bluuebunny/crossref_metadata_2025 huggingface dataset:
Range extension of invasive Cancer irroratus and native Carcinus maenas polewards in the Ascophyllum-dominated intertidal zone in north-west Iceland
Authors: Magnússon Jón T. , Hawkins Stephen J. , Gunnarsdóttir Lilja , Svavarsson Jörundur , Gunnarsson Karl
Published: February 2024

The rocky intertidal zone of sheltered shores in Breiðafjörður, north-west Iceland is dominated by monospecific stands of canopy-forming brown algae Ascophyllum nodosum, which provide habitat for mobile organisms and has been subjected to long-standing rotational harvesting. We investigated the assemblage composition of little-studied mobile brachyuran crabs in this area, to track distributional shifts in a native species responding to climate change and extent of occupancy of the intertidal by a primarily subtidal invasive non-native species. Potential interactive effects of seaweed harvesting were explored. Breiðafjörður was compared with two reference sites in Faxaflói, south-west Iceland. The study revealed clear poleward expansion of the native European green crab Carcinus maenas in the region, displacing the native spider crab Hyas araneus particularly at mid-shore levels. The invasive non-native Atlantic rock crab Cancer irroratus had negligible occupancy in the intertidal zone, indicating limited effects on the intertidal crab assemblage, composition, and abundance. The current harvesting regime of A. nodosum in Breiðafjörður did not affect the composition and abundance of the brachyuran crab assemblage in the rocky intertidal zone. H. araneus is likely being squeezed by displacement subtidally by C. irroratus, and intertidally by C. maenas. Overall, we provide insights into the potential interactions between climate change, invasive species, and human activities in the rocky intertidal zone.
Age dependent effects of early intervention in borderline personality disorder in adolescents
Authors: Kaess Michael , Thomson Madelyn , Lerch Stefan , Koenig Julian , Fischer-Waldschmidt Gloria , Reichl Corinna , Cavelti Marialuisa
Published: February 2024

Background

Psychological treatments for young people with sub-threshold or full-syndrome borderline personality disorder (BPD) are found to be effective. However, little is known about the age at which adolescents benefit from early intervention. This study investigated whether age affects the effectiveness of early intervention for BPD.

Methods

N = 626 participants (M age = 15 years, 82.7% female) were consecutively recruited from a specialized outpatient service for early intervention in BPD in adolescents aged 12- to 17-years old. DSM-IV BPD criteria were assessed at baseline, one-year (n = 339) and two-year (n = 279) follow-up.

Results

Older adolescents presented with more BPD criteria (χ2(1) = 58.23, p < 0.001) and showed a steeper decline of BPD criteria over the 2-year follow-up period compared with younger adolescents (χ2(2) = 13.53, p = 0.001). In an attempt to disentangle effects of early intervention from the natural course of BPD, a parametrized regression model was used. An exponential decrease (b = 0.10, p < 0.001) in BPD criteria was found when starting therapy over the 2-year follow-up. This deviation from the natural course was impacted by age at therapy commencement (b = 0.06, p < 0.001), although significant across all ages: older adolescents showed a clear decrease in BPD criteria, and young adolescents a smaller decrease.

Conclusions

Early intervention appears effective across adolescence, but manifests differently: preventing the normative increase of BPD pathology expected in younger adolescents, and significantly decreasing BPD pathology in older adolescents. The question as to whether developmentally adapted therapeutic interventions could lead to an even increased benefit for younger adolescents, should be explored in future studies.
Higher emotion regulation flexibility predicts more stable negative emotions and faster affective recovery in early psychosis: an experience sampling study
Authors: Li Xu , Vaessen Thomas , Lafit Ginette , van Aubel Evelyne , Hiekkaranta Anu P. , Houben Marlies , Beijer-Klippel Annelie , de Haan Lieuwe , Schirmbeck Frederike , Reininghaus Ulrich , Myin-Germeys Inez
Published: February 2024

Background

While evidence shows that people with early psychosis are flexible in using different emotion regulation (ER) strategies to manage the varying contextual demands, no studies have examined the effectiveness of such regulatory flexibility in this population. We addressed this issue by investigating whether and how ER flexibility relate to different dynamic aspects (variability, instability, inertia, and recovery) of negative affect (NA) in a combined early psychosis sample, consisting of both individuals at high clinical risk for psychosis and those diagnosed with first-episode psychosis.

