bluuebunny/crossref_metadata_2025 huggingface dataset:
Adapting Kafka’s Ape to the Twenty-First Century: Gesture, Montage, and Performance in Antonietta De Lillo’sIl Signor Rotpeter
Authors: Luciano Bernadette , Burrow Steele
Published: April 2020

This article explores Italian filmmaker Antonietta De Lillo’s cinematic adaptation of Franz Kafka’s short story ‘A Report to an Academy’ in which she incorporates elements from both literary and visual media to create a ‘re-performance’ of an earlier performance, that of Kafka’s Rotpeter. De Lillo through the extensive use of gesture, montage, shift of focus, and other cinematic devices, interrupts and disrupts the narrative ‘report’ thereby ‘shocking’ the viewer in Brechtian fashion into an awareness of the fragility of identity and of the ‘ape’ nature that remains in all of us. De Lillo’s addition of an interview to Kafka’s monologue represents an innovation in Kafka adaptation and within this framework her first person/ape narrator Signor Rotpeter is allowed to respond to what she terms our ‘loss of humanity’. He provides first person/ape evidence of this loss both verbally and through his gestural complex, addressing the disconnect between young and old, the cruelty toward animals, and the violence of everyday life, prompting the viewer to reflect on the lives of those who, like the narrator Rotpeter, are desperately seeking a ‘way out’.
High variation in last male sperm precedence and genital morphology in the emerald damselfly, Lestes sponsa
Authors: Johansson Frank , Berger David , Höglund Jacob , Meyer-Lucht Yvonne , Rödin-Mörch Patrik , Sniegula Szymon , Watts Phillip C
Published: April 2020

In organisms in which individuals mate multiply, knowledge of the proportion of offspring sired by the last male to mate (P2) under field conditions is important for a thorough understanding of how sexual selection works in nature. In many insect groups, pronounced intraspecific variation in P2 is commonplace. Interestingly, however, in stark contrast to these observations, compilation of P2 data in dragonflies and damselflies (Odonata) indicates that a high P2, seldom below 0.95, is a feature of this taxon. Here we used double digest restriction-site associated DNA sequencing to generate a panel of single nucleotide polymorphisms (SNPs) with which we could determine paternity and estimate values of P2 in the offspring of 19 field-collected pairs of the emerald damselfly Lestes sponsa. We also estimated the relationship between P2 and male genital shape of 16 males using geometric morphometric analysis. P2 was variable (range = 0.0–1.0; mean = 0.5), and there was a marginally non-significant (P = 0.069) relationship between genital shape and P2, suggesting that males with a high P2 had an aedeagus with a broader tip. We suggest that the high P2-values reported in past studies in Odonata are partly due to the methods used to infer paternity. Use of SNPs to determine patterns of paternity and P2 in odonates is needed for a better appraisal of fitness in odonates, and would open many future avenues for use of odonates as models of sexual selection.
Virtual Block Group: A Scalable Blockchain Model with Partial Node Storage and Distributed Hash Table
Authors: Yu Bin , Li Xiaofeng , Zhao He
Published: April 2020

The inability to scale is one of the most concerning problems looming in blockchain systems, where every node has to store all contents of the ledger database locally, leading to centralization and higher operation costs. In this paper, we propose a model named virtual block group (VBG), which aims at addressing the node storage scalability problem. Adopting the VBG model, each node only needs to store part of block data and saves the VBG storage index to distributed hash table by taking block data as a resource, thus improving the query efficiency of block data. With the incentive mechanism of block data storage, and the storage verification and audit mechanism of block data, the security and reliability of block data storage can be ensured. The analysis and calculation show that this model saves hard drive storage space of the node to a greater extent with a shorter time of requesting block data, in the premise of ensuring secure and reliable block data. Compared to other technologies such as sharding, our model does not change the consensus mechanism or the network topology and retains the reliability and security of the original blockchain system.
Roi de guerre ou Roi de paix? Louis XV and the French monarchy, 1740–1748
Authors: Swann Julian
Published: April 2020

This article examines debate about the nature of the French monarchy during the early years of Louis XV’s personal rule. It argues that the king, his ministers and advisers as well as the wider French public were torn between traditional models of monarchy based upon the concept of a ‘roi de guerre’ and the diplomatic and human consequences of military conflict that had caused many to urge a more restrained, pacific projection of French power. In 1748, Louis XV offered a peace that reflected the desire to avoid a repetition of his predecessor’s errors, but France lacked the strength needed to impose a Pax Francia. The subsequent separation between the Bourbon dynasty and active military service did much to undermine the monarchy in the eyes of an increasingly patriotic public opinion.
Pressure torque of torsional Alfvén modes acting on an ellipsoidal mantle
Authors: Gerick F , Jault D , Noir J , Vidal J
Published: April 2020

We investigate the pressure torque between the fluid core and the solid mantle arising from magnetohydrodynamic modes in a rapidly rotating planetary core. A 2-D reduced model of the core fluid dynamics is developed to account for the non-spherical core–mantle boundary. The simplification of such a quasi-geostrophic model rests on the assumption of invariance of the equatorial components of the fluid velocity along the rotation axis. We use this model to investigate and quantify the axial torques of linear modes, focusing on the torsional Alfvén modes (TM) in an ellipsoid. We verify that the periods of these modes do not depend on the rotation frequency. Furthermore, they possess angular momentum resulting in a net pressure torque acting on the mantle. This torque scales linearly with the equatorial ellipticity. We estimate that for the TM calculated here topographic coupling to the mantle is too weak to account for the variations in the Earth’s length-of-day.
What Defines Different Modes of Snake Locomotion?
Authors: Jayne Bruce C
Published: April 2020

