bluuebunny/crossref_metadata_2025 huggingface dataset:
Harlem, Addis, and Johannesburg: African Solidarity and African American Internationalism in Harlem from the 1960s to the 1990s
Authors: Brown Carolyn A.
Published: April 2024

This 2021 ASA Presidential Lecture combines sociopolitical history with personal reflections on Black Harlem during African decolonization. It begins at the turn of the twentieth century and traces Harlem’s transformation into an international center of pan-Africanist activism and cultural production. Brown explores solidarities that grew as Harlem politicians, grassroots leaders, and residents encountered political exiles and cultural leaders from the continent, the diaspora, and aligned political movements worldwide. These alliances and modes of protest facilitated a hardening of militant activist traditions and cultural cohesion that shaped an anti-imperialist pan-African movement and ultimately a multinational Black political movement in the 1960’s to 1990s.
Mentoring up for early career investigators: Empowering mentees to proactively engage in their mentoring relationships
Authors: Sancheznieto Fátima , Asquith Pamela , Baez Bermejo Adriana , Meagher Emma A. , Pfund Christine E.
Published: April 2024

Introduction:

Effective mentorship is recognized as critical for the professional development of clinical and translational investigators. Evidence-based mentorship training prompted the development of training for mentees at early career stages who are navigating both mentor and mentee roles. The curriculum titled, Mentoring Up for Early Career Investigators, recognizes the importance of building mentee self-efficacy across proactive mentorship skills and competencies.

Methods:

Mentoring Up for Early Career Investigators curriculum is based on the research mentor training approach in Entering Mentoring. Pilot implementations of Mentoring Up at the University of Wisconsin-Madison and University of Pennsylvania had positive training outcomes for KL2 Scholars. Subsequently, Mentoring Up was implemented and evaluated at several other institutions. For 26 implementations longer than 4 hours, data were collected on trainee demographics, satisfaction with training, skill gains across mentorship competencies, and the intent to change mentoring behaviors following training.

Results:

88% of participants rated the mentee training as valuable. Significant skill gains were reported across all mentorship competencies following training. 77% reported specific plans to change or augment their mentoring behaviors because of the training. The majority aligned with mentorship skill competencies (aligning expectations, effective communications) or mentoring up strategies (voicing needs, setting boundaries, communicating proactively).

Conclusion:

Mentoring Up training is effective in advancing mentee skills and promoting strategies to be more proactive in getting their mentoring needs met. Mentoring Up offers an expansion to the suite of mentorship education and resources to support the career advancement of all in the translational science workforce.
Exploring public health researchers’ approaches, barriers, and needs regarding dissemination: A mixed-methods exploration
Authors: Nieuwland Alicia , O’Mara Jillian Rose , Mackenbach Joreintje Dingena
Published: April 2024

Background:

Although there is growing attention to research translation, dissemination practices remain underdeveloped. This study aimed to gain insights into the dissemination approaches, barriers for dissemination, and needs for dissemination support of public health researchers of the Amsterdam Public Health (APH) research institute.

Methods:

A concurrent mixed-methods design was used, collecting quantitative and qualitative data through a survey and qualitative data from interviews. Researchers of the Health Behaviors and Chronic Diseases (HBCD) research line of APH were approached via email with a link to an online survey. For the interviews, we aimed to balance researchers in terms of career phase and position. Data were analyzed through descriptive statistics and thematic content analysis.

Results:

HBCD researchers primarily rely on traditional approaches for dissemination, e.g. academic journals (93%), conferences (93%), and reports to funders (71%). Social media (67%) was also frequently mentioned. Dissemination is often prioritized late due to time constraints and competing priorities. Researchers mentioned a lack of time, money, knowledge, and skills but also limited awareness of available support as barriers. A need for more resources, education, and a shift in mindset was expressed, suggesting a comprehensive inspiring platform and stronger in-house connections as solutions.

Conclusion:

HBCD researchers emphasized the importance of dedicated time and budget for dissemination, as well as other forms of institutional support. Overall, there is a need for a shift in mindset, more educational initiatives, greater integration of dissemination into researchers’ roles, the establishment of a comprehensive inspiring platform, and stronger in-house connections to support dissemination efforts.
The Politics of Doulas: Black Feminist Collective Action in Response to “Birthing While Black”
Authors: Fast Jina
Published: April 2024

A central function of the Black Lives Matter (BLM) movement in the United States has been to center and express the lived experiences of Black people within the social and political framework of white supremacy. Regarding reproductive justice, BLM, as well as organizations like the Black Mamas Matter Alliance and Sistersong, have drawn political attention to the oppressive parameters existing for pregnant people “birthing while Black.” Attention to disparities in health and birth outcomes for Black persons has necessary positive effects, such as the ability to produce data on the deleterious effects of anti-Blackness. However, discourses surrounding Black birthing persons can function to obfuscate the collective action undertaken by Black women and non-Black women of color. In this paper, I argue the hyper-focus on the problems Black pregnant/birthing persons face has at least four issues: (1) it encourages an ontological collapse wherein Black birthers are positioned as problems, rather than human beings facing problems; (2) obscures the collective action and care Black women undertake to support one another; (3) results in state solutions that rely on underpaid and volunteer labor of Black and non-Black women of color; and (4) focuses myopically on the time period of pregnancy and birthing for Black persons.
Influence of the boundary-layer thickness on the generation of tonal noise components by subsonic impinging jets
Authors: Vincent Hugo , Bogey Christophe
Published: April 2024

