bluuebunny/crossref_metadata_2025 huggingface dataset:
Disrupted state transition learning as a computational marker of compulsivity
Authors: Sharp Paul B. , Dolan Raymond J. , Eldar Eran
Published: September 2021

Background

Disorders involving compulsivity, fear, and anxiety are linked to beliefs that the world is less predictable. We lack a mechanistic explanation for how such beliefs arise. Here, we test a hypothesis that in people with compulsivity, fear, and anxiety, learning a probabilistic mapping between actions and environmental states is compromised.

Methods

In Study 1 (n = 174), we designed a novel online task that isolated state transition learning from other facets of learning and planning. To determine whether this impairment is due to learning that is too fast or too slow, we estimated state transition learning rates by fitting computational models to two independent datasets, which tested learning in environments in which state transitions were either stable (Study 2: n = 1413) or changing (Study 3: n = 192).

Results

Study 1 established that individuals with higher levels of compulsivity are more likely to demonstrate an impairment in state transition learning. Preliminary evidence here linked this impairment to a common factor comprising compulsivity and fear. Studies 2 and 3 showed that compulsivity is associated with learning that is too fast when it should be slow (i.e. when state transition are stable) and too slow when it should be fast (i.e. when state transitions change).

Conclusions

Together, these findings indicate that compulsivity is associated with a dysregulation of state transition learning, wherein the rate of learning is not well adapted to the task environment. Thus, dysregulated state transition learning might provide a key target for therapeutic intervention in compulsivity.
Against ontological capture: Drawing lessons from Amazonian Kichwa relationality
Authors: Reddekop Jarrad
Published: September 2021

This article offers an experiment in theorising within or across a ‘space’ of ontological disagreement – which, as numerous authors have contended, characterises much that is at stake in relations between states and Indigenous peoples in the Americas. Such ontological disagreements, I argue, contain radical potential for disrupting globally dominant and anthropocentric patterns of thinking and relating, and for generating alternatives. I substantiate this point with reference to the relational ontologies informing different Indigenous ways of analysing and practicing existence. Drawing on Amazonian Kichwa thinking and Anishinaabe accounts of treaties, I show how these relational ontologies recast the problem of how it is possible to relate with difference, in such a way as to fold an inter-human ‘international’ into a continuum of relations that include human-nonhuman ones. Distinct normative horizons emerge. I argue that non-Indigenous people can draw a range of provocations here concerning our constitution as selves and the political space in which we understand ourselves to possibly participate. I also claim, however, that this more transformative potential is predominantly squandered through processes of what I call ontological capture, which troublingly re-entrench dominant construals of reality and forestall a more radical questioning and re-patterning of accompanying lifeways.
Collective Reasons and Agent-Relativity
Authors: Dietz Alexander
Published: September 2021

Could it be true that even though we as a group ought to do something, you as an individual ought not to do your part? And under what conditions, in particular, could this happen? In this article, I discuss how a certain kind of case, introduced by David Copp, illustrates the possibility that you ought not to do your part even when you would be playing a crucial causal role in the group action. This is because you may have special agent-relative reasons against participating that are not shared by the group as a whole. I defend the claim that these are indeed cases in which you ought not to do your part in what the group ought to do. I then argue that we can expect these cases to produce a troubling kind of rational conflict.
Parent couple conflict and emotional and behavioral problems in youth with autism: Longitudinal investigation of bidirectional effects
Authors: Piro-Gambetti Brianna , Rodriguez Geovanna , Papp Lauren M. , Greenlee Jessica L. , Hartley Sigan L.
Published: September 2021

Families of youth with autism spectrum disorder (ASD) are vulnerable to maladaptive psychosocial experiences, including elevated youth emotional and behavioral problems (EBPs) and poor parent couple relationship outcomes. Yet, the extent to which these family psychosocial experiences are intertwined has been given little research attention. The present study longitudinally investigated the bidirectional associations between parent couple conflict (PCC) and youth EBPs in 188 families of children and adolescents with ASD (initially aged 5 to 12 years) across four time points (T1, T2, T3, T4), each spaced 12 months apart. Mother- and father-report of youth EBPs and PCC were entered into a cross-lagged panel model. After adjusting for youth age and intellectual disability status and parent education and couple relationship length, the results indicated that father-report of PCC predicted increased youth EBPs 12 months later (T1→T2 and T2→T3). In addition, father-report of youth EBPs predicted increased PCC 12 months later (T3→T4). Mother-report did not demonstrate cross-lagged effects. The findings suggest that fathers’ perceptions of PCC and youth emotional and behavioral functioning are transactionally related, highlighting the need for family-wide interventions.
Expansion for the critical point of site percolation: the first three terms
Authors: Heydenreich Markus , Matzke Kilian
Published: September 2021

We expand the critical point for site percolation on the d-dimensional hypercubic lattice in terms of inverse powers of 2d, and we obtain the first three terms rigorously. This is achieved using the lace expansion.
Evaluation of taxonomic and neural embedding methods for calculating semantic similarity
Authors: Yang Dongqiang , Yin Yanqin
Published: September 2021

