bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manganese excess and deficiency affects photosynthesis and metabolism in Marchantia polymorpha
Authors: Messant Marine , Hennebelle Thaïs , Guérard Florence , Gakière Bertrand , Gall Andrew , Thomine Sébastien , Krieger-Liszkay Anja 
Published: January 2022

AbstractManganese is an essential metal for plant growth. The most important Mn-containing enzyme is the Mn4CaO5 cluster that catalyses water oxidation in Photosystem II. Mn deficiency primarily affects photosynthesis, while Mn excess is generally toxic. Mn excess and deficiency were studied in the liverwort Marchantia polymorpha, an emerging model ideally suited for analysis of metal stress since it accumulates rapidly toxic substances due to the absence of well-developed vascular and radicular systems and a reduced cuticle. We established growth conditions for Mn excess and deficiency, performed analysis of metal content in thalli and isolated chloroplasts and determined metabolites. Metabolome analysis revealed a strong accumulation of N-methylalanine upon exposure to Mn excess and a different response of Marchantia to heavy metal stress than that known for higher plants. We investigated photosynthetic performance by chlorophyll fluorescence at room temperature and at 77K, P700 absorption and by studying the susceptibility of thalli to photoinhibition. In vivo super-resolution fluorescence microscopy was used to visualize changes in the organization of the thylakoid membrane under Mn excess and deficiency. Non-optimal Mn concentrations changed the ratio of photosystem I to photosystem II and altered the organisation of thylakoid membranes. Mn deficiency seems to favour cyclic electron flow around photosystem I protecting thereby photosystem II against photoinhibition.
Variability in sampling of cortex-wide neural dynamics explains individual differences in functional connectivity and behavioral phenotype
Authors: MacDowell Camden J. , Briones Brandy A. , Lenzi Michael J. , Gustison Morgan L. , Buschman Timothy J. 
Published: January 2022

AbstractIndividual differences in behavior are associated with changes in the correlation of neural activity between brain areas. Such differences in ‘functional connectivity’ are thought to reflect individual differences in brain structure that alter the flow of neural activity between regions. Here, in contrast, we show that individual differences in functional connectivity and behavior can be explained by differences in how frequently an individual expresses distinct cortex-wide spatiotemporal patterns of neural activity. This suggests variability in sampling of cortex-wide neural dynamics may underlie individuals’ unique behavioral phenotypes.
Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program
Authors: Wendt Frank R , Pathak Gita A , Vahey Jacqueline , Qin Xuejun , Koller Dora , Cabrera-Mendoza Brenda , Haeny Angela , Harrington Kelly M , Rajeevan Nallakkandi , Duong Linh M , Levey Daniel F , De Angelis Flavio , De Lillo Antonella , Bigdeli Tim B , Pyarajan Saiju ,   VA Million Veteran Program, Gaziano J. Michael , Gelernter Joel , Aslan Mihaela , Provenzale Dawn , Helmer Drew A. , Hauser Elizabeth R. , Polimanti Renato ,   Department of Veteran Affairs Cooperative Study Program (#2006)
Published: January 2022

AbstractThe Million Veteran Program (MVP) participants represent 100 years of US history, including significant social and demographic change over time. Our study assessed two aspects of the MVP: (i) longitudinal changes in population diversity and (ii) how these changes can be accounted for in genome-wide association studies (GWAS). The MVP was divided into five birth cohorts (N-range=123,888 [born from 1943-1947] to 136,699 [born from 1948-1953]). Groups of participants were defined by (i) HARE (harmonized ancestry and race/ethnicity) and (ii) a random-forest clustering approach using the 1000 Genomes Project and the Human Genome Diversity Project (1kGP+HGDP) reference panels (77 world populations representing six continental groups). In these groups, we performed GWASs of height, a trait potentially affected by population stratification. Birth cohorts demonstrate important trends in ancestry diversity over time. More recent HARE-assigned Europeans, Africans, and Hispanics had lower European ancestry proportions than older birth cohorts (0.010<Cohen’s d<0.259, p<7.80×10−4). Conversely, HARE-assigned East Asians showed an increase in European ancestry proportion over time. In GWAS of height using HARE assignments, genomic inflation due to population stratification was prevalent across all birth cohorts (linkage disequilibrium score regression intercept=1.08±0.042). The 1kGP+HGDP-based ancestry assignment significantly reduced the population stratification (mean intercept reduction=0.045±0.007, p<0.05) confounding in the GWAS statistics. This study provides a comprehensive characterization of ancestry diversity of the MVP cohort over time and highlights that more refined modeling of genetic diversity (e.g., the 1kGP+HGDP-based ancestry assignment) can more accurately capture the polygenic architecture of traits and diseases that could be affected by population stratification.
Rhythm of The Night (and Day): Predictive metabolic modeling of circadian growth in Chlamydomonas
Authors: Metcalf Alex J. , Boyle Nanette R. 
Published: January 2022