The influence of the boundary layer (BL) thickness on the tonal noise generated by subsonic impinging jets is investigated. For that, initially laminar jets at Mach numbers$0.6$and$0.9$with BL thicknesses$0.05r_0$,$0.1r_0$and$0.2r_0$, where$r_0$is the pipe-nozzle radius, impinging on a plate at$6r_0$from the nozzle, are simulated. For Mach number$0.9$, acoustic tones due to feedback loops of axisymmetric nature between the nozzle and the plate are generated at frequencies that do not vary with the BL thickness. The two dominant tones are, however,$17$and$26\ \mathrm {dB}$stronger for the thickest BL compared with the thinnest one. For Mach number$0.6$, for the thinnest BL no acoustic peaks appear, as observed in the experiments of the literature, but narrow peaks resulting from axisymmetric feedback loops emerge for thicker BLs. Therefore, low subsonic impinging jets can be resonant for specific nozzle-exit conditions. The increase in tone amplitude for Mach number$0.9$, and the establishment of feedback loops for Mach number$0.6$with increasing BL thickness, are found to result from two changes in the jet flow. The first change is that the shear-layer laminar–turbulent transition occurs farther downstream for a thicker BL, leading to a greater predominance of the axisymmetric aerodynamic fluctuations near the plate. The second change is that the amplification of the flow fluctuations between the nozzle and the plate at the tone frequencies is stronger for thicker BLs.
Regressing bubble cluster dynamics as a disordered many-body system
Authors: Maeda Kazuki , Fuster Daniel
Published: April 2024

The coherent dynamics of bubble clusters are of fundamental and industrial importance, and are elusive due to the complex interactions of disordered bubble oscillations. Here we introduce and demonstrate a method for decomposition of the Lagrangian time series of bubble dynamics data by combining theory and principal component analysis. The decomposition extracts coherent features of bubble oscillations based on their energy, in a way similar to proper orthogonal decomposition of Eulerian flow field data. This method is applied to a dataset of spherical clusters under harmonic excitation at different amplitudes, with various nuclei density and polydispersity parameters. Results indicate that the underlying correlated mode of oscillations is isolated in a single dominant feature in cavitating regimes, independent of the nuclei's parameters. A systematic data analysis procedure further suggests that this feature is globally controlled by the dynamic cloud interaction parameter of Maeda and Colonius (J. Fluid Mech., vol. 862, 2019, pp. 1105–1134) that quantifies the mean-field interactions, regardless of initial polydispersity or nonlinearity. The method provides a simplified and comprehensive representation of complex bubble dynamics as well as a new path to reduced-order modelling of cavitation and nucleation.
Levels of selection and macroevolution in organisms, colonies, and species
Authors: Simpson Carl , Halling Andrea , Leventhal Sarah
Published: April 2024

The fitness of groups is often considered to be the average fitness among constituent members. This assumption has been useful for developing models of multilevel selection, but its uncritical adoption has held back our understanding of how multilevel selection actually works in nature. If group fitness is only equal to mean member fitness, then it is a simple task to erode the importance of group-level selection in all multilevel scenarios—species selection could then be reduced to organismal selection as easily as group selection can. Because selection from different levels can act on a single trait, body size, for example, there must be a way to translate one level of fitness to another. This allows the calculation of the contributions of selection at each level. If high-level fitness is not a simple function of member fitness, then how do they interlace? Here we reintroduce Leigh Van Valen’s argument for the inclusion of expansion as a component of fitness. We show that expansion is an integral part of fitness even if one does not subscribe to the energetic view of fitness from which Van Valen originally derived it. From a hierarchical perspective, expansion is the projection of demographic fitness from one level to the next level up; differential births and deaths at one level produce differential expansion one level above. Including expansion in our conceptual tool kit helps allay concerns about our ability to identify the level of selection using a number of methods as well as allowing for the various forms of multilevel selection to be seen as manifestations of the same basic process.
Consumption of ultra-processed foods and mental health of pregnant women from the South of Brazil
Authors: Meller Fernanda Oliveira , Costa Caroline dos Santos , Quadra Micaela Rabelo , Miranda Vanessa Iribarrem Avena , Eugênio Fernanda Daminelli , da Silva Tamara Justin , Teixeira Maria Vitória Rodrigues , Schäfer Antônio Augusto
Published: April 2024

The objective of this study is to evaluate the association between the consumption of ultra-processed foods (UPF) and the mental health of pregnant women from the South of Brazil. This is a cross-sectional study carried out in Criciúma, Brazil, through face-to-face interviews, from April to December 2022. Pregnant women aged 18 or older who underwent prenatal care in the forty-eight basic health care units of the municipality and who were in their third trimester of pregnancy were included. High consumption of UPF was considered as six or more items or subgroups of UPF consumed on the day before the interview, using the Nova-UPF screener. The mental health variables were depressive symptoms, stress, sadness and anxiety. Crude and adjusted analyses were conducted using the Fisher’s exact test and the Poisson regression with robust variance. In total, 428 pregnant women were studied; most of them were aged between 20 and 25 years and were white. Pregnant women who presented high consumption of UPF were 1·42-fold (95 % CI 1·06, 1·92) more likely to experience anxiety and presented a prevalence 56 % (95 % CI 1·18, 2·07) higher of stress when compared with those who did not present high consumption of UPF. The prevalence of depressive symptoms and feelings of sadness was 1·31-fold (95 % CI 1·08, 1·60) and 3·41-fold (95 % CI 1·77, 6·58) higher among those with high consumption of UPF, respectively. The results suggest that diet quality is associated with the mental health of pregnant women. Promoting joint actions focused on food and nutritional education, and mental health, for pregnant women, is necessary.
Scopes, Specula, the Speculative: Histories of Medical Experimentation and Looking in African American Art and Fiction
Authors: TERRY JENNIFER
Published: April 2024