Modelling semantic similarity plays a fundamental role in lexical semantic applications. A natural way of calculating semantic similarity is to access handcrafted semantic networks, but similarity prediction can also be anticipated in a distributional vector space. Similarity calculation continues to be a challenging task, even with the latest breakthroughs in deep neural language models. We first examined popular methodologies in measuring taxonomic similarity, including edge-counting that solely employs semantic relations in a taxonomy, as well as the complex methods that estimate concept specificity. We further extrapolated three weighting factors in modelling taxonomic similarity. To study the distinct mechanisms between taxonomic and distributional similarity measures, we ran head-to-head comparisons of each measure with human similarity judgements from the perspectives of word frequency, polysemy degree and similarity intensity. Our findings suggest that without fine-tuning the uniform distance, taxonomic similarity measures can depend on the shortest path length as a prime factor to predict semantic similarity; in contrast to distributional semantics, edge-counting is free from sense distribution bias in use and can measure word similarity both literally and metaphorically; the synergy of retrofitting neural embeddings with concept relations in similarity prediction may indicate a new trend to leverage knowledge bases on transfer learning. It appears that a large gap still exists on computing semantic similarity among different ranges of word frequency, polysemous degree and similarity intensity.
Reexamining the Decadal Variation in the ENSO‐East Asian Winter Monsoon Relationship
Authors: Shi Jian
Published: September 2021

Although numerous studies have paid attention to the unstable relationship between the El Niño/Southern Oscillation (ENSO) and East Asian winter monsoon (EAWM), significant discrepancies have existed, especially regarding the modulation of the Pacific decadal oscillation (PDO) and Atlantic multidecadal oscillation (AMO). Here, we reexamine this issue by applying a new method that considers the changing relationship between ENSO and the spatial variations of the EAWM rather than a given EAWM index. We suggest a complicated spatial‐temporal variation in the ENSO‐EAWM relationship (EER), which consists of two major modes regulated by the PDO and AMO in distinct ways. In other words, the PDO and AMO modulate two different aspects of the decadal EER, which helps to clarify the disagreements among previous studies that are generally based on specific and regional EWAM indices.
Understanding the Cold Season Arctic Surface Warming Trend in Recent Decades
Authors: Zhang Rudong , Wang Hailong , Fu Qiang , Rasch Philip J. , Wu Mingxuan , Maslowski Wieslaw
Published: September 2021

Whether sea‐ice loss or lapse‐rate feedback dominates the Arctic amplification (AA) remains an open question. Analysis of data sets based upon observations reveals a 1.11 K per decade surface warming trend in the Arctic (70°–90°N) during 1979–2020 cold season (October–February) that is five times higher than the corresponding global mean. Based on surface energy budget analysis, we show that the largest contribution (∼82%) to this cold season warming trend is attributed to changes in clear‐sky downward longwave radiation. In contrast to that in Arctic summer and over tropics, a reduction in lower‐tropospheric inversions plays a unique role in explaining the reduction of the downward longwave radiation associated with atmospheric nonuniform temperature and corresponding moisture changes. Our analyses also suggest that Arctic lower‐tropospheric stability should be considered in conjunction with sea‐ice decline during the preceding warm season to explain AA.
An Examination of Magnetosphere‐Ionosphere Influences During a SAPS Event
Authors: Kunduri B. S. R. , Baker J. B. H. , Ruohoniemi J. M. , Coster A. J. , Vines S. K. , Anderson B. J. , Shepherd S. G. , Chartier A. T.
Published: September 2021

The sub‐auroral polarization stream (SAPS) is a region of westward high velocity plasma convection equatorward of the auroral oval that plays an important role in mid‐latitude space weather dynamics. In this study, we present observations of SAPS flows extending across the North American sector observed during the recovery phase of a minor geomagnetic storm. A resurgence in substorm activity drove a new set of field‐aligned currents (FACs) into the ionosphere, initiating the SAPS. An upward FAC system is the most prominent feature spreading across most SAPS local times, except near dusk, where a downward current system is pronounced. The location of SAPS flows remained relatively constant, firmly inside the trough, independent of the variability in the location and intensity of the FACs. The SAPS flows were sustained even after the FACs weakened and retreated polewards with a decline in geomagnetic activity. The observations indicate that the mid‐latitude trough plays a crucial role in determining the location of the SAPS and that SAPS flows can be sustained even after the magnetospheric driver has weakened.
Impacts of Diverse El Niño Events on North Tropical Atlantic Warming in Their Decaying Springs
Authors: Guo Weihao , Zhang Rongwang , Wang Xin
Published: September 2021

Previous studies have demonstrated that North Tropical Atlantic (NTA) warming can be modulated by El Niño events through atmospheric teleconnections. Considering the diversity of El Niño events, this study focuses on different responses of the NTA sea surface temperature (SST) to eastern Pacific (EP), central Pacific type I and type II (CP‐I and CP‐II) El Niño events in their decaying springs. In EP and CP‐II El Niño events, the pattern of NTA warming is well established, while the NTA SST fails to warm in CP‐I El Niño events. In EP and CP‐II El Niño events, anomalous cyclones can be excited in the subtropical Atlantic. Consequently, anomalous southwesterly winds in the NTA weaken the background northeasterly winds and suppress oceanic latent heat loss, leading to NTA warming. However, in CP‐I El Niño events, anomalous anticyclones are excited in the subtropical Atlantic and anomalous northeasterly winds in the NTA strengthen the background northeasterly winds, which facilitate oceanic latent heat loss and lead to NTA cooling. The inconsistent remote atmospheric responses of the NTA are attributed to the different patterns of warm and/or cold SST anomalies in the tropical Pacific in the decaying springs of different types of El Niño events. The physical mechanism linking the SSTs in the tropical Pacific and the NTA has been verified in a slab ocean model.
Strong Seasonal and Regional Variations in the Evaporation Rate of Liquid Water on Mars
Authors: Temel Orkun , Karatekin Özgür , Mischna Michael A. , Senel Cem Berk , Martínez Germán , Gloesener Elodie , Van Hoolst Tim
Published: September 2021

