bluuebunny/crossref_metadata_2025_split huggingface dataset:
Legacy effect of constant and diurnally oscillating temperatures on soil respiration and microbial community structure
Authors: Adekanmbi Adetunji Alex , Shu Xin , Zhou Yiran , Shaw Liz J. , Sizmur Tom 
Published: April 2021

1.0AbstractLaboratory incubation studies evaluating the temperature sensitivity of soil respiration often use measurements of respiration taken at a constant incubation temperature from soil that has been pre-incubated at the same constant temperature. However, such constant temperature incubations do not represent the field situation where soils undergo diurnal temperature oscillations. We investigated the effects of constant and diurnally oscillating temperatures on soil respiration and soil microbial community composition. A grassland soil from the UK was either incubated at a constant temperature of 5 °C, 10 °C, or 15 °C, or diurnally oscillated between 5 °C and 15 °C. Soil CO2flux was measured by temporarily moving incubated soils from each of the abovementioned treatments to 5 °C, 10 °C or 15 °C, such that soils incubated at each temperature had CO2flux measured at every temperature. We hypothesised that, irrespective of measurement temperature, CO2emitted from the 5 °C to 15 °C oscillating incubation would be most similar to the soil incubated at 10 °C. The results showed that both incubation and measurement temperatures influence soil respiration. Incubating soil at a temperature oscillating between 5 °C and 15 °C resulted in significantly greater CO2flux than constant incubations at 10 °C or 5 °C, but was not significantly different to the 15 °C incubation. The greater CO2flux from soils incubated at 15 °C, or oscillating between 5 °C and 15 °C, coincided with a depletion of dissolved organic carbon and a shift in the phospholipid fatty acid profile of the soil microbial community, consistent with the thermal adaptation of microbial communities to higher temperatures. However, diurnal temperature oscillation did not significantly alter Q10. Our results suggest that daily maximum temperatures are more important than daily minimum or daily average temperatures when considering the response of soil respiration to warming.
A specialized mRNA translation circuit instated in pluripotency presets the competence for cardiogenesis in humans
Authors: Bartsch Deniz , Kalamkar Kaustubh , Ahuja Gaurav , Lackmann Jan-Wilm , Bazzi Hisham , Clamer Massimiliano , Mendjan Sasha , Papantonis Argyris , Kurian Leo 
Published: April 2021

AbstractThe blueprints for developing organs are preset at the early stages of embryogenesis. Transcriptional and epigenetic mechanisms are proposed to preset developmental trajectories. However, we reveal that the competence for future cardiac fate of human embryonic stem cells (hESCs) is preset in pluripotency by a specialized mRNA translation circuit controlled by RBPMS. RBPMS is recruited to active ribosomes in hESCs to control the translation of essential factors needed for cardiac commitment program, including WNT signaling. Consequently, RBPMS loss specifically and severely impedes cardiac mesoderm specification leading to patterning and morphogenesis defects in human cardiac organoids. Mechanistically, RBPMS specializes mRNA translation, selectively via 3’UTR binding and globally by promoting translation initiation. Accordingly, RBPMS loss causes translation initiation defects highlighted by aberrant retention of the EIF3 complex and depletion of EIF5A from mRNAs, thereby abrogating ribosome recruitment. We reveal how future fate trajectories are preprogrammed during embryogenesis by specialized mRNA translation.Teaser: Cardiac fate competence is preprogrammed in pluripotency by specialized mRNA translation of factors initiating cardiogenesis
Optical bench simulation for intraocular lenses using field-tracing technology
Authors: Song Seok Ho , Song In Seok , Oh Se Jin , Son Hyeck-Soo , Kang Min Ho 
Published: April 2021

