bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cactaceae: uses and knowledge of rural communities in the semi-arid zones of Cucaita, Ráquira and Villa de Leyva (Boyacá, Colombia)
Authors: Porras–Flórez Daniela , Albesiano Sofía , Hernández–Herrera Kendry , Gómez–Velázco Nubia , Arrieta–Violet Leopoldo 
Published: December 2020

AbstractTaxa of the family Cactaceae presents morphological and reproductive characteristics, which are used by rural communities in arid and semi-arid areas, for food, medicinal and ornamental purposes. The objectives were to identify the most used species and to relate the socioeconomic factors of the informants with their knowledge of the species. To this end, 262 semi-structured interviews were applied, with questions such as name, age, gender, educational level, source of employment, among others; eight categories of use were established: agro-ecological, agricultural, commercial, environmental service, food, medicinal, ornamental and technological; three indexes were calculated, relative importance, the value of use for each of the species and wealth of knowledge of the interviewees. Nine species are reported, from which eight are used as food and ornamental, standing outOpuntia ficus-indicafor its diversity of uses, whileCylindropuntia tunicatadoes not report any utility. Variables such as age and residence time showed a significant relationship with the number of plants used by the interviewees. It is expected to contribute to the preservation of cacti, local knowledge and encourage large-scale cultivation since species such asMammillaria columbiana, Melocactus andinus, andMelocactus curvispinusare being used in an unsustainable way, which could cause their local extinction.
Condensins are essential forPseudomonas aeruginosacorneal virulence through their control of phenotypic programs
Authors: Zhao Hang , Clevenger April L. , Coburn Phillip S. , Callegan Michelle C. , Rybenkov Valentin 
Published: December 2020

AbstractPseudomonas aeruginosais a significant opportunistic pathogen responsible for a variety of human infections. Its high pathogenicity resides in a diverse array of virulence factors and an ability to adapt to hostile environments. We report that these factors are tied to the activity of condensins, SMC and MksBEF, which primarily function in structural chromosome maintenance. This study revealed that both proteins are required forP. aeruginosavirulence during corneal infection. The reduction in virulence was traced to broad changes in gene expression. Transcriptional signatures ofsmcandmksBmutants were largely dissimilar and non-additive, with the double mutant displaying a distinct gene expression profile. Affected regulons included those responsible for lifestyle control, primary metabolism, surface adhesion and biofilm growth, iron and sulfur assimilation, and denitrification. Additionally, numerous virulence factors were affected, including type 3 and type 6 secretion systems, hemagglutinin, pyocin and macroglobulin production, and a host of virulence regulators.in vitroproperties of condensin mutants mirrored their transcriptional profiles. MksB-deficient cells were impaired in pyocyanin, c-di-GMP production, and sessile growth whereassmcmutants mildly upregulated c-di-GMP, secreted fewer proteases and were growth deficient under nutrient-limiting conditions. Moreover, condensin mutants displayed an abnormal regulation upon transition to stationary phase. These data reveal that condensins are integrated into the control of multiple genetic programs related to epigenetic and virulent behavior, establishing condensins as an essential factor inP. aeruginosaocular infections.Author SummaryBacterial pathogenicity is a complex phenomenon dependent on the ability of a bacterium to thrive in a hostile environment while combating the host using an array of virulence factors. This study reports that pathogenicity is also tied to structural chromosome maintenance through condensins, proteins that are responsible for the global organization of the chromosome. We show that the twoPseudomonas aeruginosacondensins, SMC and MksB, act as global regulators of gene expression. The inactivation of SMC and MksB induces opposite regulatory programs in the cell that resemble those observed during the acute and chronic phases of infection. A substantial portion of this regulation is mediated by the intracellular signaling network ofP. aeruginosa. Accordingly, virulence regulation is altered in condensin mutants. The results were validated by genetic, phenotypic and virulence studies of condensin mutants. Overall, these data establish condensins as an essential factor during ocularP. aeruginosainfections revealing their involvement in the regulatory virulence network and the control of the bacterial lifestyle.
Balancing the influenza neuraminidase and hemagglutinin responses by exchanging the vaccine virus backbone
Authors: Gao Jin , Wan Hongquan , Li Xing , Martinez Mira Rakic , Gao Yamei , Ye Zhiping , Daniels Robert 
Published: December 2020

