bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct encapsulation of biomolecules in semi-permeable microcapsules produced with double-emulsions
Authors: Michielin Grégoire , Maerkl Sebastian J. 
Published: June 2022

AbstractCompartmentalization can serve different purposes such as the protection of biological active substances from the environment, or the creation of a unique combination of biomolecules for diagnostic, therapeutic, or other bioengineering applications. We present a method for direct encapsulation of molecules in biocompatible and semi-permeable microcapsules made from low-molecular weight poly(ethylene glycol) diacrylate (PEG-DA 258). Microcapsules are produced using a non-planar PDMS microfluidic chip allowing for one-step production of water-in-PEG-DA 258-in-water double-emulsions, which are polymerized with UV light into a poly-PEG-DA 258 shell. Semi-permeable PEG shells are obtained by adding an inert solvent to the PEG-diacrylate. Due to the favourable hydrophilicity of poly-PEG-DA 258, proteins didn’t adsorb to the capsule shell, and we demonstrate the direct encapsulation of enzymes, which can also be dried in the capsules to preserve activity. Finally, we leverage capsule permeability for the implementation of a two-layer communication cascade using compartmentalized DNA strand displacement reactions. This work presents the direct encapsulation of active biomolecules in semi-permeable microcapsules, and we expect our platform to facilitate the development of artificial cells and generating encapsulated diagnostics or therapeutics.
Endogenous circadian reporter cell lines as an efficient platform for studying circadian mechanisms
Authors: Park Jiyoung , Lee Kwangjun , Kim Hyeongseok , Shin Heungsop , Lee Choogon 
Published: June 2022

SummaryAdverse consequences from having a faulty circadian clock include compromised sleep quality and poor performance in the short-term, and metabolic diseases and cancer in the long- term. However, our understanding of circadian disorders is limited by the incompleteness of our molecular models and our dearth of defined mutant models. Because it would be prohibitively expensive to develop live animal models to study the full range of complicated clock mechanisms, we developedPer1-lucandPer2-lucendogenous circadian reporters in a validated clock cell model, U2OS, where the genome can be easily manipulated, and functional consequences of mutations can be accurately studied. Using these reporter cells, we uncovered critical differences between two paralogs ofPerandCry, as well as working principles of the circadian phosphotimer. Our system can be used as an efficient platform to study circadian sleep disorders such as Familial Advanced Sleep Phase Syndrome (FASPS) and their underlying molecular mechanisms.
Two unique biological response-modifier glucans beneficially regulating gut microbiota and faecal metabolome in a non-alcoholic steatohepatitis animal model, with potential for applications in human health and disease
Authors: Preethy Senthilkumar , Ikewaki Nobunao , Levy Gary A , Raghavan Kadalraja , Dedeepiya Vidyasagar Devaprasad , Yamamoto Naoki , Srinivasan Subramaniam , Ranganathan Natarajan , Iwasaki Masaru , Senthilkumar Rajappa , Abraham Samuel JK 
Published: June 2022

AbstractObjectiveThe gut microbiome and its metabolites, influenced by age and stress, reflect the metabolism and immune system’s health. We assessed the gut microbiota and faecal metabolome in a Stelic Animal Model of non-alcoholic steatohepatitis (NASH).DesignThis model was subjected to the following treatments: reverse osmosis water, AFO-202, N-163, AFO-202+N-163, and telmisartan. Faecal samples were collected at 6 weeks and 9 weeks of age. The gut microbiome was analysed using 16S ribosomal RNA sequence acquired by next-generation sequencing and the faecal metabolome using gas chromatography-mass spectrometry.ResultsThe gut microbial diversity increased greatly in the AFO-202+N-163 group. Post-intervention, the abundance of Firmicutes decreased, while that of Bacteroides increased and was the highest in the AFO-202+N-163 group. The decrease in the Enterobacteria and other Firmicutes abundance and in the Turicibacter and Bilophila abundance was the highest in the AFO-202 and N-163 groups, respectively. The Lactobacillus abundance increased the most in the AFO-202+N-163 group. The faecal metabolites spermidine and tryptophan, beneficial against inflammation and NASH, respectively, were greatly increased in the N-163 group. Succinic acid, beneficial in neurodevelopmental and neurodegenerative diseases, increased in the AFO-202 group. Decrease in fructose was the highest in the AFO-202 group. Leucine and phenylalanine decreased, whereas ornithine, which is beneficial against chronic immune-metabolic-inflammatory pathologies, increased in the AFO-202+N-163 group.ConclusionAFO-202 treatment in mice is beneficial against neurodevelopmental and neurodegenerative diseases and has prophylactic potential against metabolic conditions. N-163 treatment has anti-inflammatory effects against organ fibrosis and neuroinflammatory conditions. In combination, they present anticancer activity.Key messagesThe influence of gut microbiome on fecal metabolome and their association to several diseases is already known.This study proves the efficacy of 1,3-1,6 beta glucans with pre-biotic potentials, beneficially influencing both gut microbiome and metabolome.These results recommends for an in-depth exploration of relationship among pre-biotics, gut microbiome and gut-multi-organ axes on the fundamentals of disease onset.Hidden prophylactic and therapeutic solutions to non-contagious diseases with Aureobasidium pullulans produced 1,3-1,6 beta glucans may be unveiled.
Examining COVID-19 Mortality Rates by Race and Ethnicity Among Incarcerated People in U.S. State Prisons
Authors: Li Mimi Yen , Grebbin Shelby , Patil Ankita , Cowger Tori L. , Kunichoff Dennis , Feldman Justin , Jiménez Monik C. 
Published: June 2022

