bluuebunny/crossref_metadata_2025 huggingface dataset:
EMDR v. other psychological therapies for PTSD: a systematic review and individual participant data meta-analysis
Authors: Wright Simonne Lesley , Karyotaki Eirini , Cuijpers Pim , Bisson Jonathan , Papola Davide , Witteveen Anke , Suliman Sharain , Spies Georgina , Ahmadi Khodabakhsh , Capezzani Liuva , Carletto Sara , Karatzias Thanos , Kullack Claire , Laugharne Jonathan , Lee Christopher William , Nijdam Mirjam J. , Olff Miranda , Ostacoli Luca , Seedat Soraya , Sijbrandij Marit
Published: January 2024

Background

This systematic review and individual participant data meta-analysis (IPDMA) examined the overall effectiveness of eye movement desensitization and reprocessing (EMDR) in reducing posttraumatic stress disorder (PTSD) symptoms, achieving response and remission, and reducing treatment dropout among adults with PTSD compared to other psychological treatments. Additionally, we examined available participant-level moderators of the efficacy of EMDR.

Methods

This study included randomized controlled trials. Eligible studies were identified by a systematic search in PubMed, Embase, PsyclNFO, PTSDpubs, and CENTRAL. The target population was adults with above-threshold baseline PTSD symptoms. Trials were eligible if at least 70% of study participants had been diagnosed with PTSD using a structured clinical interview. Primary outcomes included PTSD symptom severity, treatment response, and PTSD remission. Treatment dropout was a secondary outcome. The systematic search retrieved 15 eligible randomized controlled trials (RCTs); 8 of these 15 were able to be included in this IPDMA (346 patients). Comparator treatments included relaxation therapy, emotional freedom technique, trauma-focused cognitive behavioral psychotherapies, and REM-desensitization.

Results

One-stage IPDMA found no significant difference between EMDR and other psychological treatments in reducing PTSD symptom severity (β = −0.24), achieving response (β = 0.86), attaining remission (β = 1.05), or reducing treatment dropout rates (β = −0.25). Moderator analyses found unemployed participants receiving EMDR had higher PTSD symptom severity at the post-test, and males were more likely to drop out of EMDR treatment than females.

Conclusion

The current study found no significant difference between EMDR and other psychological treatments. We found some indication of the moderating effects of gender and employment status.
“She did it!”: Meaning-making in interaction between deaf and hearing siblings in Peru
Authors: Goico Sara A.
Published: January 2024

In this article, I argue that centering multimodal practices is important in the study of human communication and sociality, and becomes particularly relevant in the presence of asymmetries in language access. Using data collected as part of a two-year linguistic ethnography of deaf youth in Iquitos, Peru, I demonstrate how three siblings engage in extended dispute routines even in the face of sensory and communicative asymmetries. The microanalysis of video-recorded sibling interaction sheds light on their use of diverse multimodal resources to navigate the common interactional work of securing an interlocutor, coordinating attention, managing misunderstandings, and establishing shared references (Sidnell 2007, 2009). Not only do the siblings utilize multimodal resources to carry out the interactional project of making an accusation and building alliances, but they also ‘co-operatively’ engage in building a shared semiotic repertoire (C. Goodwin 2018). (Deaf, sign language, linguistic ethnography, multimodality, semiotic repertoire, Peru)*
What is ‘Global Islam’? Definitions for a field of inquiry
Authors: Green Nile
Published: January 2024

The topic of ‘global Islam’ has become a prominent focus of discussion in both academic and journalistic writing, as well as in broader political discourse. Yet the cumulative effect of this abundance of commentary has been to render the term global Islam increasingly unclear. As a response to this predicament, this essay proposes a working definition of global Islam that may serve to clarify the object/s of study and, in turn, enable future research to make sense of how, where, and when the phenomena originated. Particular attention is given to the necessity of grappling with the plurality and diversity of Islamic practice worldwide, as well as to the practical analytical problems of scale. In this manner, a distinction is made between ‘global Islam’ and ‘world Islam’. Overall, the essay argues that ‘global Islam’ can serve as an analytically precise category for specific religious actors and organizations who operate in the networked places and specific timeframe of modern globalization.
Neoliberalism Studies and Media Studies
Authors: Dawes Simon
Published: January 2024

This short article provides an overview of the various theoretical and methodological approaches to analysing neoliberalism, paying particular attention to political-economic and governmental approaches (and the extent to which they can be contrasted or combined), and argues for a more theoretically- and methodologically-informed, interdisciplinary critique of neoliberalism in media studies. In emphasising the heterogeneity of approaches to studying an object such as neoliberalism, as well as the differences in how those approaches are deployed in different ‘studies’, it will thus also argue for the applicability of such concerns to research in multiple disciplines in other countries (such as France) as well.
Targeted metabolite profiling and de novo transcriptome sequencing reveal the key terpene synthase genes in medicinally important plant, Couroupita guianensis Aubl
Authors: Thulasiram Hirekodathakallu V. , Karegaonkar Shrikant Jagannathrao , Sharma Poojadevi , Kumar Ashish , Ramkumar Sudha , Pandreka Avinash
Published: January 2024

