , Lacanna G. , Pistolesi M. , Silengo M. C. , Aiuppa A. , Laiolo M. , Massimetti F. , Innocenti L. , Della Schiava M. , Bitetto M. , La Monica F. P. , Nishimura T. , Rosi M. , Mangione D. , Ricciardi A. , Genco R. , Coppola D. , Marchetti E. , Delle Donne D. 
Published: March 2021

AbstractThe mild activity of basaltic volcanoes is punctuated by violent explosive eruptions that occur without obvious precursors. Modelling the source processes of these sudden blasts is challenging. Here, we use two decades of ground deformation (tilt) records from Stromboli volcano to shed light, with unprecedented detail, on the short-term (minute-scale) conduit processes that drive such violent volcanic eruptions. We find that explosive eruptions, with source parameters spanning seven orders of magnitude, all share a common pre-blast ground inflation trend. We explain this exponential inflation using a model in which pressure build-up is caused by the rapid expansion of volatile-rich magma rising from depth into a shallow (<400 m) resident magma conduit. We show that the duration and amplitude of this inflation trend scales with the eruption magnitude, indicating that the explosive dynamics obey the same (scale-invariant) conduit process. This scale-invariance of pre-explosion ground deformation may usher in a new era of short-term eruption forecasting.
The Hindu Kush slab break-off as revealed by deep structure and crustal deformation
Authors: Kufner Sofia-Katerina , Kakar Najibullah , Bezada Maximiliano , Bloch Wasja , Metzger Sabrina , Yuan Xiaohui , Mechie James , Ratschbacher Lothar , Murodkulov Shokhruhk , Deng Zhiguo , Schurr Bernd 
Published: March 2021

AbstractBreak-off of part of the down-going plate during continental collision occurs due to tensile stresses built-up between the deep and shallow slab, for which buoyancy is increased because of continental-crust subduction. Break-off governs the subsequent orogenic evolution but real-time observations are rare as it happens over geologically short times. Here we present a finite-frequency tomography, based on jointly inverted local and remote earthquakes, for the Hindu Kush in Afghanistan, where slab break-off is ongoing. We interpret our results as crustal subduction on top of a northwards-subducting Indian lithospheric slab, whose penetration depth increases along-strike while thinning and steepening. This implies that break-off is propagating laterally and that the highest lithospheric stretching rates occur during the final pinching-off. In the Hindu Kush crust, earthquakes and geodetic data show a transition from focused to distributed deformation, which we relate to a variable degree of crust-mantle coupling presumably associated with break-off at depth.
In situ structure and organization of the influenza C virus surface glycoprotein
Authors: Halldorsson Steinar , Sader Kasim , Turner Jack , Calder Lesley J. , Rosenthal Peter B. 
Published: March 2021

AbstractThe lipid-enveloped influenza C virus contains a single surface glycoprotein, the haemagglutinin-esterase-fusion (HEF) protein, that mediates receptor binding, receptor destruction, and membrane fusion at the low pH of the endosome. Here we apply electron cryotomography and subtomogram averaging to describe the structural basis for hexagonal lattice formation by HEF on the viral surface. The conformation of the glycoprotein in situ is distinct from the structure of the isolated trimeric ectodomain, showing that a splaying of the membrane distal domains is required to mediate contacts that form the lattice. The splaying of these domains is also coupled to changes in the structure of the stem region which is involved in membrane fusion, thereby linking HEF’s membrane fusion conformation with its assembly on the virus surface. The glycoprotein lattice can form independent of other virion components but we show a major role for the matrix layer in particle formation.
Programmable site-selective labeling of oligonucleotides based on carbene catalysis
Authors: Lee Yang-Ha , Yu Eunsoo , Park Cheol-Min 
Published: March 2021

AbstractSite-selective modification of oligonucleotides serves as an indispensable tool in many fields of research including research of fundamental biological processes, biotechnology, and nanotechnology. Here we report chemo- and regioselective modification of oligonucleotides based on rhodium(I)-carbene catalysis in a programmable fashion. Extensive screening identifies a rhodium(I)-catalyst that displays robust chemoselectivity toward base-unpaired guanosines in single and double-strand oligonucleotides with structurally complex secondary structures. Moreover, high regioselectivity among multiple guanosines in a substrate is achieved by introducing guanosine-bulge loops in a duplex. This approach allows the introduction of multiple unique functional handles in an iterative fashion, the utility of which is exemplified in DNA-protein cross-linking in cell lysates.
Prospective contributions of biomass pyrolysis to China’s 2050 carbon reduction and renewable energy goals
Authors: Yang Qing , Zhou Hewen , Bartocci Pietro , Fantozzi Francesco , Mašek Ondřej , Agblevor Foster A. , Wei Zhiyu , Yang Haiping , Chen Hanping , Lu Xi , Chen Guoqian , Zheng Chuguang , Nielsen Chris P. , McElroy Michael B. 
Published: March 2021