AbstractPurposeTo evaluate the image quality of intraocular lenses (IOLs) using field-tracing optical simulation and then compare it with the image quality using conventional ray-tracing simulation.MethodsWe simulated aspheric IOLs with a decenter, tilt, and no misalignment using an aspheric corneal eye model with a positive spherical aberration. The retinal image, Strehl ratio, and modulation transfer function (MTF) were compared between the ray-tracing and field-tracing optical simulation and confirmed by the results reported in anin vitroexperiment using the same eye model.ResultsThe retinal image showed interference fringes from target due to diffraction from the object in a field-tracing simulation. When compared with the experimental results, the field tracing represented the experimental results more precisely than ray tracing after passing over 400 µm of the decentration and 4 degrees of the tilt of the IOLs. The MTF values showed similar results for the case of no IOL misalignment in both the field tracing and ray tracing. In the case of the 200-µm decentration or 8-degree tilt of IOL, the field-traced MTF shows lower values than the ray-traced one.ConclusionsThe field-tracing optical bench simulation is a reliable method to evaluate IOL performance according to the IOL misalignment. It can provide retinal image quality close to real by taking into account the wave nature of light, interference and diffraction to explain to patients having the IOL misalignment.
Heterogeneity in Proline Hydroxylation of Fibrillar Collagens Observed by Mass Spectrometry
Authors: Kirchner Michele , Deng Haiteng , Xu Yujia 
Published: April 2021

AbstractCollagen is the major protein in the extracellular matrix and plays vital roles in tissue development and function. Collagen is also one of the most processed proteins in its biosynthesis. The most prominent post-translational modification (PTM) of collagen is the hydroxylation of Pro residues in the Y-position of the characteristic (Gly-Xaa-Yaa) repeating amino acid sequence of a collagen triple helix. Recent studies using mass-spectrometry (MS) and tandem MS sequencing (MS/MS) have revealed unexpected hydroxylation of Pro residues in the X-positions (X-Hyp). The newly identified X-Hyp residues appear to be highly heterogeneous in location and percent occupancy. In order to understand the dynamic nature of the new X-Hyps and their potential impact on applications of MS and MS/MS for collagen research, we sampled four different collagen samples using standard MS and MS/MS techniques. We found considerable variations in the degree of PTMs of the same collagen from different organisms and/or tissues. The rat tail tendon type I collagen is particularly variable in terms of both over-hydroxylation of Pro in the X-position and under-hydroxylation of Pro in the Y-position. In contrast, only a few unexpected PTMs in collagens type I and type III from human placenta were observed. The reproducibility of the different sequencing efforts of the same sample is also limited especially when the modified species are present at a low population, presumably due to the unpredictable nature of the ionization process. Additionally, despite the heterogeneous preparation and sourcing, collagen samples from commercial sources do not show elevated variations in PTMs compared to samples prepared from a single tissue and/or organism. These findings will contribute to the growing body of information regarding the PTMs of collagen by MS technology, and culminate to a more comprehensive understanding of the extent and the functional roles of the PTMs of collagen.Abbreviations pageBoth the single letter and the three letter abbreviations of an amino acid will be used with the following additions: Hyp or O stands for 4R-hydroxylated proline and 3Hyp stands for 3- hydroxylated proline. When needed for clarity, the lower case single letter abbreviation will be used to represent the genomic DNA sequence, and upper case ones the sequence seen in the peptides.
Selection in a growing bacterial/yeast colony biases results of mutation accumulation experiments
Authors: Mahilkar Anjali , Kemkar Sharvari , Saini Supreet 
Published: April 2021

