bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Accelerometry-based Measures of Physical Activity
Authors: Karas Marta , Muschelli John , Leroux Andrew , Urbanek Jacek K , Wanigatunga Amal A , Bai Jiawei , Crainiceanu Ciprian M , Schrack Jennifer A 
Published: March 2022

AbstractBackgroundGiven the evolution of processing and analyzing accelerometry data over the past decade, it is of utmost importance that we as a field understand how newer (e.g., MIMS) summary measures compare to long-established ones (e.g., ActiGraph activity counts).ObjectiveOur study aims to compare and harmonize accelerometry-based measures of physical activity (PA) to increase the comparability, generalizability, and translation of findings across studies using objective measures of PA.MethodsHigh resolution accelerometry data were collected from 655 participants in the Baltimore Longitudinal Study on Aging who wore an ActiGraph GT9X device at wrist continuously for a week. Data were summarized at the minute-level as activity counts (AC; measure obtained from ActiGraph’s ActiLife software) and MIMS, ENMO, MAD, and AI (open-source measures implemented in R). The correlation between AC and other measures was quantified both marginally and conditionally on age, sex and BMI. Next, each pair of measures were harmonized using nonparametric regression of minute-level measurements.ResultsThe study sample had the following characteristics: mean (sd) age of 69.8 (14.2), BMI of 27.3 (5.0) kg/m2, 54.5% females, and 67.9% white. The marginal participant-specific correlation between AC and MIMS, ENMO, MAD, and AI were 0.988, 0.867, 0.913 and 0.970, respectively. After harmonization, the mean absolute percentage error for predicting total AC from MIMS, ENMO, MAD, and AI was 2.5, 14.3, 11.3 and 6.3, respectively. The accuracy for predicting sedentary minutes based on AC (AC > 1853) using MIMS, ENMO, MAD and AI was 0.981, 0.928, 0.904, and 0.960, respectively. An R software with a unified interface for computation of the open-source measures from raw accelerometry data was developed and published as SummarizedActigraphy R package.ConclusionsOur comparison of accelerometry-based measures of PA enables researchers to extend the knowledge from the thousands of manuscripts that have been published using ActiGraph AC to MIMS and other measures by demonstrating their high correlation and providing a harmonization mapping.
Sex and size matter: foraging ecology of offshore harbour porpoises in waters around Greenland
Authors: Louis Marie , Routledge Jennifer , Heide-Jørgensen Mads Peter , Szpak Paul , Lorenzen Eline 
Published: March 2022

AbstractIndividuals of different sex or age can vary in their resource use due to differences in behaviour, life history, energetic need, or size. Harbour porpoises are small cetaceans that rely on a constant prey supply to survive. Here, we use bone collagen carbon (δ13C) and nitrogen (δ15N) isotope compositions to elucidate sex and size differences in the foraging ecology of harbour porpoises from West Greenland. In this region, populations have a unique offshore, deep-water ecology. Female harbour porpoises are larger than males and we find that females have a higher trophic level than males, and δ15N positively correlates with size for females only. This indicates that size may matter in the ability of females to handle larger prey and/or dive deeper to catch higher trophic level prey. These results suggest that females, which also feed their calves, may be under different ecological constraints than males. We also analysed the harbour porpoise data with comparable stable isotope data from Greenland populations of belugas and narwhals. Consistent with their small body size, and a diet consisting primarily of capelin, we find that harbour porpoises have a lower trophic level than belugas and narwhals. Furthermore, harbour porpoises have the largest ecological niche of the three species, which is in accordance with tagging studies indicating they have a wide range in shelf and deep offshore waters of the sub-arctic and North Atlantic.
Visualizing the Transiently Populated Closed-State of Human HSP90 ATP Binding Domain
Authors: Henot Faustine , Rioual Elisa , Favier Adrien , Macek Pavel , Crublet Elodie , Josso Pierre , Brutscher Bernhard , Frech Matthias , Gans Pierre , Loison Claire , Boisbouvier Jerome 
Published: March 2022