AbstractVirions are a common antigen source for many viral vaccines. One limitation to using virions is that the antigen abundance is determined by the content of each protein in the virus. This caveat especially applies to viral-based influenza vaccines where the low abundance of the neuraminidase (NA) surface antigen remains a bottleneck for improving the NA antibody response. Here, we used the WHO recommended H1N1 antigens (2019-2020 season) in a systematic analysis to demonstrate that the NA to hemagglutinin (HA) ratio in virions can be improved by exchanging the viral backbone internal genes, thereby preserving the antigens. The purified inactivated virions with higher NA content show a more spherical morphology, a different balance between the HA receptor binding and NA receptor release functions, and induce a better NA inhibitory antibody response in mice. These results indicate that influenza viruses support a range of ratios for a given NA and HA pair that can be utilized to produce viral-based influenza vaccines with increased NA content which can elicit more balanced inhibitory antibody responses to NA and HA.
Mouse retinal specializations reflect knowledge of natural environment statistics
Authors: Qiu Yongrong , Zhao Zhijian , Klindt David , Kautzky Magdalena , Szatko Klaudia P. , Schaeffel Frank , Rifai Katharina , Franke Katrin , Busse Laura , Euler Thomas 
Published: December 2020

SummaryPressures for survival drive sensory circuit adaption to a species’ habitat, making it essential to statistically characterise natural scenes. Mice, a prominent visual system model, are dichromatic with enhanced sensitivity to green and UV. Their visual environment, however, is rarely considered. Here, we built a UV-green camera to record footage from mouse habitats. We found chromatic contrast to greatly diverge in the upper but not the lower visual field, an environmental difference that may underlie the species’ superior colour discrimination in the upper visual field. Moreover, training an autoencoder on upper but not lower visual field scenes was sufficient for the emergence of colour-opponent filters. Furthermore, the upper visual field was biased towards dark UV contrasts, paralleled by more light-offset-sensitive cells in the ventral retina. Finally, footage recorded at twilight suggests that UV promotes aerial predator detection. Our findings support that natural scene statistics shaped early visual processing in evolution.Lead contactFurther information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Thomas Euler (thomas.euler@cin.uni-tuebingen.de)
A Quantitative Measurement to Describe the Relative Proximity of Fluorescent Biomarkers
Authors: Dyer Joshua D. , Brown Alan R. , Owen Alex , Metz Jeremy 
Published: December 2020

AbstractDetermining the relationship between biomarkers via fluorescence microscopy is a key step in the characterisation of cellular phenotypes. We define a simple distance-based measurement termed a perimeter distance mean (PDmean) which quantifies the relative proximity of objects in one fluorescent channel to objects in a second fluorescent channel in 2D or 3D microscopy datasets. PDmeanmeasurements were able to accurately identify known changes in colocalisation in computer-generated and real-world microscopy datasets. We argue that this approach provides substantial advantages over currently used distance-based colocalisation analysis methods. We also introduce PyBioProx, an extensible open-source Python module and graphical user interface that produces PDmeanmeasurements.
Data-informed discovery of hydrolytic nanozymes
Authors: Li Sirong , Zhou Zijun , Tie Zuoxiu , Wang Bing , Ye Meng , Du Lei , Cui Ran , Liu Wei , Wan Cuihong , Liu Quanyi , Zhao Sheng , Wang Quan , Zhang Yihong , Zhang Shuo , Zhang Huigang , Du Yan , Wei Hui 
Published: December 2020

AbstractNanozyme is a collection of nanomaterials with enzyme-like activity but exhibits higher environmental tolerance and long-term stability than their natural counterparts. Improving the catalytic activity and expanding the category of nanozymes are prerequisites to complement or even supersede natural enzymes. Specifically, a powerful hydrolytic nanozyme is demanded to degrade the unsustainable substance which natural enzymes hardly achieve. However, the development of hydrolytic nanozymes is still hindered by diverse hydrolytic substrates and following complicated mechanisms. Here, we apply two strategies which are informed by data to screen and predict catalytic active sites of MOF (metal–organic framework) based hydrolytic nanozymes. One is to increase the intrinsic activity by finely tuned Lewis acidity of the metal clusters. The other is to adjust the volume density of the active sites by shortening the length of ligands. Finally, we construct a Ce-FMA-MOF-based hydrolytic nanozyme with robust cleavage ability towards phosphate bonds, amide bonds, glycosidic bonds whose energy ascend in order; and even their mixture, biofilms. This work provides a rational methodology to design hydrolytic nanozyme, enriches the diversity of nanozymes, and potentially sheds a light on the evolution of enzyme engineering in the future.
Epithelial-to-mesenchymal transition activates Bcat1 expression to promote recurrent tumor growth
Authors: Fox Douglas B. , Alvarez James V. 
Published: December 2020

