bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Incisional Negative Pressure Wound Therapy Prevent Sternal Wound Infections?
Authors: Myllykangas Heidi-Mari , Halonen Jari , Husso Annastiina , Väänänen Helli , Berg Leena T.
Published: September 2021

Background Incisional negative pressure wound therapy has been described as an effective method to prevent wound infections after open heart surgery in several publications. However, most studies have examined relatively small patient groups, only a few were randomized, and some have manufacturer-sponsorship. Most of the studies have utilized Prevena; there are only a few reports describing the PICO incisional negative pressure wound therapy system.

Methods We conducted a prospective cohort study involving a propensity score-matched analysis to evaluate the effect of PICO incisional negative pressure wound therapy after coronary artery bypass grafting. A total of 180 high-risk patients with obesity or diabetes were included in the study group. The control group included 772 high-risk patients operated before the initiation of the study protocol.

Results The rates of deep sternal wound infections in the PICO group and in the control group were 3.9 and 3.1%, respectively. The rates of superficial wound infections needing operative treatment were 3.1 and 0.8%, respectively. After propensity score matching with two groups of 174 patients, the incidence of both deep and superficial infections remained slightly elevated in the PICO group. None of the infections were due to technical difficulties or early interruption of the treatment.

Conclusion It seems that incisional negative pressure wound therapy with PICO is not effective in preventing wound infections after coronary artery bypass grafting. The main difference in this study compared with previous reports is the relatively low incidence of infections in our control group.
Outcomes of Arch Reintervention for Recurrent Coarctation in Young Children
Authors: Jiang Qi , Hu Renjie , Dong Wei , Guo Ying , Zhang Wen , Hu Jie , Zhang Haibo
Published: September 2021

Objectives To evaluate the outcomes of reintervention for postrepair recoarctation in young children.

Methods Between January 2011 and December 2020, all consecutive patients aged ≤3 years who were treated for postrepair recoarctation were included. Recoarctations were classified into two morphological types by three-dimensional imaging. Two methods, namely, surgical repair and balloon angioplasty (BA), were used to treat recoarctation.

Results This study included 50 patients with a median age of 10.5 months (range, 2.0–36.0 months) and a mean weight of 9.3 ± 3.1 kg. Hypoplastic recoarctation occurred most frequently in patients who had undergone patch aortoplasty at initial repair (p = 0.001). No hospital mortality occurred, and all patients achieved an increased diameter (p < 0.001) and a decreased pressure gradient (p < 0.001) at the recoarctation site immediately after reintervention. The median follow-up time after reintervention was 3.5 years (range, 16.0 days–9.6 years). Late mortality occurred in four patients (8.0%): two in the surgical group and two in the BA group (chi-square test= 0.414, p = 0.520). There was no difference in arch reobstruction after reintervention between the surgical and BA groups (chi-square test = 1.383, p = 0.240). Recoarctation with a hypoplastic morphology was the leading risk factor for arch reobstruction after reintervention (hazard ratio, 6.552; 95% confidence interval, 2.045–20.992; p = 0.002).

Conclusion Reintervention for recoarctation has favorable early outcomes in young children. However, late mortality is not rare, and arch reobstruction is common during close follow-up. For young children, recoarctation with hypoplastic morphology is the leading risk factor for reobstruction, while the choice of reintervention method exerts little effect on the outcomes of arch reintervention.
Valve-in-Valve TAVR versus Redo Surgical Aortic Valve Replacement: Early Outcomes
Authors: Cizmic Amila , Kuhn Elmar , Eghbalzadeh Kaveh , Weber Carolyn , Rahmanian Parwis Baradaran , Adam Matti , Mauri Victor , Rudolph Tanja , Baldus Stephan , Wahlers Thorsten
Published: September 2021

Objective This study aimed to assess short-term outcomes of patients with failed aortic valve bioprosthesis undergoing valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) or redo surgical aortic valve replacement (rSAVR).

Methods Between 2009 and 2019, 90 patients who underwent ViV-TAVR (n = 73) or rSAVR (n = 17) due to failed aortic valve bioprosthesis fulfilled the inclusion criteria. Groups were compared regarding clinical end points, including in-hospital all-cause mortality. Patients with endocarditis and in a need of combined cardiac surgery were excluded from the study.

Results ViV-TAVR patients were older (78.0 ± 7.4 vs. 62.1 ± 16.2 years, p = 0.012) and showed a higher prevalence of baseline comorbidities such as atrial fibrillation, diabetes mellitus, hyperlipidemia, and arterial hypertension. In-hospital all-cause mortality was higher for rSAVR than in the ViV-TAVR group (17.6 vs. 0%, p < 0.001), whereas intensive care unit stay was more often complicated by blood transfusions for rSAVR patients without differences in cerebrovascular events. The paravalvular leak was detected in 52.1% ViV-TAVR patients compared with 0% among rSAVR patients (p < 0.001).