We have investigated the seasonal and regional variations in the evaporation rate of both pure liquid water and liquid brine solutions on the surface of Mars. Our evaporation rate estimates are performed using a novel parameterization method taking into account the effects of concentration difference, between the evaporating liquid water solution and the atmosphere, in addition to the effects of near‐surface winds. The method is based on atmospheric surface‐layer calculations obtained from a global circulation model. We show that near‐surface winds strongly enhance strong seasonal variability in the evaporation rate of liquid solutions on Mars. The evaporation rate of a liquid brine solution can vary seasonally up to a factor of 3 and changes by two orders of magnitude depending on the surface elevation and properties of the terrain.
New Structural Percolation Transition in Fractional Wet 3D‐Porous Media: A Comparative μ‐CT Study
Authors: Geistlinger Helmut , Zulfiqar Bilal , Schlueter Steffen , Amro Mohd
Published: September 2021

Natural porous media possess spatial heterogeneous (fractional) wettability, which controls the multiphase flow behavior, that is, displacement and trapping. We used mixed hydrophilic (contact angle θ = 0°) and hydrophobic (θ = 100°) 1 mm sands and 1 mm glass beads as model systems for fractional wet porous media. Both porous media have the same morphological characteristics (Minkowski functions). A comparative μ‐CT study of such fractional wet systems is lacking in the literature. A previous study (Geistlinger & Zulfiqar, 2020, https://doi.org/10.1029/2019wr026826) showed a percolation transition of the invading fluid from compact to fractal displacement when the wettability changed from imbibition to drainage. This correlates to a transition from no to maximal trapping. For the first time, we observed in fractional wet glass bead packs, a second structural percolation transition with a percolation threshold of approximately 50% hydrophobic glass beads. Below this threshold, the percolating cluster consisted of hydrophilic glass beads, which resulted in compact displacement without any trapping. Above the threshold, the percolating cluster consisted of hydrophobic glass beads, which resulted in fractal displacement with maximal trapping. Trapping occurred only in hydrophobic environments/configurations, that is, when the trapped clusters were surrounded by hydrophobic glass beads. Fractional wet glass beads and sands show an opposite trapping behavior, that is, the trapping efficiency increases for glass beads, whereas it decreases for sands with increasing percentage of hydrophobic grains. Interestingly, the trapping efficiency approaches the same limit value for pure hydrophobic sands and glass beads. This demonstrates that bypass trapping is the dominant trapping mechanism, because it depends strongly on the pore connectivity.
1979 AGU Fellows Citations
Authors: Anonymous
Published: September 2021

William A. Bassett for his pioneering work in developing high‐pressure, high‐temperature apparatus and applying these to geophysicatly important problems of the earth's interior. His outstanding achievements are the first measurements of the compressibility of a host of mantle minerals to 300 kbar, development of high‐pressure laser heating techniques which allow mineral synthesis at 300 kbar and 3000°C, and the development of methods of measuring elastic moduli of minerals at high pressures.
Transient regulatory T-cell targeting triggers immune control of multiple myeloma and prevents disease progression
Authors: Dahlhoff Julia , Manz Hannah , Steinfatt Tim , Delgado-Tascon Julia , Seebacher Elena , Schneider Theresa , Wilnit Amy , Mokhtari Zeinab , Tabares Paula , Böckle David , Rasche Leo , Martin Kortüm K. , Lutz Manfred B. , Einsele Hermann , Brandl Andreas , Beilhack Andreas
Published: September 2021

Multiple myeloma remains a largely incurable disease of clonally expanding malignant plasma cells. The bone marrow microenvironment harbors treatment-resistant myeloma cells, which eventually lead to disease relapse in patients. In the bone marrow, CD4+FoxP3+ regulatory T cells (Tregs) are highly abundant amongst CD4+ T cells providing an immune protective niche for different long-living cell populations, e.g., hematopoietic stem cells. Here, we addressed the functional role of Tregs in multiple myeloma dissemination to bone marrow compartments and disease progression. To investigate the immune regulation of multiple myeloma, we utilized syngeneic immunocompetent murine multiple myeloma models in two different genetic backgrounds. Analyzing the spatial immune architecture of multiple myeloma revealed that the bone marrow Tregs accumulated in the vicinity of malignant plasma cells and displayed an activated phenotype. In vivo Treg depletion prevented multiple myeloma dissemination in both models. Importantly, short-term in vivo depletion of Tregs in mice with established multiple myeloma evoked a potent CD8 T cell- and NK cell-mediated immune response resulting in complete and stable remission. Conclusively, this preclinical in-vivo study suggests that Tregs are an attractive target for the treatment of multiple myeloma.
Prefrontal connectomics: from anatomy to human imaging
Authors: Haber Suzanne N. , Liu Hesheng , Seidlitz Jakob , Bullmore Ed
Published: September 2021

