bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Wearable Optical Microfibrous Biomaterial with Encapsulated Nanosensors Enables Wireless Monitoring of Oxidative Stress
Authors: Safaee Mohammad Moein , Gravely Mitchell , Roxbury Daniel 
Published: July 2020

AbstractIn an effort to facilitate personalized medical approaches, the continuous and noninvasive monitoring of biochemical information using wearable technologies can enable a detailed understanding of an individual’s physiology. Reactive oxygen species (ROS) are a class of oxygen-containing free radicals which function in a wide range of biological processes. In wound healing applications, the continuous monitoring of ROS through a wearable diagnostics platform is essential for the prevention of chronicity and pathogenic infection. Here, a versatile one-step procedure is utilized to fabricate optical core-shell microfibrous textiles incorporating single-walled carbon nanotubes (SWCNTs) for the real-time optical monitoring of hydrogen peroxide concentrations in wounds. The environmentally sensitive and non-photobleachable fluorescence of SWCNTs enables continuous analyte monitoring without a decay in signal over time. The existence of multiple chiralities of SWCNTs emitting near-infrared fluorescence with narrow bandwidths allows a ratiometric signal readout invariant to the excitation source distance and exposure time. The individual fibers encapsulate the SWCNT nanosensors for at least 21 days without apparent loss in structural integrity. Moreover, the microfibrous textiles can be utilized to spatially resolve peroxide concentrations on a wound surface using a camera and can be integrated into commercial wound bandages without being altered or losing their optical properties.
miRinGO: Prediction of biological processes indirectly targeted by human microRNAs
Authors: Sayed Mohammed , Park Juw Won 
Published: July 2020

AbstractMicroRNAs are small non-coding RNAs that are known for their role in post-transcriptional regulation of target genes. Typically, their functions are predicted by first identifying their target genes and then finding biological processes enriched in these targets. Current tools for miRNA functional analysis use only genes with physical binding sites as their targets and exclude other genes that are indirectly targeted transcriptionally through transcription factors. Here, we introduce a method to predict gene ontology (GO) annotations indirectly targeted by microRNAs. The proposed method resulted in better performance in predicting known miRNA-GO term associations compared to the canonical approach. To facilitate miRNA GO enrichment analysis, we developed an R Shiny application, miRinGO, that is freely available from GitHub athttps://github.com/Fadeel/miRinGO
A rapid ecological assessment for necrophagous flies (Diptera, Calyptratae) in a mosaic landscape of the Colombian Andes
Authors: Amat Eduardo , Medina Claudia A. 
Published: July 2020

AbstractA necrophagous flies ensemble (Diptera, Calyptratae) was rapidly assessed in four coverages of an anthropogenic landscape in the east range of the Colombian Andes. Ninetyseven individuals belonging to eight species were collected in only two hours of sampling. The highest diversity values and the occurrence of asynanthropic flies in the forest under conservation management may reflect a positively natural restoration process in the area assessed. Grassland, rural and urban coverages were similarly low in diversity and composition. A brief discussion about the flies’ bionomy and their environment association is offered. Necrophagous flies ensembles by coverage behave as an indicator of the anthropic impact on the landscape.
Minimally-overlapping words for sequence similarity search
Authors: Frith Martin C. , Noé Laurent , Kucherov Gregory 
Published: July 2020

AbstractAnalysis of genetic sequences is usually based on finding similar parts of sequences, e.g. DNA reads and/or genomes. For big data, this is typically done via “seeds”: simple similarities (e.g. exact matches) that can be found quickly. For huge data, sparse seeding is useful, where we only consider seeds at a subset of positions in a sequence.Here we study a simple sparse-seeding method: using seeds at positions of certain “words” (e.g.ac, at, gc, orgt). Sensitivity is maximized by using words with minimal overlaps. That is because, in a random sequence, minimally-overlapping words are anti-clumped. We provide evidence that this is often superior to acclaimed “minimizer” sparse-seeding methods. Our approach can be unified with design of inexact (spaced and subset) seeds, further boosting sensitivity. Thus, we present a promising approach to sequence similarity search, with open questions on how to optimize it.
Are Granulins Copper Sequestering Proteins?
Authors: Bhopatkar Anukool A. , Rangachari Vijayaraghavan 
Published: July 2020

