bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermediate adhesion maximizes fluidity and migration velocity of multicellular clusters
Authors: Roy U. , Mugler A. 
Published: July 2020

ABSTRACTCollections of cells exhibit coherent migration during morphogenesis, cancer metastasis, and wound healing. In many cases, bigger clusters split, smaller sub-clusters collide and reassemble, and gaps continually emerge. The connections between cell-level adhesion and cluster-level dynamics, as well as the resulting consequences for cluster properties such as migration velocity, remain poorly understood. Here we investigate collective migration of one- and two-dimensional cell clusters that collectively track chemical gradients using a mechanism based on contact inhibition of locomotion. We develop both a minimal description based on the lattice gas model of statistical physics, and a more realistic framework based on the cellular Potts model which captures cell shape changes and cluster rearrangement. In both cases, we find that cells have an optimal adhesion strength that maximizes cluster migration speed. The optimum negotiates a tradeoff between maintaining cell-cell contact and maintaining cluster fluidity, and we identify maximal variability in the cluster aspect ratio as a revealing signature. Our results suggest a collective benefit for intermediate cell-cell adhesion.SIGNIFICANCECells have been observed to migrate faster and more efficiently in clusters than as individuals. We conjecture that adhesion among cells and with the extracellular environment plays an important role in achieving higher-speed for the entire cluster. We carry out our analyses analytically and computationally, by employing a simplistic one-dimensional model and a realistic two-dimensional model which capture the essential features of multicellular migration. Our study demonstrates that an optimal cell-cell adhesion, which corresponds to maximal cellular rearrangement and loose packing, leads to a higher migration velocity for a multicellular cluster, acting as a crucial factor in effective movement of a collection of cells in a coordinated and directed fashion.
Spectral Signatures of L-DOPA-Induced Dyskinesia Depend on L-DOPA Dose and are Suppressed by Ketamine
Authors: Ye Tony , Bartlett Mitchell J. , Sherman Scott J. , Falk Torsten , Cowen Stephen L. 
Published: July 2020

AbstractL-DOPA-induced dyskinesias (LID) are debilitating motor symptoms of dopamine-replacement therapy for Parkinson’s disease (PD) that emerge after years of L-DOPA treatment. While there is an abundance of research into the cellular and synaptic origins of LID, less is known about how LID impacts systems-level circuits and neural synchrony, how synchrony is affected by the dose and duration of L-DOPA exposure, or how potential novel treatments for LID, such as sub-anesthetic ketamine, alter this activity. Sub-anesthetic ketamine treatments have recently been shown to reduce LID, and ketamine is known to affect neural synchrony. To investigate these questions, we measured movement and local-field potential (LFP) activity from the motor cortex (M1) and the striatum of preclinical rodent models of PD and LID. In the first experiment, we investigated the effect of the LID priming procedures and L-DOPA dose on neural signatures of LID. Two common priming procedures were compared: a high-dose procedure that exposed unilateral 6-hydroxydopamine-lesioned rats to 12 mg/kg L-DOPA for 7 days, and a low-dose procedure that exposed rats to 7 mg/kg L-DOPA for 21 days. Consistent with reports from other groups, 12 mg/kg L-DOPA triggered LID and 80-Hz oscillations; however, these 80-Hz oscillations were not observed after 7 mg/kg administration despite clear evidence of LID, indicating that 80-Hz oscillations are not an exclusive signature of LID. We also found that weeks-long low-dose priming resulted in the emergence of non-oscillatory broadband gamma activity (> 30 Hz) in the striatum and theta-to-high-gamma cross-frequency coupling (CFC) in M1. In a second set of experiments, we investigated how ketamine exposure affects spectral signatures of low-dose L-DOPA priming. During each neural recording session, ketamine was delivered through 5 injections (20 mg/kg,i.p.) administered every 2 hours. We found that ketamine exposure suppressed striatal broadband gamma associated with LID but enhanced M1 broadband activity. We also found that M1 theta-to-high-gamma CFC associated with the LID on-state was suppressed by ketamine. These results suggest that ketamine’s therapeutic effects are region specific. Our findings also have clinical implications, as we are the first to report novel oscillatory signatures of the common low-dose LID priming procedure that more closely models dopamine replacement therapy in individuals with PD. We also identify neural correlates of the anti-dyskinetic activity of sub-anesthetic ketamine treatment.
Characterization of gene repression by designed transcription activator-like effector dimer proteins
Authors: Becker NA , Peters JP , Schwab TL , Phillips WJ , Wallace JP , Clark KJ , Maher LJ 
Published: July 2020