AbstractHSP90 are abundant molecular chaperones, assisting the folding of several hundred client proteins, including substrates involved in tumor growth or neurodegenerative diseases. A complex set of large ATP-driven structural changes occurs during HSP90 functional cycle. However, the existence of such structural rearrangements in apo HSP90 has remained unclear. Here, we identified a metastable excited state in the isolated HSP90 ATP binding domain. We used solution NMR and mutagenesis to characterize structures of both ground and excited states. We demonstrated that in solution the HSP90 ATP binding domain transiently samples a functionally relevant ATP-lid closed state, distant by more than 30 Å from the ground state. NMR relaxation and molecular dynamics were combined to characterize the energy landscape corresponding to the transition between these interconverting states. The precise description of the dynamics and structures sampled by human HSP90 ATP binding domain is a paramount piece of information for the future design of new therapeutic ligands.
Optimization of the precursor supply for an enhanced FK-506 production in Streptomyces tsukubaensis
Authors: Schulz Susann , Schall Christoph , Stehle Thilo , Breitmeyer Christian , Krysenko Sergii , Bera Agnieszka , Wohlleben Wolfgang 
Published: March 2022

AbstractTacrolimus (FK-506) is a macrolide widely used as immunosuppressant to prevent transplant rejection. Synthetic production of FK-506 is not efficient and costly, whereas the biosynthesis of FK-506 is complex and the level produced by the wild type strain, Streptomyces tsukubaensis, is very low. We therefore engineered FK-506 biosynthesis and the supply of the precursor L-lysine to generate strains with improved FK-506 yield. To increase FK-506 production, first the intracellular supply of the essential precursor lysine was improved in the native host S. tsukubaensis by engineering the lysine biosynthetic pathway. Therefore, a feedback deregulated aspartate kinase AskSt* of S. tsukubaensis was generated by site directed mutagenesis. Whereas overexpression of AskSt* resulted only in a 17% increase in FK-506 yield, heterologous overexpression of a feedback deregulated AskCg* from Corynebacterium glutamicum was proven to be more efficient. Combined overexpression of AskCg* and DapASt, showed a strong enhancement of the intracellular lysine pool following increase in the yield by approximately 73% compared to the wild type. Lysine is coverted into the FK-506 building block pipecolate by the lysine cyclodeaminase FkbL. Construction of a ΔfkbL mutant led to a complete abolishment of the FK-506 production, confirming the indispensability of this enzyme for FK-506 production. Chemical complementation of the ΔfkbL mutant by feeding pipecolic acid and genetic complementation with fkbL as well as with other lysine cyclodeaminase genes (pipAf, pipASt, originating from Actinoplanes friuliensis and Streptomyces pristinaespiralis, respectively) completely restored FK-506 production. Subsequently, FK-506 production was enchanced by heterologous overexpression of PipAf and PipASp in S. tsukubaensis. This resulted in a yield increase by 65% compared to the WT in the presence of PipAf from A. friuliensis. For further rational yield improvement, the crystal structure of PipAf from A. friuliensis was determined at 1.3 Å resolution with the cofactor NADH bound and at 1.4 Å with its substrate lysine. Based on the structure the Ile91 residue was replaced by Val91 in PipAf, which resulted in an overall increase of FK-506 production by approx. 100% compared to the WT.
Stress-tolerant, recyclable, and autonomously renewable biocatalyst platform enabled by engineered bacterial spores
Authors: Hui Yue , Cui Ziyu , Sim Seunghyun 
Published: March 2022

ABSTRACTHere, we describe a stress-tolerant, recyclable, and autonomously renewable biocatalyst platform based on T7 RNA polymerase-enabled high-density protein display on bacterial spores (TIED). TIED uses high-level T7 RNA polymerase-driven expression of recombinant proteins specifically in sporulating cells to allow spontaneous assembly of recombinant fusion proteins on B. subtilis spore surface. TIED enables a high loading density in the range of 106–107 recombinant enzymes per spore, robust catalytic activities of displayed enzymes comparable to the respective free enzymes, and enhanced kinetic stability of displayed enzymes in methanol and elevated temperatures. Further, we demonstrate TIED-enzymes to be not only recyclable, but fully renewable after loss of activity through induction of germination and sporulation, enabling perpetual reuse of these immobilized biocatalysts.Graphical abstractSchematic illustration of the T7 RNA polymerase-enabled high-density protein display (TIED) on bacterial spores and its unique features as a biocatalyst platform.
Effects of Transcranial Direct Current Stimulation in Children and Young People with Psychiatric Disorders: A Systematic Review
Authors: Gallop Lucy , Westwood Samuel J. , Lewis Yael D. , Campbell Iain C. , Schmidt Ulrike 
Published: March 2022

