bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Phenotypes of PCOS: a Cross-Sectional Study
Authors: Elsayed Abdalla Moustafa , Al-Kaabi Latifa Saad , Al-Abdulla Noora Mohammed , Al-Kuwari Moza Salem , Al-Mulla Asmaa Abdulsamad , Al-Shamari Raghad Shaher , Alhusban Ahmed Khaled , AlNajjar Ali Ahmed , Doi Suhail A. R.
Published: May 2023

This cross-sectional study examines the Doi-Alshoumer PCOS clinical phenotype classification in relation to measured clinical and biochemical characteristics of women with polycystic ovary syndrome (PCOS). Two cohorts of women (Kuwait and Rotterdam) diagnosed with PCOS (FAI > 4.5%) were examined. These phenotypes were created using neuroendocrine dysfunction (IRMA LH/FSH ratio > 1 or LH > 6 IU/L) and menstrual cycle status (oligo/amenorrhea) to create three phenotypes: (A) neuroendocrine dysfunction and oligo/amenorrhea, (B) without neuroendocrine dysfunction but with oligo/amenorrhea, and (C) without neuroendocrine dysfunction and with regular cycles. These phenotypes were compared in terms of hormonal, biochemical, and anthropometric measures. The three suggested phenotypes (A, B, and C) were shown to be sufficiently distinct in terms of hormonal, biochemical, and anthropometric measures. Patients who were classified as phenotype A had neuroendocrine dysfunction, excess LH (and LH/FSH ratio), irregular cycles, excess A4, infertility, excess T, highest FAI and E2, and excess 17αOHPG when compared to the other phenotypes. Patients classified as phenotype B had irregular cycles, no neuroendocrine dysfunction, obesity, acanthosis nigricans, and insulin resistance. Lastly, patients classified as phenotype C had regular cycles, acne, hirsutism, excess P4, and the highest P4 to E2 molar ratio. The differences across phenotypes suggested distinct phenotypic expression of this syndrome, and the biochemical and clinical correlates of each phenotype are likely to be useful in the management of women with PCOS. These phenotypic criteria are distinct from criteria used for diagnosis.
Clustering and Analysis of Rural E-commerce Live Broadcast Mode Based on Data Orientation
Authors: Tian Hua
Published: May 2023

The rapid development of network technology has revolutionized information dissemination and made it possible for various new communication channels to gradually seep into people’s daily lives. The primary task within the context of new media is the creation of agricultural products live e-commerce. This study first analyses and categorizes the preferences of product purchasers using a collaborative filtering process in order to achieve this. It then suggests a clustering algorithm based on ROCK that improves the link rather than the previously used distance as a criterion for cluster split and can successfully address the problem of data scarcity based on collaborative suggestion. The difficulties of live e-commerce entrepreneurship and the need of fostering new farmers’ live e-commerce entrepreneurship skills are also discussed in this essay. The case study illustrates that the research’s strategy can successfully examine the path towards developing new farmers’ live e-commerce skills.
Foreign Direct Investment Hosts and Violent Government Repression of Protests
Authors: Adelaiye Samaila Oluwatope
Published: May 2023

There has been a brewing argument on the effects of economic globalization on the repression of human rights. My argument in this article joins the optimistic perspective on the relationship between the globalizing economy and state repression. I argue that governments consider backlash from investors in their decisions about whether to use repression. Investors, motivated by international human rights norms and a fear of violent conflict, would prefer that governments not introduce brute force into a nonviolent protest. Thus, governments in countries that depend more on foreign direct investment (FDI) should be less likely to use violence against protesters than those that are less dependent on FDI. Using data analysis of protest events and inward FDI stock, I test this argument and find a negative relationship between these two variables.
Mapping the distribution of health equity research and practice across a university: a network analysis
Authors: Yousefi Nooraie Reza , Dadgostar Porooshat , Roman Gretchen , Cullen John P. , Bennett Nancy M.
Published: May 2023

Introduction:

Health equity research spans various disciplines, crossing formal organizational and departmental barriers and forming invisible communities. This study aimed to map the nomination network of scholars at the University of Rochester Medical Center who were active in racial and ethnic health equity research, education, and social/administrative activities, to identify the predictors of peer recognition.

Methods:

We conducted a snowball survey of faculty members with experience and/or interest in racial and ethnic health equity, nominating peers with relevant expertise.

Results:

Data from a total of 121 individuals (64% doing research on extent and outcomes of racial/ethnic disparities and racism, 48% research on interventions, 55% education, and 50% social/administrative activities) were gathered in six rounds of survey. The overlap between expertise categories was small with coincidence observed between education and social/administrative activities (kappa: 0.27; p < 0.001). Respondents were more likely to nominate someone if both were involved in research (OR: 3.1), if both were involved in education (OR: 1.7), and if both were affiliated with the same department (OR: 3.7). Being involved in health equity research significantly predicted the centrality of an individual in the nomination network, and the most central actors were involved in multiple expertise categories.