This article traces a speculative and critical engagement with histories of health care disparity and medical exploitation shared across fictions by Ralph Ellison and Toni Morrison, and the artwork of Ellen Gallagher. It argues that insistent returns to racialized experimentation and scientific modes of looking form a significant interrogation of a wider set of US promises and attritions. Specifically, it asks how postwar African American culture takes up scopic questions to address dominant accounts of progress and the modern, both via reference to visual orders and technologies, and via formal choices regarding iteration, perspective and scale.
The Salvation Army, Eberhard Arnold and the Bruderhof
Authors: TOMLIN SAM
Published: April 2024

This article explores the convergences and divergences between the Salvation Army, Eberhard Arnold and the Bruderhof up to 1939. While the secondary literature makes passing reference to the influence of the Salvation Army on Arnold, no study has examined what it was about this movement which initially attracted him to it and would lead to lifelong appreciation of the Booths and their Army. This article addresses this gap in the literature. It argues that it was the Salvationist presentation of a living, Spirit-filled Christianity as opposed to a dead and establishment-oriented faith in Arnold's mind that best constitutes this relationship.
Evaluating the Evidence for Lunar Calendars in Upper Palaeolithic Parietal Art
Authors: Nowell April , Bahn Paul , Le Quellec Jean-Loïc
Published: April 2024

In this paper, we examine the lunar calendar interpretation to evaluate whether it is a viable explanation for the production of Upper Palaeolithic parietal art. We consider in detail the history of this approach, focusing on recently published variations on this interpretation. We then discuss the scientific method and whether these recent studies are designed to address the research questions necessary to test a lunar calendar hypothesis. More broadly, we explore challenges related to inferring meaning in art of the deep past, the use of secondary sources and selecting appropriate ethnographic analogies. Finally, we assess claims that the lunar calendar interpretation documents the world's oldest (proto)writing system. We conclude that the lunar calendar interpretation as currently construed suffers from multiple theoretical and methodological weaknesses preventing it from being a viable explanation for the production of Upper Palaeolithic art. We further find that claims following from this interpretation to have discovered the oldest known (proto)writing system are unsubstantiated.
Successful ablation of premature ventricular contractions originating from the posterior-superior process of the left ventricle approaching from the right atrium in a 13-year-old male
Authors: Nakagawa Ryo , Yoshida Yoko , Suzuki Tsugutoshi
Published: April 2024

This is a case of a 13-year-old male with frequent premature ventricular contractions with QRS configurations of the left superior axis and left bundle branch block, which originated from the posterior–superior process of the left ventricle. Premature ventricular contractions were successfully eliminated by delivering radiofrequency energy to the inferior wall of the right atrium without causing either junctional rhythm or atrioventricular block. Ventricular arrhythmias originating from this site have been sporadically reported in adults; however, this is the first report in a child.
Purposeful Sampling: Advantages and Pitfalls
Authors: Stratton Samuel J.
Published: April 2024

This editorial monograph explores the advances and pitfalls of the common forms of purposeful sampling. Purposeful sampling is a common research design in qualitative research.
Individual Maxim Tokens, not Abstract Maxim Types
Authors: Kahn Samuel
Published: April 2024

I argue that Kant’s Categorical Imperative should be applied to individual maxim tokens rather than abstract maxim types. The article is divided into five sections. In the first, I explain my thesis. In the second, I show that my thesis disagrees with Rawls. In the third, I argue for my thesis on the basis of the wording of the Categorical Imperative and on the basis of considerations about autonomy. In the fourth, I argue for my thesis on the basis of considerations about the ‘ought implies can’ principle. In the fifth, I provide a summary of the main argumentative moves and also explain some of the philosophical advantages of my thesis.
The Ostroms on self-governance: the importance of cybernetics
Authors: Lewis Paul , Aligica Paul Dragos
Published: April 2024

This paper reveals a novel and perhaps surprising ingredient in the mix of influences that inspired and informed the work of Elinor and Vincent Ostrom on self-governance: cybernetics, understood as a theory of control via feedback mechanisms. Based on this crucial insight, the paper portrays self-governance as involving an architecture of multiple levels of so-called ‘second order’ feedback mechanisms. Such compounded systems of organization are the key to understanding any self-governance process and the paper argues that their intrinsic logic provides a critical link between the work of the Ostroms and the public choice and constitutional political economy perspectives on institutional order. The paper thereby offers both a fresh perspective on the Ostromian view of self-governance and also of also of governance theory in general.
(Small D-democratic) vacation, all I ever wanted? The effect of democratic backsliding on leisure travel in the American states
Authors: Miller David R. , Smith Serena D.
Published: April 2024