AbstractObjectiveTo estimate coronavirus disease 2019 (COVID-19) mortality rates among individuals incarcerated in U.S. state prisons by race and ethnicity (RE).DesignRetrospective population-based analysisSettingData from state-level Departments of Corrections (DOCs) from March 1 through October 1, 2020.ParticipantsPublicly available data collected by Freedom of Information Act requests representing adults in the custody of US state DOCs.Main OutcomesCumulative COVID-19 death and custody population data. Crude RE-specific cumulative death rates per 1,000 persons, by state and in aggregate, using RE-specific custody population on March 1, 2020, as the denominator. Rate ratios (RR) and 95% confidence intervals (95%CI) compared state-level and aggregate cumulative age-adjusted mortality rates as of 10/01/2020 by RE, with White individuals as reference group.ResultsOf all COVID-related deaths in U.S. prisons through October 2020, 23.35% (272 of 1165) were captured in our analyses. The average age at COVID-19 mortality was 63 years (SD=10 years) and was significantly lower among Black (60 years, SD=11 years) compared to White adults (66 years, SD=10 years; p<0.001). In age-standardized analysis, COVID-19 mortality rates were significantly higher among Black (RR=1.93, 95% CI: 1.25-2.99), Hispanic (RR=1.81, 95% CI: 1.10-2.96) and those of Other racial and ethnic groups (RR=2.60, 95% CI: 1.01-6.67) when compared to White individuals.ConclusionsAge-standardized mortality rates were higher among incarcerated Black, Hispanic and those of Other RE groups compared to their White counterparts. Greater data transparency from all carceral systems is needed to better understand populations at disproportionate risk of COVID-19 morbidity and mortality.
Neuronal identity defines α-synuclein and tau toxicity
Authors: Praschberger Roman , Kuenen Sabine , Schoovaerts Nils , Kaempf Natalie , Janssens Jasper , Swerts Jef , Nachman Eliana , Calatayud Carles , Aerts Stein , Poovathingal Suresh , Verstreken Patrik 
Published: June 2022

AbstractPathogenic α-synuclein and tau are critical drivers of neurodegeneration and their mutations cause neuronal loss in patients. Whether the underlying preferential neuronal vulnerability is a cell-type intrinsic property or a consequence of increased expression levels is an open question. Here, we explore cell-type specific α-synuclein and tau expression in human brain datasets and use deep phenotyping as well as brain-wide single-cell RNA sequencing of >200 live neuron types in fruit flies to ask which cellular environments react most to α-synuclein or tau toxicity. We detect phenotypic and transcriptomic evidence of differential neuronal vulnerability independent of α-synuclein or tau expression levels. Comparing vulnerable with resilient neurons enabled us to identify molecular signatures associated with these differential responses. We used these to verify, and then predict resilient and vulnerable neuron subtypes in human brains. This confirms substantia nigra dopaminergic neurons to be sensitive to α-synuclein, and we predict pathogenic tau vulnerable and protected cortical neuron subtypes. Our work indicates that cellular determinants confer selective vulnerability to specific types of amyloid toxicity, thus paving the way to leverage neuronal identity to uncover modifiers of neurodegeneration-associated toxic proteins.
Challenges and pitfalls of inferring microbial growth rates from lab cultures
Authors: Ghenu Ana-Hermina , Marrec Loïc , Bank Claudia 
Published: June 2022

