bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nogo-A regulates the fate of human dental pulp stem cells towards osteogenic, adipogenic, and neurogenic differentiation
Authors: Lai Chai Foong , Shen Juliet , Balic Anamaria , Pagella Pierfrancesco , Schwab Martin E. , Mitsiadis Thimios A. 
Published: September 2022

AbstractHuman teeth are highly innervated organs that contain a variety of mesenchymal stem cell populations that could be used for cell-based regenerative therapies. Specific molecules are often used in these treatments to favorably modulate stem cells function and fate. Nogo-A, a key regulator of neuronal growth and differentiation, is already used in clinical tissue regeneration trials. While the functions of Nogo-A in neuronal tissues are extensively explored, its role in teeth still remains unknown. In this work, we first immunohistochemically analyzed the distribution of Nogo-A protein in the dental pulp of human teeth. Nogo-A is localized in a variety of cellular and structural components of the dental pulp, including odontoblasts, fibroblasts, neurons and vessels. We also cross-examined Nogo expression in the various pulp cell clusters in a single cell RNA sequencing dataset of human dental pulp, which showed high levels of expression in all cell clusters, including that of stem cells. We then assessed the role of Nogo-A on the fate of human dental pulp stem cells and their differentiation capacity in vitro. Using immunostaining, Alizarin Red S and Oil Red O staining we showed that Nogo-A delayed the differentiation of cultured dental pulp stem cells towards the osteogenic, adipogenic and neurogenic lineages, while addition of the blocking anti-Nogo-A antibody had opposite effects. These results were further confirmed by qRT-PCR, which demonstrated overexpression of genes involved in osteogenic (RUNX2, ALP, SP7/OSX), adipogenic (PPAR-γ2, LPL) and neurogenic (DCX, TUBB3, NEFL) differentiation in presence of the anti-Nogo-A antibody. Conversely, the osteogenic and adipogenic genes were downregulated by Nogo-A. Taken together, our results show that the functions of Nogo-A are not restricted to neuronal cells, but are extended to other cell populations, including dental pulp stem cells. We show that Nogo-A regulates their fates towards osteogenic, adipogenic and neurogenic differentiation, thus indicating its potential use in the clinics.
Prevalence and genetic characterisation of Giardia duodenalis in river water and riverbed sediment using next-generation sequencing
Authors: Mphephu Muofhe Grace , Momba Maggy Ndombo Benteke 
Published: September 2022

ABSTRACTGiardia duodenalis has been reported in different sources such as water, human stools, animal stools, vegetable farms and markets and soil of public places. However, different assemblages of G.duodenalis harboured in riverbed sediments have not yet been investigated. Thus, in this study, we quantified and genetically characterised G.duodenalis harboured in the water column and the riverbed sediment of the Apies River to cross this frontier of the unknown in freshwater sediment. Enumeration of G.duodenalis cysts was performed by epifluorescence microscopy observation and quantitative polymerase chain reaction (qPCR). Genetic characterisation was achieved by next-generation sequencing (NGS) using the β-giardin gene and bioinformatics analysis of the NGS data. Results obtained through epifluorescence microscopy revealed a prevalence rate of 87% (140/160) of G.duodenalis cysts in river water, which was higher than that observed in riverbed sediments (78%, 125/160). However, the qPCR assay showed that gene copies of G.duodenalis, which ranged between3.27 log10 and 7.26 log10 copies/L in re-suspended riverbed sediments, and between 0.49 log10 and 3.95 log10 copies/L in river water Genetic characterisation revealed six and seven assemblages in river water (A, B, C, D, E and F) and riverbed sediment (A, B, C, D, E, F and G), respectively. Both matrices carried similar sub-assemblages belonging to assemblages A (AI, AII and AIII) and B (BI, BII, BIII, BIV and BV), whereas riverbed sediment carried an additional sub-assemblage BX belonging to the assemblage B. The present genetic characterisation results suggest that Apies River water and its bed sediment harbour considerable quantities of G.duodenalis cysts that may cause infections in humans and animals if ingested. Consequently, monitoring of both the water column and respective bed sediments for the presence of G.duodenalis is justified to develop strategies for the protection of public health. This study also calls for urgent identification of point sources that are responsible for the contamination of this freshwater source and its sediment.Author summary
Using ‘sentinel’ plants to improve early detection of invasive plant pathogens
Authors: Lovell-Read Francesca A. , Parnell Stephen R. , Cunniffe Nik J. , Thompson Robin N. 
Published: September 2022

