bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensity and longevity of SARS-CoV-2 vaccination response and efficacy of adjusted vaccination schedules in patients with immune-mediated inflammatory disease
Authors: Simon David , Tascilar Koray , Fagni Filippo , Kleyer Arnd , Krönke Gerhard , Meder Christine , Dietrich Peter , Orlemann Till , Mößner Johanna , Taubmann Julia , Mutlu Melek Yalcin , Knitza Johannes , Kemenes Stephan , Liphardt Anna-Maria , Schönau Verena , Bohr Daniela , Schuster Louis , Hartmann Fabian , Leppkes Moritz , Ramming Andreas , Pachowsky Milena , Schuch Florian , Ronneberger Monika , Kleinert Stefan , Hueber Axel J. , Manger Karin , Manger Bernhard , Atreya Raja , Berking Carola , Sticherling Michael , Neurath Markus F. , Schett Georg 
Published: April 2022

AbstractObjectivesTo investigate the intensity and longevity of SARS-CoV-2 vaccination response in patients with immune-mediated inflammatory disease (IMID) by diagnosis, treatment and adapted vaccination schedules.MethodsSARS-CoV-2 IgG antibody response after SARS-CoV-2 vaccination was measured longitudinally in a large prospective cohort of healthy controls (HC) and IMID patients between December 2020 and 2021. Demographic and disease-specific data were recorded. Humoral response was compared across treatment and disease groups, and with respect to receipt of booster vaccinations. Age and sex adjusted SARS-CoV-2 antibody response was modelled over time. Marginal mean antibody levels and marginal risks of poor response were calculated at weekly intervals starting from week-8 after the first vaccination up to week 40.ResultsAmong 5076 individuals registered, 2535 IMID patients and 1198 HC were eligible for this analysis. Mean antibody levels were higher in HC compared to IMIDs at all-time points, with peak antibody response in HC more than twice that in IMIDs (12.48 (11.52-13.52) vs. 5.71 (5.46-5.97)). Poor response to vaccination was observed in IMID patients treated with agents affecting B- and T-cell functions. Mean differences in antibody response between IMID diseases were small. After additional vaccinations, IMID patients could achieve higher antibody levels than HC vaccinated according to the two-dose schedule, even-though initial antibody levels were lower.ConclusionsIMID patients show a lower and less durable SARS-CoV-2 vaccination response and are at risk to lose humoral immune protection. Adjusted vaccination schedules with earlier boosters and/or more frequent re-doses could better protect IMID patients.
Ribo-macs derived from nucleoli: big ribosome clusters in the cytoplasm of naïve stem cells
Authors: Qin Kezhou , Sun Lei , Wu Xinyi , Wen Jitao , Xing Zhuanzhuan 
Published: April 2022

AbstractPrimed stem cells and naïve stem cells are important for understanding early development, but their ribosomes have not been focused on. In this study, we find that big ribosome clusters named Ribo-macs exist in the cytoplasm of naïve stem cells. Then, we prove that Ribo-macs are dynamic and physiological in the cytoplasm, and can synthesize proteins associated with biogenesis of endoplasmic reticulum and mitochondria. We also discover and demonstrate that Ribo-macs are the nucleoli, which of significance is promoting us to rethink our understanding of nucleoli. Besides, we reveal that Ribo-macs have a compatible relation with P-bodies and stress granules. In a word, all the results about Ribo-macs provide us with a new insight to understand how cells adapt quickly to environment.
Housekeeping gene gyrA, a potential molecular marker for Bacillus ecology study
Authors: Liu Yan , Štefanič Polonca , Miao Youzhi , Xue Yansheng , Xun Weibing , Shen Qirong , Xu Zhihui , Zhang Ruifu , Mandic-Mulec Ines 
Published: April 2022