Conclusion ViV-TAVR can be a safe and feasible alternative treatment option in patients with degenerated aortic valve bioprosthesis. The choice of treatment should include the patient's individual characteristics considering ViV-TAVR as a standard of care.
Cranioplasty
Authors: Ong Adrian A. , Manning James P. , Vincent Aurora G. , Namin Arya W. , Wang Weitao , Ducic Yadranko
Published: September 2021

Calvarial defects are commonly encountered after neurosurgical procedures, trauma, and ablative procedures of advanced head neck cancers. The goals of cranioplasty are to provide a protective barrier for the intracranial contents, to restore form, and prevent syndrome of the trephined. Autologous and alloplastic techniques are available, each with their advantages and drawbacks. A multitude of materials are available for cranioplasty, and proper timing of reconstruction with attention to the overlying skin envelope is important in minimizing complications.
Narrowing the Wide Tip via Endonasal Approach
Authors: Sulyman Omotara , Dayan Steven
Published: September 2021

Rhinoplasty is arguably the most complex and intricate surgery performed by facial plastic surgeons. Nasal tip refinement of a broad nasal tip has remained the most challenging part of rhinoplasty as sophisticated techniques are critical to achieve aesthetically pleasing and structurally sound nasal tips that can withstand the contractile forces of healing. Successful tip refinement relies on an in-depth preoperative and intraoperative understanding of the patient's nasal anatomy, well developed arsenal of techniques, the experience of the surgeon, and the aesthetic desires of the patient. Although the approach to gain access to the nasal tip so as to successfully reshape the tip has been a topic of debate over many years, the aim of this article is to outline and demonstrate how the broad nasal tip can be successfully recontoured through an endonasal approach using nondestructive techniques that have been effectively used in open rhinoplasty. We believe that there continues to be a place for endonasal tip rhinoplasty especially in this era in which patients desire less invasive procedures with shorter healing time.
Hybrid Implant Abutments: A Literature Review
Authors: Mostafavi Azam Sadat , Mojtahedi Hamid , Javanmard Afrooz
Published: September 2021

Ceramic implant abutments are becoming increasingly popular due to the growing esthetic demands of patients. Two-piece ceramic abutments have the advantages of both ceramic and titanium abutments. This study aimed to review the published articles regarding hybrid abutments and their characteristics.

Published articles regarding two-piece abutments were retrieved by electronic search of PubMed, Embase, Scopus, Medline, and Google Scholar databases using certain keywords. Articles highly relevant to our topic of interest were selected and reviewed.

The presence of titanium inserts in hybrid abutments can overcome the brittleness of ceramic, increase the overall fracture resistance, prevent the implant connection wear, and provide better marginal fit compared with one-piece zirconia abutments. Hybrid abutments enable the fabrication of monolithic metal-free implant restorations with optimal esthetics. Furthermore, the risk of porcelain chipping, which is a common complication of implant restorations, is eliminated due to the monolithic structure of these restorations.

According to the available literature, hybrid implant abutments have shown promising results with regard to optimal esthetics in the rehabilitation of the esthetic zone. However, long-term clinical studies are required to assess the long-term durability of all-ceramic restorations supported by hybrid abutments.
Photometric Study of RR Lyrae Star TV Lyn
Authors: Love She’Kayla , Susmita Hazra , Fitzgerald Michael
Published: September 2021

In this research, we are reporting the light curve of RR Lyrae type variable star TV Lyn. This star is observed in the northern hemisphere and its coordinates are 07:33:31.7 + 47:48:09.8. We have used data from Las Cumbres Observatory (LCO) which consists of a worldwide network of robotic telescopes. Photometric measurements were conducted using the SBIG 6303 0.4-meter telescope with a field of view of 29’x19’. Depending on what the color of a star is when different filters are applied to it, the luminosity will change accordingly. Our data consists of four filters, Bessell B (Blue), Bessell V (visual), SDSS-I (Infrared), and PAN-STARRS-Z (Near Infrared). Results show that this star has a variability period of 0.2407 ± 0.002 days, metallicity -1.49, and located at a distance of 1362 ± 118 pc. We have used an estimate of the reddening E(B-V) as 0.08. This research is a part of an Our Solar Sibling Project by an undergraduate student with the help of a faculty advisor and an Our Solar Sibling Project Investigator.
Quantum Inequalities and Particle Creation in the Presence of an External, Time-Dependent Mamaev-Trunov Potential
Authors: Schauer Kalista , Pfenning Michael , Cochrane Jared
Published: September 2021

In 2011, Mr. Dan Solomon proposed a model of a quantized scalar field interacting with a time-dependent Mamaev-Trunov potential in two-dimensional Minkowski spacetime. This model is governed by the Klein-Gordon wave equation with a time-dependent potential. Mr. Solomon claims that this model violates both the classical energy conditions of special relativity and the quantum energy conditions of quantum field theory in curved spacetime. Every classical energy condition can be violated, and their natural replacements are known as quantum inequalities. Mr. Solomon attempted to prove violations of the spatial and temporal quantum inequalities, and he correctly assumed that the negative energy splits into two fluxes at the Cauchy surface, where the potential is turned off. Unfortunately, Solomon neglects the contribution to the energy density due to particle creation when the potential is turned off at time t = 0. In this project, we calculate the contribution to the stress energy tensor due to particle creation. We show that while the classical energy conditions are violated, the quantum energy inequalities hold, contrary to Mr. Solomon’s statements.
Microgel Dynamics Characterization Using SEM
Authors: Tietjen Samantha , Sent Richard , Fodor Petru S. , Streletzky Kiril A.
Published: September 2021