The Lecythidaceae family tree, Couroupita guianensis Aubl, popularly known as Nagpushpa, is a widely cultivated ornamental tree with several uses in traditional medicine. The tree is revered as highly sacred in Indian traditional culture due to its uniquely shaped, fragrant flowers. Considering the significance, we were prompted to carry out the metabolite and transcriptome analysis of Nagapushpa. The flower, petals, stamen, stem and leaf of C. guianensis were metabolically profiled, and it was discovered that the flower tissue contained the highest terpenoid reservoir. A number of terpenoid pathway transcripts were also found in the flower tissue after transcriptome profiling. KEGG pathway mapping was carried out to correlate transcript sequences with the biosynthesis of different types of terpenes. We were able to clone three full-length terpene synthase gene candidates, i.e. monoterpene ocimene synthase, diterpene ent-kaurene synthase and sesquiterpene farnesene synthase. The transcript expression of selected terpene synthase genes was also verified in flower tissue. These cloned sequences were used for in silico structural investigations and protein function prediction at the level of 3D structure. The data presented in this study provide a comprehensive resource for the metabolic and transcriptomic profiles of C. guianensis. The study paves the way towards the elucidation of terpene biosynthetic pathway in C. guianensis and heterologous production of useful terpenoids in the future.
Examining the Spread of Charcoal-Burning Suicide in Taiwan
Authors: Chen Ying-Yeh , Yang Chi-Ting , Wong Long-Hin , Lam Tze-Mei , Yip Paul S. F.
Published: January 2024

Abstract: Background: Charcoal-burning has become a predominant method of suicide in many East-Asian countries since the 1990s. Aims: To explore charcoal-burning suicide trends from 1996 to 2020 in Taiwan. Methods: Joinpoint regression models were applied to identify suicide trends over the study period. Decompositional analyses quantified the contributions of age, sex, suicide method, and area of residence to suicide rate trends, accounting for age and geographical distribution of the general population, with a focus on charcoal-burning suicide. Results: There were three stages of suicide rate trends: increasing (1996–2006), descending (2006–2011), and levelling-off (2011–2020). Suicide by charcoal-burning accounted for 70% of the increasing suicide rates between 1996 and 2006 and 50% of the decreasing rates in the descending stage (2011–2020). During the levelling-off stage, suicide by charcoal-burning continued to decrease, albeit slowly. During the descending stage, there was a partial “substitution” of jumping for charcoal-burning. During the levelling-off stage, suicide by hanging partially “substituted” for suicide by charcoal-burning. Limitations: The variables included were limited by data availability. Conclusions: Charcoal-burning remains the second most common method of suicide in Taiwan today. Charcoal-burning has been partially replaced in the last 10 years by jumping and hanging. Monitoring suicide methods and trends is essential for suicide prevention interventions.
Fluid Flow, Mineralization and Deformation in an Oceanic Detachment Fault: Microtextural, Geochemical and Isotopic Evidence From Pyrite at 13°30′N on the Mid‐Atlantic Ridge
Authors: Martin Andrew J. , Jamieson John W. , Petersen Sven , Fayek Mostafa , Escartin Javier
Published: January 2024

Hydrothermal fluids in ultramafic‐hosted hydrothermal systems associated with oceanic detachment faults can be more oxidizing compared to mafic‐hosted vent sites. These fluids form a mineral assemblage of pyrite, magnetite and hematite. At 13°30′N on the Mid‐Atlantic Ridge, chlorite‐quartz breccias recovered from an exposed fault scarp contain pyrite, with abundant magnetite and hematite, indicating that the redox of the fluids was variable. In primary micron‐scale zonations in pyrite, Ni, Co, and Se have a decoupled relationship, recording fluctuations in the chemical composition and temperature of hydrothermal fluid as the grains grew. Secondary zonations that erase and overprint primary zonations are limited to the grain margin and permeable regions within the grain core. Secondary zonations formed via two processes: (a) grain dissolution followed by overgrowth, and (b) remobilization of metals during oxidizing fluid flow events. In both instances, Ni and Co have been mobilized and concentrated, and are not lost to the hydrothermal fluid. Superimposed on these features is evidence of grain scale deformation related to periods of fault movement along the detachment surface. Sulfur isotope ratios (δ34S) in pyrite systematically decrease from the grain margin to the grain core, indicating that increased amounts of sulfur were derived from thermochemical sulfate reduction of seawater. Thus, pyrite records the evolution of fluid flow and deformation events during exhumation along the detachment surface from ∼1 to 2 km below the seafloor at the base of the lava pile, with temporal fluctuations in fluid redox identified as an important process in controlling Ni and Co enrichment in pyrite.
The Age and Evolution of Lunar Micro Cold Traps at the Scale of Surface Exploration
Authors: Costello E. S. , Lucey P. G.
Published: January 2024

Cold traps are locations on the Moon that are shielded from sunlight where volatiles such as water could accumulate and persist against sublimation for geologic timescales. We model how long it takes accumulating craters to produce and then obliterate sub‐kilometer scale cold traps. Sub‐meter cold traps are extremely ephemeral, evolving in and out of existence over less than a few thousand years; however, larger 100 m to 1 km‐scale cold traps may persevere for geologic timescales and preserve a record of the volatile history of the Moon.
Elucidating the Multi‐Timescale Variability of a Canopy Urban Heat Island by Using the Short‐Time Fourier Transform
Authors: Zhang Longrui , Luo Fu , Pan Guitao , Zhang Wenjie , Ren Guoyu , Zheng Zuofang , Yang Yuanjian
Published: January 2024