AbstractAfter more than 100 years of generating monoculture batch culture growth curves, microbial ecologists and evolutionary biologists still lack a reference method for inferring growth rates. Our work highlights the challenges of estimating the growth rate from growth curve data and shows that inaccurate estimates of growth rates significantly impact the estimated relative fitness, a principal quantity in evolution and ecology. First, we conducted a literature review and found which different types of methods are currently used to estimate growth rates. These methods differ in the meaning of the estimated growth rate parameter. Kinetic models estimate the intrinsic growth rate µ whereas statistical methods – both model-based and model-free – estimate the maximum per capita growth rate µmax. Using math and simulations, we show the conditions in which µmax is not a good estimator of µ. Then, we demonstrate that inaccurate absolute estimates of µ is not overcome by calculating relative values. Importantly, we find that poor approximations for µ sometimes lead to wrongly classifying a beneficial mutant as deleterious. Finally, we re-analyzed four published data-sets using most of the methods found by our literature review. We detected no single best-fitting model across all experiments within a data-set and found that the Gompertz models, which were among the most commonly used, were often among the worst fitting. Our study provides suggestions for how experimenters can improve their growth rate and associated relative fitness estimates and highlights a neglected but fundamental problem for nearly everyone who studies microbial populations in the lab.
A Causal Model of Ion Interference Enables Assessment and Correction of Ratio Compression in Multiplex Proteomics
Authors: Madern Moritz , Reiter Wolfgang , Stanek Florian , Hartl Natascha , Mechtler Karl , Hartl Markus 
Published: June 2022

ABSTRACTMultiplex proteomics using isobaric labeling tags has emerged as a powerful tool for the simultaneous relative quantification of peptides and proteins across multiple experimental conditions. However, the quantitative accuracy of the approach is largely compromised by ion interference, a phenomenon that causes fold changes to appear compressed. The degree of compression is generally unknown, and the contributing factors are poorly understood. In this study, we thoroughly characterized ion interference at the MS2 level using a defined two-proteome experimental system with known ground-truth. We discovered remarkably poor agreement between the apparent precursor purity in the isolation window and the actual level of observed reporter ion interference in MS2-scans – a discrepancy that we found resolved by considering co-fragmentation of peptide ions hidden within the spectral “noise” of the MS1 isolation window. To address this issue, we developed a regression modeling strategy to accurately predict estimates of reporter ion interference in any dataset. Finally, we demonstrate the utility of our procedure for improved fold change estimation and unbiased PTM site-to-protein normalization. All computational tools and code required to apply this method to any MS2 TMT dataset are documented and freely available.
Gene expression as phenotype - Many small-step changes leading to little long-term phenotypic evolution
Authors: Lin Pei , Lu Guang-An , Liufu Zhongqi , Zhao Yi-Xin , Ruan Yongsen , Wu Chung-I , Wen Haijun 
Published: June 2022