AbstractBacillus is a ubiquitous microorganism and is one of the most commercially important species widely used in industry, agriculture and healthcare. Bacillus is relatively well understood at the single-cell level; however, molecular tools that determine diversity and ecology of Bacillus community are limited, which limits our understanding of how the Bacillus community works. In the present study, we investigated the potential of the housekeeping gene gyrA as a molecular marker for determining the diversity of Bacillus species. The amplification efficiency for Bacillus species diversity could be greatly improved by primer design. Therefore, we designed a novel primer pair gyrA3 that can detect at least 92 Bacillus species and related species. For Bacillus amyloliquefaciens, Bacillus pumilus, and Bacillus megaterium, we observed that the high variability of the gyrA gene allows for more detailed clustering at the subspecies level that cannot be achieved by the 16S rRNA gene. Since gyrA provides better phylogenetic resolution than 16S rRNA and informs on the diversity of the Bacillus community, we propose that gyrA gene may have broad application prospects in the study of Bacillus ecology.
Outside-in: intracellular vesicles in giant sulfur bacteria contain peptidoglycan
Authors: Flood Beverly E. , Leprich Dalton J. , Hunter Ryan C. , Delherbe Nathalie , MacGregor Barbara , Nieuwenhze Michael Van , Bailey Jake V. 
Published: April 2022

AbstractUntil recently, the cellular envelopes of bacteria were regarded as static and rigid relative to those of eukaryotes. While investigating peptidoglycan synthesis in populations of giant sulfur bacteria, Candidatus Thiomargarita spp., we observed internal vesicle-like features (VLFs). VLFs, as imaged following the active incorporation of D-amino acids, appear to begin as invaginations and delaminations of the cellular envelope. Staining with wheat germ agglutinin confirmed the presence of peptidoglycan in VLFs, while polymyxin B revealed that the outer membrane is present in some VLFs. Transmission electron microscopy revealed a complex network of interconnected VLFs. Genomes of Ca. Thiomargarita nelsonii lack a canonical divisome, while possessing homologs to genes such as actin, membrane scaffolding proteins, and dynamins that are associated with phagocytosis in eukaryotes. The physiological role of VLFs remains unclear, but the presence of sulfur globules in some suggests compartmentalization of metabolism and energy production. This is the first report of peptidoglycan and outer membrane bound intracellular vesicles within prokaryotic cells. These findings transform the canonical view of the inflexible bacterial cell envelope and further narrow the divide between prokaryotes and eukaryotes.
Measures for infection prevention and control of SARS-CoV-2 in Belgian schools between December 2020 and June 2021: a prospective cohort study
Authors: Callies Milena , Kabouche Ines , Desombere Isabelle , Merckx Joanna , Roelants Mathieu , Vermeulen Melissa , Duysburgh Els 
Published: April 2022

AbstractIntroductionAs the role of school-aged children was unclear at the onset of the COVID-19 pandemic, public health authorities recommended to implement infection prevention and control (IPC) measures in school settings. Few studies evaluated the implementation of these measures and their effect on SARS-CoV-2 infection rates among pupils and staff.AimTo describe the implementation of IPC measures in Belgian primary and secondary schools and assess its relation to the prevalence of anti-SARS-CoV-2 antibodies among pupils and staff.MethodsWe conducted a prospective cohort study in a representative sample of primary and secondary schools in Belgium. Implementation of IPC measures in schools was assessed using an online questionnaire. Saliva samples were collected from pupils and staff to determine the SARS-CoV-2 seroprevalence.ResultsA variety of IPC measures (ventilation, hygiene and physical distancing) was implemented by more than 60% of primary and secondary schools with most attention for hygiene measures. Almost no differences in implementation coverage were observed between primary and secondary schools or the Dutch and French language network. Poor implementation of IPC measures was associated with an increased anti-SARS-CoV-2 antibody prevalence among pupils from 8.6% (95% CI: 4.5 - 16.6) to 16.7% (95% CI: 10.2 - 27.4) and staff from 11.5% (95% CI: 8.1 - 16.4) to 17.6% (95% CI: 11.5 - 27.0). This association was statistically significant for all IPC measures and pupils and staff combined.ConclusionBelgian schools were relatively compliant with recommended IPC measures at the school level. Poor implementation of IPC measures was associated with higher SARS-CoV-2 seroprevalence among pupils and staff.Trial registration numberTrial registration number: NCT04613817
Blue turns to grey - Palaeogenomic insights into the evolutionary history and extinction of the blue antelope (Hippotragus leucophaeus)
Authors: Hempel Elisabeth , Bibi Faysal , Faith J. Tyler , Koepfli Klaus-Peter , Klittich Achim M. , Duchêne David A. , Brink James S. , Kalthoff Daniela C. , Dalén Love , Hofreiter Michael , Westbury Michael V. 
Published: April 2022

