bluuebunny/crossref_metadata_2025 huggingface dataset:
An analytic model for the flow induced in syringomyelia cavities
Authors: Nozaleda G.L. , Alaminos-Quesada J. , Coenen W. , Haughton V. , Sánchez A.L.
Published: January 2024

A simple two-dimensional fluid–structure interaction problem, involving viscous oscillatory flow in a channel separated by an elastic membrane from a fluid-filled slender cavity, is analysed to shed light on the flow dynamics pertaining to syringomyelia, a neurological disorder characterized by the appearance of a large tubular cavity (syrinx) within the spinal cord. The focus is on configurations in which the velocity induced in the cavity, representing the syrinx, is comparable to that found in the channel, representing the subarachnoid space surrounding the spinal cord, both flows being coupled through a linear elastic equation describing the membrane deformation. An asymptotic analysis for small stroke lengths leads to closed-form expressions for the leading-order oscillatory flow, and also for the stationary flow associated with the first-order corrections, the latter involving a steady distribution of transmembrane pressure. The magnitude of the induced flow is found to depend strongly on the frequency, with the result that for channel flow rates of non-sinusoidal waveform, as those found in the spinal canal, higher harmonics can dominate the sloshing motion in the cavity, in agreement with previous in vivo observations. Under some conditions, the cycle-averaged transmembrane pressure, also showing a marked dependence on the frequency, changes sign on increasing the cavity transverse dimension (i.e. orthogonal to the cord axis), underscoring the importance of cavity size in connection with the underlying hydrodynamics. The analytic results presented here can be instrumental in guiding future numerical investigations, needed to clarify the pathogenesis of syringomyelia cavities.
Adjoint-based linear sensitivity of a supersonic boundary layer to steady wall blowing–suction/heating–cooling
Authors: Poulain Arthur , Content Cédric , Rigas Georgios , Garnier Eric , Sipp Denis
Published: January 2024

For a Mach$4.5$flat-plate adiabatic boundary layer, we study the sensitivity of the first, second Mack modes and streaks to steady wall-normal blowing/suction and wall heat flux. The global instabilities are characterised in frequency space with resolvent gains and their gradients with respect to wall-boundary conditions are derived through a Lagrangian-based method. The implementation is performed in the open-source high-order finite-volume code BROADCAST and algorithmic differentiation is used to access the high-order state derivatives of the discretised governing equations. For the second Mack mode, the resolvent optimal gain decreases when suction is applied upstream of Fedorov's mode$S$/mode$F$synchronisation point, leading to stabilisation, and the converse when applied downstream. The largest suction gradient is in the region of branch I of mode$S$neutral curve. For heat-flux control, strong heating at the leading edge stabilises both the first and second Mack modes, the former being more sensitive to wall-temperature control. Streaks are less sensitive to any boundary control in comparison with the Mack modes. Eventually, we show that an optimal actuator consisting of a single steady heating strip located close to the leading edge manages to damp the linear growth of all three instability mechanisms.
Expanding the Scope of Institutional Logics Research
Authors: Lounsbury Michael , Wang Milo Shaoqing
Published: January 2024

The institutional logics perspective provides a powerful theory that emphasizes how symbolic beliefs and material practices are intertwined in relatively enduring configurations that can profoundly shape behavior across space and time. In this article, we build upon the arguments and insights of Haveman, Joseph-Goteiner, and Li, suggesting the need for a broader research agenda on the dynamics of institutional logics in China and around the world. Building on some of our recent writings, we argue for the need to go beyond the study of how logics have effects, to understand how logics themselves cohere, endure, and co-evolve in dynamic interrelationships with other logics.
Bradykinin actions in the central nervous system: historical overview and psychiatric implications
Authors: Graeff Frederico Guilherme , Joca Sâmia , Zangrossi Helio
Published: January 2024

Bradykinin (BK), a well-studied mediator of physiological and pathological processes in the peripheral system, has garnered less attention regarding its function in the central nervous system, particularly in behavioural regulation. This review delves into the historical progression of research focused on the behavioural effects of BK and other drugs that act via similar mechanisms to provide new insights into the pathophysiology and pharmacotherapy of psychiatric disorders. Evidence from experiments with animal models indicates that BK modulates defensive reactions associated with panic symptoms and the response to acute stressors. The mechanisms are not entirely understood but point to complex interactions with other neurotransmitter systems, such as opioids, and intracellular signalling cascades. By addressing the existing research gaps in this field, we present new proposals for future research endeavours to foster a new era of investigation regarding BK’s role in emotional regulation. Implications for psychiatry, chiefly for panic and depressive disorders are also discussed.
Voltage-gated sodium channel gene mutation and P450 gene expression are associated with the resistance of Aphis spiraecola Patch (Hemiptera: Aphididae) to lambda-cyhalothrin
Authors: Tang Hong-cheng , Zhou Yu-rong , Zuo Jun-feng , Wang Yi-xuan , Piñero Jaime C. , Peng Xiong , Chen Mao-hua
Published: January 2024