AbstractUnlike in genotypic evolution, there are few general rules governing phenotypic evolution with one of them being the small-step evolution. More specifically, natural selection tends to favor mutations of smaller phenotypic effects than of larger ones. This postulate can be viewed as a logical extension of Fisher’s Geometric Model (FGM). Testing this FGM postulate, however, is challenging as the test would require a large number of phenotypes, each with a clear genetic basis. For such a test, we treat the expression level of each gene as a phenotype. Furthermore, a mechanism of small-step expression evolution exists, namely via the control by microRNAs (miRNAs). Each miRNA in metazoans is known to weakly repress the expression of tens or hundreds of target genes. In our analysis of mammalian and Drosophila expression data, small step evolution via miRNA regulation happens frequently in long-term evolution. However, such small-step evolution does not lead to long-term phenotypic changes which would take too many such steps to accomplish. Furthermore, target site changes often cancel themselves out by continual gains and losses. The results suggest that the FGM postulate may be most appropriate for phenotypic fine-tuning near the expression optimum. In contrast, longterm expression evolution may occasionally take large steps (e.g., mutations in transcription factors) when big environmental shift happens. In another study (Lu et al. 2021), we further show how the small-step evolution of expression phenotypes is a manifestation of miRNAs’ role in developmental canalization. In conclusion, the rules of phenotypic evolution may depend crucially on the genetics of the phenotype, rather than its metric properties.
Functional traits trade-offs define plant population stability worldwide
Authors: Conti Luisa , Valencia Enrique , Galland Thomas , Götzenberger Lars , Lepš Jan , E-Vojtkó Anna , Carmona Carlos P. , Májeková Maria , Danihelka Jiří , Dengler Jürgen , Eldridge David J. , Estiarte Marc , García-González Ricardo , Garnier Eric , Gómez Daniel , Hadincová Věra , Harrison Susan P. , Herben Tomáš , Ibáñez Ricardo , Jentsch Anke , Juergens Norbert , Kertész Miklós , Klumpp Katja , Krahulec František , Louault Frédérique , Marrs Rob H. , Ónodi Gábor , Pakeman Robin J. , Pärtel Meelis , Peco Begoña , Peñuelas Josep , Rueda Marta , Schmidt Wolfgang , Schmiedel Ute , Schuetz Martin , Skalova Hana , Šmilauer Petr , Šmilauerová Marie , Smit Christian , Song MingHua , Stock Martin , Val James , Vandvik Vigdis , Ward David , Wesche Karsten , Wiser Susan K. , Woodcock Ben A. , Young Truman P. , Yu Fei-Hai , Zobel Martin , de Bello Francesco 
Published: June 2022

SummaryEcological theory posits that temporal stability patterns in plant populations are associated with differences in species’ ecological strategies. However, empirical evidence is lacking about which traits, or trade-offs, underlie species stability, specially across different ecosystems.To address this, we compiled a global collection of long-term permanent vegetation records (>7000 plots from 78 datasets) from a wide range of habitats and combined this with existing trait databases. We tested whether the observed inter-annual variability in species abundance (coefficient of variation) was related to multiple individual traits and multivariate axes of trait variations (PCoA axes).We found that species with greater leaf dry matter content and seed mass were consistently more stable over time (lower variability in species abundance) although other leaf traits played a significant role as well, albeit weaker. Using multivariate axes did not improve predictions by specific traits.Our results confirm existing theory, providing compelling empirical evidence on the importance of specific traits, which point at ecological trade-offs in different resource use and dispersal strategies, on the stability of plant populations worldwide.
Divergent evolution of early terrestrial fungi reveals the evolution of Mucormycosis pathogenicity factors
Authors: Wang Yan , Chang Ying , Ortanez Jericho , Peña Jesús F. , Carter-House Derreck , Reynolds Nicole K , Smith Matthew E , Benny Gerald , Mondo Stephen J , Salamov Asaf , Lipzen Anna , Pangilinan Jasmyn , Guo Jie , LaButti Kurt , Andreopolous William , Tritt Andrew , Keymanesh Keykhosrow , Yan Mi , Barry Kerrie , Grigoriev Igor V , Spatafora Joseph W , Stajich Jason E 
Published: June 2022

ABSTRACTFungi have evolved over millions of years and their species diversity is predicted to be the second largest on the earth. Fungi have cross-kingdom interactions with many organisms which have mutually shaped their evolutionary trajectories. Zygomycete fungi hold a pivotal position in the fungal tree of life and provide important perspectives on the early evolution of fungi from aquatic to terrestrial environments. Phylogenomic analyses have found that zygomycete fungi diversified into two separate clades, the Mucoromycota which are frequently associated with plants and Zoopagomycota that are commonly animal-associated fungi. Genetic elements that contributed to the fitness and divergence of these lineages may have been shaped by the varied interactions these fungi have had with plants, animals, bacteria and other microbes. To investigate this, we performed comparative genomic analyses of the two clades in the context of Kingdom Fungi, benefiting from our generation of a new collection of zygomycete genomes. We identified lineage-specific genomic content which may contribute to the disparate biology observed in these zygomycetes. Our findings include the discovery of undescribed diversity in CotH, a Mucormycosis pathogenicity factor, which was found in a broad set of zygomycetes. Reconciliation analysis identified multiple duplication events and an expansion of CotH copies throughout Mucoromycotina, Mortierellomycotina, Neocallimastigomycota, and Basidiobolus lineages. A kingdom-level phylogenomic analysis also identified new evolutionary relationships within the sub-phyla of Mucoromycota and Zoopagomycota.
Phage-plasmids spread antibiotic resistance genes through infection and lysogenic conversion
Authors: Pfeifer Eugen , A. Bonnin Rémy , Rocha Eduardo P.C. 
Published: June 2022