Conclusions:

Compared with equity researchers, those involved in racial equity social/administrative activities were less likely to be recognized by peers as equity experts.
Van Leeuwenhoek – the film: remaking memory in Dutch science cinema 1925–c.1960
Authors: te Hennepe Mieneke
Published: May 2023

This paper examines how the production, content and reception of the film Antony van Leeuwenhoek (1924) influenced the historical framing of science. The film features microcinematography by the pioneering Dutch filmmaker Jan Cornelis Mol (1891–1954), and was part of a dynamic process of commemorating seventeenth-century microscopy and bacteriology through an early instance of visual re-creation – a new way of using scientific material heritage, and of enabling audiences to supposedly observe the world of microscopic organisms in just the same way as the Dutch scientist Antoni van Leeuwenhoek (1632–1723) had observed them for himself. Knowledge transfer concerning material culture, around both historical and contemporary instruments, was the determining factor in the microcinematography practices applied in this film. The production and experience of the film also mirrored the seventeenth-century process of experimentation, playing with optics, and visualizing an entirely new and unknown world. Unlike other biographical science films of the 1920s, Antony van Leeuwenhoek featured abstract depictions of time and movement that allowed the audience to connect the history of science with microcinematography, contributing to the memory of Van Leeuwenhoek's work as the origins of bacteriology in the process.
Demonstrating proof of concept for value-based agreements in Europe: two real-world cases
Authors: Griffiths Elizabeth A. , Odelade Onivefu E. , Gostkorzewicz Joana , Cordero Luis
Published: May 2023

Objectives

Value-based agreements (VBAs) link access, reimbursement, or price to the real-world usage and impact of a medicine, thereby enabling patient access while reducing clinical or financial uncertainty for the payer. VBAs have the potential to support improved patient outcomes, given the value-oriented approach to care, and lead to overall savings, while enabling payers to share risk and reduce uncertainty.

Methods

This commentary outlines the key challenges, enablers, and a framework for successful implementation by comparing the experience of two VBAs for AstraZeneca medicines, aiming to increase confidence in their future use.

Results

Engagement by payers, manufacturers, physicians, and provider institutions, and robust data collection systems that are accessible, simple to use, and add little burden to physicians were key to successfully negotiating a VBA that worked for all stakeholders. In both country systems, a legal/policy framework enabled innovative contracting.

Conclusions

These examples demonstrate proof of concept for VBA implementation in different settings, and may inform future VBAs.
The War that Didn't Happen: Waiting for Ambushes in the Irish War of Independence
Authors: Ó Catháin Máirtín Seán
Published: May 2023

There is a widely held perception that the Anglo-Irish War or War of Independence was a hard-fought series of guerrilla war engagements punctuated by larger and often spectacular events in Cork, Dublin and elsewhere. However, an examination of the conflict from the perspective of a search for an alternative war, where little if anything occurred, can yield interesting and counter-intuitive results. This is exactly what this article sets out to do in order to demonstrate the often rich potential in the quest for nothing in particular, but primarily to establish that in every conflict of this type, another war often takes place, which shows itself to be largely ineffectual and futile though ultimately quite rewarding in its own way.
Autophagic activation in porcine oocytes is independent of meiotic progression
Authors: Lee SeungHoon , Jeong Haeyun , Wi Hayeon , No Jin-Gu , Lee Whi-Cheul , Kim Seokho , Yang Hyeon , Byun Sung June , Park Sejin , Kim Jong Gug
Published: May 2023

In this study, we built on our previous research that discovered that autophagy activated the metaphase I stage during porcine oocytes in vitro maturation. We investigated the relationship between autophagy and oocyte maturation. First, we confirmed whether autophagy was activated differently by different media (TCM199 and NCSU-23) during maturation. Then, we investigated whether oocyte maturation affected autophagic activation. In addition, we examined whether the inhibition of autophagy affected the nuclear maturation rate of porcine oocytes. As for the main experiment, we measured LC3-II levels using western blotting after inhibition of nuclear maturation via cAMP treatment in an in vitro culture to clarify whether nuclear maturation affected autophagy. After autophagy inhibition, we also counted matured oocytes by treating them with wortmannin or a E64d and pepstatin A mixture. Both groups, which had different treatment times of cAMP, showed the same levels of LC3-II, while the maturation rates were about four times higher after cAMP 22 h treatment than that of the 42 h treatment group. This indicated that neither cAMP nor nuclear status affected autophagy. Autophagy inhibition during in vitro oocyte maturation with wortmannin treatment reduced oocyte maturation rates by about half, while autophagy inhibition by the E64d and pepstatin A mixture treatment did not significantly affect the oocyte maturation. Therefore, wortmannin itself, or the autophagy induction step, but not the degradation step, is involved in the oocyte maturation of porcine oocytes. Overall, we propose that oocyte maturation does not stand upstream of autophagy activation, but autophagy may exist upstream of oocyte maturation.
Modulatory role of foreign language experience on the Moral Foreign Language Effect
Authors: Privitera Adam John , Li Shaohan , Zhou Yu , Wang Mengqi
Published: May 2023