Aphis spiraecola Patch is one of the most economically important tree fruit pests worldwide. The pyrethroid insecticide lambda-cyhalothrin is commonly used to control A. spiraecola. In this 2-year study, we quantified the resistance level of A. spiraecola to lambda-cyhalothrin in different regions of the Shaanxi province, China. The results showed that A. spiraecola had reached extremely high resistance levels with a 174-fold resistance ratio (RR) found in the Xunyi region. In addition, we compared the enzymatic activity and expression level of P450 genes among eight A. spiraecola populations. The P450 activity of A. spiraecola was significantly increased in five regions (Xunyi, Liquan, Fengxiang, Luochuan, and Xinping) compared to susceptible strain (SS). The expression levels of CYP6CY7, CYP6CY14, CYP6CY22, P4504C1-like, P4506a13, CYP4CZ1, CYP380C47, and CYP4CJ2 genes were significantly increased under lambda-cyhalothrin treatment and in the resistant field populations. A L1014F mutation in the sodium channel gene was found and the mutation rate was positively correlated with the LC50 of lambda-cyhalothrin. In conclusion, the levels of lambda-cyhalothrin resistance of A. spiraecola field populations were associated with P450s and L1014F mutations. Our combined findings provide evidence on the resistance mechanism of A. spiraecola to lambda-cyhalothrin and give a theoretical basis for rational and effective control of this pest species.
Exploring trauma exposure and post-traumatic stress in university students of different identity statuses in Lithuania and Japan
Authors: Truskauskaite Inga , Sugimura Kazumi , Abe Kazuaki , Hihara Shogo , Haramaki Yutaka , Jovarauskaite Lina , Kamite Yuka , Kazlauskas Evaldas
Published: January 2024

Emerging adulthood is the time when identity questions are addressed. It is also a time of excessive stress and risk for mental health problems. Different identity statuses relate to different mental health outcomes. Yet, little research has addressed how identity status is interlinked with trauma exposure and post-traumatic stress reactions, especially in multicultural contexts. The current study aimed to explore whether different traumatic experiences are related to the current identity status of university students aged between 18 and 29 years and investigate to what extent trauma-exposed emerging adults of different identity statuses report symptoms of post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD). In total, 2237 university students from Lithuania (n = 791) and Japan (n = 1345) participated in the current study. Identity profiles were revealed by using the Latent Class Analysis approach. Lithuania and Japan were comparable in terms of identity profiles and structure of PTSD/CPTSD. Trauma-exposed emerging adults reported a higher probability of being in troubled diffusion identity status; students in achievement identity status had a lower probability of CPTSD and lower rates of symptoms of disturbances in self-organization. The diffused identity of emerging adults from Lithuania and Japan is associated with trauma exposure, and positive identity is linked with fewer CPTSD reactions.
Reassessing the need for carbon dioxide removal: moral implications of alternative climate target pathways
Authors: Voget-Kleschin Lieske , Baatz Christian , Heyward Clare , Van Vuuren Detlef , Mengis Nadine
Published: January 2024

Non-technical summary

Scenarios compatible with the Paris agreement's temperature goal of 1.5 °C involve carbon dioxide removal measures – measures that actively remove CO2 from the atmosphere – on a massive scale. Such large-scale implementations raise significant ethical problems. Van Vuuren et al. (2018), as well as the current IPCC scenarios, show that reduction in energy and or food demand could reduce the need for such activities. There is some reluctance to discuss such societal changes. However, we argue that policy measures enabling societal changes are not necessarily ethically problematic. Therefore, they should be discussed alongside techno-optimistic approaches in any kind of discussions about how to respond to climate change.

Technical summary

The 1.5 °C goal has given impetus to carbon dioxide removal (CDR) measures, such as bioenergy combined with carbon capture and storage, or afforestation. However, land-based CDR options compete with food production and biodiversity protection. Van Vuuren et al. (2018) looked at alternative pathways including lifestyle changes, low-population projections, or non-CO2 greenhouse gas mitigation, to reach the 1.5 °C temperature objective. Underlined by the recently published IPCC AR6 WGIII report, they show that demand-side management measures are likely to reduce the need for CDR. Yet, policy measures entailed in these scenarios could be associated with ethical problems themselves. In this paper, we therefore investigate ethical implications of four alternative pathways as proposed by Van Vuuren et al. (2018). We find that emission reduction options such as lifestyle changes and reducing population, which are typically perceived as ethically problematic, might be less so on further inspection. In contrast, options associated with less societal transformation and more techno-optimistic approaches turn out to be in need of further scrutiny. The vast majority of emission reduction options considered are not intrinsically ethically problematic; rather everything rests on the precise implementation. Explicitly addressing ethical considerations when developing, advancing, and using integrated assessment scenarios could reignite debates about previously overlooked topics and thereby support necessary societal discourse.