AbstractAntibiotic resistance is rapidly spreading by horizontal transfer of resistance genes in mobile genetic elements. While plasmids are key drivers of this process, very few integrative phages encode antibiotic resistance genes. Here, we find that phage-plasmids, elements that are both phages and plasmids, often carry antibiotic resistance genes. We found 60 phage-plasmids with 184 antibiotic resistance genes, including broad-spectrum-cephalosporins, carbapenems, aminoglycosides, fluoroquinolones and colistin. These genes are in a few hotspots, seem to have been co-translocated with transposable elements, and are often in class I integrons, which had not been previously found in phages. We tried to induce six phage-plasmids with resistance genes (including four with resistance integrons) and succeeded in five cases. Other phage-plasmids and integrative prophages were co-induced in these experiments. As a proof of principle, we focused on a P1-like element encoding an extended spectrum β-lactamase, blaCTX-M-55. After induction, we confirmed that it’s capable to infect and convert four other E. coli strains. Its re-induction led to further conversion of a sensitive strain, confirming it’s a fully functional phage. This study shows that phage-plasmids carry a large diversity of clinically relevant antibiotic resistance genes that they transfer across bacteria. As plasmids, these elements seem very plastic and capable of acquiring genes from other plasmids. As phages, they may provide novel paths of transfer for resistance genes, because they can infect bacteria distant in time and space from the original host. As a matter of alarm, they may also eventually mediate transfer to other types of phages.ImportanceDissemination of antimicrobial resistances is a major threat to global health. Here, we show that a group of temperate bacterial viruses (=phages), termed phage-plasmids, commonly encode different and multiple types of resistance genes of high clinical importance, often in integrons. This is unexpected since phages typically do not carry resistance genes and, hence, do not confer their hosts with resistance upon infection and genome integration. Our experiments with phage-plasmids isolated from clinical settings confirmed they infect sensitive strains, rendering them antibiotic resistant. The spread of antibiotic resistance genes by phage-plasmids is worrisome because it dispenses cell-to-cell contact, necessary for the canonical plasmid transfer (=conjugation). Furthermore, their integrons are now genetic platforms for the acquisition of novel resistance genes.
Clearance of genome-damaged cells from the hematopoietic system via p53 without contribution by the cGAS/STING axis
Authors: Dressel Nicole , Natusch Loreen , Munz Clara M. , Ramon Santiago Costas , Morcos Mina N.F. , Loff Anja , Hiller Björn , Lesche Mathias , Dahl Andreas , Luksch Hella , Rösen-Wolff Angela , Roers Axel , Behrendt Rayk , Gerbaulet Alexander 
Published: June 2022

AbstractCell-intrinsic response patterns control risks arising from genome-damage, preventing malignant transformation. The DNA sensor cyclic-GMP-AMP synthase (cGAS) has emerged as a new principle detecting genome damage, as it can be triggered by aberrant self-DNA. Stimulator of interferon genes (STING)-activation downstream of cGAS can drive cells into senescence or cell death and induces antiproliferative type I interferon (IFN) and pro-apoptotic tumor necrosis factor responses. Herein, we investigated how DNA damage-driven activation of cGAS/STING signaling impacts on hematopoiesis. Defective ribonucleotide excision repair (RER) in the hematopoietic system caused chromosomal instability as well as robust activation of the cGAS/STING/IFN axis, and compromised hematopoietic stem cell function, resulting in cytopenia and ultimately leukemia. Whereas loss of p53 largely rescued RER-deficient hematopoiesis at the cost of further accelerated leukemogenesis, the additional inactivation of cGAS, STING or type I IFN signaling had no detectable effect on blood cell generation and leukemia development. Moreover, cGAS-deficient hematopoiesis showed unaltered responses to spontaneous or acute DNA damage. Our data demonstrate that the cGAS/STING pathway is dispensable for the hematopoietic system coping with chronic or acute DNA damage and does not protect against leukemic transformation in the absence of RER.