bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unsupervised learning of haptic material properties
Authors: Metzger Anna , Toscani Matteo 
Published: February 2021

AbstractWhen touching the surface of an object, its spatial structure translates into a vibration on the skin. The perceptual system evolved to translate this pattern into a representation that allows to distinguish between different materials. Here we show that perceptual haptic representation of materials emerges from efficient encoding of vibratory patterns elicited by the interaction with materials. We trained a deep neural network with unsupervised learning (Autoencoder) to reconstruct vibratory patterns elicited by human haptic exploration of different materials. The learned compressed representation (i.e. latent space) allows for classification of material categories (i.e. plastic, stone, wood, fabric, leather/wool, paper, and metal). More importantly, distances between these categories in the latent space resemble perceptual distances, suggesting a similar coding. We could further show, that the temporal tuning of the emergent latent dimensions is similar to properties of human tactile receptors.
Proanthocyanidin-enriched cranberry extract induces resilient bacterial community dynamics in a gnotobiotic mouse model
Authors: Neto Catherine C. , Mortzfeld Benedikt M. , Turbitt John R. , Bhattarai Shakti K. , Yeliseyev Vladimir , DiBenedetto Nicholas , Bry Lynn , Bucci Vanni 
Published: February 2021

AbstractCranberry consumption has numerous health benefits, with experimental reports showing its anti-inflammatory and anti-tumor properties. Importantly, microbiome research has demonstrated that the gastrointestinal bacterial community modulates host immunity, raising the question whether the cranberry-derived effect may be related to its ability to modulate the microbiome. Only a few studies have investigated the effect of cranberry products on the microbiome to date. Especially because cranberry is rich in dietary fibers, we do not know the extent of microbiome modulation that is caused solely by polyphenols, particularly proanthocyanidins (PACs). Since previous work has only focused on the long-term effects of cranberry extracts, in this study we investigated the effect of a water-soluble, polyphenol-rich cranberry juice extract (CJE) on the short-term dynamics of human-derived bacterial community in a gnotobiotic mouse model. CJE characterization revealed a high enrichment in PACs (57% PACs), the highest ever utilized in a microbiome study. In a 37-day experiment with a 10-day CJE intervention and 14-day recovery time, we profiled the microbiota via 16 rDNA sequencing and applied diverse time-series analytics methods to identify individual bacterial responses. We show that daily administration of CJE induces distinct dynamical patterns in bacterial abundances during and after treatment before recovering resiliently to pre-treatment levels. Specifically, we observed an increase of the immunomodulatory mucin degradingAkkermansia muciniphilaafter treatment, suggesting intestinal mucus accumulation due to CJE. Interestingly, this expansion coincided with an increase in the abundance of butyrate-producing Clostridia, a group of microbes known to promote numerous adaptive and innate anti-inflammatory phenotypes.
Exploring the interaction network of a synthetic gut bacterial community
Authors: Weiss Anna S. , Burrichter Anna G. , Durai Raj Abilash Chakravarthy , von Strempel Alexandra , Meng Chen , Kleigrewe Karin , Münch Philipp C. , Rössler Luis , Huber Claudia , Eisenreich Wolfgang , Jochum Lara M. , Göing Stephanie , Jung Kirsten , Sanchez Alvaro , Stecher Bärbel 
Published: February 2021

AbstractA key challenge in microbiome research is to predict functionality from microbial community composition. As central microbiota functions are determined by bacterial community networks it is important to gain insight into the principles that govern bacteria-bacteria interactions. Here, we focused on growth and metabolic interactions of the Oligo-Mouse-Microbiota (OMM12) synthetic bacterial community, which is increasingly used as model system in gut microbiome research. Using a bottom-up approach, we uncovered the directionality of strain-strain interactions in mono- and pairwise co-culture experiments, as well as in community batch culture. Metabolomics analysis of spent culture supernatant of individual strains in combination with genome-informed pathway reconstruction provided insights into the metabolic potential of the individual community members. Thereby, we could show that the OMM12interaction network is shaped by both, exploitative and interference competitionin vitro.In particular,Enterococcus faecalisKB1 was identified as important driver of community composition by affecting the abundance of several other consortium members. Together, this study gives fundamental insight into key drivers and mechanistic basis of the OMM12interaction network, which serves as knowledge base for future mechanistic studies.
Local Accumulation of Axonal Mitochondria in the Optic Nerve Glial Lamina Precedes Myelination
Authors: Wilkison Samantha J. , Bright Cora L. , Vancini Ricardo , Song Daniel J. , Bomze Howard M. , Cartoni Romain 
Published: February 2021

