bluuebunny/crossref_metadata_2025 huggingface dataset:
Vínculo social, juventud y trasgresión normativa: Aspectos conceptuales y metodológicos en el estudio de la cohesión social en América Latina
Authors: Palacios Margarita , Cordero Rodrigo
Published: September 2022

El propósito de este artículo es contribuir al debate acerca de la cohesión social en América Latina a través de una propuesta conceptual y metodológica para su estudio. En particular proponemos la noción de trasgresión normativa como modo de entender la solidez-debilidad del vínculo social. A partir de los resultados de un estudio piloto realizado en la ciudad de Santiago de Chile, pudimos constatar que los niveles de trasgresión son generalmente bajos, lo que manifiesta la adhesión a los mecanismos sancionados como legítimos para participar en la sociedad. No obstante, los resultados reflejaron también la existencia de un grupo significativo de jóvenes que transgrede no sólo algunas sino que la mayoría de las reglas que rigen el comportamiento esperable en diversas esferas de la vida social (tanto a nivel de la vida privada como pública). Más importante aún, los resultados de nuestro estudio sugieren que tal actitud o comportamiento transgresor está relacionado con el debilitamiento del vínculo social.
Writing about Life Writing: Women, Autobiography and the British Industrial Revolution
Authors: Griffin Emma
Published: September 2022

Few historical problems have attracted so much attention over so many years as the social consequences of the British industrial revolution. For the most part, historians presumed that working people produced very little historical evidence that could be used to contribute to our understanding. However, projects to catalogue and encourage the use of the nation's scattered, yet extensive, archive of working-class autobiography have revealed that such evidence does, in fact, exist. The insertion of working-class autobiography helps to offer a new perspective, one which suggests a more positive interpretation of industrial life than historians have usually been willing to admit. Yet there remains a problem with the archive. During the industrial revolution, life-writing was a male art form. Women only started writing autobiographies in any number around 100 years after the conventional periodisation of the industrial revolution. This article surveys the autobiographical writing during and after the industrial revolution – around 1,000 items in all – in order to rethink the relationship between economic growth and social change. It confirms that industrial growth improved the position of working men in society, but concludes that female perspectives on this change are far more ambivalent.
Risk factors and frequency of acute and permanent femoral arterial occlusion in neonates with CHD who undergo ultrasound-guided femoral arterial access
Authors: Gokdemir Mahmut , Cindik Nimet
Published: September 2022

Objective:

We investigated frequency and risk factors of acute loss of the arterial pulse and permanent femoral arterial occlusion in neonates with CHD who underwent ultrasound-guided femoral arterial access.

Methods:

We divided the patients into groups according to the presence of acute loss of the arterial pulse and permanent femoral arterial occlusion. We obtained data related to patient characteristics and access variables of ultrasound-guided femoral arterial access from our database of cardiac catheterisation between August, 2017 and May, 2021. We used an echocardiography-S6, 12-MHz linear probe, 21-gauge needle, 0.018"guidewire, and a 4F sheath for arterial access.

Results:

Ultrasound-guided femoral arterial access was obtained in 323 (98.8%) of the 327 neonates. We identified acute loss of the arterial pulse in 130 (40.2%) patients and permanent femoral arterial occlusion in 19 (5.9%) patients. Median weight was 3.05 (Interquartile range (IQR): 2.80–3.40) kg, first attempt success rate was 88.2%, and median access time was 46 sec (IQR: 23–94). Logistic regression analysis identified coarctation of the aorta (odds ratio: 2.46; 95% CI: 1.30–4.66; p = 0.006) as independent risk factor for acute loss of the arterial pulse, but did not identify any independent risk factors for permanent femoral arterial occlusion.

Conclusions:

This study showed coarctation of the aorta as an independent risk factor for acute loss of the arterial pulse, but did not identify any independent factors for permanent femoral arterial occlusion in neonates with CHD. Although most cases of acute loss of the arterial pulse resolve in the early period, the frequency of permanent femoral arterial occlusion remains high despite effective treatment.
Individuals with Wiedemann-Steiner syndrome show nonverbal reasoning and visuospatial defects with relative verbal skill sparing
Authors: Ng Rowena , Harris Jacqueline , Fahrner Jill A. , Bjornsson Hans Tomas
Published: September 2022

Objectives:

Wiedemann-Steiner syndrome (WSS) is a rare Mendelian disorder of the epigenetic machinery caused by heterozygous pathogenic variants in KMT2A. Currently, the specific neurocognitive profile of this syndrome remains unknown. This case series provides insight into the cognitive phenotype of WSS.

Methods:

This study involves a retrospective medical chart review of 10 pediatric patients, each with a molecularly confirmed diagnosis of WSS who underwent clinical neuropsychological evaluation at an academic medical center.

Results:

The majority of patients performed in the below average to very low ranges in Nonverbal Reasoning, Visual/Spatial Perception, Visuoconstruction, Visual Memory, Attention, Working Memory and Math Computation skills. In contrast, over half the sample performed within normal limits on Receptive Vocabulary, Verbal Memory, and Word Reading. Wilcoxon signed rank test showed weaker Nonverbal versus Verbal Reasoning skills (p = .005). Most caregivers reported deficits in executive functioning, most notably in emotion regulation.