Taking the megacity of Beijing as an example, a short‐time Fourier transform (STFT) method was employed to extract the multi‐timescale evolution pattern of the canopy urban heat island intensity (CUHII) during 2000–2020. The STFT of CUHII showed a close relationship between the evolution of the CUHII in Beijing and the background meteorological forcing at intra‐annual, weather and intra‐daily scales. The intra‐annual‐scale spectrum of CUHII exhibited an increasing trend with obvious seasonal variation of the canopy urban heat island (CUHI). The intra‐daily‐scale spectrum of CUHII showed an increasing trend with the nighttime CUHI developing faster. Increasing Western Pacific Subtropical High intensity can enhance the seasonal and diurnal fluctuations of CUHII. The weather‐scale spectrum of CUHII is controlled by weather system evolution, showing that the frequency of cold/heat waves (CWs/HWs) in Beijing was significantly negatively correlated with the weather‐scale spectral intensity of the CUHII. CWs and HWs can increase the CUHII for a long duration.
Recent Opposite Trends of Atmospheric Rivers Over East Asia and Western North Pacific Driven by the Pacific Decadal Oscillation
Authors: Huang Wenshuo , Hua Lijuan , Zhong Linhao , Yang Yang , Gong Zhaohui
Published: January 2024

Atmospheric rivers (ARs) in East Asia have garnered increasing attention for their crucial roles in understanding extreme precipitation events and regional hydrological cycles. Here, we investigate the summer AR frequency over the East Asia‐western North Pacific region (EA‐WNP) during 1959–2022. Interestingly, the results show that the AR frequency over the two regions experienced opposite variations, with the boundary between them at around 135°–140°E. On interdecadal timescales, such variations are mainly synchronized with a zonal dipole pattern characterized by cyclonic (anticyclonic) anomalies centered to the northwest of Taiwan and anticyclonic (cyclonic) anomalies centered to the southeast of Japan. This interdecadal dipole pattern is induced by interdecadal changes in the western North Pacific subtropical high under different Pacific Decadal Oscillation (PDO) phases. Particularly, the internal variability accounts for about 77–90% of the observed trends in high response areas. The displacements of ARs are also consistent with the opposite trends of precipitation over EA‐WNP. ARs exert a dominant influence on the precipitation trend in the WNP region but a weaker contribution to the precipitation trend in the EA region, which reflects the different impacts of ARs on EA and WNP precipitation. These results indicate that the PDO has the potential for predicting EA‐WNP ARs on interdecadal timescales, and the opposite AR trends are crucial in understanding the complexity of precipitation over the EA‐WNP region.
An Online Assimilation Method to Improve the Numerical Forecast of Sea Fog Using Microwave Radiometer‐Retrieved Cloud Water Path
Authors: Gao Xiaoyu , Bao Xinghua , Ma Suhong , Chen Qi , Wang Bin
Published: January 2024

Numerical forecast of the sea fog is sensitive to the initial moist stratification within the marine atmospheric boundary layer (MABL). This study develops an online assimilation method to improve the MABL thermal and moist structures in sea fog ensemble forecasts based on the Weather Research and Forecasting model and Grid‐point Statistical Interpolation/EnKF system. It uses the satellite‐retrieved cloud water path (CWP) as the indicator of sea fog and low‐level stratus to determine the best ensemble members at each grid point. The relative humidity and cloud water profiles are extracted from the best members to generate a series of pseudo‐observations, which are assimilated to update all the members by EnKF method. The new method significantly improves the ensemble forecast of five widespread advection fog events over the Yellow Sea, which can be attributed to the decrease of both missed and spurious fog areas. The case study shows that assimilating the information of both humidity and cloud water outperforms assimilating either of them, while the impact of directly assimilating CWP observation is insignificant. The analysis increments of cloud water, thermal and moist structures in MABL together contribute to the correction of forecasted sea fog. The generation of pseudo‐observations can use the dynamic compatibility of the model to alleviate the impact of erroneous data in the observation, leading to the low sensitivity of the new method to CWP retrieval error.
The Roles of Bathymetry and Waves in Rip‐Channel Dynamics
Authors: Christensen D. F. , Raubenheimer B. , Elgar S.
Published: January 2024

The behavior and predictability of rip currents (strong, wave‐driven offshore‐directed surfzone currents) have been studied for decades. However, few studies have examined the effects of rip channel morphology on the rip generation or have compared morphodynamic models with observations. Here, simulations conducted with the numerical morphodynamic model MIKE21 reproduce observed trends in flows and bathymetric evolution for two channels dredged across a nearshore sandbar and terrace on an ocean beach near Duck, NC, USA. Channel dimensions, wave conditions, and flows differed between the two cases. In one case, a strong rip current was driven by moderate height, near‐normally incident waves over an approximately 1‐m deep channel with relatively little bathymetric evolution. In the other case, no rip was generated by the large, near‐normally incident waves over the shallower (∼0.5 m) channel, and the channel migrated in the direction of the mean flow and eventually filled in. The model simulated the flow directions, the generation (or not) of rip currents, and the morphological evolution of the channels reasonably well. Model simulations were then conducted for different combinations of the two channel geometries and two wave conditions to examine the relative importance of the waves and morphology to the rip current evolution. The different bathymetries were the dominant factor controlling the flow, whereas both the initial morphology and wave conditions were important for channel evolution. In addition, channel dimensions affected the spatial distribution of rip current forcings and the relative importance of terms.
Effects of Riming on Ice‐Phase Precipitation Growth and Transport Over an Orographic Barrier
Authors: DeLaFrance Andrew , McMurdie Lynn A. , Rowe Angela K. , Conrick Robert
Published: January 2024