Synopsis

Animals move in diverse ways, as indicated in part by the wide variety of gaits and modes that have been described for vertebrate locomotion. Much variation in the gaits of limbed animals is associated with changing speed, whereas different modes of snake locomotion are often associated with moving on different surfaces. For several decades different types of snake locomotion have been categorized as one of four major modes: rectilinear, lateral undulation, sidewinding, and concertina. Recent empirical work shows that the scheme of four modes of snake locomotion is overly conservative. For example, during aquatic lateral undulation, the timing between muscle activity and lateral bending changes along the length of the snake, which is unlike terrestrial lateral undulation. The motor pattern used to prevent sagging while bridging gaps also suggests that arboreal lateral undulation on narrow surfaces or with a few discrete points of support has a different motor pattern than terrestrial lateral undulation when the entire length of the snake is supported. In all types of concertina locomotion, the distance from the head to the tail changes substantially as snakes alternately flex and then extend different portions of their body. However, snakes climbing cylinders with concertina exert forces medially to attain a purchase on the branch, whereas tunnels require pushing laterally to form an anchoring region. Furthermore, different motor patterns are used for these two types of concertina movement. Some snakes climb vertical cylinders with helical wrapping completely around the cylinder, whereas all other forms of concertina bend regions of the body alternately to the left and right. Current data support rectilinear locomotion and sidewinding as being distinct modes, whereas lateral undulation and concertina are best used for defining categories of gaits with some unifying similarities. Partly as a result of different motor patterns, I propose recognizing five and four distinct types of lateral undulation and concertina, respectively, resulting in a total of 11 distinct gaits previously recognized as only four.
A High-Fat Diet Increases Influenza A Virus-Associated Cardiovascular Damage
Authors: Siegers Jurre Y , Novakovic Boris , Hulme Katina D , Marshall Rebecca J , Bloxham Conor J , Thomas Walter G , Reichelt Mellissa E , Leijten Lonneke , van Run Peter , Knox Karen , Sokolowski Kamil A , Tse Brian W C , Chew Keng Yih , Christ Angelika N , Howe Greg , Bruxner Timothy J C , Karolyi Mario , Pawelka Erich , Koch Rebecca M , Bellmann-Weiler Rosa , Burkert Francesco , Weiss Günter , Samanta Romit J , Openshaw Peter J M , Bielefeldt-Ohmann Helle , van Riel Debby , Short Kirsty R
Published: April 2020

Background

Influenza A virus (IAV) causes a wide range of extrarespiratory complications. However, the role of host factors in these complications of influenza virus infection remains to be defined.

Methods

Here, we sought to use transcriptional profiling, virology, histology, and echocardiograms to investigate the role of a high-fat diet in IAV-associated cardiac damage.

Results

Transcriptional profiling showed that, compared to their low-fat counterparts (LF mice), mice fed a high-fat diet (HF mice) had impairments in inflammatory signaling in the lung and heart after IAV infection. This was associated with increased viral titers in the heart, increased left ventricular mass, and thickening of the left ventricular wall in IAV-infected HF mice compared to both IAV-infected LF mice and uninfected HF mice. Retrospective analysis of clinical data revealed that cardiac complications were more common in patients with excess weight, an association which was significant in 2 out of 4 studies.

Conclusions

Together, these data provide the first evidence that a high-fat diet may be a risk factor for the development of IAV-associated cardiovascular damage and emphasizes the need for further clinical research in this area.
Peering Through the Glass Ceiling: A Mixed Methods Study of Faculty Perceptions of Gender Barriers to Academic Advancement in Infectious Diseases
Authors: Manne-Goehler Jennifer , Krakower Douglas , Marcelin Jasmine , Salles Arghavan , del Rio Carlos , Stead Wendy
Published: April 2020

Background

The drivers of the gap in advancement between men and women faculty in academic Infectious Diseases (ID) remain poorly understood. This study sought to identify key barriers to academic advancement among faculty in ID and offer policy suggestions to narrow this gap.

Methods

During the 2019 IDWeek, we conducted focus groups with women faculty members at all ranks and men Full Professors, then we administered a brief survey regarding work-related barriers to advancement to the Infectious Disease Society of America (IDSA) membership. We report themes from the 4 focus group discussions that are most closely linked to policy changes and descriptive analyses of the complementary survey domains.

Results

Policy change suggestions fell into 3 major categories: (1) Policy changes for IDSA to implement; (2) Future IDWeek Program Recommendations; and (3) Policy Changes for IDSA to Endorse as Best Practices for ID Divisions. Among 790 faculty respondents, fewer women reported that their institutional promotion process was transparent and women Full Professors were significantly more likely to have been sponsored.