Conclusions:

Nonverbal reasoning/memory, visuospatial/construction, attention, working memory, executive functioning, and math computation skills are areas of weakness among those with WSS. These findings overlap with research on Kabuki syndrome, which is caused by variants in KMT2D, and suggest disruption in the neurogenesis of the hippocampal formation may drive shared pathogenesis of the two syndromes.
Assessment of the Importance of COVID-19 Prevention Measures and Their Applicability in the Daily Life of Pregnant Women and Mothers of Infants
Authors: Wirtz Markus Antonius , Heiberger Andrea , Dresch Carolin , Schulz Anja Alexandra
Published: September 2022

Abstract. The COVID-19 pandemic has posed significant challenges to (expectant) mothers of infants in terms of family health protection. To meet these challenges in a health literate manner, COVID-19 protective measures must be considered important and must also be implemented appropriately in everyday life. To this end, N = 343 (expectant) mothers of infants indicated (a) how important they considered 21 COVID-19 infection prevention measures, and (b) how well they succeeded in implementing them in their daily life (20 measures). We performed data analysis using exploratory factor analysis for ordinal data and latent class analysis. One- and two-dimensional models (CFI = .960 / .978; SRMR = .053 / .039) proved to appropriately explain maternal importance ratings. The items on successfully applying COVID-19 measures in daily life can be modeled by the 5 factors hygiene measures, contact with other people, public transportation, staying at home, and checking infection status (CFI = 0.977; SRMR = .036). Six latent classes can be distinguished. Despite the largest class (39 %), classes are characterized by selective or general applicability problems. Classes reporting problems in the applicability of the measures rated them as generally less important (η = .582). Assessing and modelling importance and applicability of COVID-19 prevention measures allows for a psychometrically sound description of subjective perceptions and behaviors that are crucial for health literate practice in maternal daily life.
Wissenschaftskommunikation wissenschaftlich arbeitender Psycholog_innen im deutschsprachigen Raum
Authors: Genschow Oliver , Sauerland Melanie , Crusius Jan , Friese Malte
Published: September 2022

Zusammenfassung: Das Bundesministerium für Bildung und Forschung möchte in Zukunft Wissenschaftskommunikation gezielter fördern. Dies passt zu einer kürzlich veröffentlichten Forderung des Wissenschaftsrats, der sich von wissenschaftlich arbeitenden Psycholog_innen mehr Wissenschaftskommunikation wünscht. Um Wissenschaftskommunikation gezielt fördern zu können, bedarf es allerdings zunächst einer Bestandsaufnahme über den aktuellen Umfang und die Art geleisteter Wissenschaftskommunikation. Vor diesem Hintergrund befragten wir in einer empirischen Erhebung wissenschaftlich arbeitende Psycholog_innen im deutschsprachigen Raum ( N = 740). Die Ergebnisse deuten darauf hin, dass sich deutschsprachige Psycholog_innen insbesondere im internationalen Vergleich weniger häufig im Bereich der Wissenschaftskommunikation engagieren. Als Hauptgrund für Wissenschaftskommunikation gaben die Teilnehmer_innen an, dass ihnen Wissenschaftskommunikation Spaß macht und dass sie der Gesellschaft und den Steuerzahler_innen gegenüber die Verpflichtung zur Wissenschaftskommunikation empfinden. Als hemmende Faktoren wurden mangelnde Zeit, geringe Priorisierung und Zweifel an der notwendigen eigenen Kompetenz genannt. Zur Förderung von Wissenschaftskommunikation wünschten sich die Teilnehmer_innen insbesondere stärkere institutionelle Unterstützung bei administrativen Aufgaben und Lehrtätigkeiten. In der Diskussion ordnen wir die Ergebnisse in den Rahmen vorheriger internationaler Umfragen ein und erörtern Möglichkeiten zur Förderung von Wissenschaftskommunikation.
Die Rolle elterlicher Kommunikation in Konfliktsituationen für das Erziehungsverhalten und das psychische Wohlbefinden von Jugendlichen
Authors: Scheuring Annie Kristin , Schulz Wolfgang
Published: September 2022

Zusammenfassung: Theoretischer Hintergrund: Elterliche Konflikte stehen in Zusammenhang zur kindlichen psychischen Gesundheit. Fragestellung: Untersucht wird, ob mütterlichem und väterlichem Erziehungsverhalten eine Mediatorrolle in dieser Beziehung zukommt. Methode: Die Stichprobe besteht aus 179 Zwei-Eltern-Familien. Im Längsschnitt werden über einen Zeitraum von 10 Jahren vom Kindergarten- bis zum Jugendalter mehrere Strukturgleichungsmodelle berechnet. Ergebnisse: Destruktive Kommunikation sagte vermehrt negatives Erziehungsverhalten voraus. Mütter zeigten in Folge konstruktiver Kommunikation weniger negatives Erziehungsverhalten. In den Mütter-Modellen ohne das Erziehungsverhalten hatte konstruktive Kommunikation einen direkten Effekt auf internalisierende Auffälligkeiten sowie destruktive Kommunikation auf externalisierende Auffälligkeiten der Jugendlichen. Diskussion und Schlussfolgerung: Die Ergebnisse sprechen gegen eine Mediation und verdeutlichen die Wichtigkeit getrennter Analysen für Mütter und Väter.
Turbulent Flux Measurements of the Near‐Surface and Residual‐Layer Small Particle Events
Authors: Islam M. M. , Meskhidze N. , Rasheeda Satheesh A. , Petters M. D.
Published: September 2022