The Moral Foreign Language Effect (MFLE) is characterized by increased utilitarian decision-making when bilinguals respond to moral dilemmas in their foreign language. While previous research has given us a better understanding of this phenomenon, few studies have investigated how foreign language experience influences the MFLE. The present study investigated whether differences in foreign language proficiency, immersion, or dominance modulated the emergence of the MFLE. Mandarin–English bilingual young adults responded to a series of moral dilemmas in either their native or foreign language. Participants also provided ratings of permissibility and distress after reading each dilemma. We report a dilemma-specific MFLE that was modulated by differences in foreign language experience. Most significant was the observation that separable dimensions of foreign language experience interact when modulating the MFLE in a manner that is dilemma-specific. These findings emphasize the importance of considering differences in foreign language experience across multiple dimensions when investigating the MFLE.
The Unicity, Infinity and Unity of Space
Authors: Onof Christian
Published: May 2023

The article proposes an interpretation of Kant’s notions of form of, and formal intuition of space to explain and justify the claim that representing space as object requires a synthesis. This involves identifying the transcendental conditions of the analytic unity of consciousness of this formal intuition and distinguishing between it and its content. On this reading which builds upon recent proposals, footnote B160–1n. involves no revision of the Transcendental Aesthetic: space is essentially characterized by non-conceptual features. The article also addresses worries about the infinite magnitude and the unicity of space, by considering the characteristics and requirements of geometric constructions.
Theodore Roosevelt and the Unionist Memory of the Civil War: Experience, History, and Politics, 1861–1918
Authors: Wetzel Benjamin J.
Published: May 2023

The meaning of the Civil War, America’s most violent experience, continued to be debated well into the Gilded Age and Progressive Era. The long shadow cast by David Blight’s influential Race and Reunion: The Civil War in American Memory (2001) has meant that debates about the impact and prevalence of reconciliationist rhetoric dominate the literature. This paper adds to a growing body of scholarship that questions the reconciliationist narrative and stresses instead the partisan understanding of the Civil War still prevalent into the twentieth century. In particular, this article uses Theodore Roosevelt’s “memory” of the Civil War to explore the linkages between the Civil War Era and the Age of Empire. It makes two arguments: 1) that in an era when a “reconciliationist” understanding of the Civil War was becoming more prominent, more often than not Roosevelt used his voice as a historian and political figure to assert a “Unionist” interpretation; and 2) that Roosevelt used this memory of the Civil War to advocate for three specific political causes: American empire, the New Nationalism, and American entry into World War I. The paper’s argument and historiographical intervention help scholars of the Gilded Age and Progressive Era to re-imagine the role of Civil War memory in the half century following Appomattox Courthouse.
Seismic Azimuthal Anisotropy of Northeastern Tibetan Plateau From Ambient Noise Double Beamforming Tomography: Implications for Crustal Deformation
Authors: Wu Xiaoyang , Guo Zhen , Li Shilin , Yu Yong , Bai Qipeng , Chen Yongshun John
Published: May 2023

In this study, we obtain a three‐dimensional (3‐D) high resolution seismic anisotropy model of NE Tibet using ambient noise double beamforming (DBF) tomography with ChinArray‐Himalaya II data. DBF tomography technique allows for the simultaneous derivation of local phase velocity and azimuthal anisotropy from ambient noise cross‐correlations without performing tomographic inversion. Based on the DBF tomography results, we have constructed a high resolution 3‐D azimuthal anisotropic shear wave velocity model of NE Tibet. Our model indicates the presence of prominent low velocities and strong azimuthal anisotropy in the mid‐to lower crust beneath the Songpan‐Ganzi belt, while the mid‐to lower crust of the Qilian belt exhibits relatively weak low velocity and azimuthal anisotropy. We propose that crustal channel flow may be the primary mechanism driving crustal deformation in the Songpan‐Ganzi belt, which is in the mature part of the plateau. As the Qilian belt is at an early stage of plateau formation, it is characterized by crustal shortening with the development of a sub‐vertical foliation. Additionally, the misalignment between predicted and observed shear wave splitting reveals decoupled crust and upper mantle deformation west of the Ordos block where eastward mantle flow is deflected by the lithospheric keel of Ordos.
Distinct Seasonality in Aerosol Responses to Emission Control Over Northern China
Authors: Liu Yawen , Wang Minghuai , Yue Man , Qian Yun
Published: May 2023

Despite intensive research exploring how aerosols respond to emission control over Northern China, efforts mostly focus on the environmental benefit, especially in winter. Here we found that unlike the most substantial PM2.5 concentration reduction in winter, aerosol optical depth (AOD) declines more than 2 times faster in summer, causing an increase in aerosol radiative effects of 1.2 (5.7)Wm−2 on all‐sky (clear‐sky) conditions over 2013–2019 and largely shaping the climate impact. Low‐level aerosols are shown to be the prime contributor under the synergetic effects of aerosol composition and ambient relative humidity (RH). The dominance of the highly hygroscopic sulfate combined with high RH enables a strong extinction efficiency of the reduced summertime aerosols, while the insignificant AOD decline in wintertime result from the dominance of organic aerosols with weak hygroscopicity, and is further offset by the increased frequencies of extremely high RH. We show the environmental and climatic responses of aerosols to emission control exhibit distinctively different seasonality.
Accelerated TMS - moving quickly into the future of depression treatment
Authors: van Rooij Sanne J. H. , Arulpragasam Amanda R. , McDonald William M. , Philip Noah S.
Published: May 2023

