bluuebunny/crossref_metadata_2025_split huggingface dataset:
Grey matter reshaping of language-related regions depends on tumor lateralization
Authors: Manso-Ortega Lucia , De Frutos-Sagastuy Laura , Gisbert-Muñoz Sandra , Salamon Noriko , Qiao Joe , Walshaw Patricia , Quiñones Ileana , Połczyńska Monika M. 
Published: February 2023

AbstractA brain tumor in the left hemisphere can decrease language laterality as assessed with fMRI. However, it remains unclear whether or not this decreased language laterality is associated with a structural reshaping of the grey matter, particularly within the language network. Here, we examine if the disruption of language hubs exclusively affects macrostructural properties of contralateral homologues (as suggested by previous research), or whether it affects both hemispheres. This study uses voxel-based morphometry applied to high-resolution MR T1-weighted MPRAGE images from 31 adult patients left-dominant for language. Eighteen patients had brain tumors in the left hemisphere, and 13 had tumors in the right hemisphere. A cohort of 71 healthy individuals matched on age and sex was used as a baseline. We defined 10 ROIs per hemisphere known to subserve language function. Two separate repeated-measures ANOVAs were conducted with the volume per region as the dependent variables. For the patients, tumor lateralization (right versus left) served as a between-subject factor. The current study demonstrated that the presence of a brain tumor generates a global volumetric change affecting left language regions and their contralateral homologues. These changes are mediated by the lateralization of the lesion. Our findings suggest that compensatory functional mechanisms are supported by the rearrangement of the grey matter, although future longitudinal research should determine the temporal course of such changes.
ReplicativeAcinetobacter baumanniistrains interfere with phagosomal maturation by modulating the vacuolar pH
Authors: Distel Jesus S. , Venanzio Gisela Di , Mackel Joseph J. , Rosen David A , Feldman Mario F. 
Published: February 2023

AbstractBacterial pneumonia is a common infection of the lower respiratory tract that can afflict patients of all ages. Multidrug-resistant strains ofAcinetobacter baumanniiare increasingly responsible for causing nosocomial pneumonias, thus posing an urgent threat. Alveolar macrophages play a critical role in overcoming respiratory infections caused by this pathogen. Recently, we and others have shown that new clinical isolates ofA. baumannii, but not the common lab strain ATCC 19606 (19606), can persist and replicate in macrophages within spacious vacuoles that we calledAcinetobacterContainingVacuoles (ACV). In this work, we demonstrate that the modernA. baumanniiclinical isolate 398, but not the lab strain 19606, can infect alveolar macrophages and produce ACVsin vivoin a murine pneumonia model. Both strains initially interact with the alveolar macrophage endocytic pathway, as indicated by EEA1 and LAMP1 markers; however, the fate of these strains diverges at a later stage. While 19606 is eliminated in an autophagy pathway, 398 replicates in ACVs and are not degraded. We show that 398 reverts the natural acidification of the phagosome by secreting large amounts of ammonia, a by-product of amino acid catabolism. We propose that this ability to survive within macrophages may be critical for the persistence of clinicalA. baumanniiisolates in the lung during a respiratory infection.
Single-cell mass distributions reveal simple rules for achieving steady-state growth
Authors: Roller Benjamin R.K. , Hellerschmied Cathrine , Wu Yanqi , Miettinen Teemu P. , Manalis Scott R. , Polz Martin F. 
Published: February 2023