Social media summary

Policy measures enabling societal changes are not necessarily as ethically problematic as commonly presumed and reduce the need for large-scale CDR.
Spatial Patterns of Vegetation Activity Related to ENSO in Northern South America
Authors: Estupinan‐Suarez Lina M. , Mahecha Miguel D. , Brenning Alexander , Kraemer Guido , Poveda Germán , Reichstein Markus , Sierra Carlos A.
Published: January 2024

Interannual variability of vegetation activity (i.e., photosynthesis) is strongly correlated with El Niño Southern Oscillation (ENSO). Globally, a reduction in carbon uptake by terrestrial ecosystems has been observed during the ENSO warm phase (El Niño) and the opposite during the cold phase (La Niña). However, this global perspective obscures the heterogeneous impacts of ENSO at regional scales. Particularly, ENSO has contrasting impacts on climate in northern South America (NSA) depending on the ENSO phase and geographical location, which in turn affect the activity of vegetation. Furthermore, changes of vegetation activity during multiple ENSO events are not well understood yet. In this study, we investigated the spatial and temporal differences in vegetation activity associated with ENSO variability and its three phases (El Niño, La Niña, Neutral) to identify hotspots of ENSO impacts in NSA, a region dominated by rainforest and savannas. To achieve this, we investigated time series of vegetation variables from 2001 to 2014 at moderate spatial resolution (0.0083°). Data were aggregated through dimensionality reduction analysis (i.e., Global Principal Component Analysis). The leading principal component served as a proxy of vegetation activity (VAC). We calculated the cross‐correlation between VAC and the multivariate ENSO index separately for each ENSO phase. Our results show that El Niño phase has a stronger impact on vegetation activity both in intensity and duration than La Niña phase. Moreover, seasonally dry ecoregions were more susceptible to El Niño impacts on vegetation activity. Understanding these differences is key for regional adaptation and differentiated management of ecosystems.
Helicity: A Possible Indicator of Negative Feedback Initiation of Tropical Cyclone–Ocean Interaction
Authors: Munsi A. , Kesarkar A. P. , Bhate J. N. , Tallapragada V. S.
Published: January 2024

The development of large‐scale vortex dynamo during tropical cyclogenesis through the mutual intensification of primary and secondary circulation in terms of helical evolution is well studied. However, the influence of atmospheric helicity on ocean surface heat and moisture fluxes associated with tropical cyclone (TC) evolution is yet to be understood. At its development stage, the heat and moisture flux from the ocean surface increases with the increase in intensity of the TC. This time, TC‐Ocean interaction works in a positive feedback mechanism. However, after a particular stage, the very intense wind of the TC causes strong turbulent mixing in the underlying ocean. Hence, the upper ocean layer temperature starts decreasing, leading to a decrease in heat and moisture flux exchange to the TC. We have analyzed the emergence of vortex helical structure in TC and the role of helicity in modulating surface heat and moisture fluxes. The result shows that helical development is associated with the axisymetrization of the vertical velocity and diabatic heating at the middle and upper troposphere. There is no definite TC intensity at which the initiation of negative feedback of TC‐upper ocean interaction occurs. However, the increase in helicity above 200 × 10−2 ms−2 reversed the TC‐ocean interaction trend. Therefore, TC helicity evolution and upper ocean interaction are essential to understand TC evolution.
Impact of Uncertainties in Land Surface Processes on Subseasonal Predictability of Heat Waves Onset Over the Yangtze River Valley
Authors: Zhang Qiyu , Sun Guodong , Dai Guokun , Mu Mu
Published: January 2024

Land surface processes are strongly associated with heat waves (HWs). However, how the uncertainties in land surface processes owing to inaccurate physical parameters influence subseasonal HW predictions has rarely been explored. To examine the impact of parameter errors of land surface processes on the uncertainty of subseasonal HW predictions, five strong and long‐lasting HW events over the middle and lower reaches of the Yangtze River are investigated. Based on the Weather Research and Forecasting model, the conditional nonlinear optimal perturbation related to parameters (CNOP‐P) approach is employed to address the aforementioned issues. Numerical results demonstrate that the CNOP‐P type errors of physical parameters cause large prediction errors for five HW event onsets. Two types of CNOP‐Ps are obtained for HW events, called the type‐1 CNOP‐P and the type‐2 CNOP‐P. The type‐1 (type‐2) CNOP‐P causes an approximately 3°C (2°C) warm (cold) bias during the HW period. Surface sensible and latent heat flux errors, especially flux exchange between vegetation canopy and canopy air, provide considerable uncertainty in subseasonal HW predictions. The type‐1 (type‐2) CNOP‐P exhibits an underestimation (overestimation) of transpiration. Furthermore, it should be noted that the type‐1 CNOP‐P results in a substantial difference in soil moisture, a phenomenon that is demonstrated to be challenging to observe in the type‐2 CNOP‐P. The results indicate that understanding vegetation‐atmosphere dynamics is crucial for improving subseasonal HW predictions. Jointly lowering soil‒atmosphere and vegetation‐atmosphere uncertainty can notably improve subseasonal HW prediction skills.
Future Change in Urban Flooding Using New Convection‐Permitting Climate Projections
Authors: Archer L. , Hatchard S. , Devitt L. , Neal J. C. , Coxon G. , Bates P. D. , Kendon E. J. , Savage J.
Published: January 2024