AbstractGene regulation by control of transcription initiation is a fundamental property of living cells. Much of our understanding of gene repression originated from studies of theE. coli lacoperon switch, where DNA looping plays an essential role. To validate and generalize principles fromlacfor practical applications, we previously described artificial DNA looping driven by designed Transcription Activator-Like Effector Dimer (TALED) proteins. Because TALE monomers bind the idealized symmetricallacoperator sequence in two orientations, our prior studies detected repression due to multiple DNA loops. We now quantitatively characterize gene repression in livingE. coliby a collection of individual TALED loops with systematic loop length variation. Fitting of a thermodynamic model allows unequivocal demonstration of looping and comparison of the engineered TALED repression system with the natural lac repressor system.Statement of SignificanceWe are designing and testing in living bacteria artificial DNA looping proteins engineered based on principles learned from studies of theE. colilac repressor. The engineered proteins are based on artificial dimers of Transcription Activator-Like Effector (TALE) proteins that have programmable DNA binding specificities. The current work is the first to create unique DNA repression loops using this approach. Systematic study of repression as a function of loop size, with data fitting to a thermodynamic model, now allows this system to be compared in detail with lac repressor loops, and relevant biophysical parameters to be estimated. This approach has implications for the artificial regulation of gene expression.
Human saphenous vein provides a unique source of anti-calcific pericytes for prosthetic cardiac valve engineering
Authors: Jover Eva , Fagnano Marco , Meng William Cathery , Slater Sadie , Pisanu Emanuela , Gu Yue , Avolio Elisa , Bruno Domenico , Baz-Lopez Daniel , Faulkner Ashton , Carrabba Michele , Angelini Gianni , Madeddu Paolo 
Published: July 2020

AbstractAimsTissue engineering seeks to improve the longevity of prosthetic heart valves, but the cell source of choice has yet to be determined. This study aimed to establish a mechanistic rationale supporting the suitability of human adventitial pericytes (APCs).Methods and ResultsAntigenicallyAPCs were immunomagnetically sorted from saphenous vein leftovers of patients undergoing coronary artery surgery and antigenically characterized for purity. Unlike bone marrow-derived mesenchymal stromal cells (BM-MSCs), APCs were resistant to osteochondrogenic induction by high phosphate (HP), as assessed by cytochemistry and expression of osteogenic markers. MiR-132 is natively expressed by APCs, with copy numbers being enhanced by HP stimulation.In silicobioinformatic analysis, followed by luciferase assays in HEK293 cells and miR-132 titration using agomiR and antagomiR in APCs, demonstrated that several osteochondrogenic genes were negatively regulated by miR-132. Among these, the glycolytic marker GLUT1 was downregulated in HP-stimulated APCs. In contrast to BM-APCs, APCs showed no increase in glycolysis under HP. Interestingly, incubation with APC-derived conditioned medium conferred swine cardiac valves with resistance to osteogenic transformation by HP; whereas, conditioned media from miR-132-knocked-down APCs failed to prevent the expression of these markers. Finally, we demonstrated the feasibility of using APCs to engineer bovine pericardium patches. APCs proliferate in the patch and secrete factors able to attract aortic endothelial cells under HP.ConclusionsHuman APCs are resistant to calcification compared with BM-MSCs and convey the anti-calcific phenotype to heart valves through miR-132. These findings may open new important avenues for prosthetic valve cellularization.
Primary and secondary motoneurons use different calcium channel types to control escape and swimming behaviors in zebrafish
Authors: Wen Hua , Eckenstein Kazumi , Weihrauch Vivien , Stigloher Christian , Brehm Paul 
Published: July 2020