AbstractOptical density is a common method for measuring exponential growth in bacterial batch cultures. However, there is a misconception that such exponential growth is equivalent to steady-state growth, which is a distinct physiological state that improves experimental reproducibility. Determining precisely when steady-state growth occurs is technically challenging and is aided by paired single-cell and population-level measurements. Using microfluidic mass sensors and optical density, we explore when in typical laboratory batch cultures steady-state growth occurs. We show that cell mass increases by an order of magnitude within a few hours of dilution into fresh medium and that steady-state growth is only achieved when cultures are inoculated with high dilutions from overnight stationary phase cultures. At high dilutions,Escherichia coliandVibrio cyclitrophicusgrown in different rich media achieve steady-state growth approximately 4 total biomass doublings after inoculation. We can decompose these dynamics into 3 doublings of average cell mass and 1 doubling of cell number for both species. We also show that batch cultures in rich media depart steady-state growth early in their growth curves at low cell and biomass concentrations. Achieving and maintaining steady-state growth in batch culture is a delicate balancing act, and we provide general guidance for commonly used rich media. Quantifying single-cell mass outside of steady-state growth is an important first step towards understanding how microbes grow in their natural context, where fluctuations pervade at the scale of individual cells.ImportanceMicrobiologists have watched clear liquid turn cloudy for over 100 years. While the cloudiness of a culture is proportional to its total biomass, growth rates using such optical density measurements are challenging to interpret when cells change size. Many bacteria adjust their size at different steady-state growth rates, but also when shifting between starvation and growth. Optical density cannot disentangle how mass is distributed among cells of different sizes, and directly measuring how mass is distributed among cells has been a major challenge. Here we use single-cell mass measurements to demonstrate that a population of cells in batch culture achieves a stable mass distribution for only a short period of time. Achieving steady-state growth in rich medium requires low initial biomass concentrations and enough time for the coordination of individual cell and population growth. Steady-state growth is important for reliable cell mass distributions in a culture and we discuss how mass variation outside of steady-state can impact physiology, ecology, and evolution experiments.
Identification of “missing links” in C- and D-ring cleavage of steroids byComamonas testosteroniTA441
Authors: Horinouchi Masae , Hayashi Toshiaki 
Published: February 2023

ABSTRACTComamonas testosteroniTA441 degrades steroids aerobically via aromatization and cleavage of the A- and B-ring, followed by D- and C-ring cleavage via b-oxidation. We previously characterized most of the above degradation steps; however, a few intermediate compounds remained unaccounted for. We hypothesized that cleavage of the D-ring at C13-17 required the ScdY hydratase and was followed by cleavage of the C-ring via the ScdL1L2 transferase. The reaction was expected to produce 6-methyl-3,7-dioxo-decane-1,10-dioic acid-Coenzyme A (CoA) ester. To verify this hypothesis, we constructed a plasmid that enabled targeted gene induction in TA441 mutant strains. The major product of ScdL1L2 was found to be 3-hydroxy-6-methyl-7-oxo-decane-1,10-dioic acid-CoA ester; whereas the substrate of ScdY was revealed to be a geminal diol, 17-dihydroxy-9-oxo-1,2,3,4,5,6,10,19-octanorandrost-8(14)-en-7-oic acid-CoA ester. This finding suggests that ScdY catalyzes the addition of a water molecule at C14 of 17-dihydroxy-9-oxo-1,2,3,4,5,6,10,19-octanorandrost-8(14)-en-7-oic acid-CoA ester, leading to D-ring cleavage at C13-17. The C9 ketone of the D-ring cleavage product is then converted to a hydroxyl group, followed by C-ring cleavage to produce 3-hydroxy-6-methyl-7-oxo-decane-1,10-dioic acid-CoA ester. Precise bacterial bile acid degradation pathway will be one of the key to investigate the gut–microbiota–brain axis, which affects human health and disease.IMPORTANCEStudies on bacterial steroid degradation were initiated more than 50 years ago primarily to obtain substrates for steroid drugs. The role of steroid-degrading bacteria in relation to human health is attracting growing attention.Comamonas testosteroniTA441 is the leading bacterial model of aerobic steroid degradation and the overall pathway has been outlined previously. However, a few intermediate compounds in C- and D-ring cleavage processes have remained unknown. Here, we identified the missing compounds and can now propose the complete A-, B-, C-, and D-ring cleavage pathway employed by steroid-degrading bacteria. This finding will facilitate the application of such microorganisms for the synthesis of specific steroid derivatives.
Comprehensive summary of steroid metabolism inComamonas testosteroniTA441; entire degradation process of basic four rings and removal of C12 hydroxyl group
Authors: Horinouchi Masae , Hayashi Toshiaki 
Published: February 2023