AbstractMitochondria are essential for neurons and must be optimally distributed along their axon to fulfil local functions. A high density of mitochondria has been observed in retinal ganglion cell (RGC) axons of an unmyelinated region of the optic nerve, called the glial lamina (GL) in mouse (lamina cribrosa in human). In glaucoma, the world’s leading cause of irreversible blindness, the GL is the epicenter of RGC degeneration and is connected to mitochondrial dysfunction. It is generally accepted that the local accumulation of mitochondria in the GL is established due to the higher energy requirement of unmyelinated axons. Here we revisit the connection between mitochondrial positioning and myelin in RGC axons. We show that the high density of mitochondria in the GL is restricted to larger axons and is established before myelination. Thus, contrary to a longstanding belief in the field, the myelination pattern is not responsible for the establishment of the local accumulation of mitochondria in GL axons. Our findings open new research avenues likely critical to understanding the pathophysiology of glaucoma.
Defining kinetic roles of transcriptional activators in the early Drosophila embryo
Authors: Harden Timothy T. , Vincent Ben J. , DePace Angela H. 
Published: February 2021

SUMMARYMost animal transcription factors are categorized as activators or repressors without specifying their mechanisms of action. Defining their specific roles is critical for deciphering the logic of transcriptional regulation and predicting the function of regulatory sequences. Here, we define the kinetic roles of three activating transcription factors in the Drosophila embryo—Zelda, Bicoid and Stat92E—by introducing their binding sites into theeven skippedstripe 2 enhancer and measuring transcriptional output with live imaging. We find that these transcription factors act on different subsets of kinetic parameters, and these subsets can change over the course of nuclear cycle (NC) 14. These transcription factors all increase the fraction of active nuclei. Zelda dramatically shortens the time interval between the start of NC 14 and initial activation, and Stat92E increases the duration of active transcription intervals throughout NC 14. Zelda also decreases the time intervals between instances of active transcription early in NC 14, while Stat92E does so later. Different transcription factors therefore play distinct kinetic roles in activating transcription; this has consequences for understanding both regulatory DNA sequences as well as the biochemical function of transcription factors.
The Diameter Factor of Aligned Membranes Facilitates Cutaneous Wound Healing by Promoting Epithelialization in an Immune Way
Authors: Wang Chenbing , Chu Chenyu , Zhao Xiwen , Hu Chen , Liu Li , Li Jidong , Qu Yili , Man Yi 
Published: February 2021

AbstractTopographical properties (such as pattern and diameter) of biomaterials play important roles in influencing cell activities and manipulating the related immune response during the skin wound healing. We prepared aligned electrospinning membranes with different fiber diameters including 319±100 nm (A300), 588±132 nm (A600) and 1048±130 nm (A1000). The A300 membranes significantly improved cell proliferation and spreading, and facilitated skin wound healing (epithelization and vascularization) with the regeneration of hair follicles. The transcriptome revealed the underlying molecular mechanism that A300 could promote macrophages transformation to reparative phenotypes with highly expressed IL10 and TGFβ, subsequently promoting epidermal cell migration via secreting matrix metalloproteinases 12 (MMP12). All the results indicate the A300 to be a potential candidate for guided skin regeneration applications.Graphic abstract
Termination of DNA replication at Tus-terbarriers results in under-replication of template DNA
Authors: Jameson Katie H. , Rudolph Christian J. , Hawkins Michelle 
Published: February 2021