Conclusions

Sponsorship and informed advising about institutional promotions tracks may help to narrow the advancement gap. The Infectious Disease Society of America should consider ambitious policy changes within the society and setting expectations for best practices among ID divisions across the United States.
Molecular epidemiology of imipenem resistance in invasive Haemophilus influenzae infections in Germany in 2016
Authors: Lâm Thiên-Trí , Nürnberg Sebastian , Claus Heike , Vogel Ulrich
Published: April 2020

Background

The carbapenems imipenem and meropenem play an important role in the empirical anti-infective treatment of critically ill patients. Carbapenem resistance in Haemophilus influenzae (Hi) has rarely been reported.

Objectives

We provide prevalence data for resistance to carbapenems from laboratory surveillance of invasive Hi infections in Germany in 2016.

Methods

Phenotypic susceptibility testing against ampicillin, amoxicillin/clavulanate, cefotaxime and imipenem was carried out on 474 isolates from blood and CSF. The isolates were collected as part of the national laboratory surveillance programme. Imipenem-resistant strains were further tested for meropenem susceptibility. Molecular analysis was done by ftsI sequencing to detect mutations in PBP3, by acrR sequencing to detect alterations in the regulatory protein of the AcrAB-TolC efflux pump and by MLST.

Results

No resistance to meropenem was detected. Cefotaxime resistance was rare (n = 3; 0.6%). Imipenem resistance was found in 64 strains (13.5%) using gradient agar diffusion and was confirmed in 26 isolates by broth microdilution (5.5%). Imipenem resistance occurred predominantly in Hi that were β-lactamase negative but ampicillin resistant and in those that were β-lactamase positive but nevertheless amoxicillin/clavulanate resistant. This finding suggested a β-lactamase-independent mechanism. Accordingly, sequence analysis of PBP3 identified previously described mutations. MLST of the imipenem-resistant strains, which were all non-typeable Hi, revealed a high diversity.

Conclusions

We conclude that imipenem, but not meropenem, resistance is frequent in Hi. It is likely to be supported by PBP3 mutations.
Community antibiotic prescribing for children in France from 2015 to 2017: a cross-sectional national study
Authors: Trinh Nhung T H , Cohen Robert , Lemaitre Magali , Chahwakilian Pierre , Coulthard Gregory , Bruckner Tim A , Milic Dejan , Levy Corinne , Chalumeau Martin , Cohen Jérémie F
Published: April 2020

Objectives

To assess recent community antibiotic prescribing for French children and identify areas of potential improvement.

Methods

We analysed 221 768 paediatric (<15 years) visits in a national sample of 680 French GPs and 70 community paediatricians (IQVIA’s EPPM database), from March 2015 to February 2017, excluding well-child visits. We calculated antibiotic prescription rates per 100 visits, separately for GPs and paediatricians. For respiratory tract infections (RTIs), we described broad-spectrum antibiotic use and duration of treatment. We used Poisson regression to identify factors associated with antibiotic prescribing.

Results

GPs prescribed more antibiotics than paediatricians [prescription rate 26.1 (95% CI 25.9–26.3) versus 21.6 (95% CI 21.0–22.2) per 100 visits, respectively; P < 0.0001]. RTIs accounted for more than 80% of antibiotic prescriptions, with presumed viral RTIs being responsible for 40.8% and 23.6% of all antibiotic prescriptions by GPs and paediatricians, respectively. For RTIs, antibiotic prescription rates per 100 visits were: otitis, 68.1 and 79.8; pharyngitis, 67.3 and 53.3; sinusitis, 67.9 and 77.3; pneumonia, 80.0 and 99.2; bronchitis, 65.2 and 47.3; common cold, 21.7 and 11.6; bronchiolitis 31.6 and 20.1; and other presumed viral RTIs, 24.1 and 11.0, for GPs and paediatricians, respectively. For RTIs, GPs prescribed more broad-spectrum antibiotics [49.8% (95% CI 49.3–50.3) versus 35.6% (95% CI 34.1–37.1), P < 0.0001] and antibiotic courses of similar duration (P = 0.21). After adjustment for diagnosis, antibiotic prescription rates were not associated with season and patient age, but were significantly higher among GPs aged ≥50 years.

Conclusions

Future antibiotic stewardship campaigns should target presumed viral RTIs, broad-spectrum antibiotic use and GPs aged ≥50 years.
Collecting Deer Keds (Diptera: Hippoboscidae: Lipoptena Nitzsch, 1818 and Neolipoptena Bequaert, 1942) and Ticks (Acari: Ixodidae) From Hunter-Harvested Deer and Other Cervids
Authors: Poh Karen C , Skvarla Michael , Evans Jesse R , Machtinger Erika T
Published: April 2020