A methodology for imaging the dynamics of individual microgel particles using high resolution scanning electron microscopy (SEM) is presented. To enable this, the microgels are dispersed in an ionic liquid, which due to its low vapor pressure allows them to remain in suspension even under the high vacuum conditions present in a typical electron gun. Thus, compared with conventional electron microscopy studies of microgels, no sample drying or freezing is necessary which preserves their morphology while also allowing to probe microgel dynamics in solution. The results based on the individually tracked particles are compared with results from dynamic light scattering (DLS) which measures the mean size and diffusion properties of large collectives of particles. For the size measurements, the SEM and DLS data are in general agreement. For the particle dynamics, monitoring individual microgel motion reveals complex dynamics in which, aside from the expected thermal motion, one observes effects such as clustering, rotation and drift. This is in contrast with a control sample of hard sphere-like silica particles where the motion is primarily diffusional in good agreement with DLS studies.
Density-functional theory calculation of magnetic properties of BiFeO3 and BiCrO3 under epitaxial strain
Authors: Walden Michael R. , Ciobanu Cristian V. , Brennecka Geoff L.
Published: September 2021

This work uses density-functional theory to model the magnetic properties of bismuth-based perovskite oxides under epitaxial strain. We augment the known transition in BiFeO3 between rhombohedral-like and tetragonal-like phases occurring at 4.2% compressive epitaxial strain with the variation in magnetic behavior near this boundary. This phase boundary coincides with a transition from G- to C-type magnetic order, as well as with a 90% decrease in the magnitude of the [001]-oriented coupling coefficients. The magnitude of iron magnetization is shown to vary by no more than 3% over the entire range of compressive strain considered. In the BiCrO3 system, we report a variation in chromium magnetization of over 20%, along with transitions from bulk G-type to regions of C-type order under tensile epitaxial strain and to F-type order under both tensile and compressive epitaxial strains. The region of F-type order stabilized under compression beyond 7.9% epitaxial strain corresponds to a “super-tetragonal” phase structurally similar to the well-known phase of BiFeO3 exhibiting spontaneous polarization on the order of 150 μC/cm2.
Effect of collisions on non-adiabatic electron dynamics in ITG-driven microturbulence
Authors: C. J. Ajay , Brunner Stephan , Ball Justin
Published: September 2021

Non-adiabatic electron response leads to significant changes in ion temperature gradient (ITG) eigenmodes, leading, in particular, to fine-structures that are significantly extended along the magnetic field lines at corresponding mode rational surfaces (MRSs). These eigenmodes can nonlinearly interact with themselves to drive zonal flows via the so-called self-interaction mechanism. In this paper, the effect of collisions on these processes are studied. In the presence of non-adiabatic electrons, the linear growth rate of ITG eigenmodes decreases with the increasing collisionality. Detailed velocity space analysis of the distribution function shows that this results from collisions leading to a more adiabatic-like response of electrons away from MRSs. In linear simulations, collisions are furthermore found to broaden the radial width of the fine-structures, which translates to narrower tails of the eigenmode in extended ballooning space. The characteristic parallel scale length associated with these tails is shown to scale with the mean free path of electrons. In nonlinear turbulence simulations accounting for physically relevant values of collisionality, the fine-structures located at MRSs, together with the associated drive of zonal flows via self-interaction, are shown to persist and play a significant role.
Long-time measurements of line-integrated plasma electron density using a two-color homodyne optical fiber interferometer
Authors: Lan Tao , Zhang Sen , Ding Weixing , Zhuang Ge , Wu Zhengwei , Mao Wenzhe , Chen Chen , Lan Shijie , Xu Hangqi , Deng Tijian , Zhu Junfeng , Wu Jiaren , Zu Yiming , Kong Defeng , Zhang Shoubiao , Yao Yuan , Yuan Peng , Wei Zian , Zhou Haiyang , Wang Hai , Wen Xiaohui , Wu Jie , Zhou Chu , Liu Ahdi , Xie Jinlin , Li Hong , Xiao Chijin , Liu Wandong
Published: September 2021

A two-color homodyne Mach–Zehnder (M–Z) optical fiber interferometer with wavelengths of 1.55 and 1.31 µm was developed for long-time measurement of line-integrated plasma electron density. A novel phase difference demodulation algorithm based on a single 3 × 3 optical coupler was implemented in a two-color optical fiber interferometer scheme for the first time. Our laboratory tests showed that this new optical fiber interferometer could determine the phase shift due to the low-frequency ambient vibration and could maintain high phase resolution measurement. The resolution of the new interferometer was less than 0.04 rad in 1000 s, corresponding to a line-averaged electron density of less than 1.0 × 1019 m−2. Actual plasma discharge experiments performed on KTX-CTI, which is a new compact torus injector (CTI) constructed at the Keda Torus eXperiment (KTX), showed that this interferometer has excellent several-second stability.
Spintronic terahertz emitters: Status and prospects from a materials perspective
Authors: Bull Charlotte , Hewett Simmone M. , Ji Ruidong , Lin Cheng-Han , Thomson Thomas , Graham Darren M. , Nutter Paul W.
Published: September 2021