ABSTRACTComamonas testosteroniis one of the representative aerobic steroid-degrading bacterium. We previously revealed the mechanism of steroidal A,B,C,D-ring degradation byC. testosteroniTA441. The corresponding genes are located in two clusters at both ends of a mega-cluster of steroid degradation genes. ORF7 and ORF6 are the only two genes in these clusters, whose function has not been determined. Here, we characterized ORF7 as encoding the dehydrase responsible for converting the C12β hydroxyl group to the C10(12) double bond on the C-ring (SteC), and ORF6 as encoding the hydrogenase responsible for converting the C10(12) double bond to a single bond (SteD). SteA and SteB, encoded just upstream of SteC and SteD, are in charge of oxidizing the C12α hydroxyl group to a ketone group, and of reducing the latter to the C12β hydroxyl group, respectively. Therefore, the C12α hydroxyl group in steroids is removed with SteABCD via the C12 ketone and C12β hydroxyl groups. Given the functional characterization of ORF6 and ORF7, we disclose the entire pathway of steroidal A,B,C,D-ring breakdown byC. testosteroniTA441.IMPORTANCEStudies on bacterial steroid degradation were initiated more than 50 years ago, primarily to obtain materials for steroid drugs. Now, their implications for the environment and humans, especially in relation to the infection and the brain-gut-microbiota axis, are attracting increasing attention.Comamonas testosteroniTA441 is the leading model of bacterial aerobic steroid degradation with the ability to break down cholic acid, the main component of bile acids. Bile acids are known for their variety of physiological activities according as their substituent group(s). In this study, we identified and functionally characterized the genes for removal of C12 hydroxyl groups and provide a comprehensive summary of the entire A,B,C,D-ring degradation pathway byC. testosteroniTA441 as the representable bacterial aerobic degradation process of the steroid core structure.
Scaling Logical Density of DNA storage with Enzymatically-Ligated Composite Motifs
Authors: Yan Yiqing , Pinnamaneni Nimesh , Chalapati Sachin , Crosbie Conor , Appuswamy Raja 
Published: February 2023

AbstractDNA is a promising candidate for long-term data storage due to its high density and endurance. The key challenge in DNA storage today is the cost of synthesis. In this work, we proposecomposite motifs, a frame-work that uses a mixture of prefabricated motifs as building blocks to reduce synthesis cost by scaling logical density. To write data, we introduce Bridge Oligonucleotide Assembly, an enzymatic ligation technique for synthesizing oligos based on composite motifs. To sequence data, we introduce Direct Oligonucleotide Sequencing, a nanopore-based technique to sequence oligos without assembly and amplification. To decode data, we introduce Motif-Search, a novel consensus caller that provides accurate reconstruction despite synthesis and sequencing errors. Using the proposed methods, we present an end-to-end experiment where we store the text “HelloWorld” at a logical density of 84 bits/cycle (14–42×improvement over state-of-the-art.)
Starvation responses impact interaction dynamics of human gut bacteriaBacteroides thetaiotaomicronandRoseburia intestinalis
Authors: Liu Bin , Garza Daniel Rios , Gonze Didier , Krzynowek Anna , Simoens Kenneth , Bernaerts Kristel , Geirnaert Annelies , Faust Karoline 
Published: February 2023

AbstractBacterial growth often alters the environment, which in turn can impact interspecies interactions among bacteria. Here, we used anin vitrobatch system containing mucin beads to emulate the dynamic host environment and to study its impact on the interactions between two abundant and prevalent human gut bacteria, the primary fermenterBacteroides thetaiotaomicronand the butyrate producerRoseburia intestinalis. By combining machine learning and flow cytometry, we found that the number of viableB. thetaiotaomicroncells decreases with glucose consumption due to acid production, whileR. intestinalissurvives post-glucose depletion by entering a slow growth mode. Both species attach to mucin beads, but only viable cell counts ofB. thetaiotaomicronincrease significantly. The number of viable co-culture cells varies significantly over time compared to those of monocultures. A combination of targeted metabolomics and RNA-seq showed that the slow growth mode ofR. intestinalisrepresents a diauxic shift towards acetate and lactate consumption, whereasB. thetaiotaomicronsurvives glucose depletion and low pH by foraging on mucin sugars. In addition, most of the mucin monosaccharides we tested inhibited the growth ofR. intestinalisbut notB. thetaiotaomicron. We encoded these causal relationships in a kinetic model, which reproduced the observed dynamics. In summary, we explored howR. intestinalisandB. thetaiotaomicronrespond to nutrient scarcity and how this affects their dynamics. We highlight the importance of understanding bacterial metabolic strategies to effectively modulate microbial dynamics in changing conditions.
A rapid and flexible microneutralization assay for serological assessment of influenza viruses
Authors: Rumfelt Kalee E. , Fitzsimmons William J. , Truscon Rachel , Monto Arnold S. , Martin Emily T. , Lauring Adam S. 
Published: February 2023