Rainfall intensity in the United Kingdom is projected to increase under climate change with significant implications for rainfall‐driven (combined pluvial and fluvial) flooding. In the UK, the current recommended best practice for estimating changes in pluvial flood hazard under climate change involves applying a simple percentage uplift to spatially uniform catchment rainfall, despite the known importance of the spatial and temporal characteristics of rainfall in the generation of pluvial floods. The UKCP Local Convective Permitting Model (CPM) has for the first time provided the capacity to assess changes in flood hazard using hourly, 2.2 km CPM precipitation data that varies in space and time. Here, we use an event set of ∼13,500 precipitation events across the three UKCP Local epochs (1981–2000, 2021–2040, and 2061–2080) to simulate rainfall‐driven flooding using the LISFLOOD‐FP hydrodynamic model at 20 m resolution over a 750 km2 area of Bristol and Bath, UK. We find that both the event set and uplift approaches indicate an increase in flood hazard under near‐term (2021–2040) and future (2061–2080) climate change. However, the event set produces markedly higher estimates of flood hazard when compared to the uplift approach, ranging from 19% to 49% higher depending on the return period. This suggests including the full spatiotemporal rainfall variability and its future change in rainfall‐driven flood modeling is critical for future flood risk assessment.
Costa Rican Faults Quiver in Response to Distant Earthquakes
Authors: Dohrn Gillian
Published: January 2024

Scientists found flurries of seismic activity within weak fault zones in Costa Rica after two giant ruptures elsewhere.
Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability
Authors: Rosier Bob T. , Johnston William , Carda-Diéguez Miguel , Simpson Annabel , Cabello-Yeves Elena , Piela Krystyna , Reilly Robert , Artacho Alejandro , Easton Chris , Burleigh Mia , Culshaw Shauna , Mira Alex
Published: January 2024

The reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity (NRC) and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitrate-reducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals (P < 0.05 in all five datasets with n = 20–82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate (a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15 healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment (P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria (P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.
Ultra-simplified diffraction-based computational spectrometer
Authors: Chen Chuangchuang , Gu Honggang , Liu Shiyuan
Published: January 2024

Miniaturizing spectrometers for compact and cost-effective mobile platforms is a major challenge in current spectroscopy research, where conventional spectrometers are impractical due to their bulky footprint. Existing miniaturized designs primarily rely on precalibrated response functions of nanophotonic structures to encode spectral information captured in a snapshot by detector arrays. Accurate spectrum reconstruction is achieved through computational techniques, but this requires precise component design, high-precision fabrication, and calibration. We propose an ultra-simplified computational spectrometer that employs a one-to-broadband diffraction decomposition strategy facilitated by a numerical regularized transform that depends only on the spectrum of the diffracted radiation. The key feature of our design is the use of a simple, arbitrarily shaped pinhole as the partial disperser, eliminating the need for complex encoding designs and full spectrum calibration. Our spectrometer achieves a reconstructed spectral peak location accuracy of better than 1 nm over a 200 nm bandwidth and excellent resolution for peaks separated by 3 nm in a bimodal spectrum, all within a compact footprint of under half an inch. Notably, our approach also reveals a breakthrough in broadband coherent diffractive imaging without requiring any prior knowledge of the broadband illumination spectrum, assumptions of non-dispersive specimens, or correction for detector quantum efficiency.
Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization
Authors: Okada Naohiro , Yahata Noriaki , Koshiyama Daisuke , Morita Kentaro , Sawada Kingo , Kanata Sho , Fujikawa Shinya , Sugimoto Noriko , Toriyama Rie , Masaoka Mio , Koike Shinsuke , Araki Tsuyoshi , Kano Yukiko , Endo Kaori , Yamasaki Syudo , Ando Shuntaro , Nishida Atsushi , Hiraiwa-Hasegawa Mariko , Edden Richard A. E. , Sawa Akira , Kasai Kiyoto
Published: January 2024

Previous studies reported decreased glutamate levels in the anterior cingulate cortex (ACC) in non-treatment-resistant schizophrenia and first-episode psychosis. However, ACC glutamatergic changes in subjects at high-risk for psychosis, and the effects of commonly experienced environmental emotional/social stressors on glutamatergic function in adolescents remain unclear. In this study, adolescents recruited from the general population underwent proton magnetic resonance spectroscopy (MRS) of the pregenual ACC using a 3-Tesla scanner. We explored longitudinal data on the association of combined glutamate-glutamine (Glx) levels, measured by MRS, with subclinical psychotic experiences. Moreover, we investigated associations of bullying victimization, a risk factor for subclinical psychotic experiences, and help-seeking intentions, a coping strategy against stressors including bullying victimization, with Glx levels. Finally, path analyses were conducted to explore multivariate associations. For a contrast analysis, gamma-aminobutyric acid plus macromolecule (GABA+) levels were also analyzed. Negative associations were found between Glx levels and subclinical psychotic experiences at both Times 1 (n = 219, mean age 11.5 y) and 2 (n = 211, mean age 13.6 y), as well as for over-time changes (n = 157, mean interval 2.0 y). Moreover, effects of bullying victimization and bullying victimization × help-seeking intention interaction effects on Glx levels were found (n = 156). Specifically, bullying victimization decreased Glx levels, whereas help-seeking intention increased Glx levels only in bullied adolescents. Finally, associations among bullying victimization, help-seeking intention, Glx levels, and subclinical psychotic experiences were revealed. GABA+ analysis revealed no significant results. This is the first adolescent study to reveal longitudinal trajectories of the association between glutamatergic function and subclinical psychotic experiences and to elucidate the effect of commonly experienced environmental emotional/social stressors on glutamatergic function. Our findings may deepen the understanding of how environmental emotional/social stressors induce impaired glutamatergic neurotransmission that could be the underpinning of liability for psychotic experiences in early adolescence.
Inhibition of the YAP-MMB interaction and targeting NEK2 as potential therapeutic strategies for YAP-driven cancers
Authors: Jessen Marco , Gertzmann Dörthe , Liss Franziska , Zenk Franziska , Bähner Laura , Schöffler Victoria , Schulte Clemens , Maric Hans Michael , Ade Carsten P. , von Eyss Björn , Gaubatz Stefan
Published: January 2024