As many American states have considered policies consistent with democratic backsliding in recent years, political elites and scholars have speculated on the consequences of these policies for political behavior. We examine the effect of backsliding policies on Americans’ preferences over leisure travel destinations; because vacationing is transitory, this focus allows us to isolate the role of individuals’ democratic predispositions and values in preference formation from the implications of these policies on their self-interest that they would experience from living under those policies themselves. Through pre-registered conjoint and vignette survey experiments, we find that Americans, and especially Democrats, express less interest in vacationing in states that recently adopted backsliding policies. Our results spotlight an accountability mechanism by which Americans may sanction backsliding states, though the modest magnitude of these sanctions – less than 1% of backsliding states’ gross domestic products – may not deter backsliding behavior on their own.
Modeling the Cross‐Sectional Dynamics of Tidal Sandbanks in Sediment‐Scarce Conditions
Authors: van Veelen T. J. , Roos P. C. , Hulscher S. J. M. H.
Published: April 2024

Tidal sandbanks are large‐scale dynamic bedforms that consist of sandy sediment. They have been observed in shallow seas with varying sediment supply, including sediment‐scarce environments like the Flemish Banks, Zeeland Banks, and Norfolk Banks. However, we do not yet understand how scarcity affects sandbank evolution. Therefore, we have developed an idealized nonlinear process‐based model with the aim of studying cross‐sectional shape and migration under sediment‐scarce conditions. Scarcity is included through a non‐erodible layer from which no sediment can be entrained. Our results show that bank height and width decrease when the sediment budget decreases. The bank height is more sensitive to scarcity than bank width. Furthermore, sand scarcity decreases (and may even reverse) bank asymmetry and increases migration rate when a residual current is present. The migration rate attains a maximum for a specific sediment budget, which is controlled by the ratio of the cross‐sectional area of the sandbank and the tide‐averaged sediment flux. Our findings show that sandbank dynamics are strongly affected by scarcity, which is critical for seas with receding sediment stocks (e.g., through extraction).
The Irminger Gyre as a Key Driver of the Subpolar North Atlantic Overturning
Authors: Sanchez‐Franks A. , Holliday N. P. , Evans D. G. , Fried N. , Tooth O. , Chafik L. , Fu Y. , Li F. , de Jong M. F. , Johnson H. L.
Published: April 2024

The lower limb of the Atlantic meridional overturning circulation (AMOC) is the equatorward flow of dense waters formed through the cooling and freshening of the poleward‐flowing upper limb. In the subpolar North Atlantic (SPNA), upper limb variability is primarily set by the North Atlantic Current, whereas lower limb variability is less well understood. Using observations from a SPNA mooring array, we show that variability of the AMOC's lower limb is connected to poleward flow in the interior Irminger Sea. We identify this poleward flow as the northward branch of the Irminger Gyre (IG), accounting for 55% of the AMOC's lower limb variability. Over 2014–2018, wind stress curl fluctuations over the Labrador and Irminger Seas drive this IG and AMOC variability. On longer (>annual) timescales, however, an increasing trend in the thickness of intermediate water, from 2014 to 2020, within the Irminger Sea coincides with a decreasing trend in IG strength.
MED15 is upregulated by HIF-2α and promotes proliferation and metastasis in clear cell renal cell carcinoma via activation of SREBP-dependent fatty acid synthesis
Authors: Hua Xiaoliang , Ge Shengdong , Zhang Li , Jiang Qing , Chen Juan , Xiao Haibing , Liang Chaozhao
Published: April 2024

Emerging evidence has highlighted that dysregulation of lipid metabolism in clear cell renal cell carcinoma (ccRCC) is associated with tumor development and progression. HIF-2α plays an oncogenic role in ccRCC and is involved in abnormal lipid accumulation. However, the underlying mechanisms between these two phenomena remain unknown. Here, MED15 was demonstrated to be a dominant factor for HIF-2α-dependent lipid accumulation and tumor progression. HIF-2α promoted MED15 transcriptional activation by directly binding the MED15 promoter region, and MED15 overexpression significantly alleviated the lipid deposition inhibition and malignant tumor behavior phenotypes induced by HIF-2α knockdown. MED15 was upregulated in ccRCC and predicted poor prognosis. MED15 promoted lipid deposition and tumor progression in ccRCC. Mechanistic investigations demonstrated that MED15 acts as SREBP coactivator directly interacting with SREBPs to promote SREBP-dependent lipid biosynthesis enzyme expression, and promotes SREBP1 and SREBP2 activation through the PLK1/AKT axis. Overall, we describe a molecular regulatory network that links MED15 to lipid metabolism induced by the SREBP pathway and the classic HIF-2α pathway in ccRCC. Efforts to target MED15 or inhibit MED15 binding to SREBPs as a novel therapeutic strategy for ccRCC may be warranted.
METTL14 promotes neuroblastoma formation by inhibiting YWHAH via an m6A-YTHDF1-dependent mechanism
Authors: Wang Jianwei , Yin Hongli , Li Gen , Wu Di , Xu Yunyun , Chen Yanling , Wang Xiaodong , Xing Yujiao , Zhang Ting , Fei Danhong , Yang Pengcheng , Fang Fang , Tao Yanfang , Li Xiaolu , Yu Juanjuan , Yang Yang , Li Zhiheng , Shi Lei , Zhang Zimu , Pan Jian
Published: April 2024