Deer keds (Diptera: Hippoboscidae: Lipoptena Nitzsch, 1818 and Neolipoptena Bequaert, 1942) are blood-feeding ectoparasites that primarily attack cervids and occasionally bite humans, while ticks may be found on cervids, but are more generalized in host choice. Recent detection of pathogens such as Anaplasma and Borrelia in deer keds and historical infections of tick-borne diseases provides reason to investigate these ectoparasites as vectors. However, previous methods employed to sample deer keds and ticks vary, making it difficult to standardize and compare ectoparasite burdens on cervids. Therefore, we propose a standardized protocol to collect deer keds and ticks from hunter-harvested deer, which combines previous methods of sampling, including timing of collections, dividing sections of the deer, and materials used in the collection process. We tested a three-section and a five-section sampling scheme in 2018 and 2019, respectively, and found that dividing the deer body into five sections provided more specificity in identifying where deer keds and ticks may be found on deer. Data from 2018 suggested that deer keds and ticks were found on all three sections (head, anterior, posterior), while data from 2019 suggested that more Ixodes scapularis were found on the head and deer keds were found on all body sections (head, dorsal anterior, dorsal posterior, ventral anterior, and ventral posterior). The protocol provides an efficient way to sample deer for deer keds and ticks and allows researchers to compare ectoparasite burdens across geographical regions. Furthermore, this protocol can be used to collect other ectoparasites from deer or other cervids.
The evolutionary origins of auxin transport: what we know and what we need to know
Authors: Vosolsobě Stanislav , Skokan Roman , Petrášek Jan
Published: April 2020

Auxin, represented by indole-3-acetic acid (IAA), has for a long time been studied mainly with respect to the development of land plants, and recent evidence confirms that canonical nuclear auxin signaling is a land plant apomorphy. Increasing sequential and physiological data show that the presence of auxin transport machinery pre-dates the emergence of canonical signaling. In this review, we summarize the present state of knowledge regarding the origins of auxin transport in the green lineage (Viridiplantae), integrating both data from wet lab experiments and sequence evidence on the presence of PIN-FORMED (PIN), PIN-LIKES (PILS), and AUXIN RESISTANT 1/LIKE-AUX1 (AUX1/LAX) homologs. We discuss a high divergence of auxin carrier homologs among algal lineages and emphasize the urgent need for the establishment of good molecular biology models from within the streptophyte green algae. We further postulate and discuss two hypotheses for the ancestral role of auxin in the green lineage. First, auxin was present as a by-product of cell metabolism and the evolution of its transport was stimulated by the need for IAA sequestration and cell detoxification. Second, auxin was primarily a signaling compound, possibly of bacterial origin, and its activity in the pre-plant green algae was a consequence of long-term co-existence with bacteria in shared ecological consortia.
Interacting galaxies in the IllustrisTNG simulations - I: Triggered star formation in a cosmological context
Authors: Patton David R , Wilson Kieran D , Metrow Colin J , Ellison Sara L , Torrey Paul , Brown Westley , Hani Maan H , McAlpine Stuart , Moreno Jorge , Woo Joanna
Published: April 2020

We use the IllustrisTNG cosmological hydrodynamical simulations to investigate how the specific star formation rates (sSFRs) of massive galaxies (M* > 1010 M⊙) depend on the distance to their closest companions. We estimate sSFR enhancements by comparing with control samples that are matched in redshift, stellar mass, local density, and isolation, and we restrict our analysis to pairs with stellar mass ratios of 0.1 to 10. At small separations (∼15 kpc), the mean sSFR is enhanced by a factor of 2.0 ± 0.1 in the flagship (110.7 Mpc)3 simulation (TNG100-1). Statistically significant enhancements extend out to 3D separations of 280 kpc in the (302.6 Mpc)3 simulation (TNG300-1). We find similar trends in the EAGLE and Illustris simulations, although their sSFR enhancements are lower than those in TNG100-1 by about a factor of two. Enhancements in IllustrisTNG galaxies are seen throughout the redshift range explored (0 ≤ $z$ < 1), with the strength of the enhancements decreasing with increasing redshift for galaxies with close companions. In order to more closely compare with observational results, we separately consider 2D projected distances between galaxies in IllustrisTNG. We detect significant sSFR enhancements out to projected separations of 260 kpc in TNG300-1, with projection effects diluting the size of the enhancements by about 20 per cent below 50 kpc. We find similar sSFR enhancements in TNG100-1 and Sloan Digital Sky Survey galaxies, with enhancements extending out to projected separations of about 150 kpc for star-forming galaxies at $z$ < 0.2. Finally, by summing over all separations, we estimate that the presence of closest companions boosts the average sSFR of massive galaxies in TNG100-1 by 14.5 per cent.
A closer look at the spur, blob, wiggle, and gaps in GD-1
Authors: de Boer T J L , Erkal D , Gieles M
Published: April 2020

The GD-1 stream is one of the longest and coldest stellar streams discovered to date, and one of the best objects for constraining the dark matter properties of the Milky Way. Using data from Gaia DR2, we study the proper motions (PMs), distance, morphology, and density of the stream to uncover small-scale perturbations. The PM cleaned data show a clear distance gradient across the stream, ranging from 7 to 12 kpc. However, unlike earlier studies that found a continuous gradient, we uncover a distance minimum at φ1 ≈ −40 deg, after which the distance increases again. We can reliably trace the stream between −85 < φ1 <15 deg, showing an even further extent to GD-1 beyond the earlier extension of Price-Whelan and Bonaca. We constrain the stream track and density using a Boolean matched filter approach and find three large under densities and significant residuals in the stream track lining up with these gaps. The gaps are located at φ1 = −36, −20, and −3 deg, with the gap at −3 deg being surrounded by a clear sinusoidal wiggle. We argue that this wiggle is due to a perturbation since it has the wrong orientation to come from a progenitor. We compute a total initial stellar mass of the stream segment of 1.58 ± 0.07 × 104 M⊙. With the extended view of the spur in this work, we argue that the spur may be unrelated to the adjacent gap in the stream. Finally, we show that an interaction with the Sagittarius dwarf can create features similar to the spur.
Shock breakouts from red supergiants: analytical and numerical predictions
Authors: Kozyreva Alexandra , Nakar Ehud , Waldman Roni , Blinnikov Sergei , Baklanov Petr
Published: April 2020