ABSTRACTAlgal cells experience strong circadian rhythms under diurnal light, with regular changes in both biomass composition and transcriptomic environment. However, most metabolic models – critical tools for bioengineering organisms – assume a steady state. The conflict between these assumptions and the reality of the cellular environment make such models inappropriate for algal cells, creating a significant obstacle in engineering cells that are viable under natural light. By transforming a set of discreet transcriptomic measurements from synchronized Chlamydomonas cells grown in a 12/12 diel light regime (1) into continuous curves, we produced a complete representation of the cell’s transcriptome that can be interrogated at any arbitrary timepoint. We clustered these curves, in order to find genes that were expressed in similar patterns, and then also used it to build a metabolic model that can accumulate and catabolize different biomass components over the course of a day. This model predicts qualitative phenotypical outcomes for the sta6 mutant, including excess lipid accumulation (2) and a failure to thrive when grown diurnally in minimal media (3), representing a qualitative prediction of phenotype from genotype even under dynamic conditions. We also extended this approach to simulate all single-knockout mutants with genes represented in the model and identified potential targets for rational engineering efforts.SIGNIFICANCE STATEMENTWe have developed the first transient metabolic model for diurnal growth of algae based on experimental data and capable of predicting phenotype from genotype. This model enables us to evaluate the impact of genetic and environmental changes on the growth, biomass composition and intracellular fluxes of the model green alga, Chlamydomonas reinhardtii. The availability of this model will enable faster and more efficient design of cells for production of fuels, chemicals and pharmaceuticals.
The tyrosine phosphatase PRL regulates attachment of Toxoplasma gondii to host cells and is essential for virulence
Authors: Yang Chunlin , Blakely William J. , Arrizabalaga Gustavo 
Published: January 2022

ABSTRACTThe pathogenesis of Toxoplasma gondii is mainly due to tissue damage caused by the repeating lytic cycles of the parasite. Many proteins localized to the pellicle of the parasite, particularly kinases, have been identified as critical regulators of the Toxoplasma lytic cycle. However, little is known about the associated protein phosphatases. Phosphatase of regenerating liver (PRL), a highly conserved tyrosine phosphatase, is an oncogene that plays pivotal roles in mammalian cells and typically associates with membranes via a conserved prenylation site. PRL in Toxoplasma has a predicted prenylation motif in the C-terminus like other homologs. We have determined that TgPRL localizes to the plasma membrane and that disruption of TgPRL results in a defect in the parasite’s ability to attach to host cells. This function is dependent both on TgPRL’s membrane localization and phosphatase activity. Importantly, in vivo experiments have shown that while mice infected with parental strain parasites die within days of infection, those infected with parasites lacking TgPRL not only survive but also develop immunity that confers protection against subsequent infection with wild-type parasites. Immunoprecipitation experiments revealed that the PRL-CNNM (Cyclin M) complex, which regulates intracellular Mg2+ homeostasis in mammalian cells, is also present in Toxoplasma. Consistent with this interaction, parasites lacking TgPRL had higher intracellular Mg2+ levels than the parental or complemented strains, suggesting TgPRL is involved in regulating intracellular Mg2+ homeostasis. Thus, TgPRL is a vital regulator of the Toxoplasma lytic cycle and virulence, showing its potential as a target of therapeutic intervention.IMPORTANCEInfection with Toxoplasma gondii can lead to severe and even life-threatening diseases in people with compromised or suppressed immune systems. Unfortunately, drugs to combat the parasite are limited, highly toxic, and ineffective against the chronic stage of the parasite. Consequently, there is a strong demand for the discovery of new treatments. A comprehensive understanding of how the parasite propagates in the host cells and which proteins contribute to the parasite’s virulence will facilitate the discovery of new drug targets. Our study meets this objective and adds new insights to understanding the lytic cycle regulation and virulence of Toxoplasma by determining that the protein phosphatase TgPRL plays a vital role in the parasite’s ability to attach to host cells and that it is essential for parasite virulence.
Estimating Under-diagnosis of Patients in Chronically-ill Populations
Authors: Stocking Andrew , Duncan Ian , Huynh Nhan 
Published: January 2022