AbstractBackgroundTranscranial Direct Current Stimulation (tDCS) has demonstrated benefits in adults with various psychiatric disorders, but its clinical utility in children and young people (CYP) remains unclear.ObjectiveThis PRISMA systematic review used published and ongoing studies to examine the effects of tDCS on disorder-specific symptoms, mood and neurocognition in CYP with psychiatric disorders.MethodsWe searched Medline via PubMed, Embase, PsychINFO via OVID, and Clinicaltrials.gov up to January 2022. Eligible studies involved multiple session (i.e. treatment) tDCS in CYP (≤ 25 years-old) with psychiatric disorders. Two independent raters assessed the eligibility of studies and extracted data using a custom-built form.ResultsOf 28 eligible studies (participant N= 379), the majority (n = 23) reported an improvement in at least one outcome measure of disorder-specific symptoms. Few studies (n = 9) examined tDCS effects on mood and/or neurocognition, but findings were mainly positive. Overall, tDCS was well-tolerated with minimal side-effects. Of 11 eligible ongoing studies, many are sham-controlled RCTs (n = 9) with better blinding techniques and a larger estimated participant enrolment (M = 74.7; range: 11-172) than published studies.ConclusionsFindings provide encouraging evidence of tDCS-related improvement in disorder-specific symptoms, but evidence remains limited, especially in terms of mood and neurocognitive outcomes. Ongoing studies appear to be of improved methodological quality; however, future studies should broaden outcome measures to more comprehensively assess the effects of tDCS and develop dosage guidance (i.e. treatment regimens).
Relative effectiveness of booster vs. 2-dose mRNA Covid-19 vaccination in the Veterans Health Administration: Self-controlled risk interval analysis
Authors: Korves Caroline , Izurieta Hector S. , Smith Jeremy , Zwain Gabrielle M. , Powell Ethan I. , Balajee Abirami , Ryder Kathryn , Young-Xu Yinong 
Published: March 2022

ABSTRACTImportancePrevious studies have analyzed effectiveness of booster mRNA Covid-19 vaccination and compared it with 2-dose primary series for both Delta and Omicron variants. Observational studies that estimate effectiveness by comparing outcomes among vaccinated and unvaccinated individuals may suffer from residual confounding and exposure misclassification.ObjectiveTo estimate relative effectiveness of booster vaccination versus the 2-dose primary series with self-controlled study designDesign, Setting and ParticipantsWe used the Veterans Health Administration (VHA) Corporate Data Warehouse to identify U.S. Veterans enrolled in care ≥2 years who received the 2-dose primary mRNA Covid-19 vaccine series and a mRNA Covid-19 booster following expanded recommendation for booster vaccination, and who had a positive SARS-CoV-2 test during the Delta (9/23/2021-11/30/2021) or Omicron (1/1/22-3/1/22) predominant period. Among them, we conducted a self-controlled risk interval (SCRI) analysis to compare odds of SARS-CoV-2 infection during a booster exposure interval versus a control interval.Exposurescontrol interval (days 4-6 post-booster vaccination, presumably prior to gain of booster immunity), and booster exposure interval (days 14-16 post-booster vaccination, presumably following gain of booster immunity)Outcomes and MeasuresPositive PCR or antigen SARS-CoV-2 test. Separately for Delta and Omicron periods, we used conditional logistic regression to calculate odds ratios (OR) of a positive test for the booster versus control interval and calculated relative effectiveness of booster versus 2-dose primary series as (1-OR)*100. The SCRI approach implicitly controlled for time-fixed confounders.ResultsWe found 42 individuals with a positive SARS-CoV-2 test in the control interval and 14 in the booster exposure interval during Delta period, and 137 and 66, respectively, in Omicron period. For the booster versus 2-dose primary series, the odds of infection were 70% (95%CI: 42%, 84%) lower during the Delta period and 56% (95%CI: 38%, 67%) lower during Omicron. Results were similar for ages <65 and ≥65 years in the Omicron period. In sensitivity analyses among those with prior Covid-19 history, and age stratification, ORs were similar to the main analysis.ConclusionsBooster vaccination was more effective relative to a 2-dose primary series, the relative effectiveness was consistent across age groups and was higher during the Delta predominant period than during the Omicron period.
Toxoplasma gondii infection and insomnia: a case control seroprevalence study
Authors: Alvarado-Esquivel Cosme , Estrada-Martínez Sergio , Pérez-Álamos Alma Rosa , Ramos-Nevarez Agar , Botello-Calderon Karina , Alvarado-Félix Ángel Osvaldo , Vaquera-Enríquez Raquel , Alvarado-Félix Gustavo Alexis , Sifuentes-Alvarez Antonio , Guido-Arreola Carlos Alberto , Rábago-Sánchez Elizabeth , Saenz-Soto Leandro 
Published: March 2022