AbstractBranched-chain amino acid metabolism has emerged as a crucial regulator of tumor proliferation. In particular, the branched-chain amino acid transaminase 1 (BCAT1), which catalyzes the conversion of branched-chain amino acids to α-keto acids in the cytoplasm, has been identified as a promising therapeutic target for several different cancer types, including gliomas and leukemias. BCAT1 expression has also been associated with resistance to anti-estrogen therapy in breast cancer, suggesting a role in therapeutic resistance and tumor progression. Yet a functional role for BCAT1 in promoting breast cancer recurrence has not been described. Further, BCAT1 expression is restricted to just a few specialized tissues, such as the testes and central nervous system, and the mechanism by which it becomes transcriptionally activated in tumors that arise from tissues that do not typically express BCAT1 is unclear. Here, we report that Bcat1 is upregulated in recurrent breast tumors to promote recurrent tumor growth. We find that Bcat1 is upregulated by the epithelial-to-mesenchymal transition (EMT) in mammary epithelial cells and breast cancer cells. Finally, we analyze human tumor datasets to show that BCAT1 expression is strongly correlated with epithelial-to-mesenchymal gene signatures, suggesting that EMT is the predominant regulator of BCAT1 expression in cancer. Because EMT is associated with therapy resistance, metastasis, and tumor recurrence, these findings suggest a broad clinical potential for BCAT1 inhibition.
Unusual Features of the Membrane Kinome ofTrypanosoma brucei
Authors: Jensen Bryan C. , Vaney Pashmi , Flaspohler John , Coppens Isabelle , Parsons Marilyn 
Published: December 2020

AbstractIn many eukaryotes, multiple protein kinases are situated in the plasma membrane where they respond to extracellular ligands. Ligand binding elicits a signal that is transmitted across the membrane, leading to activation of the cytosolic kinase domain. Humans have over 100 receptor protein kinases. In contrast, our search of theTrypanosoma bruceikinome showed that there were only ten protein kinases with predicted transmembrane domains, and unlike other eukaryotic transmembrane kinases, seven are predicted to bear multiple transmembrane domains. Most of the ten kinases, including their transmembrane domains, are conserved in bothTrypanosoma cruziandLeishmaniaspecies. Several possess accessory domains, such as Kelch, nucleotide cyclase, and forkhead-associated domains. Surprisingly, two contain multiple regions with predicted structural similarity to domains in bacterial signaling proteins. A few of the protein kinases have previously been localized to subcellular structures such as endosomes or lipid bodies. We examine here the localization of epitope-tagged versions of seven of the predicted transmembrane kinases inT. bruceibloodstream forms and show that five localized to the endoplasmic reticulum. The last two kinases are integral membrane proteins associated with the flagellum, flagellar pocket, or adjacent structures, as shown by both fluorescence and immunoelectron microscopy. Thus, these kinases are positioned in structures suggesting participation in signal transduction from the external environment.
Persistent Cellular Immunity to SARS-CoV-2 Infection
Authors: Breton Gaëlle , Mendoza Pilar , Hagglof Thomas , Oliveira Thiago Y. , Schaefer-Babajew Dennis , Gaebler Christian , Turroja Martina , Hurley Arlene , Caskey Marina , Nussenzweig Michel C. 
Published: December 2020

AbstractSARS-CoV-2 is responsible for an ongoing pandemic that affected millions of individuals around the globe. To gain further understanding of the immune response in recovered individuals we measured T cell responses in paired samples obtained an average of 1.3 and 6.1 months after infection from 41 individuals. The data indicate that recovered individuals show persistent polyfunctional SARS-CoV-2 antigen specific memory that could contribute to rapid recall responses. In addition, recovered individuals show enduring immune alterations in relative numbers of CD4+and CD8+T cells, expression of activation/exhaustion markers, and cell division.SummaryWe show that SARS-CoV-2 infection elicits broadly reactive and highly functional memory T cell responses that persist 6 months after infection. In addition, recovered individuals show enduring immune alterations in CD4+and CD8+T cells compartments.
The effects of multi-echo fMRI combination and rapidT2*-mapping on offline and real-time BOLD sensitivity
Authors: Heunis Stephan , Breeuwer Marcel , Caballero-Gaudes César , Hellrung Lydia , Huijbers Willem , Jansen Jacobus FA , Lamerichs Rolf , Zinger Svitlana , Aldenkamp Albert P 
Published: December 2020