According to recent field studies, almost half of the New Particle Formation (NPF) events occur aloft, in a residual layer, near the top of the boundary layer. Therefore, measurements of the meteorological parameters, precursor gas concentrations, and aerosol loadings conducted at the ground level are often not representative of the conditions where the NPFs take place. This paper presents new measurements obtained during the Turbulent Flux Measurements of the Residual Layer Nucleation Particles, conducted at the Southern Great Plains research site. Vertical turbulent fluxes of 3–10 nm‐sized particles were measured using a sonic anemometer and two condensation particle counters with nominal cutoff diameters of 3 nm and 10 nm mounted at the top of the 10‐m telescoping tower. Aerosol number size distribution (5–300 nm) was determined through the ground‐based Scanning Mobility Particle Sizers. The size selected (15–50 nm) particle hygroscopicity was derived with the Humidified Tandem Differential Mobility Analyzer. The ground level observations were supplemented by vertically‐resolved measurements of horizontal and vertical wind speeds and aerosol backscatter. The data analysis suggests that (a) turbulent flux measurements of 3–10 nm particles can distinguish between near‐surface and residual‐layer small particle events; (b) sub‐50 nm particles had a hygroscopicity value of 0.2, suggesting that organic compounds dominate atmospheric nanoparticle chemical composition at the site; and (c) current methodologies are inadequate for estimating the dry deposition velocity of sub‐10 nm particles because it is not feasible to measure particle concentration very near the surface, in the diffusion sublayer.
Long‐Wavelength Propagation in Fractured Rock Masses (3D Stress Field)
Authors: Rached R. M. , Garcia A. V. , Santamarina J. C.
Published: September 2022

Fractured rocks affect a wide range of natural processes and engineering systems. In most cases, the seismic characterization of fractured rock masses in the field involves wavelengths much longer than the fracture spacing; reproducing this condition in the laboratory is experimentally challenging. This experimental investigation explores the effect of fracture rock fabric and the 3D stress field on P wave propagation in the long‐wavelength regime using a large‐scale true triaxial device. P wave velocities increase with stress in the propagation direction and follow a power law of the form Vp = α(σ’/kPa)β; analyses and experimental results show that stress‐sensitive fracture stiffness and fracture density define the α‐factor and β‐exponent; conversely, long‐wavelength velocity versus stress data can be analyzed to identify the stress‐dependent fracture stiffness. P wave velocities exhibit hysteretic behavior caused by inelastic fracture deformation and fabric changes. During deviatoric loading, the P wave velocity decreases in the two constant‐stress directions due to the development of internal force chains and the ensuing three‐dimensional deformation. Following a load increment, time‐dependent contact deformations result in P wave velocity changes during the first several hours for the tested carbonate rocks; the asymptotic change in velocity is more pronounced for higher stress changes and stress levels. The fracture network geometry that defines the rock fabric acts as a low‐pass filter to wave propagation, so that wavelengths must be longer than two times the fracture spacing to propagate (Brillouin dispersion); the long‐wavelength velocity and the fracture spacing determine the cutoff frequency. Fabric anisotropy contributes to anisotropic low‐pass filtering effects in the rock mass.
Five Years of Observations of the Circumpolar Cyclones of Jupiter
Authors: Mura A. , Scarica P. , Grassi D. , Adriani A. , Bracco A. , Piccioni G. , Sindoni G. , Moriconi M. L. , Plainaki C. , Ingersoll A. , Altieri F. , Cicchetti A. , Dinelli B. M. , Filacchione G. , Migliorini A. , Noschese R. , Sordini R. , Stefani S. , Tosi F. , Turrini D.
Published: September 2022

The regular polygons of circumpolar cyclones, discovered by Juno in 2017, are one of the most puzzling features of Jupiter. Here we show new recent global pictures of the North polar cyclones' structure. These are the first simultaneous images of the whole structure since 2017, and we find that it remained almost unperturbed, just like the South one. The observation of these long‐lasting structures poses questions regarding the formation mechanism of cyclones, and on their vertical structure. Data by Juno/JIRAM infrared camera collected over the last 5 years show that cyclones migrate around what may seem like equilibrium positions, with timescales of a few months but, aside from that, the cyclones systems are very stable. Our analysis of the observations shows that the motion of cyclones around their equilibrium position is uncorrelated with their position if a barotropic approximation (β‐drift) is assumed. Thus, a different dynamical explanation than the barotropic β‐drift is needed to explain the stability of the observed features. Each cyclone has a peculiar morphology, which differs from the others and is stable over the observed lapse of time in most cases.
Compositional Controls on the Distribution of Brine in Europa's Ice Shell
Authors: Wolfenbarger N. S. , Fox‐Powell M. G. , Buffo J. J. , Soderlund K. M. , Blankenship D. D.
Published: September 2022

The composition of impurities in ice controls the stability of liquid water and thus the distribution of potential aqueous habitats. We present a framework for modeling the brine volume fraction in impure water ice as a function of temperature and bulk ice salinity, inspired by models originally developed for sea ice. We applied this framework to examine the distribution of brine within the thermally conductive layer of Europa's ice shell, considering binary (NaCl and MgSO4) and multi‐ion “analog” (Cl‐dominated and SO4‐dominated) endmember impurity compositions. We found the vertical extent of brine in a conductive ice layer, expressed as a fraction of the total layer thickness, to be <12% for NaCl, <2% for MgSO4, and <18% for both the analog endmember impurity compositions, suggesting that the depth where brine is stable in an ice shell is more sensitive to composition when only two ionic species are present. For the same temperature and bulk ice salinity, the brine volume fraction is higher in a Cl‐dominated ice shell than a SO4‐dominated ice shell. Pressure, governed by the ice thickness, was found to have only a minor effect on the vertical extent of brine within an ice shell, relative to temperature and bulk ice salinity. The minimum stable bulk ice shell salinity formed through freezing of an ocean was found to be insensitive to composition and ultimately governed by the magnitude of the assumed percolation threshold.
Transport and Weathering of Large Limestone Blocks on Hillslopes in Heterolithic Sedimentary Landscapes
Authors: McCarroll Nicholas R. , Temme Arnaud J. A. M.
Published: September 2022