ABSTRACTAimTo determine the association between Toxoplasma gondii (T. gondii) infection and insomnia.Materials and methodsThrough an age-and gender-matched case-control study, 577 people with insomnia (cases) and 577 people without insomnia (controls) were tested for anti-T. gondii IgG and IgM antibodies using commercially available enzyme-immunoassays.ResultsAnti-T. gondii IgG antibodies were found in 71 (12.3%) of 577 individuals with insomnia and in 46 (8.0%) of 577 controls (OR=1.62; 95% CI: 1.09-2.39; P=0.01). Men with insomnia had a higher (16/73: 21.9%) seroprevalence of T. gondii infection than men without insomnia (5/73: 6.8%) (OR: 3.81; 95% CI: 1.31-11.06; P=0.009). The rate of high (>150 IU/ml) anti-T. gondii IgG antibody levels in cases was higher than the one in controls (OR=2.21; 95% CI: 1.13-4.31; P=0.01). Men with insomnia had a higher (8/73: 11.0%) rate of high anti-T. gondii IgG antibody levels than men without insomnia (0/73: 0.0%) (P=0.006). The rate of high anti-T. gondii IgG antibody levels in cases >50 years old (11/180: 6.1%) was higher than that (3/180: 1.7%) in controls of the same age group (OR: 3.84; 95% CI: 1.05-14.00; P=0.05). No difference in the rate of IgM seropositivity between cases and controls was found (OR=1.33; 95% CI: 0.57-3.11; P=0.50).ConclusionsResults of this seroepidemiology study suggest that infection with T. gondii is associated with insomnia. Men older than 50 years with T. gondii exposure might be prone to insomnia. Further research to confirm the association between seropositivity and serointensity to T. gondii and insomnia are needed.
Molecular and spatial epidemiology of HCV among people who inject drugs in Boston, Massachusetts
Authors: Stopka Thomas J. , Yaghi Omar , Li Min , Paintsil Elijah , Chui Kenneth , Landy David , Heimer Robert 
Published: March 2022

AbstractIntegration of genetic, social network, and spatial data has the potential to improve understanding of transmission dynamics in established HCV epidemics. Sequence data were analyzed from 63 viremic people who inject drugs recruited in the Boston area through chain referral or time-location sampling. HCV subtype 1a was most prevalent (57.1%), followed by subtype 3a (33.9%). The phylogenetic distances between sequences were no shorter comparing individuals within versus across networks, nor by location or time of first injection. Social and spatial networks, while interesting, may be too ephemeral to inform transmission dynamics when the date and location of infection are indeterminate.
Distinct genome-wide DNA methylation and gene expression signatures in classical monocytes from African American patients with systemic sclerosis
Authors: Allen Peter C. , Smith Sarah , Wilson Robert C. , Wirth Jena R. , Wilson Nathan H. , Frost DeAnna Baker , Flume Jonathan , Gilkeson Gary S. , Cunningham Melissa A. , Langefeld Carl D. , Absher Devin M. , Ramos Paula S. 
Published: March 2022

AbstractBackgroundSystemic sclerosis (SSc) is a multisystem autoimmune disorder that has an unclear etiology and disproportionately affects women and African Americans. Despite this, African Americans are dramatically underrepresented in SSc research. Additionally, monocytes show heightened activation in SSc and in African Americans relative to European Americans. In this study, we sought to investigate DNA methylation and gene expression patterns in classical monocytes in a health disparity population.MethodsClassical monocytes (CD14++CD16-) were FACS-isolated from 34 self-reported African American women. Samples from 12 SSc patients and 12 healthy controls were hybridized on MethylationEPIC BeadChip array, while RNA-seq was performed on 16 SSc patients and 18 healthy controls. Analyses were computed to identify differentially methylated CpGs (DMCs), differentially expressed genes (DEGs), and CpGs associated with changes in gene expression (eQTM analysis).ResultsWe observed modest DNA methylation and gene expression differences between cases and controls. The genes harboring the top DMCs, the top DEGs, as well as the top eQTM loci were enriched for metabolic processes. Genes involved in immune processes and pathways showed a weak upregulation in the transcriptomic analysis. While many genes were newly identified, several other have been previously reported as differentially methylated or expressed in different blood cells from patients with SSc, supporting for their potential dysregulation in SSc.ConclusionsWhile contrasting with results found in other blood cell types in largely European-descent groups, the results of this study support that variation in DNA methylation and gene expression exists among different cell types and individuals of different genetic, clinical, social, and environmental backgrounds. This finding supports the importance of including diverse, well-characterized patients to understand the different roles of DNA methylation and gene expression variability in the dysregulation of classical monocytes in diverse populations, which might help explaining the health disparities.
Structure of a Rad52 homolog from bacteriophage in complex with a novel duplex intermediate of DNA annealing
Authors: Caldwell Brian J. , Norris Andrew , Wysocki Vicki H. , Bell Charles E. 
Published: March 2022

