bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different approaches to quantify years of life lost from COVID-19
Authors: Ferenci Tamás 
Published: May 2021

AbstractThe burden of an epidemic is often characterized by death counts, but this can be misleading as it fails to acknowledge the age of the deceased patients. Years of life lost is therefore widely used as a more relevant metric, however, such calculations in the context of COVID-19 are all biased upwards: patients dying from COVID-19 are typically multimorbid, having far worse life expectation than the general population. These questions are quantitatively investigated using a unique Hungarian dataset that contains individual patient level data on comorbidities for all COVID-19 deaths in the country. To account for the comorbidities of the patients, a parametric survival model using 11 important long-term conditions was used to estimate a more realistic years of life lost. As of 12 May, 2021, Hungary reported a total of 27,837 deaths from COVID-19 in patients above 50 years of age. The usual calculation indicates 10.5 years of life lost for each death, which decreases to 9.2 years per death after adjusting for 11 comorbidities. The expected number of years lost implied by the life table, reflecting the mortality of a developed country just before the pandemic is 11.1 years. The years of life lost due to COVID-19x in Hungary is therefore 12% or 1.3 years per death lower when accounting for the comorbidities and is below its expected value, but how this should be interpreted is still a matter of debate. Further research is warranted on how to optimally integrate this information into epidemiologic risk assessments during a pandemic.
Localization and RNAi-driven inhibition of a Brugia malayi encoded Interleukin-5 Receptor Binding protein
Authors: Mejia Rojelio , Bennuru Sasisekhar , Oksov Yelena , Lustigman Sara , Munirathinam Gnanasekar , Kalyanasundaram Ramaswamy , Nutman Thomas B. 
Published: May 2021

AbstractA molecule termed BmIL5Rbp (aka Bm8757) was identified from Brugia malayi filarial worms and found to competitively inhibit human IL-5 binding to its human receptor.After the expression and purification of a recombinant BmIL5Rbp and generation of BmIL5Rbp-specific rabbit antibody, we localized the molecule on B. malayi worms through immunohistochemistry and immunoelectron microscopy. RNA interference was used to inhibit BmIL5Rbp mRNA and protein production. BmIL5Rbp was shown to localize to the cuticle of Brugia malayi and to be released in their excretory/secretory products. RNAi inhibited BmIL5Rbp mRNA production by 33% and reduced the surface protein expression by ~50% and suppressed the release of BmIL5Rbp in the excretory/secretory products. RNAi has been used successfully to knock down the mRNA and protein expression of BmIL5Rbp in the early larval stages of B. malayi and provided a proof-of-principle for the local inhibition of the human IL5 receptor. These findings provide evidence that a parasite encoded IL5R antagonist could be utilized therapeutically.
nGauge: Integrated and extensible neuron morphology analysis in Python
Authors: Walker Logan A , Williams Jennifer S , Li Ye , Roossien Douglas H , Michki Nigel S , Cai Dawen 
Published: May 2021

AbstractThe study of neuron morphology requires robust and comprehensive methods to quantify the differences between neurons of different subtypes and animal species. Several software packages have been developed for the analysis of neuron tracing results stored in the standard SWC format. However, providing relatively simple quantifications and their non-extendable architecture prohibit their use for advanced data analysis and visualization. We developed nGauge, a Python toolkit to support the parsing and analysis of neuron morphology data. As an application programming interface (API), nGauge can be referenced by other popular open-source software to create custom informatics analysis pipelines and advanced visualizations. nGauge defines an extendable data structure that handles volumetric constructions (e.g. soma), in addition to the SWC linear reconstructions, while remaining light-weight. This greatly extends nGauge’s data compatibility.
Truncating Tau Reveals Different Pathophysiological Actions of Oligomers in Single Neurons
Authors: Hill Emily , Karikari Thomas K. , Lantero-Rodriguez Juan , Zetterberg Henrik , Blennow Kaj , Richardson Magnus J , Wall Mark J 
Published: May 2021