Accelerated TMS is an emerging application of Transcranial Magnetic Stimulation (TMS) aimed to reduce treatment length and improve response time. Extant literature generally shows similar efficacy and safety profiles compared to the FDA-cleared protocols for TMS to treat major depressive disorder (MDD), yet accelerated TMS research remains at a very early stage in development. The few applied protocols have not been standardized and vary significantly across a set of core elements. In this review, we consider nine elements that include treatment parameters (i.e., frequency and inter-stimulation interval), cumulative exposure (i.e., number of treatment days, sessions per day, and pulses per session), individualized parameters (i.e., treatment target and dose), and brain state (i.e., context and concurrent treatments). Precisely which of these elements is critical and what parameters are most optimal for the treatment of MDD remains unclear. Other important considerations for accelerated TMS include durability of effect, safety profiles as doses increase over time, the possibility and advantage of individualized functional neuronavigation, use of biological readouts, and accessibility for patients most in need of the treatment. Overall, accelerated TMS appears to hold promise to reduce treatment time and achieve rapid reduction in depressive symptoms, but at this time significant work remains to be done. Rigorous clinical trials combining clinical outcomes and neuroscientific measures such as electroencephalogram, magnetic resonance imaging and e-field modeling are needed to define the future of accelerated TMS for MDD.
Post-diagnostic health behaviour scores and risk of prostate cancer progression and mortality
Authors: Langlais Crystal S. , Graff Rebecca E. , Van Blarigan Erin L. , Neuhaus John M. , Cowan Janet E. , Broering Jeanette M. , Carroll Peter , Kenfield Stacey A. , Chan June M.
Published: May 2023

Background

Individual behaviours are associated with prostate cancer (PC) progression. Behavioural scores, comprised of multiple risk factors, allow assessment of the combined impact of multiple behaviours.

Methods

We examined the association between six a priori scores and risk of PC progression and mortality among 2156 men with PC in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) cohort: two scores developed based on the PC survivorship literature (‘2021 Score [+ Diet]’); a score developed based on pre-diagnostic PC literature (‘2015 Score’); and three scores based on US recommendations for cancer prevention (‘WCRF/AICR Score’) and survival (‘ACS Score [+ Alcohol]’). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for progression and PC mortality via parametric survival models (interval censoring) and Cox models, respectively.

Results

Over a median (IQR) of 6.4 (1.3, 13.7) years, we observed 192 progression and 73 PC mortality events. Higher (i.e., healthier) 2021 Score + Diet and WCRF/AICR Scores were inversely associated with risk of PC progression (2021 + Diet: HRcontinuous = 0.76, 95% CI: 0.63–0.90. WCRF/AICR: HRcontinuous = 0.83, 95% CI: 0.67–1.02) and mortality (2021 + Diet: HRcontinuous = 0.65, 95% CI: 0.45–0.93. WCRF/AICR: HRcontinuous = 0.71; 95% CI: 0.57–0.89). The ACS Score + Alcohol was only associated with progression (HRcontinuous = 0.89, 95% CI: 0.81–0.98) while the 2021 Score was only associated with PC mortality (HRcontinuous = 0.62, 95% CI: 0.45–0.85). The 2015 was not associated with PC progression or mortality.

Conclusion

Findings strengthen the evidence that behavioural modifications following a prostate cancer diagnosis may improve clinical outcomes.
RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer
Authors: Li Fan , Sun Huizhi , Yu Yihui , Che Na , Han Jiyuan , Cheng Runfen , Zhao Nan , Guo Yuhong , Huang Chongbiao , Zhang Danfang
Published: May 2023

Necroptosis is a caspase-independent form of programmed cell death. Receptor interacting protein kinase 1 (RIPK1) is a key molecule in the initiation of necroptosis and the formation of the necrotic complex. Vasculogenic mimicry (VM) provides a blood supply to tumor cells that is not dependent on endothelial cells. However, the relationship between necroptosis and VM in triple-negative breast cancer (TNBC) is not fully understood. In this study, we found that RIPK1-dependent necroptosis promoted VM formation in TNBC. Knockdown of RIPK1 significantly suppressed the number of necroptotic cells and VM formation. Moreover, RIPK1 activated the p-AKT/eIF4E signaling pathway during necroptosis in TNBC. eIF4E was blocked by knockdown of RIPK1 or AKT inhibitors. Furthermore, we found that eIF4E promoted VM formation by promoting epithelial-mesenchymal transition (EMT) and the expression and activity of MMP2. In addition to its critical role in necroptosis-mediated VM, eIF4E was essential for VM formation. Knockdown of eIF4E significantly suppressed VM formation during necroptosis. Finally, through clinical significance, the results found that eIF4E expression in TNBC was positively correlated with the mesenchymal marker vimentin, the VM marker MMP2, and the necroptosis markers MLKL and AKT. In conclusion, RIPK1-dependent necroptosis promotes VM formation in TNBC. Necroptosis promotes VM formation by activating RIPK1/p-AKT/eIF4E signaling in TNBC. eIF4E promotes EMT and MMP2 expression and activity, leading to VM formation. Our study provides a rationale for necroptosis-mediated VM and also providing a potential therapeutic target for TNBC.
Development and validation of an online tool to assess perceived portion size norms of discretionary foods
Authors: Liu Qingzhou , Wang Leanne , Guo Siyi , Allman-Farinelli Margaret , Rangan Anna
Published: May 2023

Background

Perceived portion size norms (typical perception of how much of a given food individuals choose to eat at a single occasion) may have shifted towards larger sizes due to the ubiquity of large serving sizes. However, there is a lack of validated tools to assess such norms for energy-dense and nutrient-poor discretionary foods. This study aimed to develop and validate an online tool to examine the perceived portion size norms of discretionary foods.