The evolution of ice‐phase particles within precipitating clouds depends on the environmental properties of the cloud and on physical characteristics of the particles themselves, which can be modified by airflow over steep terrain. Through employing a unique Lagrangian particle‐based precipitation model, this study investigates the sensitivities in ice‐phase particle growth and transport due to variabilities in riming processes over an orographic barrier. This analysis is applied to two wintertime stratiform cyclones sampled by in situ aircraft over windward slopes during the Olympic Mountains Experiment. For both events, we simulate the ice‐phase particle evolution and trajectory within a two‐dimensional prescribed state representative of median observed cloud properties. Sensitivity simulations were constructed based on observed variabilities in supercooled liquid water (SLW) properties and its vertical extent above the melting level. Perturbations of SLW concentration equivalent to the 85th and 15th percentiles of observed values, which typically amounted to a change of less than 0.05 g m−3, resulted in respective increases or decreases in the ice‐phase contribution to surface precipitation mass by as much as 50% and horizontal particle trajectories differences exceeding 10 km. Similar sensitivities were found in response to varying the vertical extent of SLW above the melting level and to adjustments in mean SLW droplet size. The significant precipitation response to small variations in cloud properties principally arises from changing rates of rime mass accumulation and correspondingly, increases in particle fall speed. Considerations for the numerical representation of the riming process and its complex effects on precipitation are discussed.
Seawater Dynamics in an Underexplored Antarctic Fjord
Authors: Stanley Sarah
Published: January 2024

Wind is the major driver of salinity changes within the narrow, glacier-fed cove.
Relevance of the endoplasmic reticulum-mitochondria axis in cancer diagnosis and therapy
Authors: An Garam , Park Junho , Song Jisoo , Hong Taeyeon , Song Gwonhwa , Lim Whasun
Published: January 2024

Dynamic interactions between organelles are responsible for a variety of intercellular functions, and the endoplasmic reticulum (ER)–mitochondrial axis is recognized as a representative interorganelle system. Several studies have confirmed that most proteins in the physically tethered sites between the ER and mitochondria, called mitochondria-associated ER membranes (MAMs), are vital for intracellular physiology. MAM proteins are involved in the regulation of calcium homeostasis, lipid metabolism, and mitochondrial dynamics and are associated with processes related to intracellular stress conditions, such as oxidative stress and unfolded protein responses. Accumulating evidence has shown that, owing to their extensive involvement in cellular homeostasis, alterations in the ER–mitochondrial axis are one of the etiological factors of tumors. An in-depth understanding of MAM proteins and their impact on cell physiology, particularly in cancers, may help elucidate their potential as diagnostic and therapeutic targets for cancers. For example, the modulation of MAM proteins is utilized not only to target diverse intracellular signaling pathways within cancer cells but also to increase the sensitivity of cancer cells to anticancer reagents and regulate immune cell activities. Therefore, the current review summarizes and discusses recent advances in research on the functional roles of MAM proteins and their characteristics in cancers from a diagnostic perspective. Additionally, this review provides insights into diverse therapeutic strategies that target MAM proteins in various cancer types.
Spatial architectures of somatic mutations in normal prostate, benign prostatic hyperplasia and coexisting prostate cancer
Authors: Chae Jeesoo , Jung Seung-Hyun , Choi Eun Ji , Kim Jae Woong , Kim Na Yung , Moon Sung Won , Lee Ji Youl , Chung Yeun-Jun , Lee Sug Hyung
Published: January 2024

This study aimed to identify somatic mutations in nontumor cells (NSMs) in normal prostate and benign prostatic hyperplasia (BPH) and to determine their relatedness to prostate cancer (PCA). From 22 PCA patients, two prostates were sampled for 3-dimensional mapping (50 normal, 46 BPH and 1 PCA samples), and 20 prostates were trio-sampled (two normal or BPH samples and one PCA sample) and analyzed by whole-genome sequencing. Normal and BPH tissues harbored several driver NSMs and copy number alterations (CNAs), including in FOXA1, but the variations exhibited low incidence, rare recurrence, and rare overlap with PCAs. CNAs, structural variants, and mutation signatures were similar between normal and BPH samples, while BPHs harbored a higher mutation burden, shorter telomere length, larger clone size, and more private NSMs than normal prostates. We identified peripheral-zonal dominance and right-side asymmetry in NSMs, but the asymmetry was heterogeneous between samples. In one normal prostate, private oncogenic RAS-signaling NSMs were detected, suggesting convergence in clonal maintenance. Early embryonic mutations exhibited two distinct distributions, characterized as layered and mixed patterns. Our study identified that the BPH genome differed from the normal prostate genome but was still closer to the normal genome than to the PCA genome, suggesting that BPH might be more related to aging or environmental stress than to tumorigenic processes.
Personal care product use patterns in association with phthalate and replacement biomarkers across pregnancy
Authors: Rosen Emma M. , Stevens Danielle R. , Ramos Amanda M. , McNell Erin E. , Wood Mollie E. , Engel Stephanie M. , Keil Alexander P. , Calafat Antonia M. , Botelho Julianne Cook , Sinkovskaya Elena , Przybylska Ann , Saade George , Abuhamad Alfred , Ferguson Kelly K.
Published: January 2024

Background

Humans are exposed to phthalates, a class of non-persistent chemicals, through multiple products, including personal care and cosmetics. Associations between specific phthalates and product use have been inconsistent. However, determining these connections could provide avenues for exposure reduction.