AbstractTau protein is involved in maintaining neuronal structure. In Alzheimer’s disease, small numbers of tau molecules can aggregate to forms oligomers. However, how these oligomers produce changes in neuronal function remains unclear. Previously, oligomers made from full-length human tau were found to have multiple effects on neuronal properties. Here we have cut the tau molecule into two parts: the first 123 amino acids and the remaining 124-441 amino acids. These truncated tau molecules had specific effects on neuronal properties, allowing us to assign the actions of full-length tau to different regions of the molecule. We identified one key target for the effects of tau, the voltage gated sodium channel, which could account for the effects of tau on the action potential. By truncating the tau molecule, we have probed the mechanisms that underlie tau dysfunction, and this increased understanding of tau’s pathological actions, will build towards developing future tau-targeting therapies.
A Genome-Scale TF-DNA Interaction Network of Transcriptional Regulation of Arabidopsis Primary and Specialized Metabolism
Authors: Tang Michelle , Li Baohua , Zhou Xue , Bolt Tayah , Li Jia Jie , Cruz Neiman , Gaudinier Allison , Ngo Richard , Clark-Wiest Caitlin , Kliebenstein Daniel J. , Brady Siobhan M. 
Published: May 2021

SummaryIn single-celled microbes, transcriptional regulation by single transcription factors is sufficient to shift primary metabolism. Corresponding genome-level transcriptional regulatory maps of metabolism reveal the underlying design principles responsible for these shifts as a model in which master regulators largely coordinate specific metabolic pathways. Relative to individual microbes, plant metabolism is more complex. Primary and specialized metabolism occur within innumerable cell types, and their reactions shift depending on internal and external cues. Given the importance of plants and their metabolites in providing humanity with food, fiber and medicine, we set out to develop a genome-scale transcriptional regulatory map of Arabidopsis metabolic genes. A comprehensive set of protein-DNA interactions between Arabidopsis thaliana transcription factors and promoters of primary metabolism and specialized metabolism were mapped. To demonstrate the utility of this resource, we identified and functionally validated regulators of the TCA cycle. The resulting network suggests that plant metabolic design principles are distinct from that of microbes. Instead, metabolism appears to be transcriptionally coordinated via developmental- and stress-conditional processes that can coordinate across primary and specialized metabolism. These data represent the most comprehensive resource of interactions between TFs and metabolic genes in plants.
PEN receptor GPR83 in anxiety-like behaviors: differential regulation in global vs amygdalar knockdown
Authors: Fakira Amanda K. , Lueptow Lindsay M. , Trimbake Nikita A. , Devi Lakshmi A. 
Published: May 2021

AbstractAnxiety disorders are prevalent across the United States and result in a large personal and societal burden. Currently, numerous therapeutic and pharmaceutical treatment options exist. However, drugs to classical receptor targets have shown limited efficacy and often come with unpleasant side effects, highlighting the need to identify novel targets involved in the etiology and treatment of anxiety disorders. GPR83, a recently deorphanized receptor activated by the abundant neuropeptide PEN, has also been identified as a glucocorticoid regulated receptor (and named GIR) suggesting that this receptor may be involved in stress-responses that underlie anxiety. Consistent with this, GPR83 null mice have been found to be resistant to stress-induced anxiety. However, studies examining the role of GPR83 within specific brain regions or potential sex differences have been lacking. In this study, we investigate anxiety-related behaviors in male and female mice with global knockout and following local GPR83 knockdown in female mice. We find that a global knockdown of GPR83 has minimal impact on anxiety-like behaviors in female mice and a decrease in anxiety-related behaviors in male mice. In contrast, a local GPR83 knockdown in the basolateral amygdala leads to more anxiety-related behaviors in female mice. Local GPR83 knockdown in the central amygdala or nucleus accumbens showed no significant effect on anxiety-related behaviors. Finally, dexamethasone administration leads to a significant decrease in receptor expression in the amygdala and nucleus accumbens of female mice. Together, our studies uncover a significant, but divergent role for GPR83 in different brain regions in the regulation of anxiety-related behaviors, which is furthermore dependent on sex.
Predicted the impacts of climate change and extreme-weather events on the future distribution of fruit bats in Australia
Authors: Diengdoh Vishesh L. , Ondei Stefania , Hunt Mark , Brook Barry W. 
Published: May 2021