AbstractMutations provide the raw material for natural selection to act. Therefore, understanding the variety and relative frequency of different type of mutations is critical to understanding the nature of genetic diversity in a population. Mutation accumulation (MA) experiments have been used in this context to estimate parameters defining mutation rates, distribution of fitness effects (DFE), and spectrum of mutations. MA experiments performed with organisms such asDrosophilahave an effective population size of one. However, in MA experiments with bacteria and yeast, a single founder is allowed to grow to a size of a colony (~108). The effective population size in these experiments is of the order of 10. In this scenario, while it is assumed that natural selection plays a minimal role in dictating the dynamics of colony growth and therefore, the MA experiment; this effect has not been tested explicitly. In this work, we simulate colony growth and perform an MA experiment, and demonstrate that selection ensures that, in an MA experiment, fraction of all mutations that are beneficial is over represented by a factor greater than two. The DFE of beneficial and deleterious mutations are accurately captured in an MA experiment. We show that the effect of selection in a growing colony varies non-monotonically and that, in the face of natural selection dictating an MA experiment, estimates of mutation rate of an organism is not trivial. We perform experiments with 160 MA lines ofE. coli, and demonstrate that rate of change of mean fitness is a non-monotonic function of the colony size, and that selection acts differently in different sectors of a growing colony. Overall, we demonstrate that the results of MA experiments need to be revisited taking into account the action of selection in a growing colony.
Photodynamic Inactivation reduces the diversity and changes the composition of bacterial and fungal communities associated with leaf surfaces
Authors: Junker Robert R. , Ohler Lisa-Maria , Hamminger Christoph , Plaetzer Kristjan 
Published: April 2021

AbstractPlant surfaces are colonized by a myriad of microorganisms including mutualistic strains and pathogens. Particularly in agricultural systems applications are required that protect the plants against pathogens without negative side effects on the environment and humans. Photodynamic Inactivation (PDI) has been demonstrated to be a promising approach to efficiently fight plant pathogens. Based on its mechanism of action, the light-induced and photosensitizer-mediated overproduction of reactive oxygen species in target cells, PDI is likely to generally inactivates microorganisms on plants irrespective of their pathogenicity. In order to prove this hypothesis we used next-generation 16S rRNA gene amplicon sequencing to characterize the bacterial and fungal communities associated with leaf surfaces ofArabidopsis thalianabefore and after the photodynamic treatment using the chlorine e6 derivative B17-0024 as photoactive compound and showed that this treatment reduced the microbial richness and altered the microbial community composition. These findings may help to develop effective pathogen-control strategies and may also stimulate research on plant-microbe interactions exploiting the potential of PDI.
Design, Synthesis and Evaluation of WD-repeat containing protein 5 (WDR5) degraders
Authors: Dölle Anja , Adhikari Bikash , Krämer Andreas , Weckesser Janik , Berner Nicola , Berger Lena-Marie , Diebold Mathias , Szewczyk Magdalena M. , Barsyte-Lovejoy Dalia , Arrowsmith Cheryl H. , Gebel Jakob , Löhr Frank , Dötsch Volker , Eilers Martin , Heinzlmeir Stephanie , Küster Bernhard , Sotriffer Christoph , Wolf Elmar , Knapp Stefan 
Published: April 2021

AbstractHistone H3K4 methylation serves as post-translational hallmark of actively transcribed genes and is introduced by histone methyltransferases (HMT) and its regulatory scaffolding proteins. One of these is the WD-repeat containing protein 5 (WDR5) that has also been associated with controlling long non-coding RNAs and transcription factors including MYC. The wide influence of dysfunctional HMTs complexes and the typically upregulated MYC levels in diverse tumor types suggested WDR5 as an attractive drug target. Indeed, protein-protein interface inhibitors for two protein interaction interfaces on WDR5 have been developed. While such compounds only inhibit a subset of WDR5 interactions, chemically induced proteasomal degradation of WDR5 might represent an elegant way to target all oncogenic function. This study presents the design, synthesis and evaluation of two diverse WDR5 degrader series based on two WIN site binding scaffolds and shows that linker nature and length strongly influence degradation efficacy.
Genomic loci mispositioning inTmem120aknockout mice yields latent lipodystrophy
Authors: Czapiewski Rafal , Batrakou Dzmitry G. , de las Heras Jose I. , Carter Roderick N. , Sivakumar Aishwarya , Sliwinska Magdalena , Dixon Charles R. , Webb Shaun , Lattanzi Giovanna , Morton Nicholas M. , Schirmer Eric C. 
Published: April 2021