Neuroblastoma (NB) is a common childhood tumor with a high incidence worldwide. The regulatory role of RNA N6-methyladenosine (m6A) in gene expression has attracted significant attention, and the impact of methyltransferase-like 14 (METTL14) on tumor progression has been extensively studied in various types of cancer. However, the specific influence of METTL14 on NB remains unexplored. Using data from the Target database, our study revealed significant upregulation of METTL14 expression in high-risk NB patients, with strong correlation with poor prognosis. Furthermore, we identified ETS1 and YY1 as upstream regulators that control the expression of METTL14. In vitro experiments involving the knockdown of METTL14 in NB cells demonstrated significant inhibition of cell proliferation, migration, and invasion. In addition, suppressing METTL14 inhibited NB tumorigenesis in nude mouse models. Through MeRIP-seq and RNA-seq analyses, we further discovered that YWHAH is a downstream target gene of METTL14. Mechanistically, we observed that methylated YWHAH transcripts, particularly those in the 5′ UTR, were specifically recognized by the m6A “reader” protein YTHDF1, leading to the degradation of YWHAH mRNA. Moreover, the downregulation of YWHAH expression activated the PI3K/AKT signaling pathway, promoting NB cell activity. Overall, our study provides valuable insights into the oncogenic effects of METTL14 in NB cells, highlighting its role in inhibiting YWHAH expression through an m6A-YTHDF1-dependent mechanism. These findings also suggest the potential utility of a biomarker panel for prognostic prediction in NB patients.
Tspan protein family: focusing on the occurrence, progression, and treatment of cancer
Authors: Zhang Huhu , Song Qinghang , Shang Kaiwen , Li Ya , Jiang Liangqian , Yang Lina
Published: April 2024

The Tetraspanins (Tspan) protein family, also known as the tetraspanin family, contains 33 family members that interact with other protein molecules such as integrins, adhesion molecules, and T cell receptors by forming dimers or heterodimers. The Tspan protein family regulates cell proliferation, cell cycle, invasion, migration, apoptosis, autophagy, tissue differentiation, and immune response. More and more studies have shown that Tspan proteins are involved in tumorigenesis, epithelial-mesenchymal transition, thrombosis, tumor stem cell, and exosome signaling. Some drugs and microRNAs can inhibit Tspan proteins, thus providing new strategies for tumor therapy. An in-depth understanding of the functions and regulatory mechanisms of the Tspan protein family, which can promote or inhibit tumor development, will provide new strategies for targeted interventions in the future.
Neural étendue expander for ultra-wide-angle high-fidelity holographic display
Authors: Tseng Ethan , Kuo Grace , Baek Seung-Hwan , Matsuda Nathan , Maimone Andrew , Schiffers Florian , Chakravarthula Praneeth , Fu Qiang , Heidrich Wolfgang , Lanman Douglas , Heide Felix
Published: April 2024

Holographic displays can generate light fields by dynamically modulating the wavefront of a coherent beam of light using a spatial light modulator, promising rich virtual and augmented reality applications. However, the limited spatial resolution of existing dynamic spatial light modulators imposes a tight bound on the diffraction angle. As a result, modern holographic displays possess low étendue, which is the product of the display area and the maximum solid angle of diffracted light. The low étendue forces a sacrifice of either the field-of-view (FOV) or the display size. In this work, we lift this limitation by presenting neural étendue expanders. This new breed of optical elements, which is learned from a natural image dataset, enables higher diffraction angles for ultra-wide FOV while maintaining both a compact form factor and the fidelity of displayed contents to human viewers. With neural étendue expanders, we experimentally achieve 64 × étendue expansion of natural images in full color, expanding the FOV by an order of magnitude horizontally and vertically, with high-fidelity reconstruction quality (measured in PSNR) over 29 dB on retinal-resolution images.
hoxc12/c13 as key regulators for rebooting the developmental program in Xenopus limb regeneration
Authors: Kawasumi-Kita Aiko , Lee Sang-Woo , Ohtsuka Daisuke , Niimi Kaori , Asakura Yoshifumi , Kitajima Keiichi , Sakane Yuto , Tamura Koji , Ochi Haruki , Suzuki Ken-ichi T. , Morishita Yoshihiro
Published: April 2024

During organ regeneration, after the initial responses to injury, gene expression patterns similar to those in normal development are reestablished during subsequent morphogenesis phases. This supports the idea that regeneration recapitulates development and predicts the existence of genes that reboot the developmental program after the initial responses. However, such rebooting mechanisms are largely unknown. Here, we explore core rebooting factors that operate during Xenopus limb regeneration. Transcriptomic analysis of larval limb blastema reveals that hoxc12/c13 show the highest regeneration specificity in expression. Knocking out each of them through genome editing inhibits cell proliferation and expression of a group of genes that are essential for development, resulting in autopod regeneration failure, while limb development and initial blastema formation are not affected. Furthermore, the induction of hoxc12/c13 expression partially restores froglet regenerative capacity which is normally very limited compared to larval regeneration. Thus, we demonstrate the existence of genes that have a profound impact alone on rebooting of the developmental program in a regeneration-specific manner.
Multi-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease
Authors: Drury Ruth E. , Camara Susana , Chelysheva Irina , Bibi Sagida , Sanders Katherine , Felle Salle , Emary Katherine , Phillips Daniel , Voysey Merryn , Ferreira Daniela M. , Klenerman Paul , Gilbert Sarah C. , Lambe Teresa , Pollard Andrew J. , O’Connor Daniel
Published: April 2024