AbstractThe blue antelope (Hippotragus leucophaeus) is the only large African mammal species to have become extinct in historical times, yet no nuclear genomic information is available for this species. A recent study showed that many alleged blue antelope museum specimens are either roan (H. equinus) or sable (H. niger) antelopes, further reducing the possibilities for obtaining genomic information for this extinct species. While the blue antelope has a rich fossil record from South Africa, climatic conditions in the region are unfavourable to the preservation of ancient DNA. Nevertheless, we recovered two blue antelope draft genomes, one at 3.4x mean coverage from a historical specimen (~200 years old) and one at 2.1x mean coverage from a fossil specimen dating to 9,800–9,300 cal BP, making it currently the oldest palaeogenome from Africa. Phylogenomics show that blue and sable antelope are sister species, confirming previous mitogenomic results, and demonstrate ancient gene flow from roan into blue antelope. We show that blue antelope genomic diversity was much lower than in roan and sable antelopes, indicative of a low population size since at least the early Holocene. This supports observations from the fossil record documenting major decreases in the abundance of blue antelope after the Pleistocene-Holocene transition. Finally, the persistence of this species throughout the Holocene despite low population size suggests that colonial-era human impact was likely a decisive factor in the blue antelope’s extinction.
Human and murine Cryptococcus neoformans infection selects for common genomic changes in an environmental isolate
Authors: Sephton-Clark Poppy , McConnell Scott A. , Grossman Nina , Baker Rosanna , Dragotakes Quigly , Fan Yunfan , Fu Man Shun , Gerbig Gracen , Greengo Seth , Hardwick J. Marie , Kulkarni Madhura , Levitz Stuart M. , Nosanchuk Joshua D. , Shoham Shmuel , Smith Daniel , Stempinski Piotr , Wear Maggie , Cuomo Christina A. , Casadevall Arturo 
Published: April 2022

AbstractA pet cockatoo was the suspected source of Cryptococcus neoformans recovered from the cerebral spinal fluid (CSF) of an immunocompromised patient with cryptococcosis based on the molecular analyses available in 2000. Here we report whole genome sequence analysis of the clinical and cockatoo strains. Both are closely related MATα strains belonging to the VNII lineage, confirming that the human infection likely originated from pet bird exposure. The two strains differ by 61 single nucleotide polymorphisms, including 8 nonsynonymous changes involving 7 genes. To ascertain whether changes in these genes are selected during mammalian infection, we passaged the cockatoo strain in mice. Remarkably, isolates obtained from mouse tissue possess a frame-shift mutation in one of the seven genes altered in the human sample, a gene predicted to encode a SWI-SNF chromatin-remodeling complex protein. Both cockatoo and patient strains as well as mouse passaged isolates obtained from brain tissue had a premature stop codon in a homolog of ZFC3, a predicted single-zinc finger containing protein, which is associated with larger capsules when deleted and appears to have reverted to a full-length protein in the mouse passaged isolates obtained from lung tissue. The patient strain and mouse passaged isolates show variability in the expression of virulence factors, with differences in capsule size, melanization, and rates on non-lytic expulsion from macrophages observed. Our results establish that environmental strains undergo genomic and phenotypic changes during mammalian passage, suggesting that animal virulence can be a mechanism for genetic change and that the genomes of clinical isolates may provide a readout of mutations acquired during infection.
Deep Brain Magnetothermal Silencing of Dopaminergic Neurons via Endogenous TREK1 Channels Abolishes Place Preference in Mice
Authors: Liu Junting , Munshi Rahul , He Muye , Parker Sara D. , Pralle Arnd 
Published: April 2022