AbstractLittle is known about the proteins that direct the highly conserved patterns of spatial genome organisation in fat. Here we report that adipocyte-specific knockout of the gene encoding nuclear envelope protein Tmem120a disrupts fat genome organisation, thus causing a novel lipodystrophy syndrome. Tmem120a deficiency broadly suppresses lipid metabolism pathway gene expression and induces myogenic gene expression by repositioning genes, enhancers and miRNA-encoding loci between the nuclear periphery and interior. Tmem120a-/-mice, particularly females, exhibit a lipodystrophy syndrome similar to human familial partial lipodystrophy FPLD2, with profound insulin resistance and metabolic defects that manifests upon exposure to an obesogenic diet. Interestingly, similar genome organisation defects occurred in cells from FPLD2 patients that harbour nuclear envelope protein laminA mutations. Our data suggest TMEM120A may mediate/instigate novel categories of adipose tissue dysfunction across the adiposity spectrum and provide a new miRNA-based mechanism possibly driving the unexplained muscle hypertrophy in human lipodystrophy.
Normalisr: normalization and association testing for single-cell CRISPR screen and co-expression
Authors: Wang Lingfei 
Published: April 2021

AbstractSingle-cell RNA sequencing (scRNA-seq) provides unprecedented technical and statistical potential to study gene regulation but is subject to technical variations and sparsity. Here we present Normalisr, a linear-model-based normalization and statistical hypothesis testing framework that unifies single-cell differential expression, co-expression, and CRISPR scRNA-seq screen analyses. By systematically detecting and removing nonlinear confounding from library size, Normalisr achieves high sensitivity, specificity, speed, and generalizability across multiple scRNA-seq protocols and experimental conditions with unbiased P-value estimation. We use Normalisr to reconstruct robust gene regulatory networks from trans-effects of gRNAs in large-scale CRISPRi scRNA-seq screens and gene-level co-expression networks from conventional scRNA-seq.
Wnt/β-catenin regulates alloreactive T cells for the treatment of hematological malignancies
Authors: Mammadli Mahinbanu , Harris Rebecca , Mahmudlu Sara , Verma Anjali , May Adriana , Dhawan Rohan , Waickman Adam T. , Sen Jyoti Misra , Karimi Mobin 
Published: April 2021

AbstractAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most widely applied forms of adaptive immunotherapy. Both the detrimental graft-versus-host disease (GVHD) and the beneficial graft-versus-leukemia (GVL) effects occurring after allo-HSCT are largely mediated by alloantigen-reactive donor T cells in the graft. Separating GVHD from GVL effects is a formidable challenge, and a greater understanding of donor T cell biology is required to accomplish the uncoupling of GVHD from GVL. Here, we tested a novel mouse model of β-catenin (Cat-Tg) in an allo-HSCT model. Our data show that T cells fromCat-Tgmice did not cause GVHD. Surprisingly,Cat-TgT cells maintained the GVL effect. Donor T cells fromCat-Tgmice exhibited significantly lower inflammatory cytokine production and reduced donor T cell proliferation, while upregulating cytotoxic mediators that resulted in enhanced cytotoxicity. RNA sequencing data revealed changes in the expression of over 150 genes for CD4, and over 250 genes for CD8+T cells involved in essential aspects of immune response and GVHD pathophysiology. Transgenic over-expression of human β-catenin primarily affects CD8+T cell phenotype. Altogether, our data suggest that β-catenin is a druggable target for developing therapeutic strategies to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.
Interactions between SARS-CoV-2 N-protein and α-synuclein accelerate amyloid formation
Authors: Semerdzhiev Slav A. , Fakhree Mohammad A. A. , Segers-Nolten Ine , Blum Christian , Claessens Mireille M. A. E. 
Published: April 2021