ABSTRACTThe complete and accurate duplication of genomic information is vital to maintain genome stability in all domains of life. InEscherichia coli, replication termination, the final stage of the duplication process, is confined to the ‘replication fork trap’ region by multiple unidirectional fork barriers formed by the binding of Tus protein to genomictersites. Termination typically occurs away from Tus-tercomplexes, but they become part of the fork fusion process when a delay to one replisome allows the second to travel more than halfway around the chromosome. In this instance, replisome progression is blocked at the non-permissive interface of Tus-terand termination occurs when a converging replisome meets the non-permissive interface. To investigate the consequences of replication fork fusion at Tus-tercomplexes, we established a plasmid-based replication system where we could mimic the termination process at Tus-ter in vitro. We developed a termination mapping assay to measure leading strand replication fork progression and demonstrate that the DNA template is under-replicated by 15-24 bases when replication forks fuse at Tus-tercomplexes. This gap could not be closed by the inclusion of lagging strand processing enzymes as well as several helicases that promote DNA replication. Our results indicate that accurate fork fusion at Tus-terbarriers requires further enzymatic processing, highlighting large gaps that still exist in our understanding of the final stages of chromosome duplication and the evolutionary advantage of having a replication fork trap.
An integrated multi-wavelength SCATTIRSTORM microscope combining TIRFM and IRM modalities for imaging cellulases and other processive enzymes
Authors: Nong Daguan , Haviland Zachary K. , Kuntz Kate Vasquez , Tien Ming , Anderson Charles T. , Hancock William O. 
Published: February 2021

AbstractWe describe a multimodal SCATTIRSTORM microscope for visualizing processive enzymes moving on immobilized substrates. The instrument combines Interference Reflection Microscopy (IRM) with multi-wavelength Total Internal Reflectance Fluorescence Microscopy (TIRFM). The microscope can localize quantum dots with a precision of 2.8 nm at 100 frames/s, and was used to image the dynamics of the cellulase, Cel7a interacting surface-immobilized cellulose. The instrument, which was built with off-the-shelf components and controlled by custom software, is suitable for tracking other degradative enzymes such as collagenases, as well as motor proteins moving along immobilized tracks.
Early functional and cognitive declines measured by auditory evoked cortical potentials in Alzheimer’s disease mice
Authors: Mei Ling , Liu Li-Man , Chen Kaitian , Zhao Hong-Bo 
Published: February 2021

AbstractAlzheimer’s disease (AD) is characterized with a progressive loss of memory and cognitive decline. However, assessment of AD-associated functional and cognitive changes is still a big challenge. Auditory evoked cortical potential (AECP) is an event-related potential reflecting not only neural activation in the auditory cortex but also cognitive activity in the brain. In this study, we used the subdermal needle electrodes with the same electrode setting as the auditory brainstem response (ABR) recording and recorded AECP in normal aging CBA/CaJ mice and APP/PS1 AD mice. AECP in mice usually appeared three positive peaks, i.e., P1, P2, and P3, and three corresponding negative peaks N1, N2, and N3. In normal aging CBA mice, the early sensory peaks P1, N1, and P2 were reduced as age increased, whereas the later cognitive peaks N2, P3, and N3 were increased or had no changes with aging. Moreover, the latency of P1 peak was increased as age increased, although the latencies of later peaks had significant reduction with aging. In AD mice, peak P1 was significantly reduced in comparison with wild-type (WT) littermates at young ages, proceeding AD phenotype presentation. In particular, the later cognitive peak P3 was diminished after 3 months old, different from normal aging effect. However, the latencies of AECP peaks in AD mice generally had no significant delay or changes with aging. Finally, consistent with AECP changes, the accumulation of amyloid precursor protein (APP) at the auditory cortex was visible in AD mice as early as 2 months old. These data suggest that AECP could serve as an early, noninvasive, and objective biomarker for detecting AD and AD-related dementia.
Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants
Authors: Wang Lingshu , Zhou Tongqing , Zhang Yi , Yang Eun Sung , Schramm Chaim A. , Shi Wei , Pegu Amarendra , Oloninyi Olamide K. , Ransier Amy , Darko Samuel , Narpala Sandeep R. , Hatcher Christian , Martinez David R. , Tsybovsky Yaroslav , Phung Emily , Abiona Olubukola M. , Cale Evan M. , Chang Lauren A. , Corbett Kizzmekia S. , DiPiazza Anthony T. , Gordon Ingelise J. , Leung Kwanyee , Liu Tracy , Mason Rosemarie D. , Nazzari Alexandra , Novik Laura , Olia Adam S. , Doria-Rose Nicole A. , Stephens Tyler , Stringham Christopher D. , Talana Chloe Adrienna , Teng I-Ting , Wagner Danielle , Widge Alicia T. , Zhang Baoshan , Roederer Mario , Ledgerwood Julie E. , Ruckwardt Tracy J. , Gaudinski Martin R. , Baric Ralph S. , Graham Barney S. , McDermott Adrian B. , Douek Daniel C. , Kwong Peter D. , Mascola John R , Sullivan Nancy J. , Misasi John 
Published: February 2021