Objective

Examine the association between patterns of personal care product use and associations with phthalate and replacement biomarkers.

Methods

In the Human Placenta and Phthalates Study, 303 women were enrolled in early pregnancy and followed for up to 8 visits across gestation. At each visit, women completed a questionnaire about product use in the prior 24 hours and contributed urine samples, subsequently analyzed for 18 phthalate and replacement metabolites. At early, mid-, and late pregnancy, questionnaire responses were condensed and repeated metabolite concentrations were averaged. Latent class analysis (LCA) was used to determine groups of women with similar use patterns, and weighted associations between group membership and biomarker concentrations were assessed.

Results

LCA sorted women into groups which largely corresponded to: (1) low fragranced product use (16-23% of women); (2) fragranced product and low body wash use (22–26%); 3) fragranced product and low bar soap use (26–51%); and (4) low product use (7–34%). Monoethyl phthalate (MEP) urinary concentrations were 7–10% lower and concentrations of summed di(2-ethylhexyl) terephthalate metabolites were 15–21% lower among women in the “low fragranced product use” group compared to the population mean. Few other consistent associations between group and biomarker concentrations were noted.

Impact statement

Personal care products and cosmetics are a known exposure source for phthalates and potentially represent one of the most accessible intervention targets for exposure reduction. However, in this analysis accounting for concurrent use and fragranced status of products, we did not find any use patterns that corresponded to universally lower levels.
Genomic and functional impact of Trp53 inactivation in JAK2V617F myeloproliferative neoplasms
Authors: Gou Panhong , Liu Duanya , Ganesan Saravanan , Lauret Evelyne , Maslah Nabih , Parietti Veronique , Zhang Wenchao , Meignin Véronique , Kiladjian Jean-Jacques , Cassinat Bruno , Giraudier Stephane
Published: January 2024

Classical myeloproliferative neoplasms (MPNs) are characterized by the proliferation of myeloid cells and the risk of transformation into myelofibrosis or acute myeloid leukemia (AML) and TP53 mutations in MPN patients are linked to AML. However, JAK2V617F has been reported to impact the TP53 response to DNA damage, suggesting potential overlapping role of TP53 inactivation in MPN. We established a mouse model showing that JAK2V617F/Vav-Cre/Trp53−/− mice displayed a similar phenotype to JAK2V617F/Vav-Cre mice, but their proliferation was outcompeted in competitive grafts. RNA-Seq revealed that half of the genes affected by JAK2V617F were affected by p53-inactivation, including the interferon pathway. To validate this finding, mice were repopulated with a mixture of wild-type and JAK2V617F (or JAK2V617F/Vav-Cre/Trp53−/−) cells and treated with pegylated interferonα. JAK2V617F-reconstituted mice entered complete hematological remission, while JAK2V617F/Vav-Cre /Trp53−/−-reconstituted mice did not, confirming that p53 loss induced interferon-α resistance. KEGG and Gene Ontology analyses of common deregulated genes showed that these genes were mainly implicated in cytokine response, proliferation, and leukemia evolution, illustrating that in this mouse model, the development of MPN is not affected by TP53 inactivation. Taken together, our results show that many genetic modifications induced by JAK2V617F are influenced by TP53, the MPN phenotype may not be. Trp53 loss alone is insufficient to induce rapid leukemic transformation in steady-state hematopoiesis in JAK2V617F MPN, and Trp53 loss may contribute to interferon resistance in MPN.
Nuclear pore protein POM121 regulates subcellular localization and transcriptional activity of PPARγ
Authors: Yu Yanxiong , Farooq Mohammad S. , Eberhart Meessen Sabine , Jiang Yidan , Kato Dominik , Zhan Tianzuo , Weiss Christel , Seger Rony , Kang Wei , Zhang Xiang , Yu Jun , Ebert Matthias P. A. , Burgermeister Elke
Published: January 2024

Manipulation of the subcellular localization of transcription factors by preventing their shuttling via the nuclear pore complex (NPC) emerges as a novel therapeutic strategy against cancer. One transmembrane component of the NPC is POM121, encoded by a tandem gene locus POM121A/C on chromosome 7. Overexpression of POM121 is associated with metabolic diseases (e.g., diabetes) and unfavorable clinical outcome in patients with colorectal cancer (CRC). Peroxisome proliferator-activated receptor-gamma (PPARγ) is a transcription factor with anti-diabetic and anti-tumoral efficacy. It is inhibited by export from the nucleus to the cytosol via the RAS-RAF-MEK1/2-ERK1/2 signaling pathway, a major oncogenic driver of CRC. We therefore hypothesized that POM121 participates in the transport of PPARγ across the NPC to regulate its transcriptional activity on genes involved in metabolic and tumor control. We found that POM121A/C mRNA was enriched and POM121 protein co-expressed with PPARγ in tissues from CRC patients conferring poor prognosis. Its interactome was predicted to include proteins responsible for tumor metabolism and immunity, and in-silico modeling provided insights into potential 3D structures of POM121. A peptide region downstream of the nuclear localization sequence (NLS) of POM121 was identified as a cytoplasmic interactor of PPARγ. POM121 positivity correlated with the cytoplasmic localization of PPARγ in patients with KRAS mutant CRC. In contrast, POM121A/C silencing by CRISPR/Cas9 sgRNA or siRNA enforced nuclear accumulation of PPARγ and activated PPARγ target genes promoting lipid metabolism and cell cycle arrest resulting in reduced proliferation of human CRC cells. Our data suggest the POM121-PPARγ axis as a potential drugable target in CRC.
Engineered poly(A)-surrogates for translational regulation and therapeutic biocomputation in mammalian cells
Authors: Shao Jiawei , Li Shichao , Qiu Xinyuan , Jiang Jian , Zhang Lihang , Wang Pengli , Si Yaqing , Wu Yuhang , He Minghui , Xiong Qiqi , Zhao Liuqi , Li Yilin , Fan Yuxuan , Viviani Mirta , Fu Yu , Wu Chaohua , Gao Ting , Zhu Lingyun , Fussenegger Martin , Wang Hui , Xie Mingqi
Published: January 2024