AbstractInfectious diseases of plants present an ongoing and increasing threat to international biosecurity, with wide-ranging implications. An important challenge in plant disease management is achieving early detection of invading pathogens in new locations, which requires effective surveillance through the implementation of appropriate monitoring programs. However, when monitoring relies on visual inspection as a means of detection, surveillance is often hindered by a long incubation period (delay from infection to symptom onset) during which plants may be infectious but not displaying visible symptoms. ‘Sentinel’ plants – alternative susceptible host species that display visible symptoms of infection more rapidly – could be introduced to at-risk populations and included in monitoring programs to act as early warning beacons for infection. However, while sentinel hosts exhibit faster disease progression and so allow pathogens to be detected earlier, this often comes at a cost: faster disease progression typically promotes earlier onward transmission. Here, we construct a computational model of pathogen transmission to explore this trade-off and investigate how including sentinel plants in monitoring programmes could facilitate earlier detection of invasive plant pathogens. Using Xylella fastidiosa infection in Olea europaea (European olive) as a current high profile case study, for which Catharanthus roseus (Madagascan periwinkle) is a candidate sentinel host, we apply a Bayesian optimisation algorithm to determine the optimal number of sentinel hosts to introduce for a given sampling effort, as well as the optimal division of limited surveillance resources between crop and sentinel plants. Our results demonstrate that including sentinel plants in monitoring programmes can reduce the expected prevalence of infection upon outbreak detection substantially, increasing the feasibility of local outbreak containment.
ZEB2 regulates the development of CD11c+ atypical B cells
Authors: Gao Xin , Shen Qian , Roco Jonathan A. , Frith Katie , Munier C. Mee Ling , Nekrasov Maxim , Dalton Becan , He Jin-Shu , Jaeger Rebecca , Cook Matthew C. , Zaunders John J. , Cockburn Ian A. 
Published: September 2022

AbstractCD11c+ atypical B cells (ABC) are an alternative memory B cell lineage identified both in normal immune responses as well as pathogenic responses in autoimmunity. While it is clear that ABCs have a distinct transcriptional program, the factors that direct this program have not been identified. Here, we generated a human tonsil single-cell RNA-seq dataset and identified candidate transcription factors associated with the ABC population. We selected 8 of these transcription factors for further analysis based on their conserved expression in mouse ABC bulk RNA-seq datasets. Using an optimized CRSPR-Cas9 knockdown method we found that only zinc finger E-box binding homeobox 2 (Zeb2) knock-out impaired ABC formation. To assess the role of Zeb2 in ABC formation in vivo we used Zeb2fl/fl mice crossed to a CD23Cre line. Germinal center and plasma cell responses in these mice after Plasmodium sporozoite immunization were largely unaltered but we observed a specific defect in ABC formation. We further determined that ZEB2 haploinsufficient Mowat Wilson syndrome patients also have decreased circulating ABCs in the blood, supporting a role for this transcription factor in humans as well as mice. In sum, we identified Zeb2 as a key TF governing the formation of ABCs.
Interactions between culturable bacteria are highly non-additive
Authors: Baichman-Kass Amichai , Song Tingting , Friedman Jonathan 
Published: September 2022