AbstractRemote neuromodulation techniques have revolutionized our understanding of brain circuits and their role in behavior. The reversible silencing of specific neuronal populations has emerged as a powerful tool to investigate the necessity and sufficiency of these populations in behavioral responses. Here, we apply magnetothermal silencing using endogenous TREK-1 channels to selectively suppress dopaminergic reward in the ventral tegmental area (VTA) to prove that activation of this specific reward circuit is required for place preference in mice. Magnetothermal silencing entails the application of alternating magnetic fields that penetrate tissue, leading to the heating of superparamagnetic nanoparticles at the target cells, without causing any attenuation or adverse effects. The resultant slight, rapid, and reversible elevation in temperature effectively suppresses neuronal firing, without necessitating genetic modification of the neurons. We demonstrate that two-pore potassium channels, TREK-1, are responsible for this thermal neuronal silencing. Using fiber-based optogenetics we measured both the heating and neuronal silencing in the VTA brain of the animals. We show that in a place preference assay, magnetothermal neuronal silencing of the dopaminergic neurons in the VTA is sufficient to abolish the place preference. Notably, TREK1 knock-out mice exhibit immunity to magnetothermal silencing, behaving as if the magnetic field was not applied. These results underscore the critical role of dopaminergic neuronal activity in the VTA for the establishment of place preference and highlight the dependency on functional TREK1 channels in this magnetothermal silencing approach.HighlightsTREK1 is a highly efficient, thermally activated neuronal silencerFirst magnetothermal neuronal silencing in behaving miceFiber photometry quantification of local heating and silencing of target neurons in the ventral tegmental areaMagnetothermal suppression of dopaminergic reward response in the ventral tegmental area is sufficient to abolish place preference
Supramolecular architecture of the ER-mitochondria encounter structure in its native environment
Authors: Wozny Michael R. , Di Luca Andrea , Morado Dustin R. , Picco Andrea , Hoffmann Patrick C. , Miller Elizabeth A. , Vanni Stefano , Kukulski Wanda 
Published: April 2022

AbstractThe endoplasmic reticulum and mitochondria are main hubs of eukaryotic membrane biogenesis which rely on lipid exchange via membrane contact sites, but the underpinning mechanisms remain poorly understood. In yeast, tethering and lipid transfer between the two organelles is mediated by the ER-mitochondria encounter structure ERMES, a four-subunit complex of unclear stoichiometry and architecture. We determined the molecular organization of ERMES within cells using integrative structural biology, combining quantitative live-imaging, cryo-correlative microscopy, subtomogram averaging and molecular modeling. ERMES assembles into approximately 25 discrete bridge-like complexes distributed irregularly across a contact site. Each bridge consists of three lipid-binding SMP domains arranged in zig-zag fashion. Our molecular model of ERMES reveals an unconventional restrained pathway for lipids. These findings resolve a supramolecular architecture controlling interorganelle lipid fluxes.
Inflammation induced Vascular Smooth Muscle Cell expressing Angiopoietin-like 2 to promote the development of abdominal aortic aneurysm
Authors: Yang Guangcan , Guo Jie , Wu Shuang , Yu Hongyou 
Published: April 2022

AbstractObjectiveThe objective of this study is to investigate the expression of angiopoietin-like protein 2 (Angptl2) in abdominal aortic aneurysm (AAA) and the expression of Angptl2 in vascular smooth muscle cells (VSMC) under inflammation stimuli.MethodsThe mouse AAA model was induced by applying calcium chloride method based the literature and the expression of Angptl2 in AAA was investigated by immunohistochemical staining. The primary VSMCs were cultured and identified following with inflammatory stimuli by Escherichia coli lipopolysaccharide (LPS) for 30 minutes and 24 hours. The expression of Angptl2 were assessed by RT-qPCR and ELISA.ResultsThe mouse AAA model was successfully established after being induced by calcium chloride. The inflammatory cell infiltration in the arterial tissue of the mice in the experimental group was obvious, and the elastic fiber layer was thinned and broken. Immunohistochemical staining showed that the expression of Angptl2 in AAA was up-regulated; After LPS treatment, both the mRNA and protein expressions of Angptl2 were significantly up-regulated in VSMCs in the experimental group compared with control group.ConclusionAngptl2 expressed in VSMCs promotes the development of calcium chloride induced AAA.
Goldilocks calcium and the mitochondrial respiratory chain: too much, too little, just right
Authors: Vilas-Boas Eloisa A. , Cabral-Costa João Victor , Ramos Vitor M. , Caldeira da Silva Camille C. , Kowaltowski Alicia J. 
Published: April 2022