Geomorphic transport laws that describe the movement of material across landscapes generally hide the role of lithological and climatic boundary conditions behind proportionality terms. The geomorphic community aims to characterize the role of these boundary conditions and include them in mechanistic transport laws. A more detailed mechanistic understanding is needed for hillslopes formed in heterolithic rock that weathers into weak regolith and hard blocks, such as in hogbacks. The properties of such blocks may determine both the process and rate of their transport downslope. We focused on soil mantled hillslopes in the Flint Hills of Kansas in the United States, where we studied the role of block shape and size under a limestone cliff that breaks up approximately into equal amounts of cubic and tile‐shaped clasts. Based on previous studies on the transport of rock clasts, we hypothesized that cubic and tile‐shaped blocks should be transported differently, leading to different distributions of size and orientation with increasing distance from the cliff. Block shape does have significant influence over how soil collects and is stored on the hillslope near blocks. Yet, few cubic blocks appear to be transported through tumbling in contrast with assumptions in recent modeling work. We found complex relationships between block size and distance from the cliff face and we propose that this is due to weathering via fragmentation. This process produces discrete smaller fragments from a larger parent block. We suggest that at least in Kansas both cubic and tile‐shaped blocks are transported primarily by creep processes.
SMYD3 promotes aerobic glycolysis in diffuse large B-cell lymphoma via H3K4me3-mediated PKM2 transcription
Authors: Tian Tian , Li Jiwei , Shi Di , Zeng Yupeng , Yu Baohua , Li Xiaoqiu , Wei Ping , Zhou Xiaoyan
Published: September 2022

Genetic abnormalities in histone methyltransferases (HMTs) frequently occur in diffuse large B-cell lymphoma (DLBCL) and are related to its progression. SET and MYND domain containing 3 (SMYD3) is an HMT that is upregulated in various tumors and promotes their malignancy. However, to the best of our knowledge, the function of SMYD3 in DLBCL has not been investigated thus far. In the present study, 22 HMT genes related to cancer development were first selected according to current literature, and it was found that high SMYD3 expression was significantly associated with poor progression-free survival in patients with DLBCL. SMYD3 protein levels were upregulated and positively associated with poor prognosis and poor responsiveness to chemotherapy in patients with DLBCL. Functional examinations demonstrated that SMYD3 increased cell proliferation and the flux of aerobic glycolysis in DLBCL cells in vitro and in vivo and decreased cell sensitivity to doxorubicin in vitro. Moreover, SMYD3 could directly bind to specific sequences of Pyruvate Kinase M2 (PKM2) and promote DLBCL cell proliferation and aerobic glycolysis via H3K4me3-mediated PKM2 transcription. Clinically, SMYD3 expression positively correlated with that of PKM2, and high SMYD3 was significantly associated with high maximum standardized uptake value (SUVmax) detected by [(18)F]-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (PET/CT) in DLBCL samples. Concomitant expression of SMYD3 and PKM2 positively correlated with poor progression-free and overall survival in patients with DLBCL and may serve as novel biomarkers in DLBCL.
Disulfiram alleviates pristane-induced lupus via inhibiting GSDMD-mediated pyroptosis
Authors: Zhuang Lili , Luo Xiaoqing , Wu Shufan , Lin Zhangmei , Zhang Yanan , Zhai Zeqing , Yang Fangyuan , Li Yehao , Zhuang Jian , Luo Guihu , Xu Wenchao , He Yi , Sun Erwei
Published: September 2022

Activation of multiple inflammasomes in monocytes/macrophages is associated with the pathogenesis of systemic lupus erythematosus (SLE). Gasdermin D (GSDMD)-mediated pyroptosis, a common consequence of multiple activated inflammasomes, is a programmed cell death with strong inflammatory responses. This suggested that targeting monocyte/macrophage pyroptosis might provide an opportunity to cure SLE. Here, we aimed to investigate the effect of disulfiram (DSF), a small molecule inhibitor of pyroptosis, and its potential therapeutic mechanism for SLE. The mRNA expression of GSDMD and IL-1β were significantly increased in peripheral blood mononuclear cells (PBMCs) from SLE patients. Importantly, we found serum from SLE patients rather than healthy controls induced GSDMD-mediated pyroptosis in THP-1 cells, as evidenced by enhanced LDH release, increased number of PI-positive cells, and high expression of full-length GSDMD and N-terminal GSDMD. Interestingly, treatment with DSF obviously inhibited pyroptosis of THP-1 cells induced by serum from SLE patients. Of note, DSF administration reduced proteinuria, serum anti-dsDNA level, and renal immune complex. It also attenuated renal damage in PIL mice. Further research found that the high level of serum IL-β and GSDMD-mediated pyroptosis of glomerular macrophages in PIL mice were rescued with DSF treatment. These data implied that GSDMD-mediated monocytes/macrophages pyroptosis played an important role in the pathogenesis of SLE and DSF might be a potential alternative therapeutic agent for SLE.
Approaching discussions about genetics with palliative patients and their families: a qualitative exploration with genetic health professionals
Authors: White Stephanie , Turbitt Erin , Phillips Jane L. , Jacobs Chris
Published: September 2022