AbstractAimFruit bats (Megachiroptera) are important pollinators and seed dispersers whose distribution might be affected by climate change and extreme-weather events. We assessed the potential impacts of those changes, particularly more frequent and intense heatwaves, and drought, on the future distribution of fruit bats in Australia. We also focus a case study on Tasmania, the southernmost island state of Australia, which is currently devoid of fruit bats but might serve as a future climate refugium.LocationAustralia (continental-scale study) and Tasmania.MethodsSpecies distribution modelling was used to predict the occurrence of seven species of fruit bats, using an ensemble of machine-learning algorithms. Predictors included extreme-weather events (heatwave and drought), vegetation (as a proxy for habitat) and bioclimatic variables. Predictions were made for the current-day distribution and future (2050 and 2070) scenarios using multiple emission scenarios and global circulation models.ResultsChanges in climate and extreme-weather events are forecasted to impact all fruit-bat species, with the loss and gain of suitable areas being predominantly along the periphery of a species’ current distribution. A higher emission scenario resulted in a higher loss of areas for Grey-headed flying fox (Pteropus poliocephalus) and Spectacled flying fox (P. conspicillatus) but a higher gain of areas for the Northern blossom bat (Macroglossus minimus). The Grey-headed flying fox (Pteropus poliocephalus) is the only study species predicted to potentially occur in Tasmania under future scenarios.Main conclusionsFruit bats are likely to respond to climate change and extreme weather by migrating to more suitable areas, including regions not historically inhabited by those species such as Tasmania—possibly leading to human-wildlife conflicts. Conservation strategies (e.g., habitat protection) should focus on areas we found to remain suitable under future scenarios, and not be limited by state-political boundaries.
Robust and Remote Measurement of Heart Rate Based on A Surveillance Camera
Authors: Yang Yiming , Lian Chao , Zhang Hongyu , Li Liangjiang , Zhao Yuliang 
Published: May 2021

ABSTRACTArrhythmia is a marked symptom of many cardiovascular diseases (CVDs). The accurate and timely detection of heart rate can greatly reduce the harm of arrhythmia to people. However, it is still a challenge to robustly and remotely measure heart rate in daily life due to the changing environmental conditions during measurement, such as the varying light intensity, the movement of people, and the uncertain distance between the sensor to people. In this study, we propose a method to accurately measure human heart rate within a distance of 4.5 meters under different light intensities by simply using a surveillance camera. After a 20-second color video of a person’s hand is captured by the camera, a method based on the Fast Fourier Transform (FFT) algorithm is designed to extract the blood volume pulse wave to calculate the heart rate. According to the comparison between the real heart rate and results measured by electrocardiography (ECG), the proposed method achieves an accuracy of 95.8% when the measurement is performed within a distance of 4.5 meters and 90% when within 5.0 meters. Our experiments show that when the illuminance varies between 100-1000 lux (lighting level indoor), we still get the correct results. Our experiments also demonstrate that the proposed method accurately obtain heart rate even when the light intensity is below 32 lux (300-500 lux in a workplace environment). The method’s strong adaptability to changing environmental conditions makes it applicable to many scenarios, such as homes of the elderly, classrooms, and other public spaces.
Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation
Authors: Gao Longfei , Decker Matthew , Chen Haidee , Ding Lei 
Published: May 2021

AbstractThe bone marrow niche plays a critical role in hematopoietic recovery and hematopoietic stem cell (HSC) regeneration after myeloablation. However, it is not clear whether systemic factors beyond the local niche are required for these essential processes in vivo. Thrombopoietin (TPO) is a critical cytokine promoting hematopoietic rebound after myeloablation and its transcripts are expressed by multiple cellular sources. The upregulation of bone marrow-derived TPO has been proposed to be crucial for hematopoietic recovery and HSC regeneration after stress. Nonetheless, the cellular source of TPO in stress has never been investigated genetically. We assessed the functional sources of TPO following two common myeloablative perturbations: 5-fluorouracil (5-FU) administration and irradiation. Using a Tpo translational reporter, we found that the liver but not the bone marrow is the major source of TPO protein after myeloablation. Mice with conditional Tpo deletion from osteoblasts or bone marrow stromal cells showed normal recovery of HSCs and hematopoiesis after myeloablation. In contrast, mice with conditional Tpo deletion from hepatocytes showed significant defects in HSC regeneration and hematopoietic rebound after myeloablation. Thus, systemic TPO from the liver is necessary for HSC regeneration and hematopoietic recovery in myeloablative stress conditions.
Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms
Authors: Reuter Christian , Imdahl Fabian , Hauf Laura , Vafadarnejad Ehsan , Fey Philipp , Finger Tamara , Walles Heike , Saliba Antoine-Emmanuel , Groeber-Becker Florian , Engstler Markus 
Published: May 2021