AbstractRecognizing that bioenergy with carbon capture and storage (BECCS) may still take years to mature, this study focuses on another photosynthesis-based, negative-carbon technology that is readier to implement in China: biomass intermediate pyrolysis poly-generation (BIPP). Here we find that a BIPP system can be profitable without subsidies, while its national deployment could contribute to a 61% reduction of carbon emissions per unit of gross domestic product in 2030 compared to 2005 and result additionally in a reduction in air pollutant emissions. With 73% of national crop residues used between 2020 and 2030, the cumulative greenhouse gas (GHG) reduction could reach up to 8620 Mt CO2-eq by 2050, contributing 13–31% of the global GHG emission reduction goal for BECCS, and nearly 4555 Mt more than that projected for BECCS alone in China. Thus, China’s BIPP deployment could have an important influence on achieving both national and global GHG emissions reduction targets.
Xbp1s-FoxO1 axis governs lipid accumulation and contractile performance in heart failure with preserved ejection fraction
Authors: Schiattarella Gabriele G. , Altamirano Francisco , Kim Soo Young , Tong Dan , Ferdous Anwarul , Piristine Hande , Dasgupta Subhajit , Wang Xuliang , French Kristin M. , Villalobos Elisa , Spurgin Stephen B. , Waldman Maayan , Jiang Nan , May Herman I. , Hill Theodore M. , Luo Yuxuan , Yoo Heesoo , Zaha Vlad G. , Lavandero Sergio , Gillette Thomas G. , Hill Joseph A. 
Published: March 2021

AbstractHeart failure with preserved ejection fraction (HFpEF) is now the dominant form of heart failure and one for which no efficacious therapies exist. Obesity and lipid mishandling greatly contribute to HFpEF. However, molecular mechanism(s) governing metabolic alterations and perturbations in lipid homeostasis in HFpEF are largely unknown. Here, we report that cardiomyocyte steatosis in HFpEF is coupled with increases in the activity of the transcription factor FoxO1 (Forkhead box protein O1). FoxO1 depletion, as well as over-expression of the Xbp1s (spliced form of the X-box-binding protein 1) arm of the UPR (unfolded protein response) in cardiomyocytes each ameliorates the HFpEF phenotype in mice and reduces myocardial lipid accumulation. Mechanistically, forced expression of Xbp1s in cardiomyocytes triggers ubiquitination and proteasomal degradation of FoxO1 which occurs, in large part, through activation of the E3 ubiquitin ligase STUB1 (STIP1 homology and U-box-containing protein 1) a novel and direct transcriptional target of Xbp1s. Our findings uncover the Xbp1s-FoxO1 axis as a pivotal mechanism in the pathogenesis of cardiometabolic HFpEF and unveil previously unrecognized mechanisms whereby the UPR governs metabolic alterations in cardiomyocytes.
Impact of temperature-dependent phage expression on Pseudomonas aeruginosa biofilm formation
Authors: Bisht Karishma , Moore Jessica L. , Caprioli Richard M. , Skaar Eric P. , Wakeman Catherine A. 
Published: March 2021

AbstractPseudomonas aeruginosais a ubiquitous opportunistic pathogen that forms robust biofilms in the different niches it occupies. Numerous physiological adaptations are required as this organism shifts from soil or aquatic environments to a host-associated lifestyle. While many conditions differ between these niches, temperature shifts are a factor that can contribute to physiological stress during this transition. To understand how temperature impacts biofilm formation in this pathogen, we used proteomic and transcriptomic tools to elucidate physiological responses in environment-relevant vs. host-relevant temperatures. These studies uncovered differential expression of various proteins including a phage protein that is associated with the EPS matrix inP. aeruginosa. This filamentous phage was induced at host temperatures and was required for full biofilm-forming capacity specifically at human body temperature. These data highlight the importance of temperature shift in biofilm formation and suggest bacteriophage proteins could be a possible therapeutic target in biofilm-associated infections.
Benthic and coral reef community field data for Heron Reef, Southern Great Barrier Reef, Australia, 2002–2018
Authors: Roelfsema Chris , Kovacs Eva M. , Markey Kathryn , Vercelloni Julie , Rodriguez-Ramirez Alberto , Lopez-Marcano Sebastian , Gonzalez-Rivero Manuel , Hoegh-Guldberg Ove , Phinn Stuart R. 
Published: March 2021