ABSTRACTDiagnosis coding in administrative data is known to be inconsistent and incomplete, introducing inaccurate assessment of patients’ health outcomes. The under-diagnosis of members with a target chronic condition reduces the correlation of that chronic condition with associated events. Yet, only a few studies have evaluated the extent of under-reporting of chronic conditions in administrative data. In this study, we developed a novel framework to identify latent members, or those who have not yet been identified with a target chronic condition through claims-based diagnosis but are likely to have some degree of the condition. We applied our innovative approach to estimate the prevalence of a chronic-related event, based on the population of observed and latent members. We provided a detailed illustration that treats incontinence as our target chronic condition while examining four types of incontinence-related events: urinary-tract infections (UTIs), slips and falls, dermatitis, and behavioral disruptions. All analysis relied on the 5% Medicare sample for a continuously enrolled cohort between 2014-2018. Using our novel approach, we were able to increase our identification of incontinence from the 11.2% diagnosed in 2018 to an estimated prevalence in 2018 of 34.7% among fee-for-service Medicare beneficiaries over the age of 65. Similarly, our estimation of UTIs associated with those with incontinence increased from 38% to 68%, from 20% to 41% for IAD, 22% to 54% for slips and falls, and from 26% to 57% for behavior disruptions.
Metabolic strategies shared by basement residents of the Lost City hydrothermal field
Authors: Brazelton William J. , McGonigle Julia M. , Motamedi Shahrzad , Pendleton H. Lizethe , Twing Katrina I. , Miller Briggs C. , Lowe William J. , Hoffman Alessandrina M. , Prator Cecilia A. , Chadwick Grayson L. , Anderson Rika E. , Thomas Elaina , Butterfield David A. , Aquino Karmina A. , Früh-Green Gretchen L. , Schrenk Matthew O. , Lang Susan Q. 
Published: January 2022

ABSTRACTAlkaline fluids venting from chimneys of the Lost City hydrothermal field flow from a potentially vast microbial habitat within the seafloor where energy and organic molecules are released by chemical reactions within rocks uplifted from Earth’s mantle. In this study, we investigated hydrothermal fluids venting from Lost City chimneys as windows into subseafloor environments where the products of geochemical reactions, such as hydrogen (H2), formate, and methane, may be the only available sources of energy for biological activity. Our deep sequencing of metagenomes and metatranscriptomes from these hydrothermal fluids revealed a few key species of archaea and bacteria that are likely to play critical roles in the subseafloor microbial ecosystem. We identified a population of Thermodesulfovibrionales (belonging to phylum Nitrospirae) as a prevalent sulfate-reducing bacterium that may be responsible for much of the consumption of H2 and sulfate in Lost City fluids. Metagenome-assembled genomes (MAGs) classified as Methanosarcinaceae and Candidatus Bipolaricaulota were also recovered from venting fluids and represent potential methanogenic and acetogenic members of the subseafloor ecosystem. These genomes share novel hydrogenases and formate dehydrogenase-like sequences that may be unique to hydrothermal and subsurface alkaline environments where hydrogen and formate are much more abundant than carbon dioxide. The results of this study include multiple examples of metabolic strategies that appear to be advantageous in hydrothermal and subsurface environments where energy and carbon are provided by geochemical reactions.IMPORTANCEThe Lost City hydrothermal field is an iconic example of a microbial ecosystem fueled by energy and carbon from Earth’s mantle. Uplift of mantle rocks into the seafloor can trigger a process known as serpentinization that releases hydrogen and creates unusual environmental conditions where simple organic carbon molecules are more stable than dissolved inorganic carbon. This study provides an initial glimpse into the kinds of microbes that live deep within the seafloor where serpentinization takes place, by sampling hydrothermal fluids exiting from the Lost City chimneys. The metabolic strategies that these microbes appear to be using are also shared by microbes that inhabit other sites of serpentinization, including continental subsurface environments and natural springs. Therefore, the results of this study contribute to a broader, interdisciplinary effort to understand the general principles and mechanisms by which serpentinization-associated processes can support life on Earth and perhaps other worlds.
The chromosome-scale genome assembly of Jasminum sambac var. unifoliatum provide insights into the formation of floral fragrance
Authors: Zhou Chengzhe , Zhu Chen , Tian Caiyun , Xie Siyi , Xu Kai , Huang Linjie , Wen Shengjing , Zhang Cheng , Lai Zhongxiong , Lin Yuling , Guo Yuqiong 
Published: January 2022