The signal from a shock breakout (SBO) is the first signature of a supernova explosion, apart from gravitational waves and neutrinos. Observational properties of SBOs, such as bolometric luminosity and colour temperature, are connected with the parameters of the supernova progenitor and explosion. The detection of SBOs or the cooling of SBOs will constrain the progenitor and explosion models of collapsing stars. Since the recent launch of the eROSITA on the SPECTRUM-RG spacecraft, the detection rate for SBOs is a few events per year. In the current study, we examine the analytical formulae derived by Shussman, Waldman & Nakar  (arXiv:1610.05323). We use four red supergiant models from their study, while running explosions with the radiation hydrodynamics code stella. We conclude that there is a good agreement between analytical and numerical approaches for bolometric luminosity and colour temperature during SBOs. The analytical formulae for the SBO signal based on the global supernova parameters can be used instead of running time-consuming numerical simulations. We define the spectral range in which analytical formulae for SBO spectra are valid. We provide an improved analytical expression for the SBO spectral energy distribution. We confirm that the colour temperature is dependent on radius derived by analytical studies and we suggest using early time observations to confine the progenitor radius. Additionally, we show the prediction for the SBO signal from red supergiants as seen by eROSITA.
Neutrinos and gravitational waves from magnetized neutrino-dominated accretion discs with magnetic coupling
Authors: Song Cui-Ying , Liu Tong , Wei Yun-Feng
Published: April 2020

Gamma-ray bursts (GRBs) might be powered by black hole (BH) hyperaccretion systems via the Blandford–Znajek (BZ) mechanism or neutrino annihilation from neutrino-dominated accretion flows (NDAFs). Magnetic coupling (MC) between the inner disc and BH can transfer angular momentum and energy from the fast-rotating BH to the disc. The neutrino luminosity and neutrino annihilation luminosity are both efficiently enhanced by the MC process. In this paper, we study the structure, luminosity, MeV neutrinos, and gravitational waves (GWs) of magnetized NDAFs (MNDAFs) under the assumption that both the BZ and MC mechanisms are present. The results indict that the BZ mechanism will compete with the neutrino annihilation luminosity to trigger jets under the different partitions of the two magnetic mechanisms. The typical neutrino luminosity and annihilation luminosity of MNDAFs are definitely higher than those of NDAFs. The typical peak energy of neutrino spectra of MNDAFs is higher than that of NDAFs, but similar to those of core-collapse supernovae. Moreover, if the MC process is dominant, then the GWs originating from the anisotropic neutrino emission will be stronger particularly for discs with high accretion rates.
PAM recognition by miniature CRISPR–Cas12f nucleases triggers programmable double-stranded DNA target cleavage
Authors: Karvelis Tautvydas , Bigelyte Greta , Young Joshua K , Hou Zhenglin , Zedaveinyte Rimante , Budre Karolina , Paulraj Sushmitha , Djukanovic Vesna , Gasior Stephen , Silanskas Arunas , Venclovas Česlovas , Siksnys Virginijus
Published: April 2020

In recent years, CRISPR-associated (Cas) nucleases have revolutionized the genome editing field. Being guided by an RNA to cleave double-stranded (ds) DNA targets near a short sequence termed a protospacer adjacent motif (PAM), Cas9 and Cas12 offer unprecedented flexibility, however, more compact versions would simplify delivery and extend application. Here, we present a collection of 10 exceptionally compact (422–603 amino acids) CRISPR–Cas12f nucleases that recognize and cleave dsDNA in a PAM dependent manner. Categorized as class 2 type V-F, they originate from the previously identified Cas14 family and distantly related type V-U3 Cas proteins found in bacteria. Using biochemical methods, we demonstrate that a 5′ T- or C-rich PAM sequence triggers dsDNA target cleavage. Based on this discovery, we evaluated whether they can protect against invading dsDNA in Escherichia coli and find that some but not all can. Altogether, our findings show that miniature Cas12f nucleases can protect against invading dsDNA like much larger class 2 CRISPR effectors and have the potential to be harnessed as programmable nucleases for genome editing.
Weak interactions in higher-order chromatin organization
Authors: Kantidze Omar L , Razin Sergey V
Published: April 2020

The detailed principles of the hierarchical folding of eukaryotic chromosomes have been revealed during the last two decades. Along with structures composing three-dimensional (3D) genome organization (chromatin compartments, topologically associating domains, chromatin loops, etc.), the molecular mechanisms that are involved in their establishment and maintenance have been characterized. Generally, protein–protein and protein–DNA interactions underlie the spatial genome organization in eukaryotes. However, it is becoming increasingly evident that weak interactions, which exist in biological systems, also contribute to the 3D genome. Here, we provide a snapshot of our current understanding of the role of the weak interactions in the establishment and maintenance of the 3D genome organization. We discuss how weak biological forces, such as entropic forces operating in crowded solutions, electrostatic interactions of the biomolecules, liquid-liquid phase separation, DNA supercoiling, and RNA environment participate in chromosome segregation into structural and functional units and drive intranuclear functional compartmentalization.
Population Health, Prevention, Health Promotion, and Wellness Competencies in Physical Therapist Professional Education: Results of a Modified Delphi Study
Authors: Magnusson Dawn M , Rethorn Zachary D , Bradford Elissa H , Maxwell Jessica , Ingman Mary Sue , Davenport Todd E , Bezner Janet R
Published: April 2020