AbstractMicroorganisms are found in diverse communities whose structure and function are determined by interspecific interactions. Just as single species seldom exist in isolation, communities as a whole are also constantly challenged and affected by external species. Though much work has been done on characterizing how individual species affect each other through pairwise interactions, the joint effects of multiple species on a single (focal) species, remain under explored. As such, it is still unclear how single species effects combine to a community-level effect on a species of interest. To explore this relationship, we assayed over 14,000 communities of two, three, and four bacterial species, measuring the effect of single, pairs of, and trios of 61 affecting species on six different focal species. Our results demonstrate that joint effects of multiple species on a focal species are typically not given by the sum of the effects of individual affecting species. Rather, they are dominated by the strongest individual-species effect. Therefore, while joint effects of multiple species are often highly non-additive, they can still be derived from the effects of individual species, making it plausible to map complex interaction networks based on pairwise measurements. This finding is important for understanding the fate of species introduced into an occupied environment, and is relevant for applications in medicine and agriculture, such as probiotics and biocontrol agents, as well as for ecological questions surrounding migrating and invasive species.
Global Phylogeny of the Brassicaceae Provides Important Insights into Gene Discordance
Authors: Hendriks Kasper P. , Kiefer Christiane , Al-Shehbaz Ihsan A. , Bailey C. Donovan , Hooft van Huysduynen Alex , Nikolov Lachezar A. , Nauheimer Lars , Zuntini Alexandre R. , German Dmitry A. , Franzke Andreas , Koch Marcus A. , Lysak Martin A. , Toro-Núñez Óscar , Özüdoğru Barış , Invernón Vanessa R. , Walden Nora , Maurin Olivier , Hay Nikolai M. , Shushkov Philip , Mandáková Terezie , Thulin Mats , Windham Michael D. , Rešetnik Ivana , Španiel Stanislav , Ly Elfy , Pires J. Chris , Harkess Alex , Neuffer Barbara , Vogt Robert , Bräuchler Christian , Rainer Heimo , Janssens Steven B. , Schmull Michaela , Forrest Alan , Guggisberg Alessia , Zmarzty Sue , Lepschi Brendan J. , Scarlett Neville , Stauffer Fred W. , Schönberger Ines , Heenan Peter , Baker William J. , Forest Félix , Mummenhoff Klaus , Lens Frederic 
Published: September 2022

AbstractThe mustard family (Brassicaceae) is a scientifically and economically important family, containing the model plantArabidopsis thalianaand numerous crop species that feed billions worldwide. Despite its relevance, most published family phylogenies are incompletely sampled, generally contain massive polytomies, and/or show incongruent topologies between datasets. Here, we present the most complete Brassicaceae genus-level family phylogenies to date (Brassicaceae Tree of Life, or BrassiToL) based on nuclear (>1,000 genes, almost all 349 genera and 53 tribes) and plastome (60 genes, 79% of the genera, all tribes) data. We found cytonuclear discordance between nuclear and plastome-derived phylogenies, which is likely a result of rampant hybridisation among closely and more distantly related species, and highlight rogue taxa. To evaluate the impact of this rampant hybridisation on the nuclear phylogeny reconstruction, we performed four different sampling routines that increasingly removed variable data and likely paralogs. Our resulting cleaned subset of 297 nuclear genes revealed high support for the tribes, while support for the main lineages remained relatively low. Calibration based on the 20 most clock-like nuclear genes suggests a late Eocene to late Oligocene ‘icehouse origin’ of the family. Finally, we propose five new or re-established tribes, including the recognition of Arabidopsideae, a monotypic tribe to accommodateArabidopsis. With a worldwide community of thousands of researchers working on this family, our new, densely sampled family phylogeny will be an indispensable tool to further highlight Brassicaceae as an excellent model family for studies on biodiversity and plant biology.
Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration
Authors: Yu Qinghao , Walters Hannah E. , Pasquini Giovanni , Singh Sumeet Pal , Lachnit Martina , Oliveira Catarina , León-Periñán Daniel , Petzold Andreas , Kesavan Preethi , Subiran Cristina , Garteizgogeascoa Ines , Knapp Dunja , Wagner Anne , Bernardos Andrea , Alfonso María , Nadar Gayathri , Graf Alwin M. , Troyanovskiy Konstantin E. , Dahl Andreas , Busskamp Volker , Martínez-Máñez Ramón , Yun Maximina H. 
Published: September 2022

SUMMARYAxolotl limb regeneration is accompanied by the transient induction of cellular senescence within the blastema, the structure which nucleates regeneration. The precise role of this blastemal senescent cell (bSC) population, however, remains unknown. Here, through a combination of gain- and loss-of-function assays, we elucidate the functions and molecular features of cellular senescencein vivo. We demonstrate that cellular senescence plays a positive role during axolotl regeneration, by creating a pro-proliferative niche that supports progenitor cell expansion and blastema outgrowth. Senescent cells impact on their microenvironment via Wnt pathway modulation. Further, we uncover a link between Wnt signalling and senescence induction, and propose that bSC-derived Wnt signals facilitate the proliferation of neighbouring cells in part by preventing their induction into senescence. This work defines the roles of cellular senescence in regeneration of complex structures.
The oxygen tolerant reductive glycine pathway in eukaryotes – a native methanol, formate and CO2 assimilation pathway in the yeast Komagataella phaffii
Authors: Mitic Bernd M. , Troyer Christina , Hann Stephan , Mattanovich Diethard 
Published: September 2022