AbstractThe high-quality genome assembly of the JSU-FSP provides valuable information on how jasmine produces the abundant VTs and VPBs that synergistically contribute to the pleasant aroma of jasmine flower.
Norepinephrine and dopamine contribute to distinct repetitive behaviors induced by novel odorant stress in male and female mice
Authors: Lustberg Daniel J. , Liu Joyce Q. , Iannitelli Alexa F. , Vanderhoof Samantha O. , Liles L. Cameron , McCann Katharine E. , Weinshenker David 
Published: January 2022

AbstractExposure to unfamiliar odorants induces an array of repetitive defensive and non-defensive behaviors in rodents which likely reflect adaptive stress responses to the uncertain valence of novel stimuli. Mice genetically deficient for dopamine β-hydroxylase (Dbh−/−) lack the enzyme required to convert dopamine (DA) into norepinephrine (NE), resulting in globally undetectable NE and supranormal DA levels. Because catecholamines modulate novelty detection and reactivity, we investigated the effects of novel plant-derived odorants on repetitive behaviors in Dbh−/− mice and Dbh+/− littermate controls, which have catecholamine levels comparable to wild-type mice. Unlike Dbh+/− controls, which exhibited vigorous digging in response to novel odorants, Dbh−/− mice displayed excessive grooming. Drugs that block NE synthesis or neurotransmission suppressed odorant-induced digging in Dbh+/− mice, while a DA receptor antagonist attenuated grooming in Dbh−/− mice. The testing paradigm elicited high circulating levels of corticosterone regardless of Dbh genotype, indicating that NE is dispensable for this systemic stress response. Odorant exposure increased NE and DA abundance in the prefrontal cortex (PFC) of Dbh+/− mice, while Dbh−/− animals lacked NE and had elevated PFC DA levels that were unaffected by novel smells. Together, these findings suggest that novel odorant-induced increases in central NE tone contribute to repetitive digging and reflect psychological stress, while central DA signaling contributes to repetitive grooming. Further, we have established a simple method for repeated assessment of stress-induced repetitive behaviors in mice, which may be relevant for modeling neuropsychiatric disorders like Tourette syndrome or obsessive-compulsive disorder that are characterized by stress-induced exacerbation of compulsive symptoms.
Environmental change alters nitrogen fixation rates and microbial parameters in a subarctic biological soil crust
Authors: Salazar Alejandro , Warshan Denis , Vasquez-Mejia Clara , Andrésson Ólafur S. 
Published: January 2022

