bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of an alpha helix and a cysteine-cysteine disulfide bond on the resistance of bacterial adhesion pili to stress
Authors: Baker Joseph L. , Dahlberg Tobias , Bullitt Esther , Andersson Magnus 
Published: January 2021

Escherichia coliexpress adhesion pili that mediate attachment to host cell surfaces that are exposed to body fluids in the urinary and gastrointestinal tracts. Pilin subunits are organized into helical polymers, with a tip adhesin for specific host binding. Pili can elastically unwind when exposed to fluid flow force, reducing the adhesin load, thereby facilitating sustained attachment. Here we investigate biophysical and structural differences of pili commonly expressed on bacteria that inhabit the urinary and intestinal tracts. Optical tweezers measurements reveal that Class 1 pili of uropathogenicE. coli(UPEC), as well as Class 1b of enterotoxigenicE. coli(ETEC), undergo an additional conformational change beyond pilus unwinding, providing significantly more elasticity to their structure than ETEC Class 5 pili. Looking comprehensively at structural and steered molecular dynamics simulation data, we find this difference in Class 1 pili subunit behavior originates from anα-helical motif that can unfold when exposed to force. A disulfide bond cross-linkingβ-strands in Class 1 pili stabilizes subunits, allowing them to tolerate higher forces than Class 5 pili that lack this covalent bond. We suggest that these extra contributions to pilus resiliency are relevant for the UPEC niche since resident bacteria are exposed to stronger, more transient shear forces compared to those experienced by ETEC bacteria in the mucosa of the intestinal tract. Interestingly, Class 1b ETEC pili include the same structural features seen in UPEC pili, while requiring lower unwinding forces that are more similar to those of Class 5 ETEC pili.Significance StatementAdhesion pili are often essential virulence factors for attachment of pathogenic bacteria in specific environmental niches. We provide mechanistic details of structural differences impacting the biophysical properties of pili found on bacteria in the urinary and intestinal tracts. We see that pili from urinary tract bacteria are composed of subunits optimized for their microenvironment. First, they can tolerate higher forces than intestinal pili due to a disulfide bond that limits subunit unfolding. Second, their greater flexibility is due to anα-helical motif that can unfold, absorbing force that could otherwise lead to bacteria detachment. Our work provides insight into the central role of pilus structural and biophysical properties for the sustained bacterial adherence necessary to initiate disease.
Empirical abundance distributions are more uneven than expected given their statistical baseline
Authors: Diaz Renata M. , Ye Hao , Ernest S. K. Morgan 
Published: January 2021

AbstractExploring and accounting for the emergent properties of ecosystems as complex systems is a promising horizon in the search for general processes to explain common ecological patterns. For example, the ubiquitous hollow-curve form of the species abundance distribution is frequently assumed to reflect ecological processes structuring communities, but can also emerge as a statistical phenomenon from the mathematical definition of an abundance distribution. Although the hollow curve may be a statistical artefact, ecological processes may induce subtle deviations between empirical species abundance distributions and their statistically most probable forms. These deviations may reflect biological processes operating on top of mathematical constraints and provide new avenues for advancing ecological theory. Examining ∼22,000 communities, we found that empirical SADs are highly uneven and dominated by rare species compared to their statistical baselines. Efforts to detect deviations may be less informative in small communities – those with few species or individuals – because these communities have poorly-resolved statistical baselines. The uneven nature of many empirical SADs demonstrates a path forward for leveraging complexity to understand ecological processes governing the distribution of abundance, while the issues posed by small communities illustrate the limitations of using this approach to study ecological patterns in small samples.
Simultaneous single cell measurements of intranuclear proteins and gene expression
Authors: Chung Hattie , Parkhurst Christopher N. , Magee Emma M. , Phillips Devan , Habibi Ehsan , Chen Fei , Yeung Bertrand , Waldman Julia , Artis David , Regev Aviv 
Published: January 2021