YAP activation in cancer is linked to poor outcomes, making it an attractive therapeutic target. Previous research focused on blocking the interaction of YAP with TEAD transcription factors. Here, we took a different approach by disrupting YAP’s binding to the transcription factor B-MYB using MY-COMP, a fragment of B-MYB containing the YAP binding domain fused to a nuclear localization signal. MY-COMP induced cell cycle defects, nuclear abnormalities, and polyploidization. In an AKT and YAP-driven liver cancer model, MY-COMP significantly reduced liver tumorigenesis, highlighting the importance of the YAP-B-MYB interaction in tumor development. MY-COMP also perturbed the cell cycle progression of YAP-dependent uveal melanoma cells but not of YAP-independent cutaneous melanoma cell lines. It counteracted YAP-dependent expression of MMB-regulated cell cycle genes, explaining the observed effects. We also identified NIMA-related kinase (NEK2) as a downstream target of YAP and B-MYB, promoting YAP-driven transformation by facilitating centrosome clustering and inhibiting multipolar mitosis.
TREM2 macrophage promotes cardiac repair in myocardial infarction by reprogramming metabolism via SLC25A53
Authors: Gong Shiyu , Zhai Ming , Shi Jiayun , Yu Guanye , Lei Zhijun , Shi Yefei , Zeng Yanxi , Ju Peinan , Yang Na , Zhang Zhuo , Zhang Donghui , Zhuang Jianhui , Yu Qing , Zhang Xumin , Jian Weixia , Wang Wei , Peng Wenhui
Published: January 2024

Efferocytosis and metabolic reprogramming of macrophages play crucial roles in myocardial infarction (MI) repair. TREM2 has been proven to participate in phagocytosis and metabolism, but how it modulates myocardial infarction remains unclear. In this study, we showed that macrophage-specific TREM2 deficiency worsened cardiac function and impaired post-MI repair. Using RNA-seq, protein and molecular docking, and Targeted Metabolomics (LC–MS), our data demonstrated that macrophages expressing TREM2 exhibited decreased SLC25A53 transcription through the SYK-SMAD4 signaling pathway after efferocytosis, which impaired NAD+ transport into mitochondria, downregulated SLC25A53 thereby causing the breakpoint in the TCA cycle and subsequently increased itaconate production. In vitro experiments confirmed that itaconate secreted by TREM2+ macrophages inhibited cardiomyocyte apoptosis and promoted fibroblast proliferation. Conversely, overexpression of TREM2 in macrophages could improve cardiac function. In summary, our study reveals a novel role for macrophage-specific TREM2 in MI, connecting efferocytosis to immune metabolism during cardiac repair.
FUNDC1-induced mitophagy protects spinal cord neurons against ischemic injury
Authors: Chen Dehui , Zhou Linquan , Chen Gang , Lin Taotao , Lin Jiemin , Zhao Xin , Li Wenwen , Guo Shengyu , Wu Rongcan , Wang Zhenyu , Liu Wenge
Published: January 2024

Local ischemia and hypoxia are the most important pathological processes in the early phase of secondary spinal cord injury (SCI), in which mitochondria are the main target of ischemic injury. Mitochondrial autophagy, also known as mitophagy, acts as a selective autophagy that specifically identifies and degrades damaged mitochondria, thereby reducing mitochondria-dependent apoptosis. Accumulating evidence shows that the mitophagy receptor, FUN14 domain-containing 1 (FUNDC1), plays an important role in ischemic injury, but the role of FUNDC1 in SCI has not been reported. In this study, we aimed to investigate whether FUNDC1 can enhance mitophagy and inhibit neuronal apoptosis in the early stage of SCI. In a rat SCI model, we found that FUNDC1 overexpression enhanced neuronal autophagy and decreased neuronal apoptosis in the early stage of injury, thereby reducing spinal cord damage. In vitro studies showed that the neuroprotective effects of FUNDC1 were achieved by inhibiting mitochondria-dependent apoptosis and improving mitochondrial function. In addition, FUNDC1 enhanced mitophagy. The protective effects of FUNDC1 against apoptosis and mitochondrial dysfunction were reversed by 3-methyladenine (3-MA), an autophagy inhibitor. Taken together, our results confirm that FUNDC1 can protect against neuronal loss after SCI by inducing mitophagy, inhibiting mitochondria-dependent apoptosis, and improving mitochondrial function.
A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways
Authors: Zhang Zhibin , Lin Xi , Wei Ling , Wu Yiran , Xu Lu , Wu Lijie , Wei Xiaohu , Zhao Suwen , Zhu Xiangjia , Xu Fei
Published: January 2024