Genetic information can provide clinical benefits to families of palliative patients. However, integration of genetics into mainstream medicine has not focused on palliative populations. We explored the views and experiences of genetic health professionals in addressing genetics with palliative patients, and their families. We conducted an interpretive descriptive qualitative study with genetic counsellors and clinical geneticists using interviews and focus groups. Findings were generated using reflexive thematic analysis. Three themes were identified: (1) Focusing on the benefit to the family, (2) The discomfort of addressing genetics near end-of-life and (3) “It’s always on the back-burner”: Challenges to getting genetics on the palliative care agenda. Participants discussed the familial benefit of genetics in palliative care alongside the challenges when patients are near end-of-life. They perceived genetics as low priority for palliative care due to misunderstandings related to the value of genetic information. Acknowledging the challenges in the palliative care context, genetic health professionals want improved service leadership and awareness of the familial benefits of palliative genetic testing. Strong leadership to support genetic health professionals in addressing these barriers is needed for the benefits of genetic information to be realised.
Distinct ankyrin repeat subdomains control VAPYRIN locations and intracellular accommodation functions during arbuscular mycorrhizal symbiosis
Authors: Lindsay Penelope L. , Ivanov Sergey , Pumplin Nathan , Zhang Xinchun , Harrison Maria J.
Published: September 2022

Over 70% of vascular flowering plants engage in endosymbiotic associations with arbuscular mycorrhizal (AM) fungi. VAPYRIN (VPY) is a plant protein that is required for intracellular accommodation of AM fungi but how it functions is still unclear. VPY has a large ankyrin repeat domain with potential for interactions with multiple proteins. Here we show that overexpression of the ankyrin repeat domain results in a vpy-like phenotype, consistent with the sequestration of interacting proteins. We identify distinct ankyrin repeats that are essential for intracellular accommodation of arbuscules and reveal that VPY functions in both the cytoplasm and nucleus. VPY interacts with two kinases, including DOES NOT MAKE INFECTIONS3 (DMI3), a nuclear-localized symbiosis signaling kinase. Overexpression of VPY in a symbiosis-attenuated genetic background results in a dmi3 -like phenotype suggesting that VPY negatively influences DMI3 function. Overall, the data indicate a requirement for VPY in the nucleus and cytoplasm where it may coordinate signaling and cellular accommodation processes.
HIF-1 stabilization in T cells hampers the control of Mycobacterium tuberculosis infection
Authors: Liu Ruining , Muliadi Victoria , Mou Wenjun , Li Hanxiong , Yuan Juan , Holmberg Johan , Chambers Benedict J. , Ullah Nadeem , Wurth Jakob , Alzrigat Mohammad , Schlisio Susanne , Carow Berit , Larsson Lars Gunnar , Rottenberg Martin E.
Published: September 2022

The hypoxia-inducible factors (HIFs) regulate the main transcriptional pathway of response to hypoxia in T cells and are negatively regulated by von Hippel-Lindau factor (VHL). But the role of HIFs in the regulation of CD4 T cell responses during infection withM. tuberculosisisn’t well understood. Here we show that mice lacking VHL in T cells (Vhl cKO) are highly susceptible to infection withM. tuberculosis, which is associated with a low accumulation of mycobacteria-specific T cells in the lungs that display reduced proliferation, altered differentiation and enhanced expression of inhibitory receptors. In contrast, HIF-1 deficiency in T cells is redundant forM. tuberculosiscontrol.Vhl cKOmice also show reduced responses to vaccination. Further, VHL promotes proper MYC-activation, cell-growth responses, DNA synthesis, proliferation and survival of CD4 T cells after TCR activation. The VHL-deficient T cell responses are rescued by the loss of HIF-1α, indicating that the increased susceptibility toM. tuberculosisinfection and the impaired responses ofVhl-deficient T cells are HIF-1-dependent.
Augmented tactile-perception and haptic-feedback rings as human-machine interfaces aiming for immersive interactions
Authors: Sun Zhongda , Zhu Minglu , Shan Xuechuan , Lee Chengkuo
Published: September 2022

Advancements of virtual reality technology pave the way for developing wearable devices to enable somatosensory sensation, which can bring more comprehensive perception and feedback in the metaverse-based virtual society. Here, we propose augmented tactile-perception and haptic-feedback rings with multimodal sensing and feedback capabilities. This highly integrated ring consists of triboelectric and pyroelectric sensors for tactile and temperature perception, and vibrators and nichrome heaters for vibro- and thermo-haptic feedback. All these components integrated on the ring can be directly driven by a custom wireless platform of low power consumption for wearable/portable scenarios. With voltage integration processing, high-resolution continuous finger motion tracking is achieved via the triboelectric tactile sensor, which also contributes to superior performance in gesture/object recognition with artificial intelligence analysis. By fusing the multimodal sensing and feedback functions, an interactive metaverse platform with cross-space perception capability is successfully achieved, giving people a face-to-face like immersive virtual social experience.
Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration
Authors: Gerhardy Stefan , Ultsch Mark , Tang Wanjian , Green Evan , Holden Jeffrey K. , Li Wei , Estevez Alberto , Arthur Chris , Tom Irene , Rohou Alexis , Kirchhofer Daniel
Published: September 2022