ABSTRACTHuman Rad52 protein binds to ssDNA and promotes the annealing of complementary strands. This activity is central to multiple DNA repair pathways and Rad52 is a target for cancer therapeutics. Previous crystal structures of the DNA binding domain of Rad52 revealed an 11-mer ring that binds to ssDNA in an extended conformation with the bases exposed for homology recognition. While this complex is likely involved in the early stages of annealing, there is no structure of Rad52 with two strands of DNA bound simultaneously, and its mechanism of annealing is poorly understood. To approach this problem, we have turned to the RecT/Redβ family of annealing proteins from bacteriophage, which are distant homologs of Rad52 that form stable complexes with a duplex intermediate of annealing. We have used single particle cryo-electron microscopy (cryo-EM) to determine a 3.4 Å structure of a RecT homolog from a prophage of Listeria innocua (LiRecT) in complex with two complementary 83-mer oligonucleotides that were added to the protein sequentially. The structure reveals a left-handed helical filament of the protein bound to a novel conformation of DNA duplex that is highly extended and under-wound. The duplex is bound at a stoichiometry of 5 bp/monomer to a deep, narrow, positively-charged groove that runs along the outer surface of the filament. Data from native mass spectrometry confirm that the filament complex seen by cryo-EM also exists in solution. Collectively, these data provide new insights into the mechanism of annealing by LiRecT and by homologous proteins including human Rad52.
Groundwater metabolome responds to recharge in fractured sedimentary strata
Authors: Zerfaß Christian , Lehmann Robert , Ueberschaar Nico , Sanchez-Arcos Carlos , Totsche Kai-Uwe , Pohnert Georg 
Published: March 2022

AbstractUnderstanding the sources, structure and fate of dissolved organic matter (DOM) in groundwater is paramount for protection and sustainable use of this vital resource. On its passage through the Critical Zone, DOM is subject to biogeochemical conversions. Therefore, it carries valuable cross-habitat information for monitoring and predicting the stability of groundwater ecosystem services and assessing these ecosystems’ response to fluctuations caused by external impacts such as climatic extremes. Challenges arise from insufficient knowledge on groundwater metabolite composition and dynamics due to a lack of consistent analytical approaches for long-term monitoring. Our study establishes groundwater metabolomics to decipher the complex biogeochemical transport and conversion of DOM. We explore fractured sedimentary bedrock along a hillslope recharge area by a 5-year untargeted metabolomics monitoring of oxic perched and anoxic phreatic groundwater. A summer with extremely high temperatures and low precipitation was included in the monitoring. Water was accessed by a sampling well-transect and regularly collected for liquid chromatography-mass spectrometry (LC-MS) investigation. Dimension reduction of the resulting complex data set by principal component analysis revealed that metabolome dissimilarities between distant wells coincide with transient cross-stratal flow indicated by groundwater levels. Time series of the groundwater metabolome data provides detailed insights into subsurface responses to recharge dynamics. We demonstrate that dissimilarity variability between groundwater bodies with contrasting aquifer properties coincides with recharge dynamics. This includes groundwater high- and lowstands as well as recharge and recession phases. Our monitoring approach allows to survey groundwater ecosystems even under extreme conditions. The metabolome was otherwise highly variable lacking seasonal patterns and did not segregate by geographic location of sampling wells, thus ruling out vegetation or (agricultural) land use as primary driving factor. Patterns that emerge from metabolomics monitoring give insight into subsurface ecosystem functioning and water quality evolution, essential for sustainable groundwater use and climate change-adapted management.