The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between the G-protein coupling of FZD6 and the PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts.
Is food insecurity associated with dental caries?
Authors: Holmes Richard D.
Published: January 2024

Data sources

Eight electronic databases including APA PsycINFO, CINAHL, Embase, LILACS, PubMed, Ovid, Scopus and Web of Science were searched from date of inception to November 2021. An updated search was conducted in August 2022. Google Scholar was accessed including Open Grey and ProQuest. Reference lists of the included studies were analysed for potentially eligible studies.

Study selection

Observational studies (cross-sectional, case-control and cohort) that evaluated the association between dental caries and food insecurity were eligible for analysis. Qualitative studies, reviews and meeting abstracts were excluded. There were no restrictions on language or publication date.

Data extraction and synthesis

Two reviewers independently screened titles and abstracts. A third experienced researcher was consulted if there was disagreement. Food insecurity status was the exposure with dental caries the outcome. The authors retrieved effect measures, 95% CI’s and P values where available. Heterogeneity was assessed via I2 and R2. A total of 514 records were initially identified. Once duplicates were removed, 19 references were assessed in full. The association between food insecurity and dental caries were presented as odds-ratios, relative risks and prevalence ratios with 95% CIs. A random-effects model was fitted to all meta-analyses.

Results

Evaluation identified 14 studies for the qualitative synthesis and 7 studies for the quantitative synthesis. The total sample size for the 14 studies was 150,546 individuals. Quantitative data merged from two studies found food-insecure individuals more prone to dental caries than food-secure individuals (OR = 1.62; 95% CI, 1.01–2.60; P = 0.045). In two studies that used binary data to compare food security or insecurity, food insecure individuals were more likely to exhibit dental caries (OR = 1.66; 95% CI, 1.36–2.02; P < 0.0001).

Conclusions

People experiencing food insecurity are more likely to exhibit dental caries than those who have food security.
A novel DLG4 variant causes DLG4-related synaptopathy with intellectual regression
Authors: Tokunaga Sachi , Shimomura Hideki , Taniguchi Naoko , Yanagi Kumiko , Kaname Tadashi , Okamoto Nobuhiko , Takeshima Yasuhiro
Published: January 2024

DLG4-related synaptopathy is a neurodevelopmental disorder caused by a DLG4 variant. We identified a novel de novo heterozygous frameshift variant, NM_001321075.3(DLG4):c.554_563del, in a Japanese girl. Intellectual regression without motor delay was observed at 2 years of age, and she was diagnosed with autism spectrum disorder and attention-deficit/hyperactivity disorder. Recognizing the possibility of DLG4-related synaptopathy in patients with intellectual regression is important for ensuring an accurate diagnosis.
Boosting with adjuvanted SCB-2019 elicits superior Fcγ-receptor engagement driven by IgG3 to SARS-CoV-2 spike
Authors: Jung Wonyeong , Yuan Dansu , Kellman Benjamin , Gonzalez Isabela Garrido da Silva , Clemens Ralf , Milan Eveline Pipolo , Sprinz Eduardo , Cerbino Neto José , Smolenov Igor , Alter Galit , McNamara Ryan P. , Costa Clemens Sue Ann
Published: January 2024

With the continued emergence of variants of concern, the global threat of COVID-19 persists, particularly in low- and middle-income countries with limited vaccine access. Protein-based vaccines, such as SCB-2019, can be produced on a large scale at a low cost while antigen design and adjuvant use can modulate efficacy and safety. While effective humoral immunity against SARS-CoV-2 variants has been shown to depend on both neutralization and Fc-mediated immunity, data on the effectiveness of protein-based vaccines with enhanced Fc-mediated immunity is limited. Here, we assess the humoral profile, including antibody isotypes, subclasses, and Fc receptor binding generated by a boosting with a recombinant trimer-tag protein vaccine SCB-2019. Individuals who were primed with 2 doses of the ChAdOx1 vaccine were equally divided into 4 groups and boosted with following formulations: Group 1: 9 μg SCB-2019 and Alhydrogel; Group 2: 9 μg SCB-2019, CpG 1018, and Alhydrogel; Group 3: 30 μg SCB-2019, CpG 1018, and Alhydrogel; Group 4: ChAdOx1. Group 3 showed enhanced antibody FcγR binding against wild-type and variants compared to Groups 1 and 2, showing a dose-dependent enhancement of immunity conferred by the SCB-2019 vaccine. Moreover, from day 15 after vaccination, Group 3 exhibited higher IgG3 and FcγR binding across variants of concerns, including Omicron and its subvariants, compared to the ChAdOx1-boosted individuals. Overall, this highlights the potential of SCB-2019 as a cost-efficient boosting regimen effective across variants of concerns.
Single-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation
Authors: Bravo González-Blas Carmen , Matetovici Irina , Hillen Hanne , Taskiran Ibrahim Ihsan , Vandepoel Roel , Christiaens Valerie , Sansores-García Leticia , Verboven Elisabeth , Hulselmans Gert , Poovathingal Suresh , Demeulemeester Jonas , Psatha Nikoleta , Mauduit David , Halder Georg , Aerts Stein
Published: January 2024