Spintronic terahertz (THz) emitters, consisting of ferromagnetic (FM)/non-magnetic (NM) thin films, have demonstrated remarkable potential for use in THz time-domain spectroscopy and its exploitation in scientific and industrial applications. Since the discovery that novel FM/NM heterostructures can be utilized as sources of THz radiation, researchers have endeavored to find the optimum combination of materials to produce idealized spintronic emitters capable of generating pulses of THz radiation over a large spectral bandwidth. In the last decade, researchers have investigated the influence of a wide range of material properties, including the choice of materials and thicknesses of the layers, the quality of the FM/NM interface, and the stack geometry upon the emission of THz radiation. It has been found that particular combinations of these properties have greatly improved the amplitude and bandwidth of the emitted THz pulse. Significantly, studying the material properties of spintronic THz emitters has increased the understanding of the spin-to-charge current conversion processes involved in the generation of THz radiation. Ultimately, this has facilitated the development of spintronic heterostructures that can emit THz radiation without the application of an external magnetic field. In this review, we present a comprehensive overview of the experimental and theoretical findings that have led to the development of spintronic THz emitters, which hold promise for use in a wide range of THz applications. We summarize the current understanding of the mechanisms that contribute to the emission of THz radiation from the spintronic heterostructures and explore how the material properties contribute to the emission process.
Numerical study of the flow past two wall-mounted finite-length square cylinders in tandem arrangement
Authors: Zhao Ming , Mamoon Abdullah-Al , Wu Helen
Published: September 2021

Flow past two wall-mounted square cylinders in a tandem arrangement are simulated through direct numerical simulation to investigate the effects of the gap between the two cylinders on the wake. Numerical simulations are conducted for a constant Reynolds number of 500, height to width length ratio H = 4, and gap to width ratios of G = 1 to 8 with an interval of 1. The flow in the wake of the downstream cylinder is found to be significantly affected by the free shear layers from the top and sides of the upstream cylinder. At G = 1 and 2, the free-shear layer generated from the upstream cylinder reattaches the top surface of the downstream cylinder and further develops into a downwash behind the downstream cylinder. At G = 3 to 8, the downwash behind the downstream cylinder disappears because flow separation from the top upstream edge of the downstream cylinder does not occur for G = 3 to 6 and is very weak for G = 7 and 8. The disappearance of downwash in the wake of the downstream cylinder further results in very weak variation of flow along the span of the downstream cylinder. The single, reattachment, and binary wake modes at the mid-span of the cylinder occur at G = (1 and 2), (3 and 4), and (5 and above), respectively.
Charge transfer between the epitaxial monolayer WSe2 films and graphene substrates
Authors: Zhang Yongheng , Xie Xuedong , Zong Junyu , Chen Wang , Yu Fan , Tian Qichao , Meng Qinghao , Wang Can , Zhang Yi
Published: September 2021

Monolayer WSe2 with a direct bandgap shows great application potential in photon–electronic devices. Using in situ angle-resolved photoemission spectroscopy, we investigate the interfacial charge transfer between the grown WSe2 films and the graphene with different numbers of layers. For the WSe2 grown on the monolayer graphene (MLG) substrate, its band structure shifts downward by ∼140 meV compared to that grown on the bilayer graphene (BLG) substrate and by ∼230 meV compared to that grown on trilayer graphene (TLG), revealing that the MLG substrate transfers more electrons to the grown WSe2 than what the BLG and TLG do. Our results provide significant information for understanding the charge transfer behaviors and energy-level alignments in the two-dimensional (2D) stacking-heterostructures as well as the designation of future nano-devices based on 2D materials.
Scanning probe microscopy by localized surface plasmon resonance at fiber taper tips
Authors: Chen Cheng , Li Hui , Li Hongquan , Yang Tian
Published: September 2021

Plasmonic antenna probes have been widely investigated for detecting electrical permittivity changes on the nanometer scale by employing high-sensitivity localized surface plasmon resonance (LSPR). Although it is intuitive to integrate such a probe onto an atomic force microscope (AFM) to add one more measurable quantity to the family of scanning probe microscopy techniques, the strong scattering background of the AFM tip overwhelms the LSPR scattering signal. To solve this problem, we combined evanescent coupling, polarization and spatial filtering, confocal spectroscopy, and numerical methods to extract clean LSPR spectra from a gold nanosphere-antenna probe attached to the tip of a fiber taper. By mounting the fiber taper on a custom quartz-tuning-fork SPM, we achieved high-quality nanometer-scale imaging of gold nanospheres on glass slides by mapping the LSPR wavelength shift. In addition, we reported an LSPR wavelength shift enhancement by more complicated probe designs and the consequent promise for higher-sensitivity microscopy. Our optical system and spectral processing method provide an effective solution to the long-standing quest for LSPR scanning microscopy.
Birhythmicity, intrinsic entrainment, and minimal chimeras in an electrochemical experiment
Authors: Wiehl Juliane C. , Patzauer Maximilian , Krischer Katharina
Published: September 2021

The coexistence of limit cycles in a phase space, so called birhythmicity, is a phenomenon known to exist in many systems in various disciplines. Yet, detailed experimental investigations are rare, as are studies on the interaction between birhythmic components. In this article, we present experimental evidence for the existence of birhythmicity during the anodic electrodissolution of Si in a fluoride-containing electrolyte using weakly illuminated n-type Si electrodes. Moreover, we demonstrate several types of interaction between the coexisting limit cycles, in part resulting in peculiar dynamics. The two limit cycles exhibit vastly different sensitivities with respect to a small perturbation of the electrode potential, rendering the coupling essentially unidirectional. A manifestation of this is an asymmetric 1:2 intrinsic entrainment of the coexisting limit cycles on an individual uniformly oscillating electrode. In this state, the phase-space structure mediates the locking of one of the oscillators to the other one across the separatrix. Furthermore, the transition scenarios from one limit cycle to the other one at the borders of the birhythmicity go along with different types of spatial symmetry breaking. Finally, the master–slave type coupling promotes two (within the experimental limits) identical electrodes initialized on the different limit cycles to adopt states of different complexity: one of the electrodes exhibits irregular, most likely chaotic, motion, while the other one exhibits period-1 oscillations. The coexistence of coherence and incoherence is the characteristic property of a chimera state, the two coupled electrodes constituting an experimental example of a smallest chimera state in a minimal network configuration.
The differential capacitance as a probe for the electric double layer structure and the electrolyte bulk composition
Authors: Cats Peter , van Roij René
Published: September 2021