AbstractIdentifying gene regulatory targets of nuclear proteins in tissues remains a challenge. Here we describeintranuclearCellularIndexing ofTranscriptomes andEpitopes (inCITE-seq), a scalable method for measuring multiplexed intranuclear protein levels and the transcriptome in parallel in thousands of cells, enabling joint analysis of TF levels and gene expressionin vivo. We apply inCITE-seq to characterize cell state-related changes upon pharmacological induction of neuronal activity in the mouse brain. Modeling gene expression as a linear combination of quantitative protein levels revealed the genome-wide effect of each TF and recovered known targets. Cell type-specific genes associated with each TF were co-expressed as distinct modules that each corresponded to positive or negative TF levels, showing that our approach can disentangle relative contributions of TFs to gene expression and add interpretability to gene networks. InCITE-seq can illuminate how combinations of nuclear proteins shape gene expression in native tissue contexts, with direct applications to solid or frozen tissues and clinical specimens.
Low cost and sustainable hyaluronic acid production in a manufacturing platform based onBacillus subtilis3NA strain
Authors: Cerminati Sebastián , Leroux Mélanie , Anselmi Pablo , Peirú Salvador , Alonso Juan C. , Priem Bernard , Menzella Hugo G. 
Published: January 2021

AbstractHyaluronic acid (HA) is a high value glycosaminoglycan mostly used in health and cosmetic applications. Commercial HA is produced from animal tissues or in toxigenic bacteria of the genusStreptococcusgrown in complex media, which are expensive and raise environmental concerns due to the disposal of large amounts of broth with high organic loads. Other microorganisms were proposed as hosts for the heterologous production of HA, but the methods are still costly. The extraordinary capacity of this biopolymer to bind and retain water attracts interest for large scale applications where biodegradable materials are needed, but its high cost and safety concerns are barriers for its adoption.Bacillus subtilis3NA strain is prototrophic, amenable for genetic manipulation, GRAS, and can rapidly reach high cell densities in salt-based media. These phenotypic traits were exploited to create a platform for biomolecule production using HA as a proof of concept. First, the 3NA strain was engineered to produce HA; second, a chemically defined medium was formulated using commodity-priced inorganic salts combined at the stoichiometric ratios needed to build the necessary quantities of biomass and HA; and third, a scalable fermentation process, where HA can be produced at the maximum volumetric productivity (VP), was designed.A comparative economic analysis against other methods indicates that the new process may increase the operating profit of a manufacturing plant by more than 100 %. The host, the culture medium, and the rationale employed to develop the fermentation process described here, introduce an IP free platform that could be adaptable for production of other biomolecules.Key PointsA platform for the production of biomolecules was designed based onB. subtilis3NA, a chemically defined medium and a fermentation process.As proof of concept, high quality hyaluronic acid was produced with an environmentally friendly process.A techno-economic analysis indicates that the process is more that 100% profitable than current methods.
Fundamental identifiability limits in molecular epidemiology
Authors: Louca Stilianos , McLaughlin Angela , MacPherson Ailene , Joy Jeffrey B. , Pennell Matthew W. 
Published: January 2021

AbstractViral phylogenies provide crucial information on the spread of infectious diseases, and many studies fit mathematical models to phylogenetic data to estimate epidemiological parameters such as the effective reproduction ratio (Re) over time. Such phylodynamic inferences often complement or even substitute for conventional surveillance data, particularly when sampling is poor or delayed. It remains generally unknown, however, how robust phylodynamic epidemiological inferences are, especially when there is uncertainty regarding pathogen prevalence and sampling intensity. Here we use recently developed mathematical techniques to fully characterize the information that can possibly be extracted from serially collected viral phylogenetic data, in the context of the commonly used birth-death-sampling model. We show that for any candidate epidemiological scenario, there exist a myriad of alternative, markedly different and yet plausible “congruent” scenarios that cannot be distinguished using phylogenetic data alone, no matter how large the dataset. In the absence of strong constraints or rate priors across the entire study period, neither maximum-likelihood fitting nor Bayesian inference can reliably reconstruct the true epidemiological dynamics from phylogenetic data alone; rather, estimators can only converge to the “congruence class” of the true dynamics. We propose concrete and feasible strategies for making more robust epidemiological inferences from viral phylogenetic data.
Python-Microscope: A new open source Python library for the control of microscopes
Authors: Pinto David Miguel Susano , Phillips Mick A , Hall Nicholas , Mateos–Langerak Julio , Stoychev Danail , Pinto Tiago Susano , Booth Martin J , Davis Ilan , Dobbie Ian M 
Published: January 2021