AbstractThe escape response and rhythmic swimming in zebrafish are distinct behaviors mediated by two functionally distinct motoneuron (Mn) types. The primary (1°Mn) type depresses, has a large quantal content (Qc), and a high release probability (Pr). Conversely, the secondary (2°Mn) type facilitates and has low and variable Qc and Pr. This functional duality matches well the distinct associated behaviors, with the 1°Mn providing the strong, singular C-bend initiating escape and the 2°Mn confers weaker, rhythmic contractions. Contributing to these functional distinctions is our identification of P/Q type calcium channels mediating transmitter release in 1°Mns and N type channels in 2°Mns. Remarkably, despite these functional and behavioral distinctions, all ~15 individual synapses on each muscle cell are shared by a 1°Mn bouton and at least one 2°Mn bouton. This novel blueprint of synaptic sharing provides an efficient way of controlling two different behaviors at the level of a single postsynaptic cell.
Comparison of HLA ligand elution data and binding predictions reveals varying prediction performance for the multiple motifs recognized by HLA-DQ2.5
Authors: Koşaloğlu-Yalçın Zeynep , Sidney John , Chronister William , Peters Bjoern , Sette Alessandro 
Published: July 2020

ABSTRACTBinding prediction tools are commonly used to identify peptides presented on MHC class II molecules. Recently, a wealth of data in the form of naturally eluted ligands has become available and discrepancies between ligand elution data and binding predictions have been reported. Quantitative metrics for such comparisons are currently lacking. In this study, we assessed how efficiently MHC class II binding predictions can identify naturally eluted peptides, and investigated instances with discrepancies between the two methods in detail. We found that, in general, MHC class II eluted ligands are predicted to bind to their reported restriction element with high affinity. But, for several studies reporting an increased number of ligands that were not predicted to bind, we found that the reported MHC restriction was ambiguous. Additional analyses determined that most of the ligands predicted to not bind are either weak binders or predicted to bind other co-expressed MHC class II molecules. For selected alleles, we addressed discrepancies between elution data and binding predictions by experimental measurements, and found that predicted and measured affinities correlate well. For DQA1*05:01/DQB1*02:01 (DQ2.5) however, binding predictions did miss several peptides that were determined experimentally to be binders. For these peptides and several known DQ2.5 binders we determined key residues for conferring DQ2.5 binding capacity, which revealed that DQ2.5 utilizes two different binding motifs, of which only one is predicted effectively. These findings have important implications for the interpretation of ligand elution data and for the improvement of MHC class II binding predictions.
Nuclear GSK-3β and Oncogenic KRas Promote Expansion of Terminal Duct Cells and the Development of Intraductal Papillary Mucinous Neoplasm
Authors: Ding Li , Roeck Kaely , Zhang Cheng , Zidek Brooke , Rodman Esther , Hernandez-Barco Yasmin Genevieve , Zhang Jin-San , Bamlet William R. , Oberg Ann L. , Zhang Lizhi , Bardeesy Nabeel , Li Hu , Billadeau Daniel D. 
Published: July 2020

AbstractIntraductal papillary mucinous neoplasm (IPMN) represents one type of pancreatic ductal adenocarcinoma (PDA) precursor lesion, however its cell-of-origin remains unclear. Here we describe a new mouse model in which pancreas-specific Cre activation of a nuclear glycogen synthase kinase-3β transgene is combined with oncogenic KRas (referred to as KNGC). KNGC mice show accumulation of neoplastic ductal cells at 4-weeks that progressively develop into IPMN with low-grade dysplasia in advanced age. RNA-sequencing identified expression of several terminal duct cell lineage genes including Agr2 and Aqp5. Interestingly, Aqp5, a water channel, was found to be required for the development of IPMN lesions in KNGC mice. Staining of human IPMN samples indicates that these preneoplastic lesions also arise from expansion of the terminal duct population. Altogether, these data highlight the utility of the KNGC model for understanding the biology of IPMN and potential utility in defining predictive biomarkers of IPMN – PDA development.Statement of significanceUnderstanding the cell-of-origin of IPMN is crucial to developing early detection methods that specifically target aggressive precursors of PDA. This work, using a novel mouse model, identifies Aqp5-modulated development of Agr2+terminal ducts that could potentially serve as a clinical biomarker for IPMN.
TheDrosophilaEGFR ligand mSpitz is delivered to cytoplasmic capes at sites of non-canonical RNA export on the nuclear envelopeviathe endosomal system
Authors: Mattie Floyd J. , Kumar Praveen , Travor Mark D. , Browder Kristen C. , Thomas Claire M. 
Published: July 2020