Methods

An online image-series tool of 15 commonly consumed discretionary foods was developed, with eight successive portion size options included for each food. Using a randomised-crossover design, adult consumers (18–65 years) completed the validation study in a laboratory session (April-May 2022) by reporting their perceived portion size norms for each food twice, once based on food images on a computer and another time based on equivalent real food portion size options at food stations in the laboratory. Agreement between methods for each test food was examined using cross-classification and intra-class correlation (ICC).

Results

A sample of 114 subjects were recruited (mean age 24.8 years). Cross-classification indicated >90% of selections were matched in the same or adjacent portion size option. ICC was 0.85 across all foods, demonstrating a good level of agreement.

Conclusion

This novel online image-series tool developed to examine perceived portion size norms of discretionary foods showed good agreement with equivalent real food portion size options and may be valuable to investigate perceived portion size norms of common discretionary foods in future studies.
Wetting and complex remodeling of membranes by biomolecular condensates
Authors: Mangiarotti Agustín , Chen Nannan , Zhao Ziliang , Lipowsky Reinhard , Dimova Rumiana
Published: May 2023

Cells compartmentalize parts of their interiors into liquid-like condensates, which can be reconstituted in vitro. Although these condensates interact with membrane-bound organelles, their potential for membrane remodeling and the underlying mechanisms of such interactions are not well-understood. Here, we demonstrate that interactions between protein condensates - including hollow ones, and membranes can lead to remarkable morphological transformations and provide a theoretical framework to describe them. Modulation of solution salinity or membrane composition drives the condensate-membrane system through two wetting transitions, from dewetting, through a broad regime of partial wetting, to complete wetting. When sufficient membrane area is available, fingering or ruffling of the condensate-membrane interface is observed, an intriguing phenomenon producing intricately curved structures. The observed morphologies are governed by the interplay of adhesion, membrane elasticity, and interfacial tension. Our results highlight the relevance of wetting in cell biology, and pave the way for the design of synthetic membrane-droplet based biomaterials and compartments with tunable properties.
AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration
Authors: Crosas-Molist Eva , Graziani Vittoria , Maiques Oscar , Pandya Pahini , Monger Joanne , Samain Remi , George Samantha L. , Malik Saba , Salise Jerrine , Morales Valle , Le Guennec Adrien , Atkinson R. Andrew , Marti Rosa M. , Matias-Guiu Xavier , Charras Guillaume , Conte Maria R. , Elosegui-Artola Alberto , Holt Mark , Sanz-Moreno Victoria
Published: May 2023

Cell migration is crucial for cancer dissemination. We find that AMP-activated protein kinase (AMPK) controls cell migration by acting as an adhesion sensing molecular hub. In 3-dimensional matrices, fast-migrating amoeboid cancer cells exert low adhesion/low traction linked to low ATP/AMP, leading to AMPK activation. In turn, AMPK plays a dual role controlling mitochondrial dynamics and cytoskeletal remodelling. High AMPK activity in low adhering migratory cells, induces mitochondrial fission, resulting in lower oxidative phosphorylation and lower mitochondrial ATP. Concurrently, AMPK inactivates Myosin Phosphatase, increasing Myosin II-dependent amoeboid migration. Reducing adhesion or mitochondrial fusion or activating AMPK induces efficient rounded-amoeboid migration. AMPK inhibition suppresses metastatic potential of amoeboid cancer cells in vivo, while a mitochondrial/AMPK-driven switch is observed in regions of human tumours where amoeboid cells are disseminating. We unveil how mitochondrial dynamics control cell migration and suggest that AMPK is a mechano-metabolic sensor linking energetics and the cytoskeleton.
Selenomonas sputigena acts as a pathobiont mediating spatial structure and biofilm virulence in early childhood caries
Authors: Cho Hunyong , Ren Zhi , Divaris Kimon , Roach Jeffrey , Lin Bridget M. , Liu Chuwen , Azcarate-Peril M. Andrea , Simancas-Pallares Miguel A. , Shrestha Poojan , Orlenko Alena , Ginnis Jeannie , North Kari E. , Zandona Andrea G. Ferreira , Ribeiro Apoena Aguiar , Wu Di , Koo Hyun
Published: May 2023