AbstractFirst cases that point at a correlation between SARS-CoV-2 infections and the development of Parkinson’s disease have been reported. Currently it is unclear if there also is a direct causal link between these diseases. To obtain first insights into a possible molecular relation between viral infections and the aggregation of α-synuclein protein into amyloid fibrils characteristic for Parkinson’s disease, we investigated the effect of the presence of SARS-CoV-2 proteins on α-synuclein aggregation. We show, in test tube experiments, that SARS-CoV-2 S-protein has no effect on α-synuclein aggregation while SARS-CoV-2 N-protein considerably speeds up the aggregation process. We observe the formation of multi-protein complexes, and eventually amyloid fibrils. Microinjection of N-protein in SHSY-5Y cells disturbed the α-synuclein proteostasis and increased cell death. Our results point toward direct interactions between the N-protein of SARS-CoV-2 and α-synuclein as molecular basis for the observed coincidence between SARS-CoV-2 infections and Parkinsonism.
Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease
Authors: Sugiyama Michael G. , Cui Haotian , Redka Dar’ya S. , Karimzadeh Mehran , Rujas Edurne , Maan Hassaan , Hayat Sikander , Cheung Kyle , Misra Rahul , McPhee Joseph B. , Viirre Russell D. , Haller Andrew , Botelho Roberto J. , Karshafian Raffi , Sabatinos Sarah A. , Fairn Gregory D. , Tonekaboni Seyed Ali Madani , Windemuth Andreas , Julien Jean-Philippe , Shahani Vijay , MacKinnon Stephen S. , Wang Bo , Antonescu Costin N. 
Published: April 2021

AbstractThe COVID-19 pandemic has led to an urgent need for the identification of new antiviral drug therapies that can be rapidly deployed to treat patients with this disease. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of COVID-19. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cellbased experimental assessment reveals several clinically-relevant repurposing drug candidates predicted by thein silicoanalyses to have antiviral activity against human coronavirus infection. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection, which can inform further drug discovery studies.
Lululemon Athletica
Authors: Tybout Alice M. 
Published: April 2021

The case traces the development of Lululemon Athletica (Lulu) from founder Chip Wilson's first post-yoga euphoria in 1997 through the sale of all his shares in 2015. Officially founded in 1998, Lulu was built on the foundation of its “miracle” figure-enhancing yoga pants made from a proprietary stretch fiber. The case outlines Wilson's early experience in technical performance wear, which gave him the expertise needed to launch the Lululemon brand with its premium-priced, fashion-designed product line targeted at upscale women. The case also highlights the retailing and promotion approach that drove Lulu's first decade of success. The snapshot of how the Lulu brand cult was born and diffused provides the backdrop for assessing whether the brand has already hit its peak or whether it can sustain the explosive growth that effectively created the athleisure category. To aid in this determination, the case presents two competitors as comparative foils (Under Armour and Athleta) to contextualize Lulu's growth prospects.
The Lululemon case highlights the importance of the competitive frame of reference when positioning a brand and describes how this may differ for the three competitors. The case also allows for a discussion of the challenges of maintaining the congruence of a retail brand with a diverse product line. This struggle is unique to retailers who must fit ever-varied product assortments (not just a single product line) under the umbrella of a single brand proposition, and is particularly relevant to vertically integrated brands such as Lululemon.
Best Buy: Creating a Winning Customer Experience in Consumer Electronics
Authors: Sawhney Mohanbir , Goodman Pallavi , Keerthivasan Ganesan 
Published: April 2021

After a successful run for many years as a resilient consumer electronics giant, Best Buy was under intense pressure at the end of 2014. Even as competitors like Circuit City melted away, Best Buy had been able to withstand the onslaught of online behemoth Amazon and discount retailers like Target and Walmart. However, its competitive position was threatened as online shopping became more popular, particularly among millennial customers.
With a new leadership team, Best Buy had recently undertaken bold initiatives to expand and refine its online presence and position itself for success. These initiatives had produced encouraging results, but Best Buy needed to do more to stem the loss of market share to Amazon and to become more relevant to millennial customers. To address these challenges, Best Buy approached the Kellogg School of Management to solicit ideas from student teams by sponsoring a Business Challenge competition. The teams came up with several strategic initiatives. Best Buy needed to evaluate these initiatives on two criteria: First, how well did these initiatives leverage Best Buy's privileged physical assets (stores, salespeople, and Geek Squad services staff) to create a winning customer experience? Second, how effective would these initiatives be in attracting and retaining millennial customers?