AbstractThis paper describes benthic coral reef community composition point-based field data sets derived from georeferenced photoquadrats using machine learning. Annually over a 17 year period (2002–2018), data were collected using downward-looking photoquadrats that capture an approximately 1 m2 footprint along 100 m–1500 m transect surveys distributed along the reef slope and across the reef flat of Heron Reef (28 km2), Southern Great Barrier Reef, Australia. Benthic community composition for the photoquadrats was automatically interpreted through deep learning, following initial manual calibration of the algorithm. The resulting data sets support understanding of coral reef biology, ecology, mapping and dynamics. Similar methods to derive the benthic data have been published for seagrass habitats, however here we have adapted the methods for application to coral reef habitats, with the integration of automatic photoquadrat analysis. The approach presented is globally applicable for various submerged and benthic community ecological applications, and provides the basis for further studies at this site, regional to global comparative studies, and for the design of similar monitoring programs elsewhere.
Hyperinsulinaemic hypoglycaemia in non-anaesthetized Göttingen minipigs induces a counter-regulatory endocrine response and electrocardiographic changes
Authors: Lyhne Mille K. , Vegge Andreas , Povlsen Gro Klitgaard , Slaaby Rita , Kildegaard Jonas , Pedersen-Bjergaard Ulrik , Olsen Lisbeth H. 
Published: March 2021

AbstractThe potentially fatal cardiovascular effects of hypoglycaemia are not well understood and large animal models of the counter-regulatory responses and cardiovascular consequences of insulin-induced hypoglycaemia are needed to understand the mechanisms in humans. The aim of this study was to develop a human-like minipig model of hypoglycaemia including healthy and diabetic pigs to investigate endocrine, electrocardiographic and platelet effects. Hypoglycaemia was induced using a hyperinsulinaemic, hypoglycaemic clamp and an insulin bolus protocol. Plasma glucose, glucagon, C-peptide, insulin, epinephrine and platelet aggregation responses were measured before, during and after hypoglycaemia. Continuous electrocardiographic recordings were obtained. Hypoglycaemia at a plasma glucose concentration of 0.8–1.0 mM in the clamp induced 25-fold increase in epinephrine and sixfold and threefold increase in glucagon for healthy and diabetic pigs, respectively. The hypoglycaemic clamp induced QTc-interval prolongation and increase in cardiac arrhythmias. In the bolus approach, the non-diabetic group reached plasma glucose target of 1.5 mM and QTc-interval was prolonged after insulin injection, but before glucose nadir. The diabetic group did not reach hypoglycaemic target, but still demonstrated QTc-interval prolongation. These results demonstrate effects of hyperinsulinaemic hypoglycaemia closely resembling human physiology, indicating the minipig as a translational animal model of counter-regulatory endocrine and myocardial effects of hypoglycaemia.
Ion conformation and orientational order in a dicationic ionic liquid crystal studied by solid-state nuclear magnetic resonance spectroscopy
Authors: Majhi Debashis , Dvinskikh Sergey V. 
Published: March 2021

AbstractIonic liquids crystals belong to a special class of ionic liquids that exhibit thermotropic liquid-crystalline behavior. Recently, dicationic ionic liquid crystals have been reported with a cation containing two single-charged ions covalently linked by a spacer. In ionic liquid crystals, electrostatic and hydrogen bonding interactions in ionic sublayer and van der Waals interaction in hydrophobic domains are the main forces contributing to the mesophase stabilization and determining the molecular orientational order and conformation. How these properties in dicationic materials are compared to those in conventional monocationic analogs? We address this question using a combination of advanced NMR methods and DFT analysis. Dicationic salt 3,3′-(1,6-hexanediyl)bis(1-dodecylimidazolium)dibromide was studied. Local bond order parameters of flexible alkyl side chains, linker chain, and alignment of rigid polar groups were analyzed. The dynamic spacer effectively “decouples” the motion of two ionic moieties. Hence, local order and alignment in dicationic mesophase were similar to those in analogous single-chain monocationic salts. Bond order parameters in the side chains in the dicationic smectic phase were found consistently lower compared to double-chain monocationic analogs, suggesting decreasing contribution of van der Waals forces. Overall dication reorientation in the smectic phase was characterized by low values of orientational order parameterS. With increased interaction energy in the polar domain the layered structure is stabilized despite less ordered dications. The results emphasized the trends in the orientational order in ionic liquid crystals and contributed to a better understanding of interparticle interactions driving smectic assembly in this and analogous ionic mesogens.
Dynamic consolidated bioprocessing for innovative lab-scale production of bacterial alkaline phosphatase from Bacillus paralicheniformis strain APSO
Authors: Abdelgalil Soad A. , Soliman Nadia A. , Abo-Zaid Gaber A. , Abdel-Fattah Yasser R. 
Published: March 2021