AbstractGranulins (GRN 1-7) are short (∼6 kDa), cysteine-rich proteins that are generated upon the proteolytic processing of progranulin (PGRN). These modules, along with their precursor, have been implicated in multiple pathophysiological roles, especially in neurodegenerative diseases. Our previous investigations into GRN-3 and GRN-5 reveal them to be fully disordered in the reduced form and implicate redox sensitive attributes to the proteins. Such redox-dependent modulation has become associated with proteins involved in oxidative stress regulation and maintaining metal-homeostasis within cells. To probe whether GRNs play a contributory role in such functions, we tested the metal binding potential of the reduced form of GRNs -3 and -5 under neutral and acidic pH mimicking cytosolic and lysosomal conditions, respectively. We found, at neutral pH, both GRNs selectively bind Cu(II) and no other divalent cations. Binding of Cu(II) also partly triggered the oxidative multimerization of GRNs via uncoordinated cystines at both pH conditions. Furthermore, binding did not induce gain in secondary structure and the protein remained disordered. Overall, the results indicate that GRN-3 and -5 have a surprisingly strong affinity for Cu(II) in the pM range, comparable to known copper sequestering proteins. This data also hints at a potential of GRNs to reduce Cu(II) to Cu(I), a process that has significance in mitigating Cu-induced ROS cytotoxicity in cells. Together, this report uncovers a metal-coordinating capability of GRNs for the first time, which could have profound significance in their structure and function.
Direct medium-chain carboxylic-acid oil separation from a bioreactor by an electrodialysis/phase separation cell
Authors: Xu Jiajie , Guzman Juan J.L. , Angenent Largus T. 
Published: July 2020

AbstractMedium-chain carboxylic acids (MCCAs) are valuable platform chemicals with numerous industrial-scale applications. These MCCAs can be produced from waste biomass sources or syngas fermentation effluent through an anaerobic fermentation process called chain elongation. We have previously demonstrated successful approaches to separate >90%-purity oil with several MCCAs by integrating the anaerobic bioprocess with membrane-based liquid-liquid extraction (pertraction) and membrane electrolysis. However, membrane electrolysis without pertraction was not able to separate MCCA oil. Therefore, we developed an electrodialysis/phase separation cell (ED/PS) and evaluated whether it can function as a stand-alone extraction and separation unit. First, we tested an ED/PS cell, which, when evaluatedin serieswith pertraction, achieved a maximum MCCA-oil flux of 1,665 g d-1per projected area (m2) (19.3 mL oil d-1) and a MCCA-oil transfer efficiency [100%*moles MCCA-oil moles electrons-1] of 74% at 15 A m-2. This extraction system demonstrated a ∼10 times lower electric-power consumption of 1.05 kWh kg-1MCCA oil when compared to membrane electrolysisin serieswith pertration (11.1 kWh kg-1MCCA oil) at 15 A m-2. Second, we evaluated our ED/PS as a stand-alone unit when integrated with the anaerobic bioprocess (without pertraction), and demonstrated that we can selectively extract and separate MCCA oil directly from chain-elongating bioreactor broth with just an abiotic electrochemical cell. We assumed that such a stand-alone unit would reduce capital and operating costs, but electric-power consumption increased considerably due to the lower MCCA concentrations in the bioreactor broth compared to the pertraction broth. Only a full techno-economic analysis will be able to determine whether the use of the ED/PS cell should be as a stand-alone unit or after pertraction.
TheAppNL-G-Fmouse retina is a site for preclinical Alzheimer’s disease diagnosis and research
Authors: Vandenabeele Marjan , Veys Lien , Lemmens Sophie , Hadoux Xavier , Gelders Géraldine , Masin Luca , Serneels Lutgarde , Theunis Jan , Saito Takashi , Saido Takaomi C. , Jayapala Murali , De Boever Patrick , De Strooper Bart , Stalmans Ingeborg , van Wijngaarden Peter , Moons Lieve , De Groef Lies 
Published: July 2020