The fundamental importance of prefrontal cortical connectivity to information processing and, therefore, disorders of cognition, emotion, and behavior has been recognized for decades. Anatomic tracing studies in animals have formed the basis for delineating the direct monosynaptic connectivity, from cells of origin, through axon trajectories, to synaptic terminals. Advances in neuroimaging combined with network science have taken the lead in developing complex wiring diagrams or connectomes of the human brain. A key question is how well these magnetic resonance imaging (MRI)-derived networks and hubs reflect the anatomic “hard wiring” first proposed to underlie the distribution of information for large-scale network interactions. In this review, we address this challenge by focusing on what is known about monosynaptic prefrontal cortical connections in non-human primates and how this compares to MRI-derived measurements of network organization in humans. First, we outline the anatomic cortical connections and pathways for each prefrontal cortex (PFC) region. We then review the available MRI-based techniques for indirectly measuring structural and functional connectivity, and introduce graph theoretical methods for analysis of hubs, modules, and topologically integrative features of the connectome. Finally, we bring these two approaches together, using specific examples, to demonstrate how monosynaptic connections, demonstrated by tract-tracing studies, can directly inform understanding of the composition of PFC nodes and hubs, and the edges or pathways that connect PFC to cortical and subcortical areas.
Regulation of a progenitor gene program by SOX4 is essential for mammary tumor proliferation
Authors: Roukens M. Guy , Frederiks Cynthia L. , Seinstra Danielle , Braccioli Luca , Khalil Antoine A. , Pals Cornelieke , De Neck Simon , Bornes Laura , Beerling Evelyne , Mokry Michal , de Bruin Alain , Westendorp Bart , van Rheenen Jacco , Coffer Paul J.
Published: September 2021

In breast cancer the transcription factor SOX4 has been shown to be associated with poor survival, increased tumor size and metastasis formation. This has mostly been attributed to the ability of SOX4 to regulate Epithelial-to-Mesenchymal-Transition (EMT). However, SOX4 regulates target gene transcription in a context-dependent manner that is determined by the cellular and epigenetic state. In this study we have investigated the loss of SOX4 in mammary tumor development utilizing organoids derived from a PyMT genetic mouse model of breast cancer. Using CRISPR/Cas9 to abrogate SOX4 expression, we found that SOX4 is required for inhibiting differentiation by regulating a subset of genes that are highly activated in fetal mammary stem cells (fMaSC). In this way, SOX4 re-activates an oncogenic transcriptional program that is regulated in many progenitor cell-types during embryonic development. SOX4-knockout organoids are characterized by the presence of more differentiated cells that exhibit luminal or basal gene expression patterns, but lower expression of cell cycle genes. In agreement, primary tumor growth and metastatic outgrowth in the lungs are impaired in SOX4KO tumors. Finally, SOX4KO tumors show a severe loss in competitive capacity to grow out compared to SOX4-proficient cells in primary tumors. Our study identifies a novel role for SOX4 in maintaining mammary tumors in an undifferentiated and proliferative state. Therapeutic manipulation of SOX4 function could provide a novel strategy for cancer differentiation therapy, which would promote differentiation and inhibit cycling of tumor cells.
Data-driven magneto-elastic predictions with scalable classical spin-lattice dynamics
Authors: Nikolov Svetoslav , Wood Mitchell A. , Cangi Attila , Maillet Jean-Bernard , Marinica Mihai-Cosmin , Thompson Aidan P. , Desjarlais Michael P. , Tranchida Julien
Published: September 2021

A data-driven framework is presented for building magneto-elastic machine-learning interatomic potentials (ML-IAPs) for large-scale spin-lattice dynamics simulations. The magneto-elastic ML-IAPs are constructed by coupling a collective atomic spin model with an ML-IAP. Together they represent a potential energy surface from which the mechanical forces on the atoms and the precession dynamics of the atomic spins are computed. Both the atomic spin model and the ML-IAP are parametrized on data from first-principles calculations. We demonstrate the efficacy of our data-driven framework across magneto-structural phase transitions by generating a magneto-elastic ML-IAP forα-iron. The combined potential energy surface yields excellent agreement with first-principles magneto-elastic calculations and quantitative predictions of diverse materials properties including bulk modulus, magnetization, and specific heat across the ferromagnetic–paramagnetic phase transition.
Exploiting the quantum mechanically derived force field for functional materials simulations
Authors: Odinokov Alexey , Yakubovich Alexander , Son Won-Joon , Jung Yongsik , Choi Hyeonho
Published: September 2021

The computational design of functional materials relies heavily on large-scale atomistic simulations. Such simulations are often problematic for conventional classical force fields, which require tedious and time-consuming parameterization of interaction parameters. The problem can be solved using a quantum mechanically derived force field (QMDFF)—a system-specific force field derived directly from the first-principles calculations. We present a computational approach for atomistic simulations of complex molecular systems, which include the treatment of chemical reactions with the empirical valence bond approach. The accuracy of the QMDFF is verified by comparison with the experimental properties of liquid solvents. We illustrate the capabilities of our methodology to simulate functional materials in several case studies: chemical degradation of material in organic light-emitting diode (OLED), polymer chain packing, material morphology of organometallic photoresists. The presented methodology is fast, accurate, and highly automated, which allows its application in diverse areas of materials science.
The “Narratives” fMRI dataset for evaluating models of naturalistic language comprehension
Authors: Nastase Samuel A. , Liu Yun-Fei , Hillman Hanna , Zadbood Asieh , Hasenfratz Liat , Keshavarzian Neggin , Chen Janice , Honey Christopher J. , Yeshurun Yaara , Regev Mor , Nguyen Mai , Chang Claire H. C. , Baldassano Christopher , Lositsky Olga , Simony Erez , Chow Michael A. , Leong Yuan Chang , Brooks Paula P. , Micciche Emily , Choe Gina , Goldstein Ariel , Vanderwal Tamara , Halchenko Yaroslav O. , Norman Kenneth A. , Hasson Uri
Published: September 2021