The immune mechanisms mediating COVID-19 vaccine attenuation of COVID-19 remain undescribed. We conducted comprehensive analyses detailing immune responses to SARS-CoV-2 virus in blood post-vaccination with ChAdOx1 nCoV-19 or a placebo. Samples from randomised placebo-controlled trials (NCT04324606 and NCT04400838) were taken at baseline, onset of COVID-19-like symptoms, and 7 days later, confirming COVID-19 using nucleic amplification test (NAAT test) via real-time PCR (RT-PCR). Serum cytokines were measured with multiplexed immunoassays. The transcriptome was analysed with long, short and small RNA sequencing. We found attenuation of RNA inflammatory signatures in ChAdOx1 nCoV-19 compared with placebo vaccinees and reduced levels of serum proteins associated with COVID-19 severity. KREMEN1, a putative alternative SARS-CoV-2 receptor, was downregulated in placebo compared with ChAdOx1 nCoV-19 vaccinees. Vaccination ameliorates reductions in cell counts across leukocyte populations and platelets noted at COVID-19 onset, without inducing potentially deleterious Th2-skewed immune responses. Multi-omics integration links a global reduction in miRNA expression at COVID-19 onset to increased pro-inflammatory responses at the mRNA level. This study reveals insights into the role of COVID-19 vaccines in mitigating disease severity by abrogating pro-inflammatory responses associated with severe COVID-19, affirming vaccine-mediated benefit in breakthrough infection, and highlighting the importance of clinically relevant endpoints in vaccine evaluation.
Prospective de novo drug design with deep interactome learning
Authors: Atz Kenneth , Cotos Leandro , Isert Clemens , Håkansson Maria , Focht Dorota , Hilleke Mattis , Nippa David F. , Iff Michael , Ledergerber Jann , Schiebroek Carl C. G. , Romeo Valentina , Hiss Jan A. , Merk Daniel , Schneider Petra , Kuhn Bernd , Grether Uwe , Schneider Gisbert
Published: April 2024

De novo drug design aims to generate molecules from scratch that possess specific chemical and pharmacological properties. We present a computational approach utilizing interactome-based deep learning for ligand- and structure-based generation of drug-like molecules. This method capitalizes on the unique strengths of both graph neural networks and chemical language models, offering an alternative to the need for application-specific reinforcement, transfer, or few-shot learning. It enables the “zero-shot" construction of compound libraries tailored to possess specific bioactivity, synthesizability, and structural novelty. In order to proactively evaluate the deep interactome learning framework for protein structure-based drug design, potential new ligands targeting the binding site of the human peroxisome proliferator-activated receptor (PPAR) subtype gamma are generated. The top-ranking designs are chemically synthesized and computationally, biophysically, and biochemically characterized. Potent PPAR partial agonists are identified, demonstrating favorable activity and the desired selectivity profiles for both nuclear receptors and off-target interactions. Crystal structure determination of the ligand-receptor complex confirms the anticipated binding mode. This successful outcome positively advocates interactome-based de novo design for application in bioorganic and medicinal chemistry, enabling the creation of innovative bioactive molecules.
Double cross-linked 3D layered PBI proton exchange membranes for stable fuel cell performance above 200 °C
Authors: Zhang Liang , Liu Mengjiao , Zhu Danyi , Tang Mingyuan , Zhu Taizhong , Gao Congjie , Huang Fei , Xue Lixin
Published: April 2024

Phosphoric acid doped proton exchange membranes often experience performance degradation above 200 °C due to membrane creeping and phosphoric acid evaporation, migration, dehydration, and condensation. To address these issues, here we present gel-state polybenzimidazole membranes with double cross-linked three-dimensional layered structures via a polyphosphoric acid sol-gel process, enabling stable operation above 200 °C. These membranes, featuring proton-conducting cross-linking phosphate bridges and branched polybenzimidazole networks, effectively anchor and retain phosphoric acid molecules, prevent 96% of its dehydration and condensation, improve creep resistance, and maintain excellent proton conductivity stability. The resulting membrane, with superior through-plane proton conductivity of 0.348 S cm−1, delivers outstanding peak power densities ranging from 1.20–1.48 W cm−2 in fuel cells operated at 200-240 °C and a low voltage decay rate of only 0.27 mV h−1 over a 250-hour period at 220 °C, opening up possibilities for their direct integration with methanol steam reforming systems.
Catalytic role of in-situ formed C-N species for enhanced Li2CO3 decomposition
Authors: Zhang Fangli , Zhang Wenchao , Yuwono Jodie A. , Wexler David , Fan Yameng , Zou Jinshuo , Liang Gemeng , Sun Liang , Guo Zaiping
Published: April 2024