AbstractCalcium (Ca2+) is a key regulator in diverse intracellular signaling pathways, and has long been implicated in metabolic control and mitochondrial function. Mitochondria can actively take up large amounts of Ca2+, thereby acting as important intracellular Ca2+buffers and affecting cytosolic Ca2+transients. Excessive mitochondrial matrix Ca2+is known to be deleterious due to opening of the mitochondrial permeability transition pore (mPTP) and consequent membrane potential dissipation, leading to mitochondrial swelling, rupture, and cell death. Moderate Ca2+within the organelle, on the other hand, can directly or indirectly activate mitochondrial matrix enzymes, possibly impacting on ATP production. Here, we aimed to determine in a quantitative manner if extra or intramitochondrial Ca2+modulate oxidative phosphorylation in mouse liver mitochondria and intact hepatocyte cell lines. To do so, we monitored the effects of more modest versus supra-physiological increases in cytosolic and mitochondrial Ca2+on oxygen consumption rates. Isolated mitochondria present increased respiratory control ratios (a measure of oxidative phosphorylation efficiency) when incubated with low (2.4 ± 0.6 μM) and medium (22.0 ± 2.4 μM) Ca2+concentrations in the presence of complex I-linked substrates pyruvate plus malate and α-ketoglutarate, respectively, but not complex II-linked succinate. In intact cells, both low and high cytosolic Ca2+led to decreased respiratory rates, while ideal rates were present under physiological conditions. High Ca2+decreased mitochondrial respiration in a substrate-dependent manner, mediated by mPTP. Overall, our results uncover a Goldilocks effect of Ca2+on liver mitochondria, with specific “just right” concentrations that activate oxidative phosphorylation.
Optimal enzyme utilization suggests concentrations and thermodynamics favor condition-specific saturations and binding mechanisms
Authors: Sahin Asli , Weilandt Daniel Robert , Hatzimanikatis Vassily 
Published: April 2022

AbstractUnderstanding the dynamic responses of living cells upon genetic and environmental perturbations is crucial to decipher the metabolic functions of organisms. The rates of enzymatic reactions and their evolution are key to this understanding, as metabolic fluxes are limited by enzymatic activity. In this work, we investigate the optimal modes of operations for enzymes with regard that the evolutionary pressure drives enzyme kinetics toward increased catalytic efficiency. We use an efficient mixed-integer formulation to decipher the principles of optimal catalytic properties at various operating points. Our framework allows assessing the distribution of the thermodynamic forces and enzyme states, providing detailed insight into the mode of operation. Our results confirm earlier theoretical studies on the optimal kinetic design using a reversible Michaelis-Menten mechanism. The results further explored the optimal modes of operation for random-ordered multi-substrate mechanisms. We show that optimal enzyme utilization is achieved by unique or alternative modes of operations depending on the reactant’s concentrations. Our novel formulation allows investigating the optimal catalytic properties of all enzyme mechanisms with known elementary reactions. We propose that our novel framework provides the means to guide and evaluate directed evolution studies and estimate the limits of the direct evolution of enzymes.
Heterotypic Influenza Infections Mitigate Susceptibility to Secondary Bacterial Infection
Authors: Cipolla Ellyse M. , Yue Molin , Nickolich Kara L. , Huckestein Brydie R. , Antos Danielle E. , Chen Wei , Alcorn John F. 
Published: April 2022

AbstractInfluenza associated bacterial super-infections have devastating impacts on the lung and can result in increased risk of mortality. New strains of influenza circulate throughout the population yearly promoting the establishment of immune memory. Nearly all individuals have some degree of influenza memory prior to adulthood. Due to this we sought to understand the role of immune memory during bacterial super-infections. An influenza heterotypic immunity model was established using influenza A/PR/8/34 and A/X31. We report here that influenza experienced mice are more resistant to secondary bacterial infection with methicillin-resistant Staphylococcus aureus as determined by wasting, bacterial burden, pulmonary inflammation, and lung leak, despite significant ongoing lung remodeling. Multidimensional flow cytometry and lung transcriptomics revealed significant alterations in the lung environment in influenza-experienced mice compared with naïve animals. These include changes in the lung monocyte and T cell compartments, characterized by increased expansion of influenza tetramer specific CD8+ T cells. The protection that was seen in memory experienced mouse model is associated with the reduction in inflammatory mechanisms making the lung less susceptible to damage and subsequent bacterial colonization. These findings provide insight into how influenza heterotypic immunity re-shapes the lung environment and the immune response to a re-challenge event, which is highly relevant to the context of human infection.