The trimeric serine protease HTRA1 is a genetic risk factor associated with geographic atrophy (GA), a currently untreatable form of age-related macular degeneration. Here, we describe the allosteric inhibition mechanism of HTRA1 by a clinical Fab fragment, currently being evaluated for GA treatment. Using cryo-EM, X-ray crystallography and biochemical assays we identify the exposed LoopA of HTRA1 as the sole Fab epitope, which is approximately 30 Å away from the active site. The cryo-EM structure of the HTRA1:Fab complex in combination with molecular dynamics simulations revealed that Fab binding to LoopA locks HTRA1 in a non-competent conformational state, incapable of supporting catalysis. Moreover, grafting the HTRA1-LoopA epitope onto HTRA2 and HTRA3 transferred the allosteric inhibition mechanism. This suggests a conserved conformational lock mechanism across the HTRA family and a critical role of LoopA for catalysis, which was supported by the reduced activity of HTRA1-3 upon LoopA deletion or perturbation. This study reveals the long-range inhibition mechanism of the clinical Fab and identifies an essential function of the exposed LoopA for activity of HTRA family proteases.
The human thalamus orchestrates neocortical oscillations during NREM sleep
Authors: Schreiner Thomas , Kaufmann Elisabeth , Noachtar Soheyl , Mehrkens Jan-Hinnerk , Staudigl Tobias
Published: September 2022

A hallmark of non-rapid eye movement sleep is the coordinated interplay of slow oscillations (SOs) and sleep spindles. Traditionally, a cortico-thalamo-cortical loop is suggested to coordinate these rhythms: neocortically-generated SOs trigger spindles in the thalamus that are projected back to neocortex. Here, we used intrathalamic recordings from human epilepsy patients to test this canonical interplay. We show that SOs in the anterior thalamus precede neocortical SOs (peak −50 ms), whereas concurrently-recorded SOs in the mediodorsal thalamus are led by neocortical SOs (peak +50 ms). Sleep spindles, detected in both thalamic nuclei, preceded their neocortical counterparts (peak −100 ms) and were initiated during early phases of thalamic SOs. Our findings indicate an active role of the anterior thalamus in organizing sleep rhythms in the neocortex and highlight the functional diversity of thalamic nuclei in humans. The thalamic coordination of sleep oscillations could have broad implications for the mechanisms underlying memory consolidation.
X-ray crystallographic characterization of the SARS-CoV-2 main protease polyprotein cleavage sites essential for viral processing and maturation
Authors: Lee Jaeyong , Kenward Calem , Worrall Liam J. , Vuckovic Marija , Gentile Francesco , Ton Anh-Tien , Ng Myles , Cherkasov Artem , Strynadka Natalie C. J. , Paetzel Mark
Published: September 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the pathogen that causes COVID-19, produces polyproteins 1a and 1ab that contain, respectively, 11 or 16 non-structural proteins (nsp). Nsp5 is the main protease (Mpro) responsible for cleavage at eleven positions along these polyproteins, including at its own N- and C-terminal boundaries, representing essential processing events for viral assembly and maturation. Using C-terminally substituted Mpro chimeras, we have determined X-ray crystallographic structures of Mpro in complex with 10 of its 11 viral cleavage sites, bound at full occupancy intermolecularly in trans, within the active site of either the native enzyme and/or a catalytic mutant (C145A). Capture of both acyl-enzyme intermediate and product-like complex forms of a P2(Leu) substrate in the native active site provides direct comparative characterization of these mechanistic steps as well as further informs the basis for enhanced product release of Mpro’s own unique C-terminal P2(Phe) cleavage site to prevent autoinhibition. We characterize the underlying noncovalent interactions governing binding and specificity for this diverse set of substrates, showing remarkable plasticity for subsites beyond the anchoring P1(Gln)-P2(Leu/Val/Phe), representing together a near complete analysis of a multiprocessing viral protease. Collectively, these crystallographic snapshots provide valuable mechanistic and structural insights for antiviral therapeutic development.
The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells
Authors: Astanina Elena , Doronzo Gabriella , Corà Davide , Neri Francesco , Oliviero Salvatore , Genova Tullio , Mussano Federico , Middonti Emanuele , Vallariello Edoardo , Cencioni Chiara , Valdembri Donatella , Serini Guido , Limana Federica , Foglio Eleonora , Ballabio Andrea , Bussolino Federico
Published: September 2022

Epithelial-mesenchymal transition (EMT) is a complex and pivotal process involved in organogenesis and is related to several pathological processes, including cancer and fibrosis. During heart development, EMT mediates the conversion of epicardial cells into vascular smooth muscle cells and cardiac interstitial fibroblasts. Here, we show that the oncogenic transcription factor EB (TFEB) is a key regulator of EMT in epicardial cells and that its genetic overexpression in mouse epicardium is lethal due to heart defects linked to impaired EMT. TFEB specifically orchestrates the EMT-promoting function of transforming growth factor (TGF) β, and this effect results from activated transcription of thymine-guanine-interacting factor (TGIF)1, a TGFβ/Smad pathway repressor. TheTgif1promoter is activated by TFEB, and in vitro and in vivo findings demonstrate its increased expression whenTfebis overexpressed. Furthermore,Tfeboverexpression in vitro prevents TGFβ-induced EMT, and this effect is abolished byTgif1silencing.Tfebloss of function, similar to that ofTgif1, sensitizes cells to TGFβ, inducing an EMT response to low doses of TGFβ. Together, our findings reveal an unexpected function of TFEB in regulating EMT, which might provide insights into injured heart repair and control of cancer progression.
The nucleolus is the site for inflammatory RNA decay during infection
Authors: Lee Taeyun A. , Han Heonjong , Polash Ahsan , Cho Seok Keun , Lee Ji Won , Ra Eun A. , Lee Eunhye , Park Areum , Kang Sujin , Choi Junhee L. , Kim Ji Hyun , Lee Ji Eun , Min Kyung-Won , Yang Seong Wook , Hafner Markus , Lee Insuk , Yoon Je-Hyun , Lee Sungwook , Park Boyoun
Published: September 2022