AbstractThe emergence of highly transmissible SARS-CoV-2 variants of concern (VOC) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identify four receptor-binding domain targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 12 variants including the B.1.1.7 and B.1.351 VOCs. Two of them are ultrapotent, with sub-nanomolar neutralization titers (IC50<0.0006 to 0.0102 μg/mL; IC80 < 0.0006 to 0.0251 μg/mL). We define the structural and functional determinants of binding for all four VOC-targeting antibodies, and show that combinations of two antibodies decrease thein vitrogeneration of escape mutants, suggesting potential means to mitigate resistance development. These results define the basis of therapeutic cocktails against VOCs and suggest that targeted boosting of existing immunity may increase vaccine breadth against VOCs.One Sentence SummaryUltrapotent antibodies from convalescent donors neutralize and mitigate resistance of SARS-CoV-2 variants of concern.
Different underlying mechanisms for high and low arousal in probabilistic learning in humans
Authors: Ciria Luis F. , Suárez-Pinilla Marta , Williams Alex G. , Jagannathan Sridhar R. , Sanabria Daniel , Bekinschtein Tristán A. 
Published: February 2021

ABSTRACTHumans are uniquely capable of adapting to highly changing environments by updating relevant information and adjusting ongoing behaviour accordingly. Here we show how this ability —termed cognitive flexibility— is differentially modulated by high and low arousal fluctuations. We implemented a probabilistic reversal learning paradigm in healthy participants as they transitioned towards sleep or physical extenuation. The results revealed, in line with our pre-registered hypotheses, that low arousal leads to diminished behavioural performance through increased decision volatility, while performance decline under high arousal was attributed to increased perseverative behaviour. These findings provide evidence for distinct patterns of maladaptive decision-making on each side of the arousal inverted u-shaped curve, differentially affecting participants’ ability to generate stable evidence-based strategies, and introduces wake-sleep and physical exercise transitions as complementary experimental models for investigating neural and cognitive dynamics.
H3K36 methylation and DNA-binding both promote Ioc4 recruitment and Isw1b remodeller function
Authors: Li Jian , Bergmann Lena , de Almeida Andreia Rafael , Webb Kimberly M. , Gogol Madelaine M. , Voigt Philipp , Liu Yingfang , Liang Huanhuan , Smolle Michaela M. 
Published: February 2021

AbstractThe Isw1b chromatin-remodelling complex is specifically recruited to gene bodies to help retain pre-existing histones during transcription by RNA polymerase II. Recruitment is dependent on H3K36 methylation and the Isw1b subunit Ioc4, which contains an N-terminal PWWP domain. Here, we present the crystal structure of the Ioc4-PWWP domain, including a detailed functional characterization of the domain on its own as well as in the context of full-length Ioc4 and the Isw1b remodeller. The Ioc4-PWWP domain preferentially binds H3K36me3-containing nucleosomes. Its ability to bind DNA is required for nucleosome binding. It is also furthered by the unique insertion motif present in Ioc4-PWWP. The ability to bind H3K36me3 and DNA promote the interaction of full-length Ioc4 with nucleosomesin vitroand they are necessary for its recruitment to gene bodiesin vivo. Furthermore, a fully functional Ioc4-PWWP domain promotes efficient remodelling by Isw1b and the maintenance of ordered chromatinin vivo, thereby preventing the production of non-coding RNAs.
Targeted replacement of full-length CFTR in human airway stem cells by CRISPR/Cas9 for pan-mutation correction in the endogenous locus
Authors: Vaidyanathan Sriram , Baik Ron , Chen Lu , Bravo Dawn T. , Suarez Carlos J. , Abazari Shayda M. , Salahudeen Ameen A. , Dudek Amanda M. , Teran Christopher A. , Davis Timothy H. , Lee Ciaran M. , Bao Gang , Randell Scott H. , Artandi Steven E. , Wine Jeffrey J. , Kuo Calvin J. , Desai Tushar J. , Nayak Jayakar V. , Sellers Zachary M. , Porteus Matthew H. 
Published: February 2021