Objective

Physical therapists are well positioned to meet societal needs and reduce the global burden of noncommunicable diseases through the integration of evidence-based population health, prevention, health promotion, and wellness (PHPW) activities into practice. Little guidance exists regarding the specific PHPW competencies that entry-level clinicians ought to possess. The objective of this study was to establish consensus-based entry-level PHPW competencies for graduates of US-based physical therapist education programs.

Methods

In a 3-round modified Delphi study, a panel of experts (N = 37) informed the development of PHPW competencies for physical therapist professional education. The experts, including physical therapists representing diverse practice settings and geographical regions, assessed the relevance and clarity of 34 original competencies. Two criteria were used to establish consensus: a median score of 4 (very relevant) on a 5-point Likert scale, and 80% of participants perceiving the competency as very or extremely relevant.

Results

Twenty-five competencies achieved final consensus in 3 broad domains: preventive services and health promotion (n = 18), foundations of population health (n = 4), and health systems and policy (n = 3).

Conclusions

Adoption of the 25 accepted competencies would promote consistency across physical therapist education programs and help guide physical therapist educators as they seek to integrate PHPW content into professional curricula.

Impact

This is the first study to establish consensus-based competencies in the areas of PHPW for physical therapist professional education in the United States. These competencies ought to guide educators who are considering including or expanding PHPW content in their curricula. Development of such competencies is critical as we seek to contribute to the amelioration of chronic disease and transform society to improve the human experience.
DeepLC can predict retention times for peptides that carry as-yet unseen modifications
Authors: Bouwmeester Robbin , Gabriels Ralf , Hulstaert Niels , Martens Lennart , Degroeve Sven
Published: April 2020

The inclusion of peptide retention time prediction promises to remove peptide identification ambiguity in complex LC-MS identification workflows. However, due to the way peptides are encoded in current prediction models, accurate retention times cannot be predicted for modified peptides. This is especially problematic for fledgling open modification searches, which will benefit from accurate retention time prediction for modified peptides to reduce identification ambiguity. We here therefore present DeepLC, a novel deep learning peptide retention time predictor utilizing a new peptide encoding based on atomic composition that allows the retention time of (previously unseen) modified peptides to be predicted accurately. We show that DeepLC performs similarly to current state-of-the-art approaches for unmodified peptides, and, more importantly, accurately predicts retention times for modifications not seen during training. Moreover, we show that DeepLC’s ability to predict retention times for any modification enables potentially incorrect identifications to be flagged in an open modification search of CD8-positive T-cell proteome data. DeepLC is available under the permissive Apache 2.0 open source license and comes with a user-friendly graphical user interface, as well as a Python package on PyPI, Bioconda, and BioContainers for effortless workflow integration.
Science Map of the Highly Tweeted Endodontic Articles
Authors: Kolahi Jafar , Khazaei Saber , Iranmanesh Pedram
Published: April 2020

Introduction

To identify active journals, authors, institutions and hot topics in the field of Endodontics within the Twittersphere.

Methods

On December 23, 2019, the Altmetric database was searched using the titles of 11 endodontic journals. The bibliometric data of the top 5% of endodontic articles with the highest tweets number were extracted from the Web of Science and analyzed.

Results

Overall, 3,918 tweets (from 3,881 individual posts) related to endodontic articles from seven journals were identified, which were mostly from the U.S. The Journal of Endodontics received the most tweets. Systematic review and apical periodontitis were the most popular keywords. At the author level, Dummer PMH and Patel S and at institution level King’s College London and Cardiff University, had the largest number of popular articles in the Twittersphere. The number of tweets was not correlated with citations (r=0.007, P=0.929). No statistically significant differences were found between open access (n=41, Mean=11.19) and non-open access (n=136, Mean=9.38) articles regarding the number of tweets (P=0.648).

Conclusions

In the ‘Twittersphere’, the overall activity of endodontic journals and associations were low. They could be more active and increase their visibility and social impact by immediately sharing research outcomes and communicating with peers, practitioners, and patients.
Structural basis to design multi-epitope vaccines against Novel Coronavirus 19 (COVID19) infection, the ongoing pandemic emergency: an in silico approach
Authors: Srivastava Sukrit , Verma Sonia , Kamthania Mohit , Kaur Rupinder , Badyal Ruchi Kiran , Saxena Ajay Kumar , Shin Ho-Joon , Kolbe Michael , Pandey Kailash C
Published: April 2020