The “Narratives” collection aggregates a variety of functional MRI datasets collected while human subjects listened to naturalistic spoken stories. The current release includes 345 subjects, 891 functional scans, and 27 diverse stories of varying duration totaling ~4.6 hours of unique stimuli (~43,000 words). This data collection is well-suited for naturalistic neuroimaging analysis, and is intended to serve as a benchmark for models of language and narrative comprehension. We provide standardized MRI data accompanied by rich metadata, preprocessed versions of the data ready for immediate use, and the spoken story stimuli with time-stamped phoneme- and word-level transcripts. All code and data are publicly available with full provenance in keeping with current best practices in transparent and reproducible neuroimaging.
Evaluation of the relationship between the 14-3-3ε protein and LvRab11 in the shrimp Litopenaeus vannamei during WSSV infection
Authors: Boonyoung Guson , Panrat Tanate , Phongdara Amornrat , Wanna Warapond
Published: September 2021

The 14-3-3 proteins interact with a wide variety of cellular proteins for many diverse functions in biological processes. In this study, a yeast two-hybrid assay revealed that two 14-3-3ε isoforms (14-3-3ES and 14-3-3EL) interacted with Rab11 in the white shrimpLitopenaeus vannamei(LvRab11). The interaction of 14-3-3ε and LvRab11 was confirmed by a GST pull-down assay. TheLvRab11open reading frame was 645 bp long, encoding a protein of 214 amino acids. Possible complexes of 14-3-3ε isoforms and LvRab11 were elucidated by in silico analysis, in which LvRab11 showed a better binding energy score with 14-3-3EL than with 14-3-3ES. In shrimp challenged with the white spot syndrome virus (WSSV), the mRNA expression levels ofLvRab11and14-3-3εwere significantly upregulated at 48 h after challenge. To determine whether LvRab11 and binding between 14-3-3ε and LvRab11 are active against WSSV infection, an in vivo neutralization assay and RNA interference were performed. The results of in vivo neutralization showed that LvRab11 and complexes of 14-3-3ε/LvRab11 delayed mortality in shrimp challenged with WSSV. Interestingly, in the RNAi experiments, the silencing effect ofLvRab11in WSSV-infected shrimp resulted in decreasedie-1mRNA expression and WSSV copy number. Whereas suppression of complex14-3-3ε/LvRab11increased WSSV replication. This study has suggested two functions of LvRab11 in shrimp innate immunity; (1) at the early stage of WSSV infection, LvRab11 might play an important role in WSSV infection processes and (2) at the late stage of infection, the 14-3-3ε/LvRab11 interaction acquires functions that are involved in immune response against WSSV invasion.
Metformin strengthens uroepithelial immunity against E. coli infection
Authors: Majhi Rakesh Kumar , Mohanty Soumitra , Kamolvit Witchuda , White John Kerr , Scheffschick Andrea , Brauner Hanna , Brauner Annelie
Published: September 2021

Urinary tract infection frequently caused by E. coli is one of the most common bacterial infections. Increasing antibiotic resistance jeopardizes successful treatment and alternative treatment strategies are therefore mandatory. Metformin, an oral antidiabetic drug, has been shown to activate macrophages in the protection against certain infecting microorganisms. Since epithelial cells often form the first line of defense, we here investigated the effect on uroepithelial cells during E. coli infection. Metformin upregulated the human antimicrobial peptides cathelicidin LL-37 and RNase7 via modulation of the TRPA1 channel and AMPK pathway. Interestingly, metformin stimulation enriched both LL-37 and TRPA1 in lysosomes. In addition, metformin specifically increased nitric oxide and mitochondrial, but not cytosolic ROS. Moreover, metformin also triggered mRNA expression of the proinflammatory cytokines IL1B, CXCL8 and growth factor GDF15 in human uroepithelial cells. The GDF15 peptide stimulated macrophages increased LL-37 expression, with increased bacterial killing. In conclusion, metformin stimulation strengthened the innate immunity of uroepithelial cells inducing enhanced extracellular and intracellular bacterial killing suggesting a favorable role of metformin in the host defense.
Postpartum hemorrhage risk is driven by changes in blood composition through pregnancy
Authors: Robinson Matthew R. , Patxot Marion , Stojanov Miloš , Blum Sabine , Baud David
Published: September 2021