AbstractTo meet the present and forecasted market demand, bacterial alkaline phosphatase (ALP) production must be increased through innovative and efficient production strategies. Using sugarcane molasses and biogenic apatite as low-cost and easily available raw materials, this work demonstrates the scalability of ALP production from a newfound Bacillus paralicheniformis strain APSO isolated from a black liquor sample. Mathematical experimental designs including sequential Plackett–Burman followed by rotatable central composite designs were employed to select and optimize the concentrations of the statistically significant media components, which were determined to be molasses, (NH4)2NO3, and KCl. Batch cultivation in a 7-L stirred-tank bioreactor under uncontrolled pH conditions using the optimized medium resulted in a significant increase in both the volumetric and specific productivities of ALP; the alkaline phosphatase throughput 6650.9 U L−1, and µ = 0.0943 h−1; respectively, were obtained after 8 h that, ameliorated more than 20.96, 70.12 and 94 folds compared to basal media, PBD, and RCCD; respectively. However, neither the increased cell growth nor enhanced productivity of ALP was present under the pH-controlled batch cultivation. Overall, this work presents novel strategies for the statistical optimization and scaling up of bacterial ALP production using biogenic apatite.
Differential diagnostic value of rheumatic symptoms in patients with Whipple’s disease
Authors: Feurle Gerhard E. , Moos Verena , Stroux Andrea , Gehrmann-Sommer Nadine , Poddubnyy Denis , Fiehn Christoph , Schneider Thomas 
Published: March 2021

AbstractMost patients with Whipple’s disease have rheumatic symptoms. The aim of our prospective, questionnaire-based, non-interventional clinical study was to assess whether these symptoms are useful in guiding the differential diagnosis to the rheumatic disorders. Forty patients with Whipple’s disease, followed by 20 patients for validation and 30 patients with rheumatoid-, 21 with psoriatic-, 15 with palindromic- and 25 with axial spondyloarthritis were recruited for the present investigation. Patients with Whipple’s disease and patients with rheumatic disorders were asked to record rheumatic symptoms on pseudonymized questionnaires. The data obtained were subjected to multiple logistic regression analysis. Episodic pain with rapid onset, springing from joint to joint was most common in patients with palindromic arthritis and second most common and somewhat less conspicuous in Whipple’s disease. Continuous pain in the same joints predominated in patients with rheumatoid-, psoriatic-, and axial spondyloarthritis. Multiple logistic equations resulted in a predicted probability for the diagnosis of Whipple’s disease of 43.4 ± 0.19% (M ± SD) versus a significantly lower probability of 23.8 ± 0.19% (M ± SD) in the aggregate of patients with rheumatic disorders. Mean area under the curve (AUC) ± SD was 0.781 ± 0.044, 95% CI 0.695–0.867, asymptotic significance p < 0.001. The logistic equations predicted probability for the diagnosis of Whipple’s disease in the initial series of 40 patients of 43.4 ± 0.19% was not significantly different in the subsequent 20 patients of 38.2 ± 0.28% (M ± SD) (p = 0.376). The data may be useful in a predictive algorithm for diagnosing Whipple’s disease. The project is registered as clinical study DRK S0001566.
Creation and validation of models to predict response to primary treatment in serous ovarian cancer
Authors: Gonzalez Bosquet Jesus , Devor Eric J. , Newtson Andreea M. , Smith Brian J. , Bender David P. , Goodheart Michael J. , McDonald Megan E. , Braun Terry A. , Thiel Kristina W. , Leslie Kimberly K. 
Published: March 2021

AbstractNearly a third of patients with high-grade serous ovarian cancer (HGSC) do not respond to initial therapy and have an overall poor prognosis. However, there are no validated tools that accurately predict which patients will not respond. Our objective is to create and validate accurate models of prediction for treatment response in HGSC. This is a retrospective case–control study that integrates comprehensive clinical and genomic data from 88 patients with HGSC from a single institution. Responders were those patients with a progression-free survival of at least 6 months after treatment. Only patients with complete clinical information and frozen specimen at surgery were included. Gene, miRNA, exon, and long non-coding RNA (lncRNA) expression, gene copy number, genomic variation, and fusion-gene determination were extracted from RNA-sequencing data. DNA methylation analysis was performed. Initial selection of informative variables was performed with univariate ANOVA with cross-validation. Significant variables (p < 0.05) were included in multivariate lasso regression prediction models. Initial models included only one variable. Variables were then combined to create complex models. Model performance was measured with area under the curve (AUC). Validation of all models was performed using TCGA HGSC database. By integrating clinical and genomic variables, we achieved prediction performances of over 95% in AUC. Most performances in the validation set did not differ from the training set. Models with DNA methylation or lncRNA underperformed in the validation set. Integrating comprehensive clinical and genomic data from patients with HGSC results in accurate and robust prediction models of treatment response.