The 2019 novel coronavirus (COVID19 / Wuhan coronavirus), officially named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a positive-sense single-stranded RNA coronavirus. SARS-CoV-2 causes the contagious COVID19 disease also known as 2019-nCoV acute respiratory disease and has led to the ongoing 2019–20 pandemic COVID19 outbreak. The effective counter measures against SARS-CoV-2 infection require the design and development of specific and effective vaccine candidate. In the present study, we have screened and shortlisted 38 CTL, 33 HTL and 12 B cell epitopes from the eleven Protein sequences of SARS-CoV-2 by utilizing different in silico tools. The screened epitopes were further validated for their binding with their respective HLA allele binders and TAP (Transporter associated with antigen processing) molecule by molecular docking. The shortlisted screened epitopes were further utilized to design novel two multi-epitope vaccines (MEVs) composed of CTL, HTL and B cell epitopes overlaps with potential to elicit humoral as well as cellular immune response against SARS-CoV-2. To enhance the immune response for our vaccine design, truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1 (Ov-ASP-1) has been utilized as an adjuvant at N terminal of both the MEVs. Further molecular models for both the MEVs were prepared and validated for their stable molecular interactions with Toll-Like Receptor 3 (TLR 3). The codon-optimized cDNA of both the MEVs were further analyzed for their potential of high level of expression in a human cell line. The present study is very significant in terms of molecular designing of prospective CTL and HTL vaccine against SARS-CoV-2 infection with the potential to elicit cellular as well as humoral immune response. (SARS-CoV-2), Coronavirus, Human Transporter associated with antigen processing (TAP), Toll-Like Receptor (TLR), Epitope, Immunoinformatics, Molecular Docking, Molecular dynamics simulation, Multi-epitope Vaccine

Graphical abstract

The designed CTL (Cytotoxic T lymphocyte) and HTL (Helper T lymphocyte) multi-epitope vaccines (MEV) against COVID19 infection. Both the CTL and HTL MEV models show a very stable and well fit conformational complex formation tendency with the Toll like receptor 3. CTL and HTL MEVs:ribbon; Toll like receptor 3:gray cartoon; Adjuvant [truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1]:orange ribbon regions; Epitopes:cyan ribbons regions; 6xHis Tag:magenta ribbon regions.
Homeostatic scaling is driven by a translation-dependent degradation axis that recruits miRISC remodeling
Authors: Srinivasan Balakumar , Samaddar Sarbani , Mylavarapu Sivaram V.S. , Clement James P. , Banerjee Sourav
Published: April 2020

Homeostatic scaling in neurons has been attributed to the individual contribution of either translation or degradation; however there remains limited insight towards understanding how the interplay between the two processes effectuates synaptic homeostasis. Here, we report that a co-dependence between protein synthesis and degradation mechanisms drives synaptic homeostasis whereas abrogation of either prevents it. Coordination between the two processes is achieved through the formation of a tripartite complex between translation regulators, the 26S proteasome and the miRNA-induced-silencing-complex (miRISC) components such as Argonaute, MOV10 and Trim32 on actively translating transcripts or polysomes. The components of this ternary complex directly interact with each other in an RNA-dependent manner. Disruption of polysomes abolishes this ternary interaction, suggesting that translating RNAs facilitate the combinatorial action of the proteasome and the translational apparatus. We identify that synaptic downscaling involves miRISC remodeling which entails the mTORC1-dependent translation of Trim32, an E3 ligase and the subsequent degradation of its target, MOV10viathe phosphorylation of p70 S6 kinase. We find that the E3 ligase Trim32 specifically polyubiquitinates MOV10 for its degradation during synaptic downscaling. MOV10 degradation alone is sufficient to invoke downscaling by enhancing Arc translation through its 3’ UTR and causing the subsequent removal of post-synaptic AMPA receptors. Synaptic scaling was occluded when we depleted Trim32 and overexpressed MOV10 in neurons, suggesting that the Trim32-MOV10 axis is necessary for synaptic downscaling. We propose a mechanism that exploits a translation-driven protein degradation paradigm to invoke miRISC remodeling and induce homeostatic scaling during chronic network activity.
Defining the Neural Kinome: Strategies and Opportunities for Small Molecule Drug Discovery to Target Neurodegenerative Diseases
Authors: Krahn Andrea I. , Wells Carrow , Drewry David H. , Beitel Lenore K. , Durcan Thomas M. , Axtman Alison D.
Published: April 2020

Kinases are highly tractable drug targets that have reached unparalleled success in fields such as cancer but whose potential has not yet been realized in neuroscience. There are currently 55 approved small molecule kinase-targeting drugs, 48 of which have an anti-cancer indication. The intrinsic complexity linked to central nervous system (CNS) drug development and a lack of validated targets has hindered progress in developing kinase inhibitors for CNS disorders when compared to other therapeutic areas such as oncology. Identification and/or characterization of new kinases as potential drug targets for neurodegenerative diseases will create opportunities for development of CNS drugs in the future. The track record of kinase inhibitors in other disease indications supports the idea that with the best targets identified small molecule kinase modulators will become impactful therapeutics for neurodegenerative diseases.