AbstractIn this study, we report the results of a comprehensive phenotyping of the retina of theAppNL-G-Fmouse. We demonstrate that soluble Aβ accumulation is present in the retina of these mice early in life and progresses to Aβ plaque formation by midlife. This rising Aβ burden coincides with local microglia reactivity, astrogliosis, and abnormalities in retinal vein morphology. Electrophysiological recordings reveal signs of neuronal dysfunction yet no overt neurodegeneration was observed and visual performance outcomes were unaffected in theAppNL-G-Fmouse. Furthermore, we show that hyperspectral imaging can be used to quantify retinal Aβ, underscoring its potential as a biomarker for AD diagnosis and monitoring. These findings suggest that theAppNL-G-Fretina mimics the early, preclinical stages of AD, and, together with retinal imaging techniques, offers unique opportunities for drug discovery and fundamental research into preclinical AD.
NanoReviser: An Error-correction Tool for Nanopore Sequencing Based on a Deep Learning Algorithm
Authors: Wang Luotong , Qu Li , Yang Longshu , Wang Yiying , Zhu Huaiqiu 
Published: July 2020

AbstractNanopore sequencing is regarded as one of the most promising third-generation sequencing (TGS) technologies. Since 2014, Oxford Nanopore Technologies (ONT) has developed a series of devices based on nanopore sequencing to produce very long reads, with an expected impact on genomics. However, the nanopore sequencing reads are susceptible to a fairly high error rate owing to the difficulty in identifying the DNA bases from the complex electrical signals. Although several basecalling tools have been developed for nanopore sequencing over the past years, it is still challenging to correct the sequences after applying the basecalling procedure. In this study, we developed an open-source DNA basecalling reviser, NanoReviser, based on a deep learning algorithm to correct the basecalling errors introduced by current basecallers provided by default. In our module, we re-segmented the raw electrical signals based on the basecalled sequences provided by the default basecallers. By employing convolution neural networks (CNNs) and bidirectional long short-term memory (Bi-LSTM) networks, we took advantage of the information from the raw electrical signals and the basecalled sequences from the basecallers. Our results showed NanoReviser, as a post-basecalling reviser, significantly improving the basecalling quality. After being trained on standard ONT sequencing reads from publicE. coliand human NA12878 datasets, NanoReviser reduced the sequencing error rate by over 5% for both theE. colidataset and the human dataset. The performance of NanoReviser was found to be better than those of all current basecalling tools. Furthermore, we analyzed the modified bases of theE. colidataset and added the methylation information to train our module. With the methylation annotation, NanoReviser reduced the error rate by 7% for theE. colidataset and specifically reduced the error rate by over 10% for the regions of the sequence rich in methylated bases. To the best of our knowledge, NanoReviser is the first post-processing tool after basecalling to accurately correct the nanopore sequences without the time-consuming procedure of building the consensus sequence. The NanoReviser package is freely available athttps://github.com/pkubioinformatics/NanoReviser.
Temperature-dependent competitive outcomes between the fruit fliesDrosophila santomeaandD. yakuba
Authors: Comeault Aaron A. , Matute Daniel R. 
Published: July 2020

AbstractChanges in temperature associated with climate change can alter species’ distributions, drive adaptive evolution, and, in some cases, cause extinction. Research has tended to focus on the direct effects of temperature, but changes in temperature can also have indirect effects on populations and species. Here we test whether temperature can indirectly affect the fitness ofDrosophila santomeaandD. yakubaby altering interspecific competitive outcomes. We show that, when raised in isolation, bothD. santomeaandD. yakubashow maximal performance at temperatures near 22°C. However, when raised together,D. santomeaoutcompetesD. yakubaat a lower temperature (18°C), whileD. yakubaoutcompetesD. santomeaat a higher temperature (25°C). We then use a ‘coexistence’ experiment to show thatD. santomeais rapidly (within 8 generations) extirpated when maintained withD. yakubaat 25°C. By contrast,D. santomearemains as (or more) abundant thanD. yakubaover the course of ~10 generations when maintained at 18°C. Our results provide an example of how the thermal environment can indirectly affect interspecific competitive outcomes and suggest that changes in the competitive advantage of species can lead to some species becoming more prone to extinction by competitive exclusion.
Microtiter plate-based antibody-competition assay to determine binding affinities and plasma/blood stability of CXCR4 ligands
Authors: Harms Mirja , Gilg Andrea , Ständker Ludger , Beer Ambros J. , Mayer Benjamin , Rasche Volker , Gruber Christian W. , Münch Jan 
Published: July 2020