Methods

Participants were 148 individuals from the INTERACT project, a multi-center randomized controlled trial on the efficacy of acceptance and commitment therapy in early psychosis. We utilized data from the baseline assessment, during which all participants completed six days of experience sampling assessment of momentary NA, as well as end-of-day assessments of ER strategy use.

Results

Multilevel models of within-person associations showed that greater ER flexibility was associated with more stable NA, and quicker recovery of NA from stressors during the day. Linear regression analyses of between-person associations showed that people who had more variable and unstable NA reported greater ER flexibility generally. No evidence was found for associations with NA inertia.

Conclusions

The current study identified unique within-person and between-person links between ER flexibility and dynamics of NA in early psychosis. These findings further provide evidence for ER flexibility in early psychosis, emphasizing the adaptive nature of regulatory flexibility in relation to reduced instability in NA and faster recovery from NA in everyday life.
Antimicrobial resistance in the United States: Origins and future directions
Authors: Sutton Kent F. , Ashley Lucas W.
Published: February 2024

Antimicrobial resistance (AMR) remains a critical public health problem that pervades hospitals and health systems worldwide. The ongoing AMR crisis is not only concerning for patient care but also healthcare delivery and quality. This article outlines key components of the origins of AMR in the United States and how it presents across the American healthcare system. Numerous factors contributed to the crisis, including agricultural antibiotic use, wasteful prescribing practices in health care, conflicting behaviours among patients and clinicians, patient demand and satisfaction, and payment and reimbursement models that incentivize inappropriate antibiotic use. To combat AMR, clinicians, healthcare professionals, and legislators must continue to promote and implement innovative solutions, including antibiotic stewardship programmes (ASPs), hand hygiene protocols, ample supply of personal protective equipment (PPE), standardized treatment guidelines for antibiotic prescribing, clinician and patient educational programmes, and health policy initiatives. With the rising prevalence of multi-drug resistant bacterial infections, AMR must become a greater priority to policymakers and healthcare stakeholders.
THOUGHTS ON MY HES LIFE
Authors: Rutherford Malcolm
Published: February 2024

This paper outlines my own career within the History of Economics Society, my contributions to the society, and its central importance to my research endeavours. It is impossible for me to imagine having the career I have had without the HES, and my own case highlights how the society functioned to mentor and develop my academic career. This mentoring function is, in my view, the society’s most important, and one that has become only more vital in the face of the declining interest in the area within mainstream economics departments in the US, Canada, and the UK.
“I GET BY WITH A LITTLE HELP FROM MY FRIENDS … ”: AN EDITOR’S RETROSPECTIVE
Authors: Medema Steven G.
Published: February 2024

In this article, Steven Medema provides some reflections on his tenure as editor of the Journal of the History of Economic Thought (1999 – 2008). This was a time of significant transition in the life of the journal, and the successful navigation of this period provides an excellent illustration of how much an editor and a journal rely on the assistance and support of both key individuals and the broader community of scholars in the field.
The plague, the skill-premium, and the road to modern economic growth
Authors: Jensen Martin Kaae , Luo Rui
Published: February 2024

When bubonic plague arrived in Britain in the mid-14th century, it caused dramatic economic and structural change. Within 50 years, the skill-premium was reduced by half, and another 50 years on, agriculture’s share of the labor force had declined by more than 20 percentage points. This paper develops a two-sector pre-industrial growth model and draws on recent data sources covering Late Medieval and Early Modern Britain to explain these and the ensuing developments. Our main findings are that the skill-premium’s decline was related to the guild and apprenticeship system and that it and the other post-Plague adjustments were crucial determinants of the British trajectory toward industrialization. In particular, prior sectoral transformation and the skill-premium’s determination were important when the Early Modern population boom (1525–1654) threatened to reverse the adjustments caused by the Plague.
Modeling the effect of temperature on rhizome sprouting in the invasive weed silverleaf nightshade (Solanum elaeagnifolium)
Authors: Kapiluto Omer , Smirnov Evgeny , Achdary Guy , Eizenberg Hanan , Lati Ran Nisim
Published: February 2024