In the mammalian liver, hepatocytes exhibit diverse metabolic and functional profiles based on their location within the liver lobule. However, it is unclear whether this spatial variation, called zonation, is governed by a well-defined gene regulatory code. Here, using a combination of single-cell multiomics, spatial omics, massively parallel reporter assays and deep learning, we mapped enhancer-gene regulatory networks across mouse liver cell types. We found that zonation affects gene expression and chromatin accessibility in hepatocytes, among other cell types. These states are driven by the repressors TCF7L1 and TBX3, alongside other core hepatocyte transcription factors, such as HNF4A, CEBPA, FOXA1 and ONECUT1. To examine the architecture of the enhancers driving these cell states, we trained a hierarchical deep learning model called DeepLiver. Our study provides a multimodal understanding of the regulatory code underlying hepatocyte identity and their zonation state that can be used to engineer enhancers with specific activity levels and zonation patterns.
Distinct and shared genetic architectures of gestational diabetes mellitus and type 2 diabetes
Authors: Elliott Amanda , Walters Raymond K. , Pirinen Matti , Kurki Mitja , Junna Nella , Goldstein Jacqueline I. , Reeve Mary Pat , Siirtola Harri , Lemmelä Susanna M. , Turley Patrick , Lahtela Elisa , Mehtonen Juha , Reis Kadri , Elnahas Abdelrahman G. , Reigo Anu , Palta Priit , Esko Tõnu , Mägi Reedik ,   Estonian Biobank Research Team, Metspalu Andres , Nelis Mari , Milani Lili , Hudjashov Georgi ,   FinnGen, Siirtola Haari , Lahtinen Elisa , Palotie Aarno , Daly Mark J. , Widén Elisabeth
Published: January 2024

Gestational diabetes mellitus (GDM) is a common metabolic disorder affecting more than 16 million pregnancies annually worldwide1,2. GDM is related to an increased lifetime risk of type 2 diabetes (T2D)1–3, with over a third of women developing T2D within 15 years of their GDM diagnosis. The diseases are hypothesized to share a genetic predisposition1–7, but few studies have sought to uncover the genetic underpinnings of GDM. Most studies have evaluated the impact of T2D loci only8–10, and the three prior genome-wide association studies of GDM11–13 have identified only five loci, limiting the power to assess to what extent variants or biological pathways are specific to GDM. We conducted the largest genome-wide association study of GDM to date in 12,332 cases and 131,109 parous female controls in the FinnGen study and identified 13 GDM-associated loci, including nine new loci. Genetic features distinct from T2D were identified both at the locus and genomic scale. Our results suggest that the genetics of GDM risk falls into the following two distinct categories: one part conventional T2D polygenic risk and one part predominantly influencing mechanisms disrupted in pregnancy. Loci with GDM-predominant effects map to genes related to islet cells, central glucose homeostasis, steroidogenesis and placental expression.
Latent neural population dynamics underlying breathing, opioid-induced respiratory depression and gasping
Authors: Bush Nicholas Edward , Ramirez Jan-Marino
Published: January 2024

Breathing is vital and must be concurrently robust and flexible. This rhythmic behavior is generated and maintained within a rostrocaudally aligned set of medullary nuclei called the ventral respiratory column (VRC). The rhythmic properties of individual VRC nuclei are well known, yet technical challenges have limited the interrogation of the entire VRC population simultaneously. Here we characterize over 15,000 medullary units using high-density electrophysiology, opto-tagging and histological reconstruction. Population dynamics analysis reveals consistent rotational trajectories through a low-dimensional neural manifold. These rotations are robust and maintained even during opioid-induced respiratory depression. During severe hypoxia-induced gasping, the low-dimensional dynamics of the VRC reconfigure from rotational to all-or-none, ballistic efforts. Thus, latent dynamics provide a unifying lens onto the activities of large, heterogeneous populations of neurons involved in the simple, yet vital, behavior of breathing, and well describe how these populations respond to a variety of perturbations.
The potential of epigenetic therapy to target the 3D epigenome in endocrine-resistant breast cancer
Authors: Achinger-Kawecka Joanna , Stirzaker Clare , Portman Neil , Campbell Elyssa , Chia Kee-Ming , Du Qian , Laven-Law Geraldine , Nair Shalima S. , Yong Aliza , Wilkinson Ashleigh , Clifton Samuel , Milioli Heloisa H. , Alexandrou Sarah , Caldon C. Elizabeth , Song Jenny , Khoury Amanda , Meyer Braydon , Chen Wenhan , Pidsley Ruth , Qu Wenjia , Gee Julia M. W. , Schmitt Anthony , Wong Emily S. , Hickey Theresa E. , Lim Elgene , Clark Susan J.
Published: January 2024