The extent to which women differ in the course of blood cell counts throughout pregnancy, and the importance of these changes to pregnancy outcomes has not been well defined. Here, we develop a series of statistical analyses of repeated measures data to reveal the degree to which women differ in the course of pregnancy, predict the changes that occur, and determine the importance of these changes for post-partum hemorrhage (PPH) which is one of the leading causes of maternal mortality. We present a prospective cohort of 4082 births recorded at the University Hospital, Lausanne, Switzerland between 2009 and 2014 where full labour records could be obtained, along with complete blood count data taken at hospital admission. We find significant differences, at a $$p<0.001$$

p
<
0.001

level, among women in how blood count values change through pregnancy for mean corpuscular hemoglobin, mean corpuscular volume, mean platelet volume, platelet count and red cell distribution width. We find evidence that almost all complete blood count values show trimester-specific associations with PPH. For example, high platelet count (OR 1.20, 95% CI 1.01–1.53), high mean platelet volume (OR 1.58, 95% CI 1.04–2.08), and high erythrocyte levels (OR 1.36, 95% CI 1.01–1.57) in trimester 1 increased PPH, but high values in trimester 3 decreased PPH risk (OR 0.85, 0.79, 0.67 respectively). We show that differences among women in the course of blood cell counts throughout pregnancy have an important role in shaping pregnancy outcome and tracking blood count value changes through pregnancy improves identification of women at increased risk of postpartum hemorrhage. This study provides greater understanding of the complex changes in blood count values that occur through pregnancy and provides indicators to guide the stratification of patients into risk groups.
Oxysterol binding protein-like 3 (OSBPL3) is a novel driver gene that promotes tumor growth in part through R-Ras/Akt signaling in gastric cancer
Authors: Hu Qingjiang , Masuda Takaaki , Koike Kensuke , Sato Kuniaki , Tobo Taro , Kuramitsu Shotaro , Kitagawa Akihiro , Fujii Atsushi , Noda Miwa , Tsuruda Yusuke , Otsu Hajime , Kuroda Yosuke , Ito Shuhei , Oki Eiji , Mimori Koshi
Published: September 2021

Gastric cancer (GC) is one of the most lethal malignant tumors. To improve the prognosis of GC, the identification of novel driver genes as therapeutic targets is in urgent need. Here, we aimed to identify novel driver genes and clarify their roles in gastric cancer. OSBPL3 was identified as a candidate driver gene by in silico analysis of public genomic datasets. OSBPL3 expression was analyzed by RT-qPCR and immunohistochemistry in GC cells and tissues. The biological functions and mechanisms of OSBPL3 in GC were examined in vitro and in vivo using GC cells. The association between OSBPL3 expression and clinical outcome in GC patients was also evaluated. Overexpression of OSBPL3 was detected in GC cells with OSBPL3 DNA copy number gains and promoter hypomethylation. OSBPL3-knockdown reduced GC cell growth in vitro and in vivo by inhibiting cell cycle progression. Moreover, an active Ras pull-down assay and western blotting demonstrated that OSBPL3 activates the R-Ras/Akt signaling pathway in GC cells. In a clinical analysis of two GC datasets, high OSBPL3 expression was predictive of a poor prognosis. Our findings suggest that OSBPL3 is a novel driver gene stimulating the R-Ras/Akt signaling pathway and a potential therapeutic target in GC patients.
ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets
Authors: Utsumi Toshihiko , Hosokawa Takuro , Shichita Mayu , Nishiue Misato , Iwamoto Natsuko , Harada Haruna , Kiwado Aya , Yano Manami , Otsuka Motoaki , Moriya Koko
Published: September 2021

The membrane topology and intracellular localization of ANKRD22, a novel human N-myristoylated protein with a predicted single-pass transmembrane domain that was recently reported to be overexpressed in cancer, were examined. Immunofluorescence staining of COS-1 cells transfected with cDNA encoding ANKRD22 coupled with organelle markers revealed that ANKRD22 localized specifically to lipid droplets (LD). Analysis of the intracellular localization of ANKRD22 mutants C-terminally fused to glycosylatable tumor necrosis factor (GLCTNF) and assessment of their susceptibility to protein N-glycosylation revealed that ANKRD22 is synthesized on the endoplasmic reticulum (ER) membrane as an N-myristoylated hairpin-like monotopic membrane protein with the amino- and carboxyl termini facing the cytoplasm and then sorted to LD. Pro98 located at the center of the predicted membrane domain was found to be essential for the formation of the hairpin-like monotopic topology of ANKRD22. Moreover, the hairpin-like monotopic topology, and positively charged residues located near the C-terminus were demonstrated to be required for the sorting of ANKRD22 from ER to LD. Protein N-myristoylation was found to positively affect the LD localization. Thus, multiple factors, including hairpin-like monotopic membrane topology, C-terminal positively charged residues, and protein N-myristoylation cooperatively affected the intracellular targeting of ANKRD22 to LD.
Excess free volume and structural properties of inert gas condensation synthesized nanoparticles based CuZr nanoglasses
Authors: Zheng Kaifeng , Yuan Suyue , Hahn Horst , Branicio Paulo S.
Published: September 2021