Inflammatory cytokines are key signaling molecules that can promote an immune response, thus their RNA turnover must be tightly controlled during infection. Most studies investigate the RNA decay pathways in the cytosol or nucleoplasm but never focused on the nucleolus. Although this organelle has well-studied roles in ribosome biogenesis and cellular stress sensing, the mechanism of RNA decay within the nucleolus is not completely understood. Here, we report that the nucleolus is an essential site of inflammatory pre-mRNA instability during infection. RNA-sequencing analysis reveals that not only do inflammatory genes have higher intronic read densities compared with non-inflammatory genes, but their pre-mRNAs are highly enriched in nucleoli during infection. Notably, nucleolin (NCL) acts as a guide factor for recruiting cytosine or uracil (C/U)-rich sequence-containing inflammatory pre-mRNAs and the Rrp6-exosome complex to the nucleolus through a physical interaction, thereby enabling targeted RNA delivery to Rrp6-exosomes and subsequent degradation. Consequently, Ncl depletion causes aberrant hyperinflammation, resulting in a severe lethality in response to LPS. Importantly, the dynamics of NCL post-translational modifications determine its functional activity in phases of LPS. This process represents a nucleolus-dependent pathway for maintaining inflammatory gene expression integrity and immunological homeostasis during infection.
Rhodium nanocrystals on porous graphdiyne for electrocatalytic hydrogen evolution from saline water
Authors: Gao Yang , Xue Yurui , Qi Lu , Xing Chengyu , Zheng Xuchen , He Feng , Li Yuliang
Published: September 2022

The realization of the efficient hydrogen conversion with large current densities at low overpotentials represents the development trend of this field. Here we report the atomic active sites tailoring through a facile synthetic method to yield well-defined Rhodium nanocrystals in aqueous solution using formic acid as the reducing agent and graphdiyne as the stabilizing support. High-resolution high-angle annular dark-field scanning-transmission electron microscopy images show the high-density atomic steps on the faces of hexahedral Rh nanocrystals. Experimental results reveal the formation of stablesp–C~Rh bonds can stabilize Rh nanocrystals and further improve charge transfer ability in the system. Experimental and density functional theory calculation results solidly demonstrate the exposed high active stepped surfaces and various metal atomic sites affect the electronic structure of the catalyst to reduce the overpotential resulting in the large-current hydrogen production from saline water. This exciting result demonstrates unmatched electrocatalytic performance and highly stable saline water electrolysis.
Spin-selected electron transfer in liquid–solid contact electrification
Authors: Lin Shiquan , Zhu Laipan , Tang Zhen , Wang Zhong Lin
Published: September 2022

Electron transfer has been proven the dominant charge carrier during contact electrification at the liquid–solid interface. However, the effect of electron spin in contact electrification remains to be investigated. This study examines the charge transfer between different liquids and ferrimagnetic solids in a magnetic field, focusing on the contribution of O2 molecules to the liquid–solid contact electrification. The findings reveal that magnetic fields promote electron transfer at the O2-containing liquid–solid interfaces. Moreover, magnetic field-induced electron transfer increases at higher O2 concentrations in the liquids and decreases at elevated temperatures. The results indicate spin-selected electron transfer at liquid–solid interface. External magnetic fields can modulate the spin conversion of the radical pairs at the O2-containing liquid and ferrimagnetic solid interfaces due to the Zeeman interaction, promoting electron transfer. A spin-selected electron transfer model for liquid–solid contact electrification is further proposed based on the radical pair mechanism, in which the HO2 molecules and the free unpaired electrons from the ferrimagnetic solids are considered radical pairs. The spin conversion of the [HO2• •e−] pairs is affected by magnetic fields, rendering the electron transfer magnetic field-sensitive.
Organometallic complexation phenomenon observed during the natural aging of polyester urethane in the presence of iron corrosion
Authors: Lotz Hélène , Gasperuzzo Giulia , Gómez-Sánchez Elena
Published: September 2022

Shoes with polyester urethane soles have been stored for 3 decades in a museum environment after several months of mining use. Upon observation of sole material ageing under natural conditions, the shoes were laboratory stored since 2017 in order to evidence and follow signs of polyester urethane degradation. This study aims at characterizing a complex degradation material found on several shoes of the museum’s collection. Combining chemical composition analysis (EDX), mass spectroscopy (EGA-MS, py-GCMS) and vibrational spectroscopy (Raman and IR), results evidence the presence of iron carboxylates in different coordination modes. This study highlights the formation of a hitherto unknown degradation material of polyester urethane: an organometallic complex with iron ions coordinated with carboxylic rests of polyester polyol chains. The compound arises from the interaction between iron ions from the corrosion of structural metallic elements of the sole, and the polyester polyol fragments from the hydrolysis of the polyester urethane.
Cerebellar glutamatergic system impacts spontaneous motor recovery by regulating Gria1 expression
Authors: Asthana Pallavi , Kumar Gajendra , Milanowski Lukasz M. , Au Ngan Pan Bennett , Chan Siu Chung , Huang Jianpan , Feng Hemin , Kwan Kin Ming , He Jufang , Chan Kannie Wai Yan , Wszolek Zbigniew K. , Ma Chi Him Eddie
Published: September 2022