ABSTRACTC-X-C chemokine receptor type 4 (CXCR4) is involved in several intractable disease processes, including HIV infection, cancer cell metastasis, leukemia cell progression, rheumatoid arthritis, asthma and pulmonary fibrosis. Thus, CXCR4 represents a promising drug target and several CXCR4 antagonizing agents are in preclinical or clinical development. Important parameters in drug lead evaluation are determination of binding affinities to the receptor and assessment of their stability and activity in plasma or blood of animals and humans. Here, we designed a microtiter plate-based CXCR4 antibody competition assay that enables to measure inhibitory concentrations (IC50values) and affinity constants (Kivalues) of CXCR4 targeting drugs. The assay is based on the observation that most if not all CXCR4 antagonists compete with binding of the fluorescence-tagged CXCR4 antibody 12G5 to the receptor. We demonstrate that this antibody-competition assay allows a convenient and cheap determination of binding affinities of various CXCR4 antagonists in living cells within just 3 hours. Moreover, the assay can be performed in the presence of high concentrations of physiologically relevant body fluids, and thus is a useful readout to evaluate stability (i.e. half-life) of CXCR4 ligands in serum/plasma, and even whole human and mouse bloodex vivo. Thus, this optimized 12G5 antibody competition assay allows a robust and convenient determination and calculation of various important pharmacological parameters of CXCR4 receptor-drug interaction and may not only foster future drug development but also animal welfare by reducing the number of experimental animals.
Unifying framework for the diffusion of microscopic particles in mucus
Authors: Cobarrubia Antonio , Tall Jarod , Crispin-Smith Austin , Luque Antoni 
Published: July 2020

AbstractMucus is a fluid that protects animals against pathogens while promoting interactions with commensal microbes. Changes in the diffusivity of particles in mucus alter viruses’ infectivity, the efficiency of bacterial pathogens to invade a host, and the effectivity of drug delivery. Multiple physicochemical properties modulate the diffusion of microscopic particles in mucus, but their combined effect is unclear. Here, we analyzed the impact of particle size, charge, chemistry, anomalous diffusion exponent, and mucus composition in the diffusivity of particles from 106 published experiments. We used a time window sampling of one second to define a consistent, effective diffusion across experiments. The effective diffusion spanned seven orders of magnitude from 10−5to 102µm2/s. The anomalous exponent was the strongest predictor among all variables tested. It displayed an exponential relationship with the effective diffusion that explained 90% of the empirical data variance. We showed that the relationship and dominance of the anomalous diffusion exponent resulted from a general mathematical relationship obtained from first-principles for any subdiffusion mechanism. Our derivation demonstrated that the generalized diffusion coefficient is not a measurable physical quantity and must be replaced by the length and time scales associated with the underlying mobility mechanisms. This led us to a fundamental reformulation of the classic subdiffusion equation, which calls for a reinterpretation of anomalous diffusion in physical systems. We also discussed how our results impact the characterization of microscopic particle diffusion in mucus and other hydrogels.
Phylogenetics analysis of TP53 gene in humans and its use in biosensors for breast cancer diagnosis
Authors: da Silva Nascimento Sara , Félix Pierre Teodósio 
Published: July 2020