KEY CONCEPTS

Chemical probe: a high-quality small molecule that is potent, selective, and cell-active that meets the following criteria: (1)in vitrobiochemical IC50< 50 nM, (2) ≥ 30-fold selectivity relative to other kinases in a large assay panel such as DiscoverXscanMAX, and (3) cellular activity or target engagement with an IC50< 1 μM

Narrow spectrum: a selectivity threshold that can be defined as potently inhibiting ∼10% or less of all kinases screened

Kinome: all human kinases

Kinase chemogenomic set (KCGS): publicly-available curated physical library of narrow spectrum and potent kinase inhibitors for which the SGC-UNC has received permission to share the compounds; subsequent releases will increase kinome-wide coverage

Illuminating the Druggable Genome (IDG) program: several interconnected projects currently funded by the National Institutes of Health to provide information on historically understudied members within protein families that have provided drug targets; the three main focus areas are kinases, G-protein coupled receptors, and ion channels

IDG kinase: a kinase that was nominated as dark (understudied) by the National Institutes of Health IDG program (curated list found here:https://druggablegenome.net/IDGProteinList); IDG consortium members generate data and resources to aid in the illumination of the function of these kinases

DK tool: a narrow spectrum inhibitor that exhibits a defined selectivity score (S10(1 μM) < 0.05) and cellular target engagement with an IC50< 1 μM; S10(1 μM) is a measure of selectivity equal to the percentage of screened kinases biochemically inhibited by >90% at 1 μM
Disconnection somewhere down the line: Multivariate lesion-symptom mapping of the line bisection error
Authors: Wiesen Daniel , Karnath Hans-Otto , Sperber Christoph
Published: April 2020

Line Bisection is a simple task frequently used in stroke patients to diagnose disorders of spatial perception characterized by a directional bisection bias to the ipsilesional side. However, previous anatomical and behavioural findings are contradictory, and the diagnostic validity of the line bisection task has been challenged. We hereby aimed to re-analyse the anatomical basis of pathological line bisection by using multivariate lesion-symptom mapping and disconnection-symptom mapping based on support vector regression in a sample of 163 right hemispheric acute stroke patients. In line with some previous studies, we observed that pathological line bisection was related to more than a single focal lesion location. Cortical damage primarily to right parietal areas, particularly the inferior parietal lobe, including the angular gyrus, as well as damage to the right basal ganglia contributed to the pathology. In contrast to some previous studies, an involvement of frontal cortical brain areas in the line bisection task was not observed. Subcortically, damage to the right superior longitudinal fasciculus (I, II and III) and arcuate fasciculus as well as the internal capsule was associated with line bisection errors. Moreover, white matter damage of interhemispheric fibre bundles, such as the anterior commissure and posterior parts of the corpus callosum projecting into the left hemisphere, was predictive of pathological deviation in the line bisection task.
The Parkinson’s Disease GWAS Locus Browser
Authors: Grenn Francis P. , Kim Jonggeol J. , Makarious Mary B. , Iwaki Hirotaka , Illarionova Anastasia , Brolin Kajsa , Kluss Jillian H. , Schumacher-Schuh Artur F. , Leonard Hampton , Faghri Faraz , Billingsley Kimberley , Krohn Lynne , Hall Ashley , Diez-Fairen Monica , Periñán Maria Teresa , Sandor Cynthia , Webber Caleb , Gibbs J. Raphael , Nalls Mike A. , Singleton Andrew B. , Bandres-Ciga Sara , Reed Xylena , Blauwendraat Cornelis ,   on behalf of the International Parkinson’s Disease Genomics Consortium (IPDGC)
Published: April 2020

Parkinson’s disease (PD) is a neurodegenerative disease with an often complex genetic component identifiable by genome-wide association studies (GWAS). The most recent large scale PD GWASes have identified more than 90 independent risk variants for PD risk and progression across 80 loci. One major challenge in current genomics is identifying the causal gene(s) and variant(s) from each GWAS locus. Here we present a GWAS locus browser application that combines data from multiple databases to aid in the prioritization of genes associated with PD GWAS loci. We included 92 independent genome-wide significant signals from multiple recent PD GWAS studies including the PD risk GWAS, age-at-onset GWAS and progression GWAS. We gathered data for all 2336 genes within 1Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self-ranked criteria. Our aim is that the information contained in this browser (https://pdgenetics.shinyapps.io/GWASBrowser/) will assist the PD research community with the prioritization of genes for follow-up functional studies and as potential therapeutic targets.
Voluntary modification of rapid tactile-motor responses during reaching differs from its visuo-motor counterpart
Authors: Reschechtko Sasha , Pruszynski J. Andrew
Published: April 2020

People commonly hold and manipulate a variety of objects in everyday life, and these objects have different physical properties. In order to successfully control this wide range of objects, people must associate new patterns of tactile stimuli with appropriate motor outputs. We performed a series of experiments investigating the extent to which people can voluntarily modify tactile-motor associations in the context of a rapid tactile-motor response guiding the hand to a moving target (previously described in Pruszynski et al. 2016) by using an anti-reach paradigm in which participants were instructed to move their hands in the opposite direction of a target jump. We compared performance to that observed when people make visually guided reaches to a moving target (cf. Day & Lyon 2000, Pisella et al. 2000). When participants had visual feedback, motor responses during the anti-reach task showed early automatic responses toward the moving target before voluntary modification to move in the instructed direction. When the same participants had only tactile feedback, however, they were able to suppress this early phase of the motor response, which occurs less than 100 ms after the target jump. Our results indicate that, while the tactile motor and visual motor systems both support rapid responses that appear similar under some conditions, these responses show sharp distinctions in terms of their malleability.