Streptococcus mutanshas been implicated as the primary pathogen in childhood caries (tooth decay). While the role of polymicrobial communities is appreciated, it remains unclear whether other microorganisms are active contributors or interact with pathogens. Here, we integrate multi-omics of supragingival biofilm (dental plaque) from 416 preschool-age children (208 males and 208 females) in a discovery-validation pipeline to identify disease-relevant inter-species interactions. Sixteen taxa associate with childhood caries in metagenomics-metatranscriptomics analyses. Using multiscale/computational imaging and virulence assays, we examine biofilm formation dynamics, spatial arrangement, and metabolic activity ofSelenomonas sputigena, Prevotella salivaeandLeptotrichia wadei, either individually or withS. mutans. We show thatS. sputigena, a flagellated anaerobe with previously unknown role in supragingival biofilm, becomes trapped in streptococcal exoglucans, loses motility but actively proliferates to build a honeycomb-like multicellular-superstructure encapsulatingS. mutans, enhancing acidogenesis. Rodent model experiments reveal an unrecognized ability ofS. sputigenato colonize supragingival tooth surfaces. While incapable of causing caries on its own, when co-infected withS. mutans, S. sputigenacauses extensive tooth enamel lesions and exacerbates disease severity in vivo. In summary, we discover a pathobiont cooperating with a known pathogen to build a unique spatial structure and heighten biofilm virulence in a prevalent human disease.
Nonthermal acceleration of protein hydration by sub-terahertz irradiation
Authors: Sugiyama Jun-ichi , Tokunaga Yuji , Hishida Mafumi , Tanaka Masahito , Takeuchi Koh , Satoh Daisuke , Imashimizu Masahiko
Published: May 2023

The collective intermolecular dynamics of protein and water molecules, which overlap in the sub-terahertz (THz) frequency region, are relevant for expressing protein functions but remain largely unknown. This study used dielectric relaxation (DR) measurements to investigate how externally applied sub-THz electromagnetic fields perturb the rapid collective dynamics and influence the considerably slower chemical processes in protein–water systems. We analyzed an aqueous lysozyme solution, whose hydration is not thermally equilibrated. By detecting time-lapse differences in microwave DR, we demonstrated that sub-THz irradiation gradually decreases the dielectric permittivity of the lysozyme solution by reducing the orientational polarization of water molecules. Comprehensive analysis combining THz and nuclear magnetic resonance spectroscopies suggested that the gradual decrease in the dielectric permittivity is not induced by heating but is due to a slow shift toward the hydrophobic hydration structure in lysozyme. Our findings can be used to investigate hydration-mediated protein functions based on sub-THz irradiation.
Anion redox as a means to derive layered manganese oxychalcogenides with exotic intergrowth structures
Authors: Sasaki Shunsuke , Giri Souvik , Cassidy Simon J. , Dey Sunita , Batuk Maria , Vandemeulebroucke Daphne , Cibin Giannantonio , Smith Ronald I. , Holdship Philip , Grey Clare P. , Hadermann Joke , Clarke Simon J.
Published: May 2023

Topochemistry enables step-by-step conversions of solid-state materials often leading to metastable structures that retain initial structural motifs. Recent advances in this field revealed many examples where relatively bulky anionic constituents were actively involved in redox reactions during (de)intercalation processes. Such reactions are often accompanied by anion-anion bond formation, which heralds possibilities to design novel structure types disparate from known precursors, in a controlled manner. Here we present the multistep conversion of layered oxychalcogenides Sr2MnO2Cu1.5Ch2 (Ch = S, Se) into Cu-deintercalated phases where antifluorite type [Cu1.5Ch2]2.5- slabs collapsed into two-dimensional arrays of chalcogen dimers. The collapse of the chalcogenide layers on deintercalation led to various stacking types of Sr2MnO2Ch2 slabs, which formed polychalcogenide structures unattainable by conventional high-temperature syntheses. Anion-redox topochemistry is demonstrated to be of interest not only for electrochemical applications but also as a means to design complex layered architectures.
An asymmetric electrolyte to simultaneously meet contradictory requirements of anode and cathode
Authors: Chen Shengmei , Ying Yiran , Ma Longtao , Zhu Daming , Huang Haitao , Song Li , Zhi Chunyi
Published: May 2023

One of the major obstacles hindering the application of zinc metal batteries is the contradictory demands from the Zn metal anode and cathodes. At the anode side, water induces serious corrosion and dendrite growth, remarkably suppressing the reversibility of Zn plating/stripping. At the cathode side, water is essential because many cathode materials require both H+ and Zn2+ insertion/extraction to achieve a high capacity and long lifespan. Herein, an asymmetric design of inorganic solid-state electrolyte combined with hydrogel electrolyte is presented to simultaneously meet the as-mentioned contrary requirements. The inorganic solid-state electrolyte is toward the Zn anode to realize a dendrite-free and corrosion-free highly reversible Zn plating/stripping, and the hydrogel electrolyte enables consequent H+ and Zn2+ insertion/extraction at the cathode side for high performance. Therefore, there is no hydrogen and dendrite growth detected in cells with a super high-areal-capacity up to 10 mAh·cm−2 (Zn//Zn), ~5.5 mAh·cm−2 (Zn//MnO2) and ~7.2 mAh·cm−2 (Zn//V2O5). These Zn//MnO2 and Zn//V2O5 batteries show remarkable cycling stability over 1000 cycles with 92.4% and over 400 cycles with 90.5% initial capacity retained, respectively.
Vaccinia E5 is a major inhibitor of the DNA sensor cGAS
Authors: Yang Ning , Wang Yi , Dai Peihong , Li Tuo , Zierhut Christian , Tan Adrian , Zhang Tuo , Xiang Jenny Zhaoying , Ordureau Alban , Funabiki Hironori , Chen Zhijian , Deng Liang
Published: May 2023