AbstractTogether, Biological Soil Crust (BSC) and other cryptogamic groundcovers can contribute up to half of the global nitrogen (N) fixation. BSC also stabilizes the soil (reducing erosion and dust emissions), fixes carbon (C), retains moisture, and acts as a hotspot of microbial diversity and activity. Much of the knowledge about how climate change is affecting the composition and functioning of BSC comes from hot arid and semiarid regions. The comparatively smaller body of research on BSC from cold and mesic environments has been primarily observational, for example along chronosequences after a glacier retreat. Few studies have experimentally investigated the effects of the environment on BSC from high latitudes. Such experiments allow unraveling of relationships at a resolution that can only be achieved by controlling for confounding factors. We measured short-term (2-4 days) responses of a liverwort-based (Anthelia juratzkana) BSC from the south of Iceland to a range of temperature, moisture and light conditions. Warming increased N fixation rates, especially when moisture was at a saturation level, and only when light was not limiting. A correlation analysis suggests that increases in N fixation rates were linked to cyanobacterial abundance on the BSC surface and to the rates of their metabolic activity. Warming and moisture changes also induced compositional and structural modification of the bacterial community, with consequences at the functional level. In contrast to many observations on BSC from hot drylands, the BSC from our cold and mesic study site is more limited by low temperature and light than by moisture. Our findings show possible ways in which BSC from cold and mesic ecosystems can respond to short-term manifestations of climate change, such as increasingly frequent heat waves.
ARPC5 Isoforms and Their Regulation by Calcium-Calmodulin-N-WASP Drive Distinct Arp2/3-dependent Actin Remodeling Events in CD4 T Cells
Authors: Sadhu Lopamudra , Tsopoulidis Nikolaos , Laketa Vibor , Way Michael , Fackler Oliver T. 
Published: January 2022

AbstractArp2/3-dependent formation of nuclear F-actin networks of different morphology and stability is observed in an increasing number of biological processes. In CD4 T cells, T cell receptor (TCR) signaling induces cytoplasmic and nuclear F-actin assembly via Arp2/3 to strengthen contacts to antigen presenting cells and to regulate gene expression, respectively. How Arp2/3 complex is regulated to mediate these distinct actin polymerization events in response to a common stimulus is unknown. Arp2/3-complex consists of 7 subunits where ARP3, ARPC1 and ARPC5 exist as two different isoforms in humans that can assemble in complexes with different properties. Examining whether specific Arp2/3 subunit isoforms govern distinct actin remodeling events in CD4 T cells, we find that the ARPC5L isoform drives nuclear actin polymerization, while cytoplasmic actin dynamics and TCR proximal signalling selectively relies on ARPC5. In contrast, formation of stable nuclear F-actin networks triggered by DNA replication stress in CD4 T cells requires ARPC5 and is independent of ARPC5L. Moreover, nuclear actin polymerization induced by TCR signaling but not by DNA replication stress is controlled by nuclear calcium-calmodulin signalling and N-WASP. Specific ARPC5 isoforms thus govern Arp2/3 complex activity in distinct actin polymerization events. ARPC5 isoform diversity thus emerges as a mechanism to tailor Arp2/3 activity to different physiological stimuli.
Visual uncertainty unveils the distinct role of haptic cues in multisensory grasping
Authors: Camponogara Ivan , Volcic Robert 
Published: January 2022

AbstractMultisensory grasping movements (i.e., seeing and feeling a handheld object while grasping it with the contralateral hand) are superior to movements guided by each separate modality. This multisensory advantage might be driven by the integration of vision with either the haptic position only or with both position and size cues. To contrast these two hypotheses, we manipulated visual uncertainty (central vs. peripheral vision) and the availability of haptic cues during multisensory grasping. We showed a multisensory benefit irrespective of the degree of visual uncertainty suggesting that the integration process involved in multisensory grasping can be flexibly modulated by the contribution of each modality. Increasing visual uncertainty revealed the role of the distinct haptic cues. The haptic position cue was sufficient to promote multisensory benefits evidenced by faster actions with smaller grip apertures, whereas the haptic size was fundamental in fine-tuning the grip aperture scaling. These results support the hypothesis that, in multisensory grasping, vision is integrated with all haptic cues, with the haptic position cue playing the key part. Our findings highlight the important role of non-visual sensory inputs in sensorimotor control and hint at the potential contributions of the haptic modality in developing and maintaining visuomotor functions.