Here, we present a gene regulation strategy enabling programmable control over eukaryotic translational initiation. By excising the natural poly-adenylation (poly-A) signal of target genes and replacing it with a synthetic control region harboring RNA-binding protein (RBP)-specific aptamers, cap-dependent translation is rendered exclusively dependent on synthetic translation initiation factors (STIFs) containing different RBPs engineered to conditionally associate with different eIF4F-binding proteins (eIFBPs). This modular design framework facilitates the engineering of various gene switches and intracellular sensors responding to many user-defined trigger signals of interest, demonstrating tightly controlled, rapid and reversible regulation of transgene expression in mammalian cells as well as compatibility with various clinically applicable delivery routes of in vivo gene therapy. Therapeutic efficacy was demonstrated in two animal models. To exemplify disease treatments that require on-demand drug secretion, we show that a custom-designed gene switch triggered by the FDA-approved drug grazoprevir can effectively control insulin expression and restore glucose homeostasis in diabetic mice. For diseases that require instantaneous sense-and-response treatment programs, we create highly specific sensors for various subcellularly (mis)localized protein markers (such as cancer-related fusion proteins) and show that translation-based protein sensors can be used either alone or in combination with other cell-state classification strategies to create therapeutic biocomputers driving self-sufficient elimination of tumor cells in mice. This design strategy demonstrates unprecedented flexibility for translational regulation and could form the basis for a novel class of programmable gene therapies in vivo.
Role of the structure order in the transport and magnetic properties of high-entropy alloy films
Authors: Chen Jia-Wei , Chen Shih-Hsun , Shafer Padraic , Tzeng Wen-Yen , Chen Yi-Cheng , Luo Chih-Wei , Wu Wen-Wei , Yeh Jien-Wei , Chu Ying-Hao
Published: January 2024

The fabrication and development of high-entropy alloys (HEAs) with exceptional functionalities is a rapidly expanding field with numerous applications. When the role of entropy in HEAs is considered, the extrinsic factors, such as the existence of grains and different phases, need to be separated from the intrinsic configurations of the atomic lattice. Here, we fabricated the CoCrFeNi2Al0.5 HEA/muscovite heterostructures, and some were prepared as epitaxial bilayers and others were prepared as an amorphous system. These two systems are classified into atomic-site disordered (ASD) and structurally disordered (SD) states, respectively, without the extrinsic effects for the determination of the crystal lattice role in high-entropy states. In this study, we determined the role of the structure order in correlation with the structural, electronic, and magnetic properties of HEAs using a combination of energy-dispersive X-ray spectrometry, X-ray diffraction, transmission electron microscopy, magneto-transport, ac magnetometry, and X-ray absorption spectroscopy with magnetic circular dichroism. The ASD state showed fully metallic behavior. In contrast, the SD state showed a metallic behavior with intense magnetic saturation, which was called Kondo-like behavior, under 50 K with a low-temperature coefficient of resistivity of ~64 ppm/°C. The difference between the saturation magnetic moment and the electron relaxation behavior in the ASD and SD states resulted from the existence of the structural order affecting the atomic distance and periodicity to modify the exchange interaction and tune the electron-phonon interaction for scattering. The ferromagnetic behavior contributed by Co, Fe, and Ni atoms was probed by X-ray absorption and magnetic circular dichroism to understand the magnetic interactions in the ASD and SD states.
Spin relaxation of electron and hole polarons in ambipolar conjugated polymers
Authors: Carey Remington L. , Giannini Samuele , Schott Sam , Lemaur Vincent , Xiao Mingfei , Prodhan Suryoday , Wang Linjun , Bovoloni Michelangelo , Quarti Claudio , Beljonne David , Sirringhaus Henning
Published: January 2024

The charge-transport properties of conjugated polymers have been studied extensively for opto-electronic device applications. Some polymer semiconductors not only support the ambipolar transport of electrons and holes, but do so with comparable carrier mobilities. This opens the possibility of gaining deeper insight into the charge-transport physics of these complex materials via comparison between electron and hole dynamics while keeping other factors, such as polymer microstructure, equal. Here, we use field-induced electron spin resonance spectroscopy to compare the spin relaxation behavior of electron and hole polarons in three ambipolar conjugated polymers. Our experiments show unique relaxation regimes as a function of temperature for electrons and holes, whereby at lower temperatures electrons relax slower than holes, but at higher temperatures, in the so-called spin-shuttling regime, the trend is reversed. On the basis of theoretical simulations, we attribute this to differences in the delocalization of electron and hole wavefunctions and show that spin relaxation in the spin shuttling regimes provides a sensitive probe of the intimate coupling between charge and structural dynamics.
TET2-mediated tumor cGAS triggers endothelial STING activation to regulate vasculature remodeling and anti-tumor immunity in liver cancer
Authors: Lv Hongwei , Zong Qianni , Chen Cian , Lv Guishuai , Xiang Wei , Xing Fuxue , Jiang Guoqing , Yan Bing , Sun Xiaoyan , Ma Yue , Wang Liang , Wu Zixin , Cui Xiuliang , Wang Hongyang , Yang Wen
Published: January 2024