AbstractBiosensors are small devices that use biological reactions to detect target analytes. Such devices combine a biological component with a physical transducer, which converts bio-recognition processes into measurable signals. Its use brings a number of advantages, as they are highly sensitive and selective, relatively easy in terms of development, as well as accessible and ready to use. Biosensors can be of direct detection, using a non-catalytic ligand, such as cell receptors and antibodies, or indirect detection, in which there is the use of fluorescently marked antibodies or catalytic elements, such as enzymes. They also appear as bio-affinity devices, depending only on the selective binding of the target analyte to the ligative attached to the surface (e.g., oligonucleotide probe). The objectives were to evaluate the levels of genetic diversity existing in fragments of the TP53 gene deposited in molecular databases and to study its viability as a biosensor in the detection of breast cancer. The methodology used was to recover and analyze 301 sequences of a fragment of the TP53 gene of humans from GENBANK, which, after being aligned with the MEGA software version 6.06, were tested for the phylogenetic signal using TREE-PUZZLE 5.2. Trees of maximum likelihood were generated through PAUP version 4.0b10 and the consistency of the branches was verified with the bootstrap test with 1000 pseudo-replications. After aligning, 783 of the 791 sites remained conserved. The maximum likelihood had a slight manifestation since the gamma distribution used 05 categories + G for the evolutionary rates between sites with (0.90 0.96, 1.00, 1.04 and 1.10 substitutions per site). To estimate ML values, a tree topology was automatically computed with a maximum Log of −1058,195 for this calculation. All positions containing missing gaps or data were deleted, leaving a total of 755 sites in the final dataset. The evolutionary history was represented by consensus trees generated by 500 replications, which according to neighbor-join and BioNJ algorithms set up a matrix with minimal distances between haplotypes, corroborating the high degree of conservation for the TP53 gene. GENE TP53 seems to be a strong candidate in the construction of Biosensors for breast cancer diagnosis in human populations.
Megadalton-sized dityrosine aggregates of α-synuclein retain high degrees of structural disorder and internal dynamics
Authors: Verzini Silvia , Shah Maliah , Theillet Francois-Xavier , Belsom Adam , Bieschke Jan , Wanker Erich E. , Rappsilber Juri , Binolfi Andres , Selenko Philipp 
Published: July 2020

AbstractHeterogeneous aggregates of the human protein α-synuclein (αSyn) are abundantly found in Lewy body inclusions of Parkinson’s disease patients. While structural information on classical αSyn amyloid fibrils is available, little is known about the conformational properties of disease-relevant, non-canonical aggregates. Here, we analyze the structural and dynamic properties of megadalton-sized dityrosine adducts of αSyn that form in the presence of reactive oxygen species and cytochromec, a proapoptotic peroxidase that is released from mitochondria during sustained oxidative stress. In contrast to canonical cross-β amyloids, these aggregates retain high degrees of internal dynamics, which enables their characterization by solution-state NMR spectroscopy. We find that intermolecular dityrosine crosslinks restrict αSyn motions only locally whereas large segments of concatenated molecules remain flexible and disordered. Indistinguishable aggregates form in crowdedin vitrosolutions and in complex environments of mammalian cell lysates, where relative amounts of free reactive oxygen species rather than cytochromecare rate limiting. We further establish that dityrosine adducts inhibit classical amyloid formation by maintaining αSyn in its monomeric form and that they are non-cytotoxic despite retaining basic membrane-binding properties. Our results suggest that oxidative αSyn aggregation scavenges cytochromec’s activity into the formation of amorphous, high molecular-weight structures that may contribute to aggregate diversity in Lewy body deposits.
De novodesigned transmembrane domains tune engineered receptor functions
Authors: Elazar Assaf , Chandler Nicholas J. , Davey Ashleigh S. , Weinstein Jonathan Y. , Nguyen Julie V. , Trenker Raphael , Cross Ryan S. , Jenkins Misty R. , Call Melissa J. , Call Matthew E. , Fleishman Sarel J. 
Published: July 2020

AbstractDe novodesigned receptor transmembrane domains (TMDs) present opportunities for precise control of cellular receptor functions. We developed ade novodesign strategy for generating programmed membrane proteins (proMPs): single-pass α-helical TMDs that self-assemble through computationally defined and crystallographically validated interfaces. We used these proMPs to program specific oligomeric interactions into a chimeric antigen receptor (CAR) and found that bothin vitroCAR T cell cytokine release andin vivoantitumor activity scaled linearly with the oligomeric state encoded by the receptor TMD, from monomers up to tetramers. All programmed CARs (proCARs) stimulated substantially lower T cell cytokine release relative to the commonly used CD28 TMD, which we show elevated cytokine release through lateral recruitment of the endogenous T cell costimulatory receptor CD28. Precise design using orthogonal and modular TMDs thus provides a new way to program receptor structure and predictably tune activity for basic or applied synthetic biology.