AbstractThe current climate change is mainly driven by excessive anthropogenic CO2 emissions. As industrial bioprocesses depend mostly on food competing organic feedstocks or fossil raw materials, we regard CO2 co-assimilation or the use of CO2-derived methanol or formate as carbon source as pathbreaking contribution to the solution of this global problem. The number of industrially relevant microorganisms that can use these two carbon sources is limited, and even less can concurrently co-assimilate CO2. Hence, we searched for alternative native methanol and native formate assimilation pathways which co-assimilate CO2 in the industrially relevant methylotrophic yeast Komagataella phaffii (Pichia pastoris). Using 13C-tracer-based metabolomics techniques and metabolic engineering approaches we discovered and confirmed a natively active pathway that can perform all three assimilations: the oxygen tolerant reductive glycine pathway. This finding paves the way towards metabolic engineering of formate and CO2 utilisation for the production of proteins, biomass or chemicals in yeast.
ONECUT2 restricts Microfold cell numbers in the small intestine; a multi-omics study
Authors: Luna Velez Maria V. , Neikes Hannah K. , Snabel Rebecca R. , Quint Yarah , Qian Chen , Martens Aniek , Veenstra Gert Jan C. , Freeman Michael R. , van Heeringen Simon J. , Vermeulen Michiel 
Published: September 2022

AbstractMicrofold (M) cells reside in the intestinal epithelium of Peyer’s patches. Their unique ability to take up and transport antigens from the intestinal lumen to the underlying lymphoid tissue is key in the regulation of the gut-associated immune response. Here, we applied a (single-cell) multi-omics approach to investigate the molecular mechanisms that drive M cell differentiation in mouse small intestinal organoids. We generated a comprehensive profile of chromatin accessibility changes and transcription factor dynamics duringin vitroM cell differentiation, allowing us to uncover numerous cell type-specific regulatory elements and associated transcription factors. Single-cell RNA sequencing resulted in the identification of an M cell precursor population. Our new computational tool SCEPIA determined that these precursor cells were characterized by high expression of and motif activity for the transcription factor ONECUT2. Subsequent perturbation experiments revealed that ONECUT2 acts downstream of the RANK/RANKL signalling to support Enterocyte differentiation and restrict M cell lineage specificationin vitroandin vivo, thereby regulating mucosal immunity. This study provides a useful blueprint for future investigations of cell fate switches in the intestinal epithelium.
Inferring protein fitness landscapes from laboratory evolution experiments
Authors: D’Costa Sameer , Hinds Emily C. , Freschlin Chase R. , Song Hyebin , Romero Philip A. 
Published: September 2022

ABSTRACTDirected laboratory evolution applies iterative rounds of mutation and selection to explore the protein fitness landscape and provides rich information regarding the underlying relationships between protein sequence, structure, and function. Laboratory evolution data consist of protein sequences sampled from evolving populations over multiple generations and this data type does not fit into established supervised and unsupervised machine learning approaches. We develop a statistical learning framework that models the evolutionary process and can infer the protein fitness landscape from multiple snapshots along an evolutionary trajectory. We apply our modeling approach to dihydrofolate reductase (DHFR) laboratory evolution data and the resulting landscape parameters capture important aspects of DHFR structure and function. We use the resulting model to understand the structure of the fitness landscape and find numerous examples of epistasis but an overall global peak that is evolutionarily accessible from most starting sequences. Finally, we use the model to perform an in silico extrapolation of the DHFR laboratory evolution trajectory and computationally design proteins from future evolutionary rounds.
Hallucination of closed repeat proteins containing central pockets
Authors: An Linna , Hicks Derrick R , Zorine Dmitri , Dauparas Justas , Wicky Basile I. M. , Milles Lukas F. , Courbet Alexis , Bera Asim K. , Nguyen Hannah , Kang Alex , Carter Lauren , Baker David 
Published: September 2022