Silverleaf nightshade (Solanum elaeagnifolium Cav.), a noxious, highly invasive perennial weed, poses a significant threat to irrigated summer crops, vegetables, and orchards. This weed has the ability to reproduce both sexually through seed production and asexually via an extensive underground rhizome network, the latter playing a major role in the weed’s invasion, establishment, and persistence. Our aims were thus to assess the impact of temperature on rhizome sprouting for fragments of different lengths and to model the sprouting dynamics. The influence of temperature on the sprouting of rhizome fragments (2.5-, 5-, 7.5-, or 10-cm long) was investigated in growth chambers at eight temperatures ranging from 10 to 45 C. The highest sprouting proportions for 10-cm rhizome fragments were recorded at 30 and 35 C in complete darkness. The highest sprouting time for all fragment lengths was observed at 15 C in complete darkness. Modeling sprouting rates as a function of temperature gave the cardinal temperatures for the four different rhizome fragment lengths, with Tb (base temperature) values of 12.80, 9.34, 9.14, and 9.50 C, To (optimal temperature) values of 38.9
$$0$$
, 36.60, 35.16, and 34.86 C, and Tc (ceiling temperature) values of 39.80, 40.08, 40.50, and 40.80 C for rhizome lengths of 2.5, 5, 7.5, and 10 cm, respectively. Based on these findings, the potential for S. elaeagnifolium to spread to new areas and possible new management strategies are discussed; these offer a novel approach for informed decision making regarding the control of this weed.
Design of a wearable shoulder exoskeleton robot with dual-purpose gravity compensation and a compliant misalignment compensation mechanism
Authors: Atkins John , Chang Dongjune , Lee Hyunglae
Published: February 2024

This paper presents the design and validation of a wearable shoulder exoskeleton robot intended to serve as a platform for assistive controllers that can mitigate the risk of musculoskeletal disorders seen in workers. The design features a four-bar mechanism that moves the exoskeleton’s center of mass from the upper shoulders to the user’s torso, dual-purpose gravity compensation mechanism located inside the four-bar’s linkages that supports the full gravitational loading from the exoskeleton with partial user’s arm weight compensation, and a novel 6 degree-of-freedom (DoF) compliant misalignment compensation mechanism located between the end effector and the user’s arm to allow shoulder translation while maintaining control of the arm’s direction. Simulations show the four-bar design lowers the center of mass by$ 11 $ cm and the kinematic chain can follow the motion of common upper arm trajectories. Experimental tests show the gravity compensation mechanism compensates gravitational loading within$ \pm 0.5 $ Nm over the range of shoulder motion and the misalignment compensation mechanism has the desired 6 DoF stiffness characteristics and range of motion to adjust for shoulder center translation. Finally, a workspace admittance controller was implemented and evaluated showing the system is capable of accurately reproducing simulated impedance behavior with transparent low-impedance human operation.
Observational Evidence Reveals Compound Humid Heat Stress‐Extreme Rainfall Hotspots in India
Authors: Ganguli Poulomi , Merz Bruno
Published: February 2024

Sequential climate hazards, such as “warm and wet” compound extremes, have direct societal implications for highly urbanized regions and agricultural production. While typically extreme temperatures and rainfall are inversely correlated during the summer, extreme humid heatwaves often lead to atmospheric instability and moisture convection, increasing the likelihood of extreme precipitation (EP). Little is known about how heatwave characteristics, such as peak intensity and duration, influence EP at a regional scale. Using high‐resolution, sub‐daily station‐based observational records over five decades (1971–2021) across India, we find a robust increase in the frequency of compound humid heat‐peak precipitation events in all seasons. Our sensitivity analysis of the impact of humid heatwave characteristics on the subsequent sub‐daily rainfall extremes reveals that, with an increase in peak heatwave intensity for a given heatwave duration, >50% of sites show an increase in the magnitude of rainfall; conversely, with an increase in heatwave duration for a given peak heatwave intensity, around 67% sites show a decline in sub‐daily rainfall extremes. An asymmetrical shift toward above‐average precipitation extremes in response to humid heat stress is mainly clustered around low‐elevation, densely populated coastal areas and the irrigation‐intensive Indo‐Gangetic Plains.
Evening Solar Terminator Waves in Earth's Thermosphere: Neutral Wind Signatures Observed by ICON‐MIGHTI
Authors: Gasque L. Claire , Harding Brian J. , Immel Thomas J. , Wu Yen‐Jung , Triplett Colin C. , Vadas Sharon L. , Becker Erich , Maute Astrid
Published: February 2024