AbstractBackgroundSerological responses from influenza vaccination or infection are typically measured by Hemagglutinin Inhibition (HAI) or Microneutralization (MN). Both methods are limited in feasibility, standardization, and generalizability. We describe a luciferase MN (LMN) assay that combines the advantages of the conventional MN assay with the ease of the HAI assayMethodsSera were obtained from the HIVE study. Plasmid transfection was used to generate recombinant influenza viruses expressing the hemagglutinin and neuraminidase of test strains, all other viral proteins from A/WSN33, and a NanoLuc reporter. Serum neutralization of luciferase-expressing targets was quantified as a reduction in Relative Light Unit (RLU) emission from infected cells. Neutralization titers were measured for cell- and egg-adapted versions of A/H3N2/Hong Kong/4801/2014 and A/H3N2/Singapore/INFIMH-16-0019/2016 and compared to HAI titers against egg-grown antigens.Results333 sera were collected from 259 participants between May 2016 and July 2018. Sampled participants ranged from 7 to 68 years of age and >80% were vaccinated against influenza. HAI and LMN titers were correlated for A/H3N2/Hong Kong/4801/2014 (ρ=0.45, p≤0.01) and A/H3N2/Singapore/INFIMH-16-0019/2016 (ρ=0.75, p≤0.01). LMN titers were lower for cell strains compared to egg strains (A/H3N2/Hong Kong/4801/2014 mean log2fold change = −2.66, p≤0.01 and A/H3N2/Singapore/INFIMH-16-0019/2016 mean log2fold change= −3.15, p≤0.01).ConclusionsThe LMN assay was feasible using limited sample volumes and was able to differentiate small antigenic differences, specifically between egg-adapted and cell-derived strains. The correspondence of these results with the commonly-used HAI confirms the potential utility of this assay for high-throughput studies of correlates of protection and vaccine response.
Rapid evolution of the embryonically-expressed homeobox geneLEUTXwithin primates
Authors: Lewin Thomas D. , Blagrove Josephine R. , Holland Peter W. H. 
Published: February 2023

AbstractLEUTX is a homeodomain transcription factor expressed in the very early embryo with a function around embryonic genome activation. TheLEUTXgene is found only in eutherian mammals, including humans, but unlike the majority of homeobox genes, the encoded amino acid sequence is very different between divergent mammalian species. However, whether dynamic evolution has also occurred between closely related mammalian species remains unclear. In this work, we perform a comparative genomics study ofLEUTXwithin the primates, revealing dramatic evolutionary sequence change between closely related species. Positive selection has acted on sites in the LEUTX protein, including six sites within the homeodomain; this suggests that selection may have driven changes in the set of downstream targets. Transfection into cell culture followed by transcriptomic analysis reveals small functional differences between human and marmoset LEUTX, suggesting rapid sequence evolution has fine-tuned the role of this homeodomain protein within the primates.SignificanceHomeobox genes are key regulators of animal development and are therefore often highly conserved between divergent species. However, recent work has uncovered several apparently fast-evolving homeobox genes expressed during mammalian development, one of which isLEUTX. Here we show that theLEUTXgenes of primates are highly variable, and that these sequence changes have resulted in small modifications to its protein function. This continued rapid divergence of an embryonic gene between closely related species is significant to the areas of evolutionary, developmental and genome biology.
ATP synthase-associated CHCH domain proteins are critical for mitochondrial function inToxoplasma gondii
Authors: Usey Madelaine M. , Huet Diego 
Published: February 2023

ABSTRACTCoiled-coil-helix-coiled-coil-helix (CHCH) domains consist of two pairs of cysteine residues that are oxidized to form disulfide bonds upon mitochondrial import. Proteins containing these domains play important roles in mitochondrial ultrastructure and in the biogenesis, function, and stability of electron transport chain complexes. Interestingly, recent investigations of theToxoplasma gondiiATP synthase identified subunits containing CHCH domains. As CHCH domain proteins have never been found in any other ATP synthase, their role inT. gondiiwas unclear. Using conditional gene knockdown systems, we show that twoT. gondiiATP synthase subunits containing CHCH domains are essential for the lytic cycle as well as stability and function of the ATP synthase. Further, we illustrated that knockdown disrupts multiple aspects of mitochondrial morphology. Mutation of key residues in the CHCH domains also caused mislocalization of the proteins. This work provides insight into the divergent aspects of the apicomplexan ATP synthase, which could uncover future drug targets.
ATM phosphorylates the FATC domain of DNA-PKcsat threonine 4102 to promote non-homologous end joining
Authors: Lu Huiming , Zhang Qin , Laverty Daniel J. , Puncheon Andrew C. , Williams Gareth J. , Nagel Zachary D. , Chen Benjamin PC , Davis Anthony J. 
Published: February 2023