Nanoglass (NG) as a new structure-tunable material has been investigated using both experiments and computational modeling. Experimentally, inert gas condensation (IGC) is commonly employed to prepare metallic glass (MG) nanoparticles that are consolidated using cold compression to generate an NG. In computational modeling, various methods have been used to generate NGs. However, due to the high computational cost involved, heretofore modeling investigations have not followed the experimental synthesis route. In this work, we use molecular dynamics simulations to generate an NG model by consolidating IGC-prepared Cu64Zr36 nanoparticles following a workflow similar to that of experiments. The resulting structure is compared with those of NGs produced following two alternative procedures previously used: direct generation employing Voronoi tessellation and consolidation of spherical nanoparticles carved from an MG sample. We focus on the characterization of the excess free volume and the Voronoi polyhedral statistics in order to identify and quantify contrasting features of the glass-glass interfaces in the three NG samples prepared using distinct methods. Results indicate that glass-glass interfaces in IGC-based NGs are thicker and display higher structural contrast with their parent MG structure. Nanoparticle-based methods display excess free volume exceeding 4%, in agreement with experiments. IGC-prepared nanoparticles, which display Cu segregation to their surfaces, generate the highest glass-glass interface excess free volume levels and the largest relative interface volume with excess free volume higher than 3%. Voronoi polyhedral analysis indicates a sharp drop in the full icosahedral motif fraction in the glass-glass interfaces in nanoparticle-based NG as compared to their parent MG.
Separation-related behavior of dogs shows association with their reactions to everyday situations that may elicit frustration or fear
Authors: Lenkei Rita , Faragó Tamás , Bakos Viktória , Pongrácz Péter
Published: September 2021

Separation related disorder in dogs is a multi-faceted phenomenon. Dogs can react to the absence of their owner due to different inner states such as fear, panic or frustration. We hypothesized that dogs that are prone to frustration or fearfulness in other contexts would show a different behavioral response to separation from the owner. We investigated the association between inner states in different contexts and separation behaviors by combining a questionnaire with a separation test. Fear-related questionnaire components were rather associated with whining and the absence of barking. Dogs that received higher scores in the demanding component of the questionnaire, which might be in association of the frustration threshold of the dog, barked more and were more likely to scratch the door. Finally, dogs that were more prone to phobic reactions whined somewhat more and tried to escape. We provide empirical support for the assumption that separation-related behavioral responses of dogs might be triggered by different emotions.
TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer
Authors: Kuno Ikumi , Takayanagi Daisuke , Asami Yuka , Murakami Naoya , Matsuda Maiko , Shimada Yoko , Hirose Sou , Kato Mayumi Kobayashi , Komatsu Masaaki , Hamamoto Ryuji , Okuma Kae , Kohno Takashi , Itami Jun , Yoshida Hiroshi , Shiraishi Kouya , Kato Tomoyasu
Published: September 2021

Targeted sequencing for somatic mutations across the hotspots of 50 cancer-related genes was performed using biopsy specimens to investigate whether clinicopathological factors and genomic alterations correlated with prognosis in locally advanced cervical cancer. Seventy patients diagnosed with International Federation of Obstetrics and Gynecology (FIGO) stage III to IVA cervical cancer underwent radiotherapy or concurrent chemoradiotherapy at the National Cancer Center Hospital between January 2008 and December 2017. Mutations were detected in 47 of 70 [67% of cases; frequency of genetic alterations was as follows: PIK3CA (51%), FBXW7 (10%), PTEN (7.1%), and TP53 (5.7%)]. The Cancer Genome Atlas (TCGA) datasets showed a similar distribution of somatic mutations, but PIK3CA mutation frequency was significantly higher in our cohort than in TCGA datasets (P = 0.028). Patients with TP53 mutation were significantly related to poor progression-free survival (PFS) (hazard ratio [HR] = 3.53, P = 0.042). Patients with tumor diameters > 70 mm were associated with poor prognosis (HR = 2.96, P = 0.0048). Patients with non-HPV16/18 genotypes had worse prognosis than those with HPV16/18 genotypes (HR = 2.15, P = 0.030). Hence, patients with locally advanced cervical cancer, TP53 mutation, large tumor diameter, and non-HPV16/18 genotype were independently correlated with poor PFS, despite concurrent chemoradiotherapy.
A non-lethal method to assess element content in the endangered Pinna nobilis
Authors: Montroni Devis , Simoni Andrea , Pasquini Viviana , Dinelli Enrico , Ciavatta Claudio , Triunfo Carla , Secci Marco , Marzadori Claudio , Addis Pierantonio , Falini Giuseppe
Published: September 2021

The fan shell Pinna nobilis is the largest bivalve endemic to the Mediterranean and is actually a strongly endangered species. Due to the biological, ecological, and historical relevance of this species, the research of a non-lethal method to relate the element content in organism’s tissues and environment can provide information potentially useful to evaluate environmental pollution and organism physiological status. In this study, a screening on element concentration in the animal growing environment (seawater and sediments) and in four soft tissues (hepatopancreas, gills, mantle, and muscle), and two acellular tissues (calcite shell layer, and byssus) was performed. The comparison among these results was used to assess whether the no-lethal acellular tissue element concentration can be used to reveal the element presence in the environment and soft tissues. Elements, such as B, Ag, As, Mn, Mo, Pb, or Se, showed a possible relationship between their presence in the byssus and soft tissues. In the byssus Cr, Sb, Sn, and V have shown to be mostly related to the environment, more than the soft tissues, and might be used to draw a historical record of the exposure of the organism. The element concentration in the calcite shell layer did not relate with environmental element concentrations. Essential elements, like Cu, Fe, Ni, and Zn, were present in calcite shell layer and byssus and are likely related to their biological activity in the organism. The research also gave an overview on the presence of pollution and on the preferential intake route of the element. In summary, this study, performed on a limited number of specimens of this protected species, indicated that element concentration in the byssus can be applied as non-lethal method to monitor this endangered species and its interaction with the elements in the growing environment.
Real-world effectiveness of hyperbaric oxygen therapy for delayed neuropsychiatric sequelae after carbon monoxide poisoning
Authors: Liao Shu-Chen , Shao Shih-Chieh , Yang Kun-Ju , Yang Chen-Chang
Published: September 2021