The moving solar terminator (ST) generates atmospheric disturbances, broadly termed solar terminator waves (STWs). Despite theoretically recurring daily, STWs remain poorly understood, partially due to measurement challenges near the ST. Analyzing Michelson Interferometer for Global High‐resolution Thermospheric Imaging (MIGHTI) data from NASA's Ionospheric Connection Explorer (ICON) observatory, we present observations of STW signatures in thermospheric neutral winds, including the first reported meridional wind signatures. Seasonal analysis reveals STWs are most prominent during solstices, when they intersect the ST about ∼20° latitude from the equator in the winter hemisphere and have phase fronts inclined at a ∼40° angle to the ST. We also provide the first observed STW altitude profiles, revealing large vertical wavelengths above 200 km. Comparing these observations to four different models suggests the STWs likely originate directly or indirectly from waves from below 97 km. STWs may play an under‐recognized role in the daily variability of the thermosphere‐ionosphere system, warranting further study.
MJO Seasonality in Its Scale Selection: Perspectives From Space‐Time Spectral Analysis of Moisture Budget
Authors: Wei Yuntao , Ren Hong‐Li
Published: February 2024

The Madden–Julian Oscillation (MJO) displays an evident seasonality in its spatiotemporal scale selection. In boreal winter, the MJO is best behaved at wavenumber 2 and oscillates on a narrow time scale centering on a ∼55‐day period. In contrast, a wavenumber‐1 selection and a broad oscillation frequency centering on a ∼33‐day period are observed in boreal summer. Using the space‐time cross‐spectral analysis between convection and moisture budget, we reveal that column processes determine seasonal variations in the MJO spatial organization, while the MJO is strongly damped by the horizontal moisture advection mainly due to its meridional component (Vadv). A timescale decomposition analysis suggests that the damping effect of Vadv results primarily from high‐frequency synoptic‐scale disturbances, and the Vadv component related to the seasonal‐mean moisture generally supports the MJO growth at large wavenumbers while inhibits the growth of small wavenumbers, which is the most evident in boreal summer. The advection of seasonal‐mean moisture by anomalous zonal winds supports the MJO growth at all wavenumbers in boreal winter, but in boreal summer the growth becomes weak and even turns negative for small wavenumbers. Furthermore, different MJO timescale selections in winter versus summer are rooted in the Vadv, as both the column processes and zonal moisture advection mainly support the propagation of high‐frequency modes. Observational results related to the horizontal seasonal‐mean moisture advection are reasonably validated in a dynamical moisture model. These findings advance our understanding of the MJO seasonality and offer alternative diagnoses for evaluating the MJO simulation fidelity in contemporary climate models.
Characterizing Erosion and Deposition in and Around Riparian Vegetation Patches: Complex Flow Hydraulics, Sediment Supply, and Morphodynamic Feedbacks
Authors: Tranmer Andrew W. , Ji Un , Ahn Myeonghui , Jung Sang Hwa , Yager Elowyn M.
Published: February 2024

Riparian vegetation plays a fundamental role in alluvial channel evolution by modifying flow and sedimentation dynamics. To elucidate the roles of sediment supply, flow‐dependent transport capacity, and morphodynamic feedbacks on the evolution of emergent vegetation patches over a single hydrograph, we conducted two experiments with different reach‐scale sediment supplies: a high‐supply experiment (HSE) and low‐supply experiment (LSE). We measured flow velocities, bedload transport, and topographic changes around a full‐scale patch of live emergent willows in an outdoor laboratory flume. Erosion occurred in the patch‐adjacent channel areas irrespective of the sediment supply, whereas deposition within the patch interior was suppressed in the LSE and enhanced in the HSE. The magnitude of patch deposition in each experiment was controlled by the local sediment supply to the patch and local sediment mobility during each discharge in the hydrograph. The local sediment supply was affected by bed morphodynamics at the patch head, which modulated the reach‐scale sediment supply by redistributing the bedload in the channel. Sediment mobility within the patch was flow‐dependent and a function of velocity and turbulent kinetic energy. For different discharges, the velocity in the patch changed proportionally with the freestream velocity; however, the turbulent kinetic energy was more sensitive, being elevated compared with the freestream during high flows and inhibited at low flows. Therefore, deposition and erosion within vegetation patches are not simply functions of the reach‐scale sediment supply or patch flow characteristics, as is often assumed, but additionally depend on the local sediment supply to the patch interior.
Variations in Bedrock and Vegetation Cover Modulate Subsurface Water Flow Dynamics of a Mountainous Hillslope
Authors: Uhlemann S. , Peruzzo L. , Chou C. , Williams K. H. , Wielandt S. , Wang C. , Falco N. , Wu Y. , Carr B. , Meldrum P. , Chambers J. , Dafflon B.
Published: February 2024