ABSTRACTAtaxia-telangiectasia mutated (ATM) drives the DNA damage response via modulation of multiple signal transduction and DNA repair pathways. Previously, ATM activity was implicated in promoting the non-homologous end joining (NHEJ) pathway to repair a subset of DNA double strand breaks (DSBs), but how ATM performs this function is still unclear. In this study, we identified that ATM phosphorylates the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a core NHEJ factor, at its extreme C-terminus at threonine 4102 (T4102) in response to DSBs. Phosphorylation at T4102 stabilizes the interaction between DNA-PKcsand the Ku-DNA complex and promotes assembly and stabilization of the NHEJ machinery at DSBs. Ablating phosphorylation at this site results in decreased NHEJ, radiosensitivity, and increased radiation-induced genomic instability. Collectively, these findings establish a key role for ATM in NHEJ-dependent repair of DSBs through positive regulation of DNA-PKcs.
Antigenic diversity in malaria parasites is maintained on extrachromosomal DNA
Authors: Ebel Emily R. , Kim Bernard Y. , McDew-White Marina , Egan Elizabeth S. , Anderson Timothy J.C. , Petrov Dmitri A. 
Published: February 2023

AbstractSequence variation among antigenicvargenes enablesPlasmodium falciparummalaria parasites to evade host immunity. Using long sequence reads from haploid clones from a mutation accumulation experiment, we detectvardiversity inconsistent with simple chromosomal inheritance. We discover putatively circular DNA that is strongly enriched forvargenes, which exist in multiple alleles per locus separated by recombination and indel events. Extrachromosomal DNA likely contributes to rapid antigenic diversification inP. falciparum.
Why is there so much variability in crop multi-model studies?
Authors: Wallach Daniel , Palosuo Taru , Mielenz Henrike , Buis Samuel , Thorburn Peter , Asseng Senthold , Dumont Benjamin , Ferrise Roberto , Gayler Sebastian , Ghahramani Afshin , Harrison Matthew Tom , Hochman Zvi , Hoogenboom Gerrit , Huang Mingxia , Jing Qi , Justes Eric , Kersebaum Kurt Christian , Launay Marie , Lewan Elisabet , Liu Ke , Luo Qunying , Mequanint Fasil , Nendel Claas , Padovan Gloria , Olesen Jørgen Eivind , Pullens Johannes Wilhelmus Maria , Qian Budong , Seserman Diana-Maria , Shelia Vakhtang , Souissi Amir , Specka Xenia , Wang Jing , Weber Tobias K.D. , Weihermüller Lutz , Seidel Sabine J. 
Published: February 2023

AbstractIt has become common to compare crop model results in multi-model simulation experiments. In general, one observes a large variability in such studies, which reduces the confidence one can have in such models. It is important to understand the causes of this variability as a first step toward reducing it. For a given data set, the variability in a multi-model study can arise from uncertainty in structure or in parameter values for a given structure. Previous studies have made assumptions about the origin of parameter uncertainty, and then quantified its contribution, generally finding that parameter uncertainty is less important than structure uncertainty. However, those studies do not take account of the full parameter variability in multi-model studies. Here we propose estimating parameter uncertainty based on open-call multi-model ensembles where the same structure is used by more than one modeling group. The variability in such a case is due to the full variability of parameters among modeling groups. Then structure and parameter contributions can be estimated sing random effects analysis of variance. Based on three multi-model studies for simulating wheat phenology, it is found that the contribution of parameter uncertainty to total uncertainty is, on average, more than twice as large as the uncertainty from structure. A second estimate, based on a comparison of two different calibration approaches for multiple models leads to a very similar result. We conclude that improvement of crop models requires as much attention to parameters as to model structure.