AbstractCystic fibrosis (CF) is a monogenic disease caused by impaired production and/or function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Although we have previously shown correction of the most common pathogenic mutation, there are many other pathogenic mutations throughout the CF gene. An autologous airway stem cell therapy in which the CFTR cDNA is precisely inserted into the CFTR locus may enable the development of a durable cure for almost all CF patients, irrespective of the causal mutation. Here, we use CRISPR/Cas9 and two adeno-associated viruses (AAV) carrying the two halves of the CFTR cDNA to sequentially insert the full CFTR cDNA along with a truncated CD19 (tCD19) enrichment tag in upper airway basal stem cells (UABCs) and human bronchial basal stem cells (HBECs). The modified cells were enriched to obtain 60-80% tCD19+UABCs and HBECs from 11 different CF donors with a variety of mutations. Differentiated epithelial monolayers cultured at air-liquid interface showed restored CFTR function that was >70% of the CFTR function in non-CF controls. Thus, our study enables the development of a therapy for almost all CF patients, including patients who cannot be treated using recently approved modulator therapies.
Quantitative mapping of dense microtubule arrays in mammalian neurons
Authors: Katrukha Eugene A. , Jurriens Daphne , Pastene Desiree Salas , Kapitein Lukas C. 
Published: February 2021

ABSTRACTThe neuronal microtubule cytoskeleton underlies the polarization and proper functioning of neurons, amongst others by providing tracks for motor proteins that drive intracellular transport. Different subsets of neuronal microtubules, varying in composition, stability and motor preference, are known to exist, but the high density of microtubules has so far precluded mapping their relative abundance and three-dimensional organization. Here we use different super-resolution techniques (STED, Expansion Microscopy) to explore the nanoscale organization of the neuronal microtubule network. This revealed that in dendrites stable, acetylated microtubules are enriched in the core of the dendritic shaft, while dynamic, tyrosinated microtubules enrich near the plasma membrane, thus forming a shell around the stable microtubules. Moreover, using a novel analysis pipeline we quantified the absolute number of acetylated and tyrosinated microtubules within dendrites and found that they account for 65-75% and ∼20-30% of all microtubules, respectively, leaving only few microtubules that do not fall in either category. Because these different microtubule subtypes facilitate different motor proteins, these novel insights help to understand the spatial regulation of intracellular transport.
Activity-induced fluidization of arrested coalescence in fusion of cellular aggregates
Authors: Ongenae Steven , Cuvelier Maxim , Vangheel Jef , Ramon Herman , Smeets Bart 
Published: February 2021

AbstractAt long time scales, tissue spheroids may flow or appear solid depending on their capacity to reorganize their internal structure. Understanding the relationship between intrinsic mechanical properties at the single cell level, and the tissue spheroids dynamics at the long-time scale is key for artificial tissue constructs, which are assembled from multiple tissue spheroids that over time fuse to form coherent structures. The dynamics of this fusion process are frequently analyzed in the framework of liquid theory, wherein the time scale of coalescence of two droplets is governed by its radius, viscosity and surface tension. In this work, we extend this framework to glassy or jammed cell behavior which can be observed in spheroid fusion. Using simulations of an individual-cell based model, we demonstrate how the spheroid fusion process can be steered from liquid to arrested by varying active cell motility and repulsive energy as established by cortical tension. The divergence of visco-elastic relaxation times indicates glassy relaxation near the transition towards arrested coalescence. Finally, we investigate the role of cell growth in spheroid fusion dynamics. We show that the presence of cell division introduces plasticity in the material and thereby increases coalescence during fusion.