Three-dimensional (3D) epigenome remodeling is an important mechanism of gene deregulation in cancer. However, its potential as a target to counteract therapy resistance remains largely unaddressed. Here, we show that epigenetic therapy with decitabine (5-Aza-mC) suppresses tumor growth in xenograft models of pre-clinical metastatic estrogen receptor positive (ER+) breast tumor. Decitabine-induced genome-wide DNA hypomethylation results in large-scale 3D epigenome deregulation, including de-compaction of higher-order chromatin structure and loss of boundary insulation of topologically associated domains. Significant DNA hypomethylation associates with ectopic activation of ER-enhancers, gain in ER binding, creation of new 3D enhancer–promoter interactions and concordant up-regulation of ER-mediated transcription pathways. Importantly, long-term withdrawal of epigenetic therapy partially restores methylation at ER-enhancer elements, resulting in a loss of ectopic 3D enhancer–promoter interactions and associated gene repression. Our study illustrates the potential of epigenetic therapy to target ER+ endocrine-resistant breast cancer by DNA methylation-dependent rewiring of 3D chromatin interactions, which are associated with the suppression of tumor growth.
UBE2A and UBE2B are recruited by an atypical E3 ligase module in UBR4
Authors: Barnsby-Greer Lucy , Mabbitt Peter D. , Dery Marc-Andre , Squair Daniel R. , Wood Nicola T. , Lamoliatte Frederic , Lange Sven M. , Virdee Satpal
Published: January 2024

UBR4 is a 574 kDa E3 ligase (E3) of the N-degron pathway with roles in neurodevelopment, age-associated muscular atrophy and cancer. The catalytic module that carries out ubiquitin (Ub) transfer remains unknown. Here we identify and characterize a distinct E3 module within human UBR4 consisting of a ‘hemiRING’ zinc finger, a helical-rich UBR zinc-finger interacting (UZI) subdomain, and an N-terminal region that can serve as an affinity factor for the E2 conjugating enzyme (E2). The structure of an E2–E3 complex provides atomic-level insight into the specificity determinants of the hemiRING toward the cognate E2s UBE2A/UBE2B. Via an allosteric mechanism, the UZI subdomain modestly activates the Ub-loaded E2 (E2∼Ub). We propose attenuated activation is complemented by the intrinsically high lysine reactivity of UBE2A, and their cooperation imparts a reactivity profile important for substrate specificity and optimal degradation kinetics. These findings reveal the mechanistic underpinnings of a neuronal N-degron E3, its specific recruitment of UBE2A, and highlight the underappreciated architectural diversity of cross-brace domains with Ub E3 activity.
ModE-RA: a global monthly paleo-reanalysis of the modern era 1421 to 2008
Authors: Valler Veronika , Franke Jörg , Brugnara Yuri , Samakinwa Eric , Hand Ralf , Lundstad Elin , Burgdorf Angela-Maria , Lipfert Laura , Friedman Andrew Ronald , Brönnimann Stefan
Published: January 2024

The Modern Era Reanalysis (ModE-RA) is a global monthly paleo-reanalysis covering the period between 1421 and 2008. To reconstruct past climate fields an offline data assimilation approach is used, blending together information from an ensemble of transient atmospheric model simulations and observations. In the early period, ModE-RA utilizes natural proxies and documentary data, while from the 17th century onward instrumental measurements are also assimilated. The impact of each observation on the reconstruction is stored in the observation feedback archive, which provides additional information on the input data such as preprocessing steps and the regression-based forward models. The monthly resolved reconstructions include estimates of the most important climate fields. Furthermore, we provide a reconstruction, ModE-RAclim, which together with ModE-RA and the model simulations allows to disentangle the role of observations and model forcings. ModE-RA is best suited to study intra-annual to multi-decadal climate variability and to analyze the causes and mechanisms of past extreme climate events.
High-resolution climate projection dataset based on CMIP6 for Peru and Ecuador: BASD-CMIP6-PE
Authors: Fernandez-Palomino Carlos Antonio , Hattermann Fred F. , Krysanova Valentina , Vega-Jácome Fiorella , Menz Christoph , Gleixner Stephanie , Bronstert Axel
Published: January 2024

Here, we present BASD-CMIP6-PE, a high-resolution (1d, 10 km) climate dataset for Peru and Ecuador based on the bias-adjusted and statistically downscaled CMIP6 climate projections of 10 GCMs. This dataset includes both historical simulations (1850–2014) and future projections (2015–2100) for precipitation and minimum, mean, and maximum temperature under three Shared Socioeconomic Pathways (SSP1-2.6, SSP3-7.0, and SSP5-8.5). The BASD-CMIP6-PE climate data were generated using the trend-preserving Bias Adjustment and Statistical Downscaling (BASD) method. The BASD performance was evaluated using observational data and through hydrological modeling across Peruvian and Ecuadorian river basins in the historical period. Results demonstrated that BASD significantly reduced biases between CMIP6-GCM simulations and observational data, enhancing long-term statistical representations, including mean and extreme values, and seasonal patterns. Furthermore, the hydrological evaluation highlighted the appropriateness of adjusted GCM simulations for simulating streamflow, including mean, low, and high flows. These findings underscore the reliability of BASD-CMIP6-PE in assessing regional climate change impacts on agriculture, water resources, and hydrological extremes.