AbstractCustom built microscopes often require control of multiple hardware devices and precise hardware coordination. It is also desirable to have a solution that is scalable to complex systems and translatable between components from different manufacturers. Here we report Python-Microscope, a free and open source Python library for high performance control of arbitrarily complex and scalable custom microscope systems. Python-Microscope offers simple to use Python-based tools, abstracting differences between physical devices by providing a defined interface for different device types. Concrete implementations are provided for a range of specific hardware and a framework exists for further expansion. Python-Microscope supports the distribution of devices over multiple computers while maintaining synchronisation via highly precise hardware triggers. We discuss the architecture choices of Python-Microscope that overcome the performance problems often raised against Python and demonstrate the different use cases that drove its design: its integration in user facing projects, namely in the Microscope-Cockpit project; in controlling complex microscopes at high speed while using the Python programming language; and as a microscope simulation tool for software development.
Experimental re-infected cats do not transmit SARS-CoV-2
Authors: Gaudreault Natasha N. , Carossino Mariano , Morozov Igor , Trujillo Jessie D. , Meekins David A. , Madden Daniel W. , Cool Konner , Artiaga Bianca Libanori , McDowell Chester , Bold Dashzeveg , Balaraman Velmurugan , Kwon Taeyong , Ma Wenjun , Henningson Jamie , Wilson Dennis W. , Wilson William C. , Balasuriya Udeni B. R. , García-Sastre Adolfo , Richt Juergen A. 
Published: January 2021

AbstractSARS-CoV-2 is the causative agent of COVID-19 and responsible for the current global pandemic. We and others have previously demonstrated that cats are susceptible to SARS-CoV-2 infection and can efficiently transmit the virus to naïve cats. Here, we address whether cats previously exposed to SARS-CoV-2 can be re-infected with SARS-CoV-2. In two independent studies, SARS-CoV-2-infected cats were re-challenged with SARS-CoV-2 at 21 days post primary challenge (DPC) and necropsies performed at 4, 7 and 14 days post-secondary challenge (DP2C). Sentinels were co-mingled with the re-challenged cats at 1 DP2C. Clinical signs were recorded, and nasal, oropharyngeal, and rectal swabs, blood, and serum were collected and tissues examined for histologic lesions. Viral RNA was transiently shed via the nasal, oropharyngeal and rectal cavities of the re-challenged cats. Viral RNA was detected in various tissues of re-challenged cats euthanized at 4 DP2C, mainly in the upper respiratory tract and lymphoid tissues, but less frequently and at lower levels in the lower respiratory tract when compared to primary SARS-CoV-2 challenged cats at 4 DPC. Histologic lesions that characterized primary SARS-CoV-2 infected cats at 4 DPC were absent in the re-challenged cats. Naïve sentinels co-housed with the re-challenged cats did not shed virus or seroconvert. Together, our results indicate that cats previously infected with SARS-CoV-2 can be experimentally re-infected with SARS-CoV-2; however, the levels of virus shed was insufficient for transmission to co-housed naïve sentinels. We conclude that SARS-CoV-2 infection in cats induces immune responses that provide partial, non-sterilizing immune protection against reinfection.
mmSIM: An open toolbox for accessible structured illumination microscopy
Authors: Russell Craig T. , Shaw Michael 
Published: January 2021