Induction of tumor vascular normalization is a crucial measure to enhance immunotherapy efficacy. cGAS-STING pathway is vital for anti-tumor immunity, but its role in tumor vasculature is unclear. Herein, using preclinical liver cancer models in Cgas/Sting-deficient male mice, we report that the interdependence between tumor cGAS and host STING mediates vascular normalization and anti-tumor immune response. Mechanistically, TET2 mediated IL-2/STAT5A signaling epigenetically upregulates tumor cGAS expression and produces cGAMP. Subsequently, cGAMP is transported via LRRC8C channels to activate STING in endothelial cells, enhancing recruitment and transendothelial migration of lymphocytes. In vivo studies in male mice also reveal that administration of vitamin C, a promising anti-cancer agent, stimulates TET2 activity, induces tumor vascular normalization and enhances the efficacy of anti-PD-L1 therapy alone or in combination with IL-2. Our findings elucidate a crosstalk between tumor and vascular endothelial cells in the tumor immune microenvironment, providing strategies to enhance the efficacy of combinational immunotherapy for liver cancer.
Petascale pipeline for precise alignment of images from serial section electron microscopy
Authors: Popovych Sergiy , Macrina Thomas , Kemnitz Nico , Castro Manuel , Nehoran Barak , Jia Zhen , Bae J. Alexander , Mitchell Eric , Mu Shang , Trautman Eric T. , Saalfeld Stephan , Li Kai , Seung H. Sebastian
Published: January 2024

The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy is often limited by the preceding step of aligning 2D section images to create a 3D image stack. Precise and robust alignment in the presence of image artifacts is challenging, especially as datasets are attaining the petascale. We present a computational pipeline for aligning ssEM images with several key elements. Self-supervised convolutional nets are trained via metric learning to encode and align image pairs, and they are used to initialize iterative fine-tuning of alignment. A procedure called vector voting increases robustness to image artifacts or missing image data. For speedup the series is divided into blocks that are distributed to computational workers for alignment. The blocks are aligned to each other by composing transformations with decay, which achieves a global alignment without resorting to a time-consuming global optimization. We apply our pipeline to a whole fly brain dataset, and show improved accuracy relative to prior state of the art. We also demonstrate that our pipeline scales to a cubic millimeter of mouse visual cortex. Our pipeline is publicly available through two open source Python packages.
A stapled lipopeptide platform for preventing and treating highly pathogenic viruses of pandemic potential
Authors: Bird Gregory H. , Patten J. J. , Zavadoski William , Barucci Nicole , Godes Marina , Moyer Benjamin M. , Owen Callum D. , DaSilva-Jardine Paul , Neuberg Donna S. , Bowen Richard A. , Davey Robert A. , Walensky Loren D.
Published: January 2024

The continued emergence of highly pathogenic viruses, which either thwart immune- and small molecule-based therapies or lack interventions entirely, mandates alternative approaches, particularly for prompt and facile pre- and post-exposure prophylaxis. Many highly pathogenic viruses, including coronaviruses, employ the six-helix bundle heptad repeat membrane fusion mechanism to achieve infection. Although heptad-repeat-2 decoys can inhibit viral entry by blocking six-helix bundle assembly, the biophysical and pharmacologic liabilities of peptides have hindered their clinical development. Here, we develop a chemically stapled lipopeptide inhibitor of SARS-CoV-2 as proof-of-concept for the platform. We show that our lead compound blocks infection by a spectrum of SARS-CoV-2 variants, exhibits mucosal persistence upon nasal administration, demonstrates enhanced stability compared to prior analogs, and mitigates infection in hamsters. We further demonstrate that our stapled lipopeptide platform yields nanomolar inhibitors of respiratory syncytial, Ebola, and Nipah viruses by targeting heptad-repeat-1 domains, which exhibit strikingly low mutation rates, enabling on-demand therapeutic intervention to combat viral outbreaks.
Dental morphology in Homo habilis and its implications for the evolution of early Homo
Authors: Davies Thomas W. , Gunz Philipp , Spoor Fred , Alemseged Zeresenay , Gidna Agness , Hublin Jean-Jacques , Kimbel William H. , Kullmer Ottmar , Plummer William P. , Zanolli Clément , Skinner Matthew M.
Published: January 2024

The phylogenetic position ofHomo habilisis central to debates over the origin and early evolution of the genusHomo. A large portion of the species hypodigm consists of dental remains, but they have only been studied at the often worn enamel surface. We investigate the morphology of theH. habilisenamel-dentine junction (EDJ), which is preserved in cases of moderate tooth wear and known to carry a strong taxonomic signal. Geometric morphometrics is used to characterise dentine crown shape and size across the entire mandibular and maxillary tooth rows, compared with a broad comparative sample (n = 712). We find that EDJ morphology inH. habilisis for the most part remarkably primitive, supporting the hypothesis that theH. habilishypodigm has more in common withAustralopithecusthan laterHomo. Additionally, the chronologically younger specimen OH 16 displays a suite of derived features; its inclusion inH. habilisleads to excessive levels of variation.
The juxtamembrane linker of synaptotagmin 1 regulates Ca2+ binding via liquid-liquid phase separation
Authors: Mehta Nikunj , Mondal Sayantan , Watson Emma T. , Cui Qiang , Chapman Edwin R.
Published: January 2024