Sluggish kinetics of the CO2 reduction/evolution reactions lead to the accumulation of Li2CO3 residuals and thus possible catalyst deactivation, which hinders the long-term cycling stability of Li-CO2 batteries. Apart from catalyst design, constructing a fluorinated solid-electrolyte interphase is a conventional strategy to minimize parasitic reactions and prolong cycle life. However, the catalytic effects of solid-electrolyte interphase components have been overlooked and remain unclear. Herein, we systematically regulate the compositions of solid-electrolyte interphase via tuning electrolyte solvation structures, anion coordination, and binding free energy between Li ion and anion. The cells exhibit distinct improvement in cycling performance with increasing content of C-N species in solid-electrolyte interphase layers. The enhancement originates from a catalytic effect towards accelerating the Li2CO3 formation/decomposition kinetics. Theoretical analysis reveals that C-N species provide strong adsorption sites and promote charge transfer from interface to *CO22− during discharge, and from Li2CO3 to C-N species during charge, thereby building a bidirectional fast-reacting bridge for CO2 reduction/evolution reactions. This finding enables us to design a C-N rich solid-electrolyte interphase via dual-salt electrolytes, improving cycle life of Li-CO2 batteries to twice that using traditional electrolytes. Our work provides an insight into interfacial design by tuning of catalytic properties towards CO2 reduction/evolution reactions.
Phosphorylation of the F-BAR protein Hof1 drives septin ring splitting in budding yeast
Authors: Varela Salgado Maritzaida , Adriaans Ingrid E. , Touati Sandra A. , Ibanes Sandy , Lai-Kee-Him Joséphine , Ancelin Aurélie , Cipelletti Luca , Picas Laura , Piatti Simonetta
Published: April 2024

A double septin ring accompanies cytokinesis in yeasts and mammalian cells. In budding yeast, reorganisation of the septin collar at the bud neck into a dynamic double ring is essential for actomyosin ring constriction and cytokinesis. Septin reorganisation requires the Mitotic Exit Network (MEN), a kinase cascade essential for cytokinesis. However, the effectors of MEN in this process are unknown. Here we identify the F-BAR protein Hof1 as a critical target of MEN in septin remodelling. Phospho-mimicking HOF1 mutant alleles overcome the inability of MEN mutants to undergo septin reorganisation by decreasing Hof1 binding to septins and facilitating its translocation to the actomyosin ring. Hof1-mediated septin rearrangement requires its F-BAR domain, suggesting that it may involve a local membrane remodelling that leads to septin reorganisation. In vitro Hof1 can induce the formation of intertwined septin bundles, while a phosphomimetic Hof1 protein has impaired septin-bundling activity. Altogether, our data indicate that Hof1 modulates septin architecture in distinct ways depending on its phosphorylation status.
Highly efficient anion exchange membrane water electrolyzers via chromium-doped amorphous electrocatalysts
Authors: Li Sicheng , Liu Tong , Zhang Wei , Wang Mingzhen , Zhang Huijuan , Qin Chunlan , Zhang Lingling , Chen Yudan , Jiang Shuaiwei , Liu Dong , Liu Xiaokang , Wang Huijuan , Luo Qiquan , Ding Tao , Yao Tao
Published: April 2024

In-depth comprehension and modulation of the electronic structure of the active metal sites is crucial to enhance their intrinsic activity of electrocatalytic oxygen evolution reaction (OER) toward anion exchange membrane water electrolyzers (AEMWEs). Here, we elaborate a series of amorphous metal oxide catalysts (FeCrOx, CoCrOx and NiCrOx) with high performance AEMWEs by high-valent chromium dopant. We discover that the positive effect of the transition from low to high valence of the Co site on the adsorption energy of the intermediate and the lower oxidation barrier is the key factor for its increased activity by synchrotron radiation in-situ techniques. Particularly, the CoCrOx anode catalyst achieves the high current density of 1.5 A cm−2 at 2.1 V and maintains for over 120 h with attenuation less than 4.9 mV h−1 in AEMWE testing. Such exceptional performance demonstrates a promising prospect for industrial application and providing general guidelines for the design of high-efficiency AEMWEs systems.
Selective lipid recruitment by an archaeal DPANN symbiont from its host
Authors: Ding Su , Hamm Joshua N. , Bale Nicole J. , Sinninghe Damsté Jaap S. , Spang Anja
Published: April 2024

The symbiont Ca. Nanohaloarchaeum antarcticus is obligately dependent on its host Halorubrum lacusprofundi for lipids and other metabolites due to its lack of certain biosynthetic genes. However, it remains unclear which specific lipids or metabolites are acquired from its host, and how the host responds to infection. Here, we explored the lipidome dynamics of the Ca. Nha. antarcticus – Hrr. lacusprofundi symbiotic relationship during co-cultivation. By using a comprehensive untargeted lipidomic methodology, our study reveals that Ca. Nha. antarcticus selectively recruits 110 lipid species from its host, i.e., nearly two-thirds of the total number of host lipids. Lipid profiles of co-cultures displayed shifts in abundances of bacterioruberins and menaquinones and changes in degree of bilayer-forming glycerolipid unsaturation. This likely results in increased membrane fluidity and improved resistance to membrane disruptions, consistent with compensation for higher metabolic load and mechanical stress on host membranes when in contact with Ca. Nha. antarcticus cells. Notably, our findings differ from previous observations of other DPANN symbiont-host systems, where no differences in lipidome composition were reported. Altogether, our work emphasizes the strength of employing untargeted lipidomics approaches to provide details into the dynamics underlying a DPANN symbiont-host system.
Clinical associations with a polygenic predisposition to benign lower white blood cell counts
Authors: Mosley Jonathan D. , Shelley John P. , Dickson Alyson L. , Zanussi Jacy , Daniel Laura L. , Zheng Neil S. , Bastarache Lisa , Wei Wei-Qi , Shi Mingjian , Jarvik Gail P. , Rosenthal Elisabeth A. , Khan Atlas , Sherafati Alborz , Kullo Iftikhar J. , Walunas Theresa L. , Glessner Joseph , Hakonarson Hakon , Cox Nancy J. , Roden Dan M. , Frangakis Stephan G. , Vanderwerff Brett , Stein C. Michael , Van Driest Sara L. , Borinstein Scott C. , Shu Xiao-Ou , Zawistowski Matthew , Chung Cecilia P. , Kawai Vivian K.
Published: April 2024