SummaryTransmission of Trypanosoma brucei by tsetse flies involves the deposition of the cell cycle-arrested metacyclic life cycle stage into mammalian skin at the site of the fly’s bite. In the skin, the metacyclic parasites reactivate and differentiate into proliferative trypanosomes before colonizing the host’s blood and tissues. We generated an advanced human skin equivalent and used tsetse flies to naturally infect the artificial skin with trypanosomes. We detailed the chronological order of the parasites’ development in the skin, and found a rapid activation of metacyclic trypanosomes and differentiation to proliferative parasites. Single-cell parasite transcriptomics were used to document the biological events during differentiation and host invasion at five different timepoints. After the establishment of a proliferative trypanosome population in the skin, the parasites entered a reversible quiescent state characterized by slow replication and a strongly reduced metabolism. We termed these quiescent trypanosomes skin tissue forms (STF), a parasite population that may play an important role in maintaining the infection over long time periods and in asymptomatic infected individuals.
Composition and Biophysical Properties of the Sorting Platform Pods in the Shigella Type III Secretion System
Authors: Tachiyama Shoichi , Skaar Ryan , Chang Yunjie , Carroll Brittany , Muthuramalingam Meenakumari , Whittier Sean K. , Barta Michael L. , Picking Wendy L. , Liu Jun , Picking William D. 
Published: May 2021

AbstractShigella flexneri, causative agent of bacillary dysentery (shigellosis), uses a type III secretion system (T3SS) as its primary virulence factor. The T3SS injectisome delivers effector proteins into host cells to promote entry and create an important intracellular niche. The injectisome’s cytoplasmic sorting platform (SP) is a critical assembly that contributes to substrate selection and energizing secretion. The SP consists of oligomeric Spa33 “pods” that associate with the basal body via MxiK and connect to the Spa47 ATPase via MxiN. The pods contain heterotrimers of Spa33 with one full-length copy associated with two copies of a C-terminal domain (Spa33C). The structure of Spa33C is known, but the precise makeup and structure of the pods in situ remains elusive. We show here that recombinant wild-type Spa33 can be prepared as a heterotrimer that forms distinct stable complexes with MxiK and MxiN. In two-hybrid analyses, association of the Spa33 complex with these proteins occurs via the full-length Spa33 component. Furthermore, these complexes each have distinct biophysical properties. Based on these properties, new high-resolution cryo-electron tomography data and architectural similarities between the Spa33 and flagellar FliM-FliN complexes, we provide a preliminary model of the Spa33 heterotrimers within the SP pods. From these findings and evolving models of SP interfaces and dynamics in the Yersinia and Salmonella T3SS, we suggest a model for SP function in which two distinct complexes come together within the context of the SP to contribute to form the complete pod structures during the recruitment of T3SS secretion substrates.
Mechanistic model: Analysis of diffusion dynamics of Lugol’s chromoendoscopy in Basal layer-type squamous cell carcinoma in situ via Euler’s method and Law of mass action
Authors: Xiong Fei 
Published: May 2021