In this work, we theoretically study the differential capacitance of an aqueous electrolyte in contact with a planar electrode, using classical density functional theory, and show how this measurable quantity can be used as a probe to better understand the structure and composition of the electric double layer at play. Specifically, we show how small trace amounts of divalent ions can influence the differential capacitance greatly and also how small ions dominate its behavior for high electrode potentials. In this study, we consider primitive model electrolytes and not only use the standard definition of the differential capacitance but also derive a new expression from mechanical equilibrium in a planar geometry. This expression reveals explicitly that the first layer of ions near the charged surface is key to its understanding. Our insights might be used as a guide in experiments to better understand the electrolyte–electrode interface as well as the (composition of the) bulk electrolyte.
The sequence–ensemble relationship in fuzzy protein complexes
Authors: Hadži San , Loris Remy , Lah Jurij
Published: September 2021

Significance

Intrinsically disordered proteins (IDPs) do not possess a stable three-dimensional structure but populate partially folded, transient structures. They are involved in numerous cellular processes, often in cooperation with globular proteins. In such complexes, the protein-bound IDPs can be structurally very heterogeneous ranging from folded, stable conformations to those that are dynamic and disordered. The underlaying principles governing this heterogeneity, known also as fuzziness, are obscure. We developed a simple statistical thermodynamic model based on the helix–coil theory that rationalizes diversity of the target-bound IDP ensembles. The model successfully reproduces bound-state IDP dynamics and explains how ensembles modulate their structure and interaction affinity due to mutations. Collectively, this sheds light on the sequence–ensemble relationship of fuzzy IDP–protein complexes.
Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites
Authors: Teruya Takayuki , Chen Yung-Ju , Fukuji Yasuhide , Kondoh Hiroshi , Yanagida Mitsuhiro
Published: September 2021

Dementia is caused by factors that damage neurons. We quantified small molecular markers in whole blood of dementia patients, using nontargeted liquid chromatography–mass spectroscopy (LC-MS). Thirty-three metabolites, classified into five groups (A to E), differed significantly in dementia patients, compared with healthy elderly subjects. Seven A metabolites present in plasma, including quinolinic acid, kynurenine, and indoxyl-sulfate, increased. Possibly they act as neurotoxins in the central nervous system (CNS). The remaining 26 compounds (B to E) decreased, possibly causing a loss of support or protection of the brain in dementia. Six B metabolites, normally enriched in red blood cells (RBCs), all contain trimethylated ammonium moieties. These metabolites include ergothioneine and structurally related compounds that have scarcely been investigated as dementia markers, validating the examination of RBC metabolites. Ergothioneine, a potent antioxidant, is significantly decreased in various cognition-related disorders, such as mild cognitive impairment and frailty. C compounds also include some oxidoreductants and are normally abundant in RBCs (NADP
+
, glutathione, adenosine triphosphate, pantothenate,
S
-adenosyl-methionine, and gluconate). Their decreased levels in dementia patients may also contribute to depressed brain function. Twelve D metabolites contains plasma compounds, such as amino acids, glycerophosphocholine, dodecanoyl-carnitine, and 2-hydroxybutyrate, which normally protect the brain, but their diminution in dementia may reduce that protection. Seven D compounds have been identified previously as dementia markers. B to E compounds may be critical to maintain the CNS by acting directly or indirectly. How RBC metabolites act in the CNS and why they diminish significantly in dementia remain to be determined.
Bcl6 controls meningeal Th17–B cell interaction in murine neuroinflammation
Authors: Hartlehnert Maike , Börsch Anna-Lena , Li Xiaolin , Burmeister Miriam , Gerwien Hanna , Schafflick David , Heming Michael , Lu I-Na , Narayanan Venu , Strecker Jan-Kolja , Kolz Anna , Peters Anneli , Wu Gregory F. , Wiendl Heinz , Sorokin Lydia , Meyer zu Horste Gerd
Published: September 2021

Significance

The meninges protect the central nervous system but also host lymphocytes in neuroinflammation. In human multiple sclerosis, preferentially B cells accumulate in the meninges. By generating a compartment-specific transcriptional map of meningeal versus parenchymal leukocytes in experimental neuroinflammation, we found a follicular phenotype of meningeal B cells and a corresponding follicular helper-like phenotype in meningeal Th17 cells. The meninges thus instructed a site-specific local phenotype to proinflammatory autoreactive T cells. We identified the transcription factor Bcl6 in Th17 cells to promote interactions with meningeal B cells, isotype-switching, and B cell-supporting chemokines. This may describe a mechanism controlling meningeal autoimmunity and helps understanding how the meninges, as a recently recognized immunologically active site, contribute to autoimmune tissue damage in multiple sclerosis.
Ancestral polymorphisms shape the adaptive radiation ofMetrosiderosacross the Hawaiian Islands
Authors: Choi Jae Young , Dai Xiaoguang , Alam Ornob , Peng Julie Z. , Rughani Priyesh , Hickey Scott , Harrington Eoghan , Juul Sissel , Ayroles Julien F. , Purugganan Michael D. , Stacy Elizabeth A.
Published: September 2021