Synaptotagmin (syt) 1, a Ca2+ sensor for synaptic vesicle exocytosis, functions in vivo as a multimer. Syt1 senses Ca2+ via tandem C2-domains that are connected to a single transmembrane domain via a juxtamembrane linker. Here, we show that this linker segment harbors a lysine-rich, intrinsically disordered region that is necessary and sufficient to mediate liquid-liquid phase separation (LLPS). Interestingly, condensate formation negatively regulates the Ca2+-sensitivity of syt1. Moreover, Ca2+ and anionic phospholipids facilitate the observed phase separation, and increases in [Ca2+]i promote the fusion of syt1 droplets in living cells. Together, these observations suggest a condensate-mediated feedback loop that serves to fine-tune the ability of syt1 to trigger release, via alterations in Ca2+ binding activity and potentially through the impact of LLPS on membrane curvature during fusion reactions. In summary, the juxtamembrane linker of syt1 emerges as a regulator of syt1 function by driving self-association via LLPS.
Creating pairs of exceptional points for arbitrary polarization control: asymmetric vectorial wavefront modulation
Authors: Yang Zijin , Huang Po-Sheng , Lin Yu-Tsung , Qin Haoye , Zúñiga-Pérez Jesús , Shi Yuzhi , Wang Zhanshan , Cheng Xinbin , Tang Man-Chung , Han Sanyang , Kanté Boubacar , Li Bo , Wu Pin Chieh , Genevet Patrice , Song Qinghua
Published: January 2024

Exceptional points (EPs) can achieve intriguing asymmetric control in non-Hermitian systems due to the degeneracy of eigenstates. Here, we present a general method that extends this specific asymmetric response of EP photonic systems to address any arbitrary fully-polarized light. By rotating the meta-structures at EP, Pancharatnam-Berry (PB) phase can be exclusively encoded on one of the circular polarization-conversion channels. To address any arbitrary wavefront, we superpose the optical signals originating from two orthogonally polarized -yet degenerate- EP eigenmodes. The construction of such orthogonal EP eigenstates pairs is achieved by applying mirror-symmetry to the nanostructure geometry flipping thereby the EP eigenmode handedness from left to right circular polarization. Non-Hermitian reflective PB metasurfaces designed using such EP superposition enable arbitrary, yet unidirectional, vectorial wavefront shaping devices. Our results open new avenues for topological wave control and illustrate the capabilities of topological photonics to distinctively operate on arbitrary polarization-state with enhanced performances.
Nonlinear transport and radio frequency rectification in BiTeBr at room temperature
Authors: Lu Xiu Fang , Zhang Cheng-Ping , Wang Naizhou , Zhao Dan , Zhou Xin , Gao Weibo , Chen Xian Hui , Law K. T. , Loh Kian Ping
Published: January 2024

Materials showing second-order nonlinear transport under time reversal symmetry can be used for Radio Frequency (RF) rectification, but practical application demands room temperature operation and sensitivity to microwatts level RF signals in the ambient. In this study, we demonstrate that BiTeBr exhibits a giant nonlinear response which persists up to 350 K. Through scaling and symmetry analysis, we show that skew scattering is the dominant mechanism. Additionally, the sign of the nonlinear response can be electrically switched by tuning the Fermi energy. Theoretical analysis suggests that the large Rashba spin-orbit interactions (SOI), which gives rise to the chirality of the Bloch electrons, provide the microscopic origin of the observed nonlinear response. Our BiTeBr rectifier is capable of rectifying radiation within the frequency range of 0.2 to 6 gigahertz at room temperature, even at extremely low power levels of −15 dBm, and without the need for external biasing. Our work highlights that materials exhibiting large Rashba SOI have the potential to exhibit nonlinear responses at room temperature, making them promising candidates for harvesting high-frequency and low-power ambient electromagnetic energy.
Quantitative analysis of printed nanostructured networks using high-resolution 3D FIB-SEM nanotomography
Authors: Gabbett Cian , Doolan Luke , Synnatschke Kevin , Gambini Laura , Coleman Emmet , Kelly Adam G. , Liu Shixin , Caffrey Eoin , Munuera Jose , Murphy Catriona , Sanvito Stefano , Jones Lewys , Coleman Jonathan N.
Published: January 2024

Networks of solution-processed nanomaterials are becoming increasingly important across applications in electronics, sensing and energy storage/generation. Although the physical properties of these devices are often completely dominated by network morphology, the network structure itself remains difficult to interrogate. Here, we utilise focused ion beam – scanning electron microscopy nanotomography (FIB-SEM-NT) to quantitatively characterise the morphology of printed nanostructured networks and their devices using nanometre-resolution 3D images. The influence of nanosheet/nanowire size on network structure in printed films of graphene, WS2 and silver nanosheets (AgNSs), as well as networks of silver nanowires (AgNWs), is investigated. We present a comprehensive toolkit to extract morphological characteristics including network porosity, tortuosity, specific surface area, pore dimensions and nanosheet orientation, which we link to network resistivity. By extending this technique to interrogate the structure and interfaces within printed vertical heterostacks, we demonstrate the potential of this technique for device characterisation and optimisation.