SummarySince the first practical super-resolution structured illumination fluorescence microscopes (SIM) were demonstrated more than two decades ago the method has become increasingly popular for a wide range of bioimaging applications. The high cost and relative inflexibility of commercial systems, coupled with the conceptual simplicity of the approach and the desire to exploit and customise existing hardware, have led to the development of a large number of home-built systems. Several detailed hardware designs are available in the scientific literature, complemented by open-source software tools for SIM image validation and reconstruction. However, there remains a lack of simple open-source software to control these systems and manage the synchronization between hardware components, which is critical for effective SIM imaging. This article describes a new suite of software tools based on the popular Micro-Manager package, which enable the keen microscopist to develop and run a SIM system. We use the software to control two custom-built, high-speed, spatial light modulator-based SIM systems, evaluating their performance by imaging a range of fluorescent samples. By simplifying the process of SIM hardware development, we aim to support wider adoption of the technique.
ΔFBA: Predicting metabolic flux alterations using genome-scale metabolic models and differential transcriptomic data
Authors: Ravi Sudharshan , Gunawan Rudiyanto 
Published: January 2021

AbstractGenome-scale metabolic models (GEMs) provide a powerful framework for simulating the entire set of biochemical reactions occurring in a cell. Constraint-based modeling tools like flux balance analysis (FBA) developed for the purposes of predicting metabolic flux distribution using GEMs face considerable difficulties in estimating metabolic flux alterations between experimental conditions. Particularly, the most appropriate metabolic objective for FBA is not always obvious, likely context-specific, and not necessarily the same between conditions. Here, we propose a new method, called ΔFBA (deltaFBA), that employs constraint-based modeling, in combination with differential gene expression data, to evaluate changes in the intracellular flux distribution between two conditions. Notably, ΔFBA does not require specifying the cellular objective to produce the flux change predictions. We showcased the performance of ΔFBA through several case studies involving the prediction of metabolic alterations caused by genetic and environmental perturbations inEscherichia coliand caused by Type-2 diabetes in human muscle.
Drosophilare-zero their path integrator at the center of a fictive food patch
Authors: Behbahani Amir H. , Palmer Emily H. , Corfas Román A. , Dickinson Michael H. 
Published: January 2021

SUMMARYThe ability to keep track of one’s location in space is a critical behavior for animals navigating to and from a salient location, and its computational basis is now beginning to be unraveled. Here, we tracked flies in a ring-shaped channel as they executed bouts of search triggered by optogenetic activation of sugar receptors. Unlike experiments in open field arenas, which produce highly tortuous search trajectories, our geometrically constrained paradigm enabled us to monitor flies’ decisions to move toward or away from the fictive food. Our results suggest that flies use path integration to remember the location of a food site even after it has disappeared, and that flies can remember the location of a former food site even after walking around the arena one or more times. To determine the behavioral algorithms underlyingDrosophilasearch, we developed multiple state transition models and found that flies likely accomplish path integration by combining odometry and compass navigation to keep track of their position relative to the fictive food. Our results indicate that whereas flies re-zero their path integrator at food when only one feeding site is present, they adjust their path integrator to a central location between sites when experiencing food at two or more locations. Together, this work provides a simple experimental paradigm and theoretical framework to advance investigations of the neural basis of path integration.
Molecular programs of fibrotic change in aging human lung
Authors: Lee Jasmine , Islam Mohammad Naimul , Boostanpour Kaveh , Aran Dvir , Christenson Stephanie , Matthay Michael A. , Eckalbar Walter , DePianto Daryle J. , Arron Joseph R. , Magee Liam , Bhattacharya Sunita , Matsumoto Rei , Kubota Masaru , Farber Donna L. , Bhattacharya Jahar , Wolters Paul J. , Bhattacharya Mallar 
Published: January 2021