Significance

Some of the most spectacular adaptive radiations of plants and animals occur on remote oceanic islands, yet such radiations are preceded by founding events that severely limit genetic variation. How genetically depauperate founder populations give rise to the spectacular phenotypic and ecological diversity characteristic of island adaptive radiations is not known. We generated genomic resources for HawaiianMetrosideros––a hyper-variable adaptive radiation of woody taxa—for insights into the paradox of remote island radiations. We posit that divergent selection and differential sorting of an unexpectedly rich pool of ancestral variation drove the diversification of lineages. Recurring use of ancient variants from a richer-than-expected gene pool may explain how lineages can diversify to fill countless niches on remote islands.
Wetting of phase-separated droplets on plant vacuole membranes leads to a competition between tonoplast budding and nanotube formation
Authors: Kusumaatmaja Halim , May Alexander I. , Feeney Mistianne , McKenna Joseph F. , Mizushima Noboru , Frigerio Lorenzo , Knorr Roland L.
Published: September 2021

Seeds of dicotyledonous plants store proteins in dedicated membrane-bounded organelles called protein storage vacuoles (PSVs). Formed during seed development through morphological and functional reconfiguration of lytic vacuoles in embryos [M. Feeney
et al.
,
Plant Physiol.
177, 241–254 (2018)], PSVs undergo division during the later stages of seed maturation. Here, we study the biophysical mechanism of PSV morphogenesis in vivo, discovering that micrometer-sized liquid droplets containing storage proteins form within the vacuolar lumen through phase separation and wet the tonoplast (vacuolar membrane). We identify distinct tonoplast shapes that arise in response to membrane wetting by droplets and derive a simple theoretical model that conceptualizes these geometries. Conditions of low membrane spontaneous curvature and moderate contact angle (i.e., wettability) favor droplet-induced membrane budding, thereby likely serving to generate multiple, physically separated PSVs in seeds. In contrast, high membrane spontaneous curvature and strong wettability promote an intricate and previously unreported membrane nanotube network that forms at the droplet interface, allowing molecule exchange between droplets and the vacuolar interior. Furthermore, our model predicts that with decreasing wettability, this nanotube structure transitions to a regime with bud and nanotube coexistence, which we confirmed in vitro. As such, we identify intracellular wetting [J. Agudo-Canalejo et al., Nature 591, 142–146 (2021)] as the mechanism underlying PSV morphogenesis and provide evidence suggesting that interconvertible membrane wetting morphologies play a role in the organization of liquid phases in cells.
Blood pressure, executive function, and network connectivity in middle-aged adults at risk of dementia in late life
Authors: Jenkins Lisanne M. , Kogan Alexandr , Malinab Matthew , Ingo Carson , Sedaghat Sanaz , Bryan Nick R. , Yaffe Kristine , Parrish Todd B. , Nemeth Alexander J. , Lloyd-Jones Donald M. , Launer Lenore J. , Wang Lei , Sorond Farzaneh
Published: September 2021

Significance

The contribution of midlife vascular risk factors to brain structure and cognition in late life is well established. In this large cohort of midlife individuals, we replicated and extended previous findings of relationships between functional brain network connectivity and executive function in the context of white matter hyperintensities (WMH) and extended them to our measure of cumulative blood pressure exposure over 30 y from young adulthood. We report mediation of the relationship between WMH and executive function via functional connectivity. Our results support conclusions that neuroplastic reorganization of network connectivity may follow disruption to white matter tracks and furthermore suggest that this reorganization occurs early in the preclinical stage, prior to the onset of overt disease.
Cytokine receptor cluster size impacts its endocytosis and signaling
Authors: Salavessa Laura , Lagache Thibault , Malardé Valérie , Grassart Alexandre , Olivo-Marin Jean-Christophe , Canette Alexis , Trichet Michael , Sansonetti Philippe J. , Sauvonnet Nathalie
Published: September 2021

Significance

The IL-2R is a key receptor of the immune system, promoting both immunity and tolerance through activation of signaling cascades on lymphocytes. This receptor induces responses that include T cell expansion, development and suppression of autoreactive lymphocytes, being critical in the prevention of autoimmune diseases. These functions are regulated by the internalization and intracellular trafficking of IL-2R, which undergoes a coat-independent mechanism of endocytosis. Our work shows that clustering of IL-2R at the cell surface is fundamental in the efficient internalization of the receptor and that an optimal cluster size is required for this. Disorganization of IL-2R clustering, through perturbation of the actin cytoskeleton or membrane cholesterol, affects endocytosis and modifies IL-2–induced signaling.
Quantum teleportation of physical qubits into logical code spaces
Authors: Luo Yi-Han , Chen Ming-Cheng , Erhard Manuel , Zhong Han-Sen , Wu Dian , Tang Hao-Yang , Zhao Qi , Wang Xi-Lin , Fujii Keisuke , Li Li , Liu Nai-Le , Nemoto Kae , Munro William J. , Lu Chao-Yang , Zeilinger Anton , Pan Jian-Wei
Published: September 2021