To assess real-world effectiveness of hyperbaric oxygen therapy (HBOT) on delayed neuropsychiatric sequelae (DNS) after carbon monoxide (CO) poisoning we conducted a retrospective review of patients with CO poisoning admitted to Linkou Chang-Gung Memorial Hospital, Taiwan’s largest medical center, during 2009–2015. We included patients developing DNS after CO poisoning and compared improvements in neuropsychiatric function, with and without HBOT, after 12 months post-DNS to understand differences in recovery rates. DNS improvement-associated factors were also evaluated. We used receiver operating characteristic (ROC) curve analysis to assess the role of time elapsed between DNS diagnosis and HBOT initiation in predicting DNS improvement. A total of 62 patients developed DNS, of whom 11 recovered while the rest did not. Possible factors predicting DNS improvement included receiving HBOT post-DNS (72.7% vs 25.5%; P = 0.006), and treatment with more than three HBOT sessions during acute stage CO poisoning (81.8% vs 27.5%; P = 0.003). The relevant area under the ROC curve was 0.789 (95% CI 0.603–0.974), and the best cut-off point was 3 days post-DNS diagnosis, with 87.5% sensitivity and 61.5% specificity. Early HBOT in patients who developed DNS after CO poisoning significantly improved their DNS symptoms, with treatment effects sustained for 1 year after DNS diagnosis.
Effects of Aβ-derived peptide fragments on fibrillogenesis of Aβ
Authors: Abedin Faisal , Kandel Nabin , Tatulian Suren A.
Published: September 2021

Amyloid β (Aβ) peptide aggregation plays a central role in Alzheimer’s disease (AD) etiology. AD drug candidates have included small molecules or peptides directed towards inhibition of Aβ fibrillogenesis. Although some Aβ-derived peptide fragments suppress Aβ fibril growth, comprehensive analysis of inhibitory potencies of peptide fragments along the whole Aβ sequence has not been reported. The aim of this work is (a) to identify the region(s) of Aβ with highest propensities for aggregation and (b) to use those fragments to inhibit Aβ fibrillogenesis. Structural and aggregation properties of the parent Aβ1–42 peptide and seven overlapping peptide fragments have been studied, i.e. Aβ1–10 (P1), Aβ6–15 (P2), Aβ11–20 (P3), Aβ16–25 (P4), Aβ21–30 (P5), Aβ26–36 (P6), and Aβ31–42 (P7). Structural transitions of the peptides in aqueous buffer have been monitored by circular dichroism and Fourier transform infrared spectroscopy. Aggregation and fibrillogenesis were analyzed by light scattering and thioflavin-T fluorescence. The mode of peptide-peptide interactions was characterized by fluorescence resonance energy transfer. Three peptide fragments, P3, P6, and P7, exhibited exceptionally high propensity for β-sheet formation and aggregation. Remarkably, only P3 and P6 exerted strong inhibitory effect on the aggregation of Aβ1–42, whereas P7 and P2 displayed moderate inhibitory potency. It is proposed that P3 and P6 intercalate between Aβ1–42 molecules and thereby inhibit Aβ1–42 aggregation. These findings may facilitate therapeutic strategies of inhibition of Aβ fibrillogenesis by Aβ-derived peptides.
Portable all-in-one automated microfluidic system (PAMICON) with 3D-printed chip using novel fluid control mechanism
Authors: Zhang Yushen , Tseng Tsun-Ming , Schlichtmann Ulf
Published: September 2021

State-of-the-art microfluidic systems rely on relatively expensive and bulky off-chip infrastructures. The core of a system—the microfluidic chip—requires a clean room and dedicated skills to be fabricated. Thus, state-of-the-art microfluidic systems are barely accessible, especially for the do-it-yourself (DIY) community or enthusiasts. Recent emerging technology—3D-printing—has shown promise to fabricate microfluidic chips more simply, but the resulting chip is mainly hardened and single-layered and can hardly replace the state-of-the-art Polydimethylsiloxane (PDMS) chip. There exists no convenient fluidic control mechanism yet suitable for the hardened single-layered chip, and particularly, the hardened single-layered chip cannot replicate the pneumatic valve—an essential actuator for automatically controlled microfluidics. Instead, 3D-printable non-pneumatic or manually actuated valve designs are reported, but their application is limited. Here, we present a low-cost accessible all-in-one portable microfluidic system, which uses an easy-to-print single-layered 3D-printed microfluidic chip along with a novel active control mechanism for fluids to enable more applications. This active control mechanism is based on air or gas interception and can, e.g., block, direct, and transport fluid. As a demonstration, we show the system can automatically control the fluid in microfluidic chips, which we designed and printed with a consumer-grade 3D-printer. The system is comparably compact and can automatically perform user-programmed experiments. All operations can be done directly on the system with no additional host device required. This work could support the spread of low budget accessible microfluidic systems as portable, usable on-the-go devices and increase the application field of 3D-printed microfluidic devices.