Polygenic variation unrelated to disease contributes to interindividual variation in baseline white blood cell (WBC) counts, but its clinical significance is uncharacterized. We investigated the clinical consequences of a genetic predisposition toward lower WBC counts among 89,559 biobank participants from tertiary care centers using a polygenic score for WBC count (PGSWBC) comprising single nucleotide polymorphisms not associated with disease. A predisposition to lower WBC counts was associated with a decreased risk of identifying pathology on a bone marrow biopsy performed for a low WBC count (odds-ratio = 0.55 per standard deviation increase in PGSWBC [95%CI, 0.30−0.94], p = 0.04), an increased risk of leukopenia (a low WBC count) when treated with a chemotherapeutic (n = 1724, hazard ratio [HR] = 0.78 [0.69−0.88], p = 4.0 × 10−5) or immunosuppressant (n = 354, HR = 0.61 [0.38–0.99], p = 0.04). A predisposition to benign lower WBC counts was associated with an increased risk of discontinuing azathioprine treatment (n = 1,466, HR = 0.62 [0.44−0.87], p = 0.006). Collectively, these findings suggest that there are genetically predisposed individuals who are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit.
An approach to identify gene-environment interactions and reveal new biological insight in complex traits
Authors: Zhu Xiaofeng , Yang Yihe , Lorincz-Comi Noah , Li Gen , Bentley Amy R. , de Vries Paul S. , Brown Michael , Morrison Alanna C. , Rotimi Charles N. , Gauderman W. James , Rao Dabeeru C. , Aschard Hugues ,   the CHARGE Gene-lifestyle Interactions Working Group
Published: April 2024

There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. To address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework. We identify and confirm 5 loci (6 independent signals) interacted with either cigarette smoking or alcohol consumption for serum lipids, and empirically demonstrate that interaction and mediation are the major contributors to genetic effect size heterogeneity across populations. The estimated lower bound of the interaction and environmentally mediated heritability is significant (P < 0.02) for low-density lipoprotein cholesterol and triglycerides in Cross-Population data. Our study improves the understanding of the genetic architecture and environmental contributions to complex traits.
An organic proton cage that is ultra-resistant to hydroxide-promoted degradation
Authors: Radford Chase L. , Saatkamp Torben , Bennet Andrew J. , Holdcroft Steven
Published: April 2024

Alkaline polymer membrane electrochemical energy conversion devices offer the prospect of using non-platinum group catalysts. However, their cationic functionalities are currently not sufficiently stable for vapor-phase applications, such as fuel cells. Herein, we report 1,6-diazabicyclo[4.4.4]tetradecan-1,6-ium (in-DBD), a cationic proton cage, that is orders of magnitude more resistant to hydroxide-promoted degradation than state-of-the-art organic cations under ultra-dry conditions and elevated temperature, and the first organic cation-hydroxide to persist at critically low hydration levels ( < 10% RH at 80 °C). This high stability against hydroxide-promoted degradation is due to the unique combination of endohedral protection and intra-bridgehead hydrogen bonding that prevents the removal of the inter-cavity proton and lowers the susceptibility to Hofmann elimination. We anticipate this discovery will facilitate a step-change in the advancement of materials and electrochemical devices utilizing anion-exchange membranes based on in-DBD that will enable stable operation under extreme alkaline conditions.
High-throughput approach to explore cold metals for electronic and thermoelectric devices
Authors: Zhang Ligong , Liu Fei
Published: April 2024

Cold metals with an energy gap around the Fermi level have been shown a great potential for reducing the power dissipation of transistors and diodes. However, only a limited number of 2D cold metals have been studied. In this work, we explored 3D cold metals through a systematic material search and found 252 types in the database. We performed first-principles calculations to investigate the conductance and work functions of 30 cold metals for material selection. Additionally, we studied the thermoelectric properties of four typical cold metals, which possess much larger Seebeck coefficients and figure-of-merits than conventional metals, by one and two orders of magnitude, respectively. Specifically, we constructed a monolayer MoS2transistor with a cold metal contact of ZrRuSb. Our quantum transport simulations indicate that cold metal contacted MoS2FETs exhibit a subthreshold swing smaller than 60 mV decade−1over four decades, and on-state currents over 1 mA μm−1are achieved at a supply voltage of 0.5 V. Our research provides a theoretical foundation and material basis for exploring 3D cold metals in developing electronic and thermoelectric devices.