Peripheral nerve injury (PNI) often results in spontaneous motor recovery; however, how disrupted cerebellar circuitry affects PNI-associated motor recovery is unknown. Here, we demonstrated disrupted cerebellar circuitry and poor motor recovery in ataxia mice after PNI. This effect was mimicked by deep cerebellar nuclei (DCN) lesion, but not by damaging non-motor area hippocampus. By restoring cerebellar circuitry through DCN stimulation, and reversal of neurotransmitter imbalance using baclofen, ataxia mice achieve full motor recovery after PNI. Mechanistically, elevated glutamate-glutamine level was detected in DCN of ataxia mice by magnetic resonance spectroscopy. Transcriptomic study revealed that Gria1, an ionotropic glutamate receptor, was upregulated in DCN of control mice but failed to be upregulated in ataxia mice after sciatic nerve crush. AAV-mediated overexpression of Gria1 in DCN rescued motor deficits of ataxia mice after PNI. Finally, we found a correlative decrease in human GRIA1 mRNA expression in the cerebellum of patients with ataxia-telangiectasia and spinocerebellar ataxia type 6 patient iPSC-derived Purkinje cells, pointing to the clinical relevance of glutamatergic system. By conducting a large-scale analysis of 9,655,320 patients with ataxia, they failed to recover from carpal tunnel decompression surgery and tibial neuropathy, while aged-match non-ataxia patients fully recovered. Our results provide insight into cerebellar disorders and motor deficits after PNI.
Automated reconstruction of whole-embryo cell lineages by learning from sparse annotations
Authors: Malin-Mayor Caroline , Hirsch Peter , Guignard Leo , McDole Katie , Wan Yinan , Lemon William C. , Kainmueller Dagmar , Keller Philipp J. , Preibisch Stephan , Funke Jan
Published: September 2022

We present a method to automatically identify and track nuclei in time-lapse microscopy recordings of entire developing embryos. The method combines deep learning and global optimization. On a mouse dataset, it reconstructs 75.8% of cell lineages spanning 1 h, as compared to 31.8% for the competing method. Our approach improves understanding of where and when cell fate decisions are made in developing embryos, tissues, and organs.
A harmonized dataset of sediment diatoms from hundreds of lakes in the northeastern United States
Authors: Potapova Marina G. , Lee Sylvia S. , Spaulding Sarah A. , Schulte Nicholas O.
Published: September 2022

Sediment diatoms are widely used to track environmental histories of lakes and their watersheds, but merging datasets generated by different researchers for further large-scale studies is challenging because of taxonomic discrepancies caused by rapidly evolving diatom nomenclature and taxonomic concepts. We collated five datasets of lake sediment diatoms from the Northeastern USA using a harmonization process which included updating synonyms, tracking the identity of inconsistently identified taxa, and grouping those that could not be resolved taxonomically. Each harmonization step led to an increase in variation explained by environmental variables and a parallel reduction of variation attributable to taxonomic inconsistency. To maximize future use of the data and underlying specimens we provide the original and harmonized counts for 1327 core samples from 607 lakes, name translation schemes, sample metadata, specimen museum locations, and the Northeast Lakes Voucher Flora, which is a set of light microscope images grouped into 1154 morphological operational taxonomic units. Post-hoc harmonization enables data quality control when other approaches (e.g., upfront management of taxonomic consistency) are not possible.
Learning to predict synchronization of coupled oscillators on randomly generated graphs
Authors: Bassi Hardeep , Yim Richard P. , Vendrow Joshua , Koduluka Rohith , Zhu Cherlin , Lyu Hanbaek
Published: September 2022

Suppose we are given a system of coupled oscillators on an unknown graph along with the trajectory of the system during some period. Can we predict whether the system will eventually synchronize? Even with a known underlying graph structure, this is an important yet analytically intractable question in general. In this work, we take an alternative approach to the synchronization prediction problem by viewing it as a classification problem based on the fact that any given system will eventually synchronize or converge to a non-synchronizing limit cycle. By only using some basic statistics of the underlying graphs such as edge density and diameter, our method can achieve perfect accuracy when there is a significant difference in the topology of the underlying graphs between the synchronizing and the non-synchronizing examples. However, in the problem setting where these graph statistics cannot distinguish the two classes very well (e.g., when the graphs are generated from the same random graph model), we find that pairing a few iterations of the initial dynamics along with the graph statistics as the input to our classification algorithms can lead to significant improvement in accuracy; far exceeding what is known by the classical oscillator theory. More surprisingly, we find that in almost all such settings, dropping out the basic graph statistics and training our algorithms with only initial dynamics achieves nearly the same accuracy. We demonstrate our method on three models of continuous and discrete coupled oscillators—the Kuramoto model, Firefly Cellular Automata, and Greenberg-Hastings model. Finally, we also propose an “ensemble prediction” algorithm that successfully scales our method to large graphs by training on dynamics observed from multiple random subgraphs.