The DNA sensor cyclic GMP-AMP synthase (cGAS) is critical in host antiviral immunity. Vaccinia virus (VACV) is a large cytoplasmic DNA virus that belongs to the poxvirus family. How vaccinia virus antagonizes the cGAS-mediated cytosolic DNA-sensing pathway is not well understood. In this study, we screened 80 vaccinia genes to identify potential viral inhibitors of the cGAS/Stimulator of interferon gene (STING) pathway. We discovered that vaccinia E5 is a virulence factor and a major inhibitor of cGAS. E5 is responsible for abolishing cGAMP production during vaccinia virus (Western Reserve strain) infection of dendritic cells. E5 localizes to the cytoplasm and nucleus of infected cells. Cytosolic E5 triggers ubiquitination of cGAS and proteasome-dependent degradation via interacting with cGAS. Deleting the E5R gene from the Modified vaccinia virus Ankara (MVA) genome strongly induces type I IFN production by dendritic cells (DCs) and promotes DC maturation, and thereby improves antigen-specific T cell responses.
Base editing-mediated one-step inactivation of the Dnmt gene family reveals critical roles of DNA methylation during mouse gastrulation
Authors: Li Qing , Lu Jiansen , Yin Xidi , Chang Yunjian , Wang Chao , Yan Meng , Feng Li , Cheng Yanbo , Gao Yun , Xu Beiying , Zhang Yao , Wang Yingyi , Cui Guizhong , Xu Luang , Sun Yidi , Zeng Rong , Li Yixue , Jing Naihe , Xu Guo-Liang , Wu Ligang , Tang Fuchou , Li Jinsong
Published: May 2023

During embryo development, DNA methylation is established by DNMT3A/3B and subsequently maintained by DNMT1. While much research has been done in this field, the functional significance of DNA methylation in embryogenesis remains unknown. Here, we establish a system of simultaneous inactivation of multiple endogenous genes in zygotes through screening for base editors that can efficiently introduce a stop codon. Embryos with mutations in Dnmts and/or Tets can be generated in one step with IMGZ. Dnmt-null embryos display gastrulation failure at E7.5. Interestingly, although DNA methylation is absent, gastrulation-related pathways are down-regulated in Dnmt-null embryos. Moreover, DNMT1, DNMT3A, and DNMT3B are critical for gastrulation, and their functions are independent of TET proteins. Hypermethylation can be sustained by either DNMT1 or DNMT3A/3B at some promoters, which are related to the suppression of miRNAs. The introduction of a single mutant allele of six miRNAs and paternal IG-DMR partially restores primitive streak elongation in Dnmt-null embryos. Thus, our results unveil an epigenetic correlation between promoter methylation and suppression of miRNA expression for gastrulation and demonstrate that IMGZ can accelerate deciphering the functions of multiple genes in vivo.
Probing the atomically diffuse interfaces in Pd@Pt core-shell nanoparticles in three dimensions
Authors: Li Zezhou , Xie Zhiheng , Zhang Yao , Mu Xilong , Xie Jisheng , Yin Hai-Jing , Zhang Ya-Wen , Ophus Colin , Zhou Jihan
Published: May 2023

Deciphering the three-dimensional atomic structure of solid-solid interfaces in core-shell nanomaterials is the key to understand their catalytical, optical and electronic properties. Here, we probe the three-dimensional atomic structures of palladium-platinum core-shell nanoparticles at the single-atom level using atomic resolution electron tomography. We quantify the rich structural variety of core-shell nanoparticles with heteroepitaxy in 3D at atomic resolution. Instead of forming an atomically-sharp boundary, the core-shell interface is found to be atomically diffuse with an average thickness of 4.2 Å, irrespective of the particle’s morphology or crystallographic texture. The high concentration of Pd in the diffusive interface is highly related to the free Pd atoms dissolved from the Pd seeds, which is confirmed by atomic images of Pd and Pt single atoms and sub-nanometer clusters using cryogenic electron microscopy. These results advance our understanding of core-shell structures at the fundamental level, providing potential strategies into precise nanomaterial manipulation and chemical property regulation.
Intramolecular charge transfer enables highly-efficient X-ray luminescence in cluster scintillators
Authors: Zhang Nan , Qu Lei , Dai Shuheng , Xie Guohua , Han Chunmiao , Zhang Jing , Huo Ran , Hu Huan , Chen Qiushui , Huang Wei , Xu Hui
Published: May 2023