Predicting the hydrological response of watersheds to climate disturbances requires a detailed understanding of the processes connecting hillslopes and streams. Using a network of soil moisture and temperature sensors, electrical resistivity tomography monitoring, and a weather station we assess the above and below‐ground processes driving the hydrological response of a hillslope during snowmelt and summer monsoon. The transect covers bedrock and vegetation gradients, with a steep upper part characterized by shallow bedrock, and gentle lower part underlain by colluvium. The main vegetation cover is conifers on the upper, and grass and veratrum on the lower part. Combined with a simplified hydrological model, we show that the thin soil layer of the steep slope acts as a preferential flow path, leading to mostly shallow lateral flow, interrupted by vertical flow, mostly at tree locations, and likely facilitated by flow along fractures and roots. Vertical flow and upstream‐driven groundwater dynamics are prevailing at the colluvium, presenting a very different hydrological behavior compared to the upper part. These results show that subsurface structure and features have a strong control on the hydrological response of a hillslope and that those can create considerably varying hydrological dynamics across small spatial scales.
Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma
Authors: Rampioni Vinciguerra Gian Luca , Capece Marina , Reggiani Bonetti Luca , Nigita Giovanni , Calore Federica , Rentsch Sydney , Magistri Paolo , Ballarin Roberto , Di Benedetto Fabrizio , Distefano Rosario , Cirombella Roberto , Vecchione Andrea , Belletti Barbara , Baldassarre Gustavo , Lovat Francesca , Croce Carlo M.
Published: February 2024

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient supplies. PDAC aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor microenvironment. Dysregulation of the onco-suppressor miR-15a has been extensively documented in PDAC. Here, we identified the transcription factor Fos-related antigen-2 (Fra-2) as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient deprivation. We report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC patients. Mechanistically, we discovered that miR-15a repressed IGF1R expression via Fra-2 targeting. In miR-15a-low context, IGF1R hyperactivated mTOR, modulated the autophagic flux and sustained PDAC growth in nutrient deprivation. In a genetic mouse model, Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet restriction. Consistently, nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent manner. Overall, our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.
Histone demethylase KDM7A regulates bone homeostasis through balancing osteoblast and osteoclast differentiation
Authors: Shan Liying , Yang Xiaoli , Liao Xiaoxia , Yang Zheng , Zhou Jie , Li Xiaoxia , Wang Baoli
Published: February 2024

Histone methylation plays a crucial role in various cellular processes. We previously reported the in vitro function of histone lysine demethylase 7 A (KDM7A) in osteoblast and adipocyte differentiation. The current study was undertaken to investigate the physiological role of KDM7A in bone homeostasis and elucidate the underlying mechanisms. A conditional strategy was employed to delete the Kdm7a gene specifically in osterix-expressing osteoprogenitor cells in mice. The resulting mutant mice exhibited a significant increase in cancellous bone mass, accompanied by an increase in osteoblasts and bone formation, as well as a reduction in osteoclasts, marrow adipocytes and bone resorption. The bone marrow stromal cells (BMSCs) and calvarial pre-osteoblastic cells derived from the mutant mice exhibited enhanced osteogenic differentiation and suppressed adipogenic differentiation. Additionally, osteoclastic precursor cells from the mutant mice exhibited impaired osteoclast differentiation. Co-culturing BMSCs from the mutant mice with wild-type osteoclast precursor cells resulted in the inhibition of osteoclast differentiation. Mechanistic investigation revealed that KDM7A was able to upregulate the expression of fibroblast activation protein α (FAP) and receptor activator of nuclear factor κB ligand (RANKL) in BMSCs through removing repressive di-methylation marks of H3K9 and H3K27 from Fap and Rankl promoters. Moreover, recombinant FAP attenuated the dysregulation of osteoblast and adipocyte differentiation in BMSCs from Kdm7a deficient mice. Finally, Kdm7a deficiency prevented ovariectomy-induced bone loss in mice. This study establish the role of KDM7A in bone homeostasis through its epigenetic regulation of osteoblast and osteoclast differentiation. Consequently, inhibiting KDM7A may prove beneficial in ameliorating osteoporosis.
Deoxycytidine kinase inactivation enhances gemcitabine resistance and sensitizes mitochondrial metabolism interference in pancreatic cancer
Authors: Dash Suman , Ueda Takeshi , Komuro Akiyoshi , Honda Masahiko , Sugisawa Ryoichi , Okada Hitoshi
Published: February 2024