AbstractNuclear-cytoplasmic communication is not limited to nuclear pores, with both proteins and RNA using alternative routes between these compartments. We previously characterized cytoplasmic capes (large invaginations of the nuclear envelope inDrosophila), which are enriched for the membrane-bound EGF receptor ligand mSpitz, endosome-related organelles and ubiquitylated proteins. Closely associated with capes are groups of perinuclear vesicles resembling those seen at sites of RNP exportviaa budding mechanism. Here, we demonstrate that mSpitz delivery to capes requires passage through the endosomal system. We also show that capes are closely associated with sites of non-canonical RNP export as well as the dFrizzled2 receptor C terminal fragment, a core component of this export pathway. Video microscopy of glands in intact larvae indicates that cytoplasmic capes are stable structures that persist for at least 90 minutes without conspicuous growth. We further show that capes appear with the growth of the salivary gland rather than its developmental stage. Finally, we show that the large F-actin binding protein βH-spectrin, which modulates endosomal trafficking, as well as its partner α-spectrin are required for cape formation. Cytoplasmic capes therefore represent a subspecialization of the nuclear envelope where endosomal trafficking and RNP export are closely associated.SynopsisWe further characterize large invaginations of the nuclear envelope called cytoplasmic capes inDrosophila. The EGF receptor ligand mSpitz is concentrated in capes and we show that it traffics to this compartmentviaendosomes. The presence of RNP and the dFrizzled2 receptor C-terminal fragment also indicates that non-canonical RNA export is concentrated at capes.In vivoimaging shows that capes persist for at least 90 minutes. Finally, the large F-actin crosslinker α/β◻-spectrin is shown to be required for cape formation.Abstract Figure
Cetacean habitat modelling to inform conservation management, marine spatial planning, and as a basis for anthropogenic threat mitigation in Indonesia
Authors: Sahri Achmad , Putra Mochamad Iqbal Herwata , Mustika Putu Liza Kusuma , Kreb Danielle , Murk Albertinka J. 
Published: July 2020

ABSTRACTIndonesia harbours a high diversity of cetaceans, yet effective conservation is hampered by a lack of knowledge about cetacean spatial distribution and habitat preferences. This study aims to address this knowledge gap at an adequate resolution to support national cetacean conservation and management planning. Maximum Entropy (Maxent) modelling was used to map the distribution of 15 selected cetacean species in seven areas within Indonesian waters using recent cetacean presence datasets as well as environmental predictors (topographic and oceanographic variables). We then combined the individual species suitable habitat maps and overlaid them with provincial marine spatial planning (MSP) jurisdictions, marine protected areas (MPAs), oil and gas contract areas, and marine traffic density. Our results reflect a great heterogeneity in distribution among species and within species among different locations. This heterogeneity reflects an interrelated influence of topographic variables and oceanographic processes on the distribution of cetacean species. Bathymetry, distance to-coast and −200m isobaths, and Chl and SST were important variables influencing distribution of most species in many regions. Areas rich in species were mainly related to high coastal or insular-reef complexity, representing high productivity and upwelling-modified waters. Although some important suitable habitats currently fall within MPAs, other areas are not and overlap with oil and gas exploration activities and marine traffic, indicating potentially high risk areas for cetaceans. The results of this study can support national cetacean conservation and management planning, and be used to reduce or avoid adverse anthropogenic threats. We advise considering currently unprotected suitable cetacean habitats in MPA and MSP development.
An fMRI dataset in response to “The Grand Budapest Hotel”, a socially-rich, naturalistic movie
Authors: di Oleggio Castello Matteo Visconti , Chauhan Vassiki , Jiahui Guo , Gobbini M. Ida 
Published: July 2020