Luminescence clusters composed of organic ligands and metals have gained significant interests as scintillators owing to their great potential in high X-ray absorption, customizable radioluminescence, and solution processability at low temperatures. However, X-ray luminescence efficiency in clusters is primarily governed by the competition between radiative states from organic ligands and nonradiative cluster-centered charge transfer. Here we report that a class of Cu4I4 cubes exhibit highly emissive radioluminescence in response to X-ray irradiation through functionalizing biphosphine ligands with acridine. Mechanistic studies show that these clusters can efficiently absorb radiation ionization to generate electron-hole pairs and transfer them to ligands during thermalization for efficient radioluminescence through precise control over intramolecular charge transfer. Our experimental results indicate that copper/iodine-to-ligand and intraligand charge transfer states are predominant in radiative processes. We demonstrate that photoluminescence and electroluminescence quantum efficiencies of the clusters reach 95% and 25.6%, with the assistance of external triplet-to-singlet conversion by a thermally activated delayed fluorescence matrix. We further show the utility of the Cu4I4 scintillators in achieving a lowest X-ray detection limit of 77 nGy s−1 and a high X-ray imaging resolution of 12 line pairs per millimeter. Our study offers insights into universal luminescent mechanism and ligand engineering of cluster scintillators.
Molecular basis of differential HLA class I-restricted T cell recognition of a highly networked HIV peptide
Authors: Li Xiaolong , Singh Nishant Kumar , Collins David R. , Ng Robert , Zhang Angela , Lamothe-Molina Pedro A. , Shahinian Peter , Xu Shutong , Tan Kemin , Piechocka-Trocha Alicja , Urbach Jonathan M. , Weber Jeffrey K. , Gaiha Gaurav D. , Takou Mbah Overbeck Christian , Huynh Tien , Cheever Sophia , Chen James , Birnbaum Michael , Zhou Ruhong , Walker Bruce D. , Wang Jia-huai
Published: May 2023

Cytotoxic-T-lymphocyte (CTL) mediated control of HIV-1 is enhanced by targeting highly networked epitopes in complex with human-leukocyte-antigen-class-I (HLA-I). However, the extent to which the presenting HLA allele contributes to this process is unknown. Here we examine the CTL response to QW9, a highly networked epitope presented by the disease-protective HLA-B57 and disease-neutral HLA-B53. Despite robust targeting of QW9 in persons expressing either allele, T cell receptor (TCR) cross-recognition of the naturally occurring variant QW9_S3T is consistently reduced when presented by HLA-B53 but not by HLA-B57. Crystal structures show substantial conformational changes from QW9-HLA to QW9_S3T-HLA by both alleles. The TCR-QW9-B53 ternary complex structure manifests how the QW9-B53 can elicit effective CTLs and suggests sterically hindered cross-recognition by QW9_S3T-B53. We observe populations of cross-reactive TCRs for B57, but not B53 and also find greater peptide-HLA stability for B57 in comparison to B53. These data demonstrate differential impacts of HLAs on TCR cross-recognition and antigen presentation of a naturally arising variant, with important implications for vaccine design.
Semantic novelty modulates neural responses to visual change across the human brain
Authors: Nentwich Maximilian , Leszczynski Marcin , Russ Brian E. , Hirsch Lukas , Markowitz Noah , Sapru Kaustubh , Schroeder Charles E. , Mehta Ashesh D. , Bickel Stephan , Parra Lucas C.
Published: May 2023

Our continuous visual experience in daily life is dominated by change. Previous research has focused on visual change due to stimulus motion, eye movements or unfolding events, but not their combined impact across the brain, or their interactions with semantic novelty. We investigate the neural responses to these sources of novelty during film viewing. We analyzed intracranial recordings in humans across 6328 electrodes from 23 individuals. Responses associated with saccades and film cuts were dominant across the entire brain. Film cuts at semantic event boundaries were particularly effective in the temporal and medial temporal lobe. Saccades to visual targets with high visual novelty were also associated with strong neural responses. Specific locations in higher-order association areas showed selectivity to either high or low-novelty saccades. We conclude that neural activity associated with film cuts and eye movements is widespread across the brain and is modulated by semantic novelty.
Spatially-optimized urban greening for reduction of population exposure to land surface temperature extremes
Authors: Massaro Emanuele , Schifanella Rossano , Piccardo Matteo , Caporaso Luca , Taubenböck Hannes , Cescatti Alessandro , Duveiller Gregory
Published: May 2023

The population experiencing high temperatures in cities is rising due to anthropogenic climate change, settlement expansion, and population growth. Yet, efficient tools to evaluate potential intervention strategies to reduce population exposure to Land Surface Temperature (LST) extremes are still lacking. Here, we implement a spatial regression model based on remote sensing data that is able to assess the population exposure to LST extremes in urban environments across 200 cities based on surface properties like vegetation cover and distance to water bodies. We define exposure as the number of days per year where LST exceeds a given threshold multiplied by the total urban population exposed, in person ⋅ day. Our findings reveal that urban vegetation plays a considerable role in decreasing the exposure of the urban population to LST extremes. We show that targeting high-exposure areas reduces vegetation needed for the same decrease in exposure compared to uniform treatment.
Structures of human SGLT in the occluded state reveal conformational changes during sugar transport
Authors: Cui Wenhao , Niu Yange , Sun Zejian , Liu Rui , Chen Lei
Published: May 2023

Sodium-Glucose Cotransporters (SGLT) mediate the uphill uptake of extracellular sugars and play fundamental roles in sugar metabolism. Although their structures in inward-open and outward-open conformations are emerging from structural studies, the trajectory of how SGLTs transit from the outward-facing to the inward-facing conformation remains unknown. Here, we present the cryo-EM structures of human SGLT1 and SGLT2 in the substrate-bound state. Both structures show an occluded conformation, with not only the extracellular gate but also the intracellular gate tightly sealed. The sugar substrate are caged inside a cavity surrounded by TM1, TM2, TM3, TM6, TM7, and TM10. Further structural analysis reveals the conformational changes associated with the binding and release of substrates. These structures fill a gap in our understanding of the structural mechanisms of SGLT transporters.