AbstractIn pseudocyclic proteins such as TIM barrels, β barrels, and some helical transmembrane channels, a single subunit is repeated in a cyclic pattern, giving rise to a central cavity which can serve as a pocket for ligand binding or enzymatic activity. Inspired by these proteins, we devised a deep learning-based approach to broadly exploring the space of closed repeat proteins starting from only a specification of the repeat number and length. Biophysical data for 38 structurally diverse pseudocyclic designs produced in E. coli are consistent with the design models, and two crystal structures we were able to obtain are very close to the designed structures. Docking studies suggest the diversity of folds and central pockets provide effective starting points for designing small molecule binders or enzymes.
Comparison of Culture Results between Specimens from Corneal Scraping with Microhomogenization and Corneal Swab in Moderate and Severe Bacterial Corneal Ulcers
Authors: Martha Faraby , Edwar Lukman , Karuniawati Anis , Fuady Ahmad , Tuasikal Ramadhiana Maktazula 
Published: September 2022

AbstractPurposeTo compare bacterial culture results from corneal infiltrate specimens taken by corneal scrapping followed by microhomogenization and direct scraping methods.MethodsThis study was a comparative cross-sectional, with 18 subjects divided into two randomized groups; Group A (first scrapings then swab), and group B (first swab then scrapings). Both scraping and swab methods are separated and then compared in data analysis.ResultsThe proportion of Gram according to culture in the scraping-microhomogenization technique was 6/13 (46.2%) and the proportion of Gram according to cultures in the swab technique was 5/13 (38.5%). McNemar test p-value is 1.000 (p>0.05). The proportion of positive cultures in the scraping-microhomogenization technique was 13/18 (72.2%) and the proportion of positive culture in swab technique was 9/18 (50%). McNemar test p-value is 0.219 (p> 0.05). The Kappa suitability test value from scraping-microhomogenization technique against the corneal swab is 0.333.ConclusionThe results of bacterial culture from specimens taken by the corneal scraping followed by microhomogenization have a higher positive culture compared to those taken by corneal swab, but not statistically significant.
Age-related differences in cancer relative survival in the US: a SEER-18 analysis
Authors: Withrow Diana R , Nicholson Brian D , Morris Eva JA , Wong Melisa L , Pilleron Sophie 
Published: September 2022

AbstractCancer survival has improved since the 1990s, but to different extents across age groups, with a disadvantage for older adults. We aimed to quantify age-related differences in relative survival (RS - one-year, and one-year conditioning on surviving one year) for 10 common cancer types by stage at diagnosis. We used data from 18 United States Surveillance Epidemiology and End Results cancer registries and included cancers diagnosed between 2012-2016 followed until December 31, 2017. We estimated absolute differences in RS between the 50-64 age group and the 75-84 age group. The smallest differences were observed for prostate and breast cancers (1.8%-points [95% confidence interval (CI):1.5-2.1] and 1.9%-points [95%CI:1.5-2.3], respectively). The largest was for ovarian cancer (27%-points, 95%CI:24-29). For other cancers, differences ranged between 7 (95%CI:5-9, esophagus) and 18%-points (95%CI: 17-19, pancreas). Except for pancreatic cancer, cancer type and stage combinations with very high (>95%) or very low (<40%) 1-year RS tended to have smaller age-related differences in survival than those with mid-range prognoses. Age-related differences in one-year survival conditioning on having survived one-year were small for most cancer and stage combinations. The broad variation in survival differences by age across cancer types and stages, especially in the first year, age-related differences in survival are likely influenced by amenability to treatment. Future work to measure the extent of age-related differences that are avoidable, and identify how to narrow the survival gap, may have most benefit by prioritizing cancers with relatively large age-related differences in survival (e.g., stomach, esophagus, liver and pancreas).Novelty and ImpactIn this analysis of United States population-based cancer registry data, age-related differences in cancer survival varied widely, ranging from less than 1% absolute difference in localized breast and prostate cancer survival to over 30% absolute difference in localized pancreatic cancer survival. Focused efforts to reduce age-related differences in cancer survival may have greatest impact by prioritizing cancer site and stage combinations with the widest differences.