AbstractBasal layer-type squamous cell carcinoma in situ(BLSCC) is an aggressive malignancy tumor. In the past, it usually went ignored because its aggressive biological behavior is different from typical esophageal squamous cancer(SCC). For our mechanistic model, we analyzed diffusion dynamics of iodine stain in BLSCC with the help of Euler’s method. We used the law of mass action description of the forming process of the iodine-glycogen Complex. Based on the above analysis, our mechanistic model reveals that the efficacy of Lugol’s chromoendoscopy is determined by the thickness of the squamous epithelial cell layer, which contains glycogen granules, and the convection of the interpupillary capillary loop(IPCL). A further inference can be made: the unique histological structure of BLSCC suggests Lugol’s chromoendoscopy does not detect some components of it because these components neither break enough squamous epithelial cells which contain glycogen granules nor contain enough number of IPCL in a specific time frame. Besides, if our mechanistic model starting point is BLSCC and typical SCC share the same evolution path, we found both their cytoplasm tends to solid phase from the iodine diffusion dynamics analysis in “pink color sign.”
Understanding Microbeads Stacking in Deformable Nano-Sieve for Efficient Plasma Separation and Blood Cell Retrieval
Authors: Chen Xinye , Zhang Shuhuan , Gan Yu , Liu Rui , Wang Ruo-Qian , Du Ke 
Published: May 2021

AbstractEfficient separation of blood cells and plasma is key for numerous molecular diagnosis and therapeutics applications. Despite various microfluidics-based separation strategies have been developed, a simple, reliable, and multiplexing separation device that can process a large volume of blood is still missing. Here we show a microbead packed deformable microfluidic system that can efficiently separate highly purified plasma from whole blood as well as retrieve blocked blood cells from the device. Combining microscope imaging, optical tomography scanning, and computational fluidic modeling, a highly accurate model is constructed to understand the link between the mechanical properties of the microfluidics, flow rate, and microbeads packing/leaking, which supports and rationalizes the experimental observations. This deformable nano-sieve device establishes a key technology for centrifuge-free diagnosis and treatment of bloodborne diseases and may be important for the design of next-generation deformable microfluidics for separation applications.
Competition for fluctuating resources reproduces statistics of species abundance over time across wide-ranging microbiotas
Authors: Ho Po-Yi , Good Benjamin , Huang Kerwyn Casey 
Published: May 2021

AbstractAcross diverse microbiotas, species abundances vary in time with distinctive statistical behaviors that appear to generalize across hosts, but the origins and implications of these patterns remain unclear. Here, we show that many of these patterns can be quantitatively recapitulated by a simple class of resource-competition models, in which the metabolic capabilities of different species are randomly drawn from a common statistical ensemble. Our coarse-grained model parametrizes the intrinsic consumer-resource properties of a community using a small number of macroscopic parameters, including the total number of resources, typical resource fluctuations over time, and the average overlap in resource-consumption profiles across species. We elucidate how variation in these parameters affects various time series statistics, enabling macroscopic parameter estimation and comparison across wide-ranging microbiotas, including the human gut, saliva, and vagina, as well as mouse gut and rice. The successful recapitulation of time series statistics across microbiotas suggests that resource competition generally acts as a dominant driver of community dynamics. Our work unifies numerous time series patterns under one model, clarifies their origins, and provides a framework to infer macroscopic parameters of resource competition from longitudinal studies of microbial communities.
Crystal structure of the uranyl arsenate mineral hügelite, Pb2(UO2)3O2(AsO4)2(H2O)5, revisited: a correct unit cell, twinning and hydrogen bonding
Authors: Plášil Jakub , Petříček Václav , Škácha Pavel 
Published: May 2021

Revisiting the structure of uranyl arsenate mineral hügelite provided some corrections to the available structural data. The previous twinning model (by reticular merohedry) in hügelite has been corrected. Twinning of the monoclinic unit cell [a = 7.0189 (7) Å,b = 17.1374 (10) Å,c = 8.1310 (10) Å and β = 108.904 (10)°], which can be expressed as a mirror in [100], leads to a pseudo-orthorhombic unit cell (a = 7.019 Å,b = 17.137 Å,c = 61.539 Å and β = 90.02°), which is eight times larger, with respect to the unit-cell volume, than a real cell. Moreover, the unit cell of chosen here and the unit cell given by the previous structure description both lead to the same supercell. A new structure refinement undertaken on an untwinned crystal of hügelite resulted inR = 4.82% for 12 864 reflections withIobs> 3σ(I) and GOF = 1.12. The hydrogen-bonding scheme has been proposed for hügelite for the first time.