AbstractA variety of strategies are used to combine multi-echo functional magnetic resonance imaging (fMRI) data, yet recent literature lacks a systematic comparison of the available options. Here we compare six different approaches derived from multi-echo data and evaluate their influences on BOLD sensitivity for offline and in particular real-time use cases: a single-echo time series (based on Echo 2), the real-timeT2*-mapped time series (T2*FIT) and four combined time series (T2*-weighted, tSNR-weighted, TE-weighted, and a new combination scheme termedT2*FIT-weighted). We compare the influences of these six multi-echo derived time series on BOLD sensitivity using a healthy participant dataset (N=28) with four task-based fMRI runs and two resting state runs. We show that theT2*FIT-weighted combination yields the largest increase in temporal signal-to-noise ratio across task and resting state runs. We demonstrate additionally for all tasks that theT2*FITtime series consistently yields the largest offline effect size measures and real-time region-of-interest based functional contrasts. These improvements show the possible utility of multi-echo fMRI for studies employing real-time paradigms, while caution is still advised due to decreased tSNR of theT2*FITtime series. We recommend the use and continued exploration ofT2*FITfor offline task-based and real-time fMRI analysis. Supporting information includes: a data repository (https://dataverse.nl/dataverse/rt-me-fmri), an interactive web-based application to explore the data (https://rt-me-fmri.herokuapp.com/), and further materials and code for reproducibility (https://github.com/jsheunis/rt-me-fMRI).
Single dose immunization with a COVID-19 DNA vaccine encoding a chimeric homodimeric protein targeting receptor binding domain (RBD) to antigen-presenting cells induces rapid, strong and long-lasting neutralizing IgG, Th1 dominated CD4+T cells and strong CD8+T cell responses in mice
Authors: Norheim Gunnstein , Stubsrud Elisabeth , Skullerud Lise Madelene , Stankovic Branislava , Chellappa Stalin , Bjerkan Louise , Kuczkowska Katarzyna , Müller Elisabeth , Sekelja Monika , Fredriksen Agnete B. 
Published: December 2020

AbstractThe pandemic caused by the SARS-CoV-2 virus in 2020 has led to a global public health emergency, and non-pharmaceutical interventions required to limit the viral spread are severely affecting health and economies across the world. A vaccine providing rapid and persistent protection across populations is urgently needed to prevent disease and transmission. We here describe the development of novel COVID-19 DNA plasmid vaccines encoding homodimers consisting of a targeting unit that binds chemokine receptors on antigen-presenting cells (human MIP-1α /LD78β), a dimerization unit (derived from the hinge and CH3 exons of human IgG3), and an antigenic unit (Spike or the receptor-binding domain (RBD) from SARS-CoV-2). The candidate encoding the longest RBD variant (VB2060) demonstrated high secretion of a functional protein and induced rapid and dose-dependent RBD IgG antibody responses that persisted up to at least 3 months after a single dose of the vaccine in mice. Neutralizing antibody (nAb) titers against the live virus were detected from day 7 after one dose. All tested dose regimens reached titers that were higher or comparable to those seen in sera from human convalescent COVID-19 patients from day 28. T cell responses were detected already at day 7, and were subsequently characterized to be multifunctional CD8+and Th1 dominated CD4+T cells. Responses remained at sustained high levels until at least 3 months after a single vaccination, being further strongly boosted by a second vaccination at day 89. These findings, together with the simplicity and scalability of plasmid DNA manufacturing, safety data on the vaccine platform in clinical trials, low cost of goods, data indicating potential long term storage at +2° to 8°C and simple administration, suggests the VB2060 candidate is a promising second generation candidate to prevent COVID-19.
Adaptation of a fluoroquinolone-sensitiveShigella sonneito norfloxacin exposure
Authors: Wong Bao Chi , Law Soffi Kei Kei , Md Zoqratt Muhammad Zarul Hanifah , Ayub Qasim , Tan Hock Siew 
Published: December 2020