AbstractNaturalistic stimuli evoke strong, consistent, and information-rich patterns of brain activity, and engage large extents of the human brain. They allow researchers to compare highly similar brain responses across subjects, and to study how complex representations are encoded in brain activity. Here, we describe and share a dataset where 25 subjects watched part of the feature film “The Grand Budapest Hotel” by Wes Anderson. The movie has a large cast with many famous actors. Throughout the story, the camera shots highlight faces and expressions, which are fundamental to understand the complex narrative of the movie. This movie was chosen to sample brain activity specifically related to social interactions and face processing. This dataset provides researchers with fMRI data that can be used to explore social cognitive processes and face processing, adding to the existing neuroimaging datasets that sample brain activity with naturalistic movies.
Diversity in rest-activity patterns among Lake Malawi cichlid fishes suggests novel axis of habitat partitioning
Authors: Lloyd Evan , Chhouk Brian , Keene Alex C. , Albertson R. Craig 
Published: July 2020

AbstractAnimals display remarkable diversity in rest and activity patterns that are regulated by endogenous foraging strategies, social behaviors, and predator avoidance. Alteration in the circadian timing of activity or the duration of rest-wake cycles provide a central mechanism for animals to exploit novel niches. The diversity of the 3000+ cichlid species throughout the world provides a unique opportunity to examine variation in locomotor activity and rest. Lake Malawi alone is home to over 500 species of cichlids that display divergent behaviors and inhabit well-defined niches throughout the lake. These species are presumed to be diurnal, though this has never been tested systematically. Here, we measure locomotor activity across the circadian cycle in 12 cichlid species from divergent lineages and distinct habitats. We document surprising variability in the circadian time of locomotor activity and the duration of rest. In particular, we identify a single species,Tropheopssp. “red cheek” that is nocturnal. Nocturnal behavior was maintained when fish were provided shelter, but not under constant darkness, suggesting it results from acute response to light rather than an endogenous circadian rhythm. Finally, we show that nocturnality is associated with increased eye size, suggesting a link between visual processing and nighttime activity. Together, these findings identify diversity of locomotor behavior in Lake Malawi cichlids and provide a system for investigating the molecular and neural basis underlying the evolution of nocturnal activity.
Automatic processing of numerosity in human neocortex evidenced by occipital and parietal neuromagnetic responses
Authors: Van Rinsveld Amandine , Wens Vincent , Guillaume Mathieu , Beuel Anthony , Gevers Wim , De Tiège Xavier , Content Alain 
Published: July 2020

AbstractHumans and other animal species are endowed with the ability tosense, represent, and mentally manipulate the number of items in a set without needing to count them. One central hypothesis is that this ability relies on an automated functional system dedicated tonumerosity, the perception of the discrete numerical magnitude of a set of items. This system has classically been associated with intraparietal regions, however accumulating evidence in favor of an earlyvisual number sensecalls into question the functional role of parietal regions in numerosity processing. Targeting specifically numerosity among other visual features in the earliest stages of processing requires high temporal and spatial resolution. We used frequency-tagged magnetoencephalography (MEG) to investigate the early automatic processing of numerical magnitudes and measured the steady-state brain responses specifically evoked by numerical and other visual changes in the visual scene. The neuromagnetic responses showed implicit discrimination of numerosity, total occupied area, and convex hull. The source reconstruction corresponding to the implicit discrimination responses showed common and separate sources along the ventral and dorsal visual pathways. Occipital sources attested the perceptual salience of numerosity similarly to both other implicitly discriminable visual features. Crucially, we found parietal responses uniquely associated with numerosity discrimination, showing automatic processing of numerosity in the parietal cortex, even when not relevant to the task. Taken together, these results provide further insights into the functional roles of parietal and occipital regions in numerosity encoding along the visual hierarchy.Significance StatementApproximating the number of items in a set has been identified as a building block of mathematical cognition but the processing of numerosity is not fully understood. The natural correlation between numerosity and other visual features makes it difficult to test whether the number of items is a perceptual primitive or whether it needs to be recombined at a higher level. We used frequency-tagged magnetoencephalography to localize the implicit discrimination of numerosity within the visual hierarchy. We found that numerosity yielded occipital responses, supporting that the human visual system can grasp it at a single glance. Crucially, numerosity also yielded specific parietal responses, showing that numerosity is a perceptual primitive with a unique automatic involvement of parietal cortex.