AbstractAging is associated with both overt and subclinical lung fibrosis, which increases risk for mortality from viruses and other respiratory pathogens. The molecular programs that induce fibrosis in the aging lung are not well understood. To overcome this knowledge gap, we undertook multimodal profiling of distal lung samples from healthy human donors across the lifespan. Telomere shortening, a cause of cell senescence and fibrosis, was progressive with age in a sample of 86 lungs and was associated with foci of DNA damage. Bulk RNA sequencing confirmed activation of cellular senescence and pro-fibrotic pathways as well as genes necessary for collagen processing with increasing age. These findings were validated in independent datasets for lung and sun-exposed skin, but not other organs including heart, liver and kidney. Cell type deconvolution analysis revealed a progressive loss of lung epithelial cells and an increasing proportion of fibroblasts. Consistent with the observed pro-fibrotic transcriptional profile, second harmonic imaging demonstrated increased density of interstitial collagen in aged human lungs. Furthermore, regions of parenchymal fibrosis were associated with decreased alveolar expansion and surfactant secretion. These findings reveal the transcriptional and structural features of fibrosis and associated physiologic impairments in normal lung aging.
Biceps femoris long head sarcomere and fascicle length adaptations after three weeks of eccentric exercise training
Authors: Pincheira Patricio A. , Boswell Melissa A. , Franchi Martino V. , Delp Scott L. , Lichtwark Glen A. 
Published: January 2021

AbstractPurposeEccentric exercise is widely used to increase muscle fascicle lengths and thus decrease the risk of muscle strain injuries. However, the mechanisms behind this protection are still unknown. The aim of this study was to determine whether Biceps femoris long head (BFlh) fascicle length increases in response to three weeks of eccentric exercise training are the result of addition of in-series sarcomeres within muscle fibres.MethodsTen recreationally active participants (age: 27 ± 3 years, mass: 70 ± 14 kg, height: 174 ± 9 cm) completed three weeks of Nordic hamstring exercise (NHE) training. We collected in vivo sarcomere and muscle fascicle images of the BFlh in two regions (central and distal), utilising microendoscopy and 3D ultrasonography. These images allowed us to estimate sarcomere length, sarcomere number and fascicle lengths before and after the training intervention.ResultsEccentric knee flexion strength increased after the training (15%, P < 0.001, ηp2= 0.75). Further, we found a significant increase in fascicle (21%, P < 0.001, ηp2= 0.81) and sarcomere (17%, P < 0.001, ηp2= 0.9) lengths in the distal but not in the central portion of the muscle. The estimated number of in series sarcomeres did not change in either region.ConclusionFascicle length adaptations appear to be heterogeneous in the BFlf in response to three weeks of NHE training. An increase in sarcomere length, rather than the addition of sarcomeres in series, appears to be underlying this adaptation. The mechanism driving regional increases in fascicle and sarcomere length remain unknown, but we speculate it may be driven by regional changes in the passive tension of muscle or connective tissue adaptations.
DBPOM: a comprehensive database of pharmaco-omics for cancer precision medicine
Authors: Liu Yijun , Song Fuhu , Li Zhi , Chen Liang , Xu Ying , Sun Huiyan , Chang Yi 
Published: January 2021

AbstractDuring the course of cancer treatment, both efficacy and the adverse effects of drugs on patients should be taken into account. Although some public databases and modeling frameworks have been developed through studies on drug response, the negative effects of drugs are always neglected. Furthermore, most of them only considered the ramifications of the drug on the cell line, but the effects on the patient still require a huge amount of work to integrate data from various databases and calculations, especially in relation to precision treatment. In order to address these issues, we developed the DBPOM (http://www.dbpom.net/, a comprehensive database of pharmaco-omics for cancer precision medicine), which explores various drugs’ efficacy levels by calculating their potency in reverse, or enhancing cancer-associated gene expression changes. When compared with existing databases, the DBPOM could estimate the effectiveness of a drug on individual patients through the mapping of various cell lines to each person according to their genetic mutation similarities. The DBPOM is an easy-to-use and one-stop database for clinicians and drug researchers to search and analyze the overall effect of a drug or a drug combination on cancer patients as well as the biological functions that they target. We anticipate that DBPOM will become an important resource and analysis platform for drug development, drug mechanism studies and the discovery of new therapies.