1.SummaryShigellacauses shigellosis that requires antibiotic treatment in severe cases. Sub-lethal antibiotic concentrations can promote resistance, but their effect on antibiotic-sensitive bacteria before resistance development is unknown. This study investigated the effects of sublethal norfloxacin (NOR) challenges on a norfloxacin-sensitive strain,Shigella sonneiUKMCC1015. Firstly, the whole genome ofS. sonneiUKMCC1015 was assembled, and 45 antimicrobial resistance (AMR) genes were identified. However, transcriptomic analysis showed that low NOR levels do not change the expression of AMR genes and norfloxacin targets. Instead, multiple ribosomal protein genes were downregulated, which could be attributed to decreased ribosomal protein promoter activity, modulated by elevated ppGpp levels. This alarmone is involved in the bacterial stringent response during environmental stress, and it is mainly produced from the ppGpp synthetase (relA). However, high levels of ppGpp (due torelAoverexpression) are detrimental to the continued survival ofS. sonneiduring prolonged exposure to NOR. This study revealed that a norfloxacin-sensitive strain responds differently to sub-lethal NOR than commonly reported in resistant strains. Overexpression ofrelA(high ppGpp levels) may reduce the mutability ofS. sonneiUKMCC1015 in response to NOR exposure and affect NOR tolerance.
Quantitative 3D Imaging of the Cranial Microvascular Environment at Single-Cell Resolution
Authors: Rindone Alexandra N. , Liu Xiaonan , Farhat Stephanie , Perdomo-Pantoja Alexander , Witham Timothy F. , Coutu Daniel L. , Wan Mei , Grayson Warren L. 
Published: December 2020

AbstractVascularization is critical for skull development, maintenance, and healing. Yet, there remains a significant knowledge gap in the relationship of blood vessels to cranial skeletal progenitors during these processes. Here, we introduce a quantitative 3D imaging platform to enable visualization and analysis of high-resolution datasets (>100 GB) throughout the entire murine calvarium. Using this technique, we provide single-cell resolution 3D maps of vessel phenotypes and skeletal progenitors in the frontoparietal cranial bones. Through these high-resolution datasets, we demonstrate that CD31hiEmcnhivessels are spatially correlated with both Osterix+ and Gli1+ skeletal progenitors during postnatal growth, healing, and stimulated remodeling, and are concentrated at transcortical canals and osteogenic fronts. Interestingly, this relationship was weakened in mice with a conditional knockout of PDGF-BB in TRAP+ osteoclasts, suggesting a potential role for osteoclasts in maintaining the native cranial microvascular environment. Our findings provide a foundational framework for understanding how blood vessels and skeletal progenitors spatially interact in cranial bone, and will enable more targeted studies into the mechanisms of skull disease pathologies and treatments. Additionally, our technique can be readily adapted to study numerous cell types and investigate other elusive phenomena in cranial bone biology.
Global Age-Specific Patterns of Cyclic Gene Expression Revealed by Tunicate Transcriptome Atlas
Authors: Voskoboynik Yotam , Glina Aidan , Kowarsky Mark , Anselmi Chiara , Neff Norma F , Ishizuka Katherine J , Palmeri Karla J , Rosental Benyamin , Gordon Tal , Quake Stephen R , Weissman Irving L , Ben-Shlomo Rachel , Sahoo Debashis , Voskoboynik Ayelet 
Published: December 2020

AbstractExpression levels of circadian clock genes, which regulate 24-hour rhythms of behavior and physiology, have been shown to change with age. However, a study holistically linking aging and circadian gene expression is missing. Using the colonial chordateBotryllus schlosseri, we combined transcriptome sequencing and stem cell-mediated aging phenomena to test how circadian gene expression changes with age. This revealed thatB. schlossericlock and clock-controlled genes oscillate organism-wide, with daily, age-specific amplitudes and frequencies. These age-related, circadian patterns persist at the tissue level, where dramatic variations in cyclic gene expression of tissue profiles link to morphological and cellular aging phenotypes. Similar cyclical expression differences were found in hundreds of pathways associated with known hallmarks of aging, as well as pathways that were not previously linked to aging. The atlas we developed points to alterations in circadian gene expression as a key regulator of aging.One Sentence SummaryThe Ticking Clock: Systemic changes in circadian gene expression correlates with wide-ranging phenotypes of aging