Significance

Quantum teleportation and quantum error correction play crucial roles in fault-tolerant quantum computing. Here, we implemented error-correctable quantum teleportation to manipulate a logical qubit and observed the protection of quantum information. Our work presents a useful technology for scalable quantum computing and can serve as a quantum simulator for holographic quantum gravity.
Scaffolding mechanism of arrestin-2 in the cRaf/MEK1/ERK signaling cascade
Authors: Qu Changxiu , Park Ji Young , Yun Min Woo , He Qing-tao , Yang Fan , Kim Kiae , Ham Donghee , Li Rui-rui , Iverson T. M. , Gurevich Vsevolod V. , Sun Jin-Peng , Chung Ka Young
Published: September 2021

Significance

In addition to desensitizing and internalizing G protein–coupled receptors, arrestins mediate ERK1/2 activation by scaffolding three kinases: ERK1/2, MEK1, and Raf. The structural mechanism by which arrestins scaffold the ERK1/2 signaling cascade remains undetermined. Here, we investigated the mechanism of arrestin-2 scaffolding of the cRaf-MEK1-ERK2 signaling module. We identified the binding interfaces of arrestin-2 and these three kinases. We found that the binding of ERK2 and MEK1 was affected by the activation status of arrestin-2, and its interactions with MEK1 and ERK2 were affected by ATP. These results provide insights into the general scaffolding mechanism of the ERK1/2 cascade.
Near-germline human monoclonal antibodies neutralize and protect against multiple arthritogenic alphaviruses
Authors: Malonis Ryan J. , Earnest James T. , Kim Arthur S. , Angeliadis Matthew , Holtsberg Frederick W. , Aman M. Javad , Jangra Rohit K. , Chandran Kartik , Daily Johanna P. , Diamond Michael S. , Kielian Margaret , Lai Jonathan R.
Published: September 2021

Significance

Arthritogenic alphaviruses, such as Chikungunya virus (CHIKV) and Mayaro virus (MAYV), cause febrile illness, rash, and a debilitating chronic polyarthritis in humans. Currently, there are no approved vaccines or antiviral therapies for the prevention or treatment of alphavirus infection. Here, we identified and characterized 33 monoclonal antibodies (mAbs) from a CHIKV-convalescent donor that cross-react with other arthritogenic alphaviruses. We demonstrate that five broadly neutralizing mAbs can inhibit multiple arthritogenic alphaviruses and map their epitopes through binding and viral escape mutant analysis. Finally, we show that two mAbs, DC2.M16 and DC2.M357, protect against alphavirus disease in mice. These studies inform our understanding of how the human immune system combats alphavirus infection and may guide the development of antiviral treatments and vaccines.
CREBA and CREBB in two identified neurons gate long-term memory formation in
Drosophila
Authors: Lin Hsuan-Wen , Chen Chun-Chao , de Belle J. Steven , Tully Tim , Chiang Ann-Shyn
Published: September 2021

Significance

Most animals record only labile memories of single events, whereas the formation of persistent long-term memories (LTMs) usually requires recurrent experiences. Our study distinguishes these different memory types through a deconvolution of molecular/biochemical processes within specific neurons of an identified memory circuit. A training-responsive gene activator, CREBA, engages paired DAL neurons in this circuit by promoting protein synthesis–dependent LTMs, which can otherwise be antagonized by CREBB repressor proteins. Increased CREBA expression or elevated membrane excitability enhances LTMs even after only one training cycle. These findings exemplify a circuit gating mechanism via cellular changes in specific single neurons to distinguish one-time experiences from multiple sessions of learning for storage as persistent memory.
Differential ligand-selective control of opposing enzymatic activities within a bifunctional c-di-GMP enzyme
Authors: Patterson Dayna C. , Ruiz Myrrh Perez , Yoon Hyerin , Walker Johnnie A. , Armache Jean-Paul , Yennawar Neela H. , Weinert Emily E.
Published: September 2021

Significance

Bifunctional enzymes are widely distributed throughout bacteria and are involved in modulating bacterial phenotypes; however, regulatory mechanisms that control the activities of the opposing output domains have remained elusive. Studies on DcpG demonstrate that binding of ligands to the sensor globin domain differentially affect GGDEF and EAL domain activities and highlight a role for protein conformational changes in modulating enzymatic activity. Unusual sensor globin domain characteristics, including heme midpoint potentials, are likely important for the unique regulatory properties of DcpG. AsPaenibacillus dendritiformisresponds to changes in the gaseous environment by modulating biofilm formation, DcpG is likely important in modulating physiological responses to changes in O2and NO levels, identifying a role for heme sensor signaling in the bacterium.
Cancer-associated mutations in the p85α N-terminal SH2 domain activate a spectrum of receptor tyrosine kinases
Authors: Li Xinran , Lau Amy Y. T. , Ng Angel S. N. , Aldehaiman Abdullah , Zhou Yuan , Ng Patrick K. S. , Arold Stefan T. , Cheung Lydia W. T.
Published: September 2021

Significance

Phosphoinositide 3-kinase activation typically occurs following stimulation by upstream receptor tyrosine kinases (RTKs), which alleviate p110α inhibition by p85α. p85α and p110α driver mutations have been reported to activate p110α by disrupting the inhibitory interface between p85α and p110α. This study revealed that driver mutations in the p85α N-terminal SH2 domain can enhance p110α activity by inducing the activation of multiple RTKs. Furthermore, combination treatment with RTK and AKT inhibitors provides synergistic therapeutic efficacy. This previously uncharacterized oncogenic mechanism presents the exploitable vulnerability of a class of p85α mutant tumors.
Localized blood–brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions–controlled focused ultrasound
Authors: Anastasiadis Pavlos , Gandhi Dheeraj , Guo Yutong , Ahmed Abdul-Kareem , Bentzen Soren M. , Arvanitis Costas , Woodworth Graeme F.
Published: September 2021

Significance

The blood–brain barrier (BBB) is a critical obstacle to delivering most therapeutics into the brain. In this study, we report combined MRI, histological, and real-time acoustic emissions monitoring findings from a Phase 0 clinical trial examining microbubble-enhanced transcranial focused ultrasound for controlled BBB opening in patients with infiltrating gliomas. The data revealed the capability of this technology to provide safe, controlled, and tightly monitored BBB opening through the intact skull. Our findings demonstrate the capability of this technology to tune BBB opening in real-time, creating opportunities for improved treatment of brain tumors.
Rational design of ASCT2 inhibitors using an integrated experimental-computational approach
Authors: Garibsingh Rachel-Ann A. , Ndaru Elias , Garaeva Alisa A. , Shi Yueyue , Zielewicz Laura , Zakrepine Paul , Bonomi Massimiliano , Slotboom Dirk J. , Paulino Cristina , Grewer Christof , Schlessinger Avner
Published: September 2021

Significance

The glutamine transporter ASCT2 is an emerging therapeutic target for various cancer types. Here, we use an integrated computational and experimental approach to develop unique ASCT2 inhibitors targeting a conformational state useful for rational drug design. We apply computational chemistry tools such as molecular docking and molecular dynamics simulations, in combination with structure determination with cryo-electron microscopy and synthetic chemistry, to design multiple ASCT2 inhibitors. Our results reveal a unique mechanism of stereospecific inhibition of ASCT2 and highlight the utility of combining state-of-the-art computational and experimental approaches in characterizing challenging human membrane protein targets.
Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons
Authors: Keshari Ravi Shankar , Popescu Narcis Ioan , Silasi Robert , Regmi Girija , Lupu Cristina , Simmons Joe H. , Ricardo Alonso , Coggeshall K. Mark , Lupu Florea
Published: September 2021

Significance

Late-stage anthrax leads to sepsis, characterized by uncontrolled host responses that contribute to organ damage and death. Using a nonhuman primate model, we demonstrate that bacterial wall peptidoglycan is the major trigger of complement activation. Terminal complement activation products promote secondary hemolytic uremic syndrome (HUS), characterized by hemolytic anemia, toxic accumulation of iron in the kidneys, and subsequent acute renal injury. Inhibition of C5 cleavage and subsequent formation of the lytic terminal complex C5b-9 prevented intravascular hemolysis and heme cytotoxicity and protected against peptidoglycan-induced acute kidney failure. Overall, treatment with C5 inhibitor significantly improved the survival of baboons with sepsis, suggesting a potentially important strategy to treat HUS secondary to gram-positive bacterial infections.
Diphthamide promotes TOR signaling by increasing the translation of proteins in the TORC1 pathway
Authors: Zhang Yugang , Lin Zhewang , Zhu Julia , Wang Miao , Lin Hening
Published: September 2021

Significance

Diphthamide is a posttranslational modification that has been known since the 1970s. It is conserved in all eukaryotic cells, and its biosynthesis requires at least seven proteins. However, its exact biological function has remained unclear. Our results demonstrate that diphthamide promotes target of rapamycin (TOR) signaling by promoting the translation of two proteins in the target of rapamycin complex 1 (TORC1) pathway that contain slippery sequences in their messenger RNA (mRNA). Our finding explained why diphthamide is evolutionarily conserved and why it is crucial in animal development. Our results also suggest that regulating the translation of slippery sequences by diphthamide could be a widely used mechanism to tune translation in eukaryotes, which is different from the recoding hypothesis.
A simple model for control of COVID-19 infections on an urban campus
Authors: Brown Robert A.
Published: September 2021

Significance

A simple model shows that control of COVID-19 infection driven by asymptomatic transmission on an urban, residential college campus is possible by instituting comprehensive public health protocols founded on surveillance testing and contact tracing. The model gives expressions for the number of infections expected as a function of these protocols and compares well with data from a large residential university for fall 2020.
On the microstructural origin of brain white matter hydraulic permeability
Authors: Vidotto Marco , Bernardini Andrea , Trovatelli Marco , De Momi Elena , Dini Daniele
Published: September 2021

Significance

Unveiling the mechanisms that drive mass transport in brain tissue is fundamental, not only to plan accurate surgical procedures, but also to shed light on the way solutes move in the extracellular space during the physiological or pathological state. The relation between the white matter (WM) spatial organization and relevant parameters such as permeability is still an unsolved question. Here, we simulate the interstitial flow between the axons of two WM areas reconstructed through three-dimensional electron microscopy imaging. We show that the permeability computed parallel to the axons is significantly higher than the one calculated perpendicularly and that corpus callosum exhibits a higher permeability than fornix, hence demonstrating the importance of the anisotropic and heterogeneous behavior of WM.