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most lethal forms of cancer. Although in the last decade, an increase in 5-year patient survival has been observed, the mortality rate remains high. As a first-line treatment for PDAC, gemcitabine alone or in combination (gemcitabine plus paclitaxel) has been used; however, drug resistance to this regimen is a growing issue. In our previous study, we reported MYC/glutamine dependency as a therapeutic target in gemcitabine-resistant PDAC secondary to deoxycytidine kinase (DCK) inactivation. Moreover, enrichment of oxidative phosphorylation (OXPHOS)-associated genes was a common property shared by PDAC cell lines, and patient clinical samples coupled with low DCK expression was also demonstrated, which implicates DCK in cancer metabolism. In this article, we reveal that the expression of most genes encoding mitochondrial complexes is remarkably upregulated in PDAC patients with low DCK expression. The DCK-knockout (DCK KO) CFPAC-1 PDAC cell line model reiterated this observation. Particularly, OXPHOS was functionally enhanced in DCK KO cells as shown by a higher oxygen consumption rate and mitochondrial ATP production. Electron microscopic observations revealed abnormal mitochondrial morphology in DCK KO cells. Furthermore, DCK inactivation exhibited reactive oxygen species (ROS) reduction accompanied with ROS-scavenging gene activation, such as SOD1 and SOD2. SOD2 inhibition in DCK KO cells clearly induced cell growth suppression. In combination with increased anti-apoptotic gene BCL2 expression in DCK KO cells, we finally reveal that venetoclax and a mitochondrial complex I inhibitor are therapeutically efficacious for DCK-inactivated CFPAC-1 cells in in vitro and xenograft models. Hence, our work provides insight into inhibition of mitochondrial metabolism as a novel therapeutic approach to overcome DCK inactivation-mediated gemcitabine resistance in PDAC patient treatment.
Optical Tellegen metamaterial with spontaneous magnetization
Authors: Safaei Jazi Shadi , Faniayeu Ihar , Cichelero Rafael , Tzarouchis Dimitrios C. , Asgari Mohammad Mahdi , Dmitriev Alexandre , Fan Shanhui , Asadchy Viktar
Published: February 2024

The nonreciprocal magnetoelectric effect, also known as the Tellegen effect, promises a number of groundbreaking phenomena connected to fundamental (e.g., electrodynamics of axion and relativistic matter) and applied physics (e.g., magnetless isolators). We propose a three-dimensional metamaterial with an isotropic and resonant Tellegen response in the visible frequency range. The metamaterial is formed by randomly oriented bi-material nanocylinders in a host medium. Each nanocylinder consists of a ferromagnet in a single-domain magnetic state and a high-permittivity dielectric operating near the magnetic Mie-type resonance. The proposed metamaterial requires no external magnetic bias and operates on the spontaneous magnetization of the nanocylinders. By leveraging the emerging magnetic Weyl semimetals, we further show how a giant bulk effective magnetoelectric effect can be achieved in a proposed metamaterial, exceeding that of natural materials by almost four orders of magnitude.
Biomimetic mercury immobilization by selenium functionalized polyphenylene sulfide fabric
Authors: Li Hailong , Meng Fanyue , Zhu Penglin , Zu Hongxiao , Yang Zequn , Qu Wenqi , Yang Jianping
Published: February 2024

Highly efficient decontamination of elemental mercury (Hg0) remains an enormous challenge for public health and ecosystem protection. The artificial conversion of Hg0 into mercury chalcogenides could achieve Hg0 detoxification and close the global mercury cycle. Herein, taking inspiration from the bio-detoxification of mercury, in which selenium preferentially converts mercury from sulfoproteins to HgSe, we propose a biomimetic approach to enhance the conversion of Hg0 into mercury chalcogenides. In this proof-of-concept design, we use sulfur-rich polyphenylene sulfide (PPS) as the Hg0 transporter. The relatively stable, sulfur-linked aromatic rings result in weak adsorption of Hg0 on the PPS rather than the formation of metastable HgS. The weakly adsorbed mercury subsequently migrates to the adjacent selenium sites for permanent immobilization. The sulfur-selenium pair affords an unprecedented Hg0 adsorption capacity and uptake rate of 1621.9 mg g−1 and 1005.6 μg g−1 min−1, respectively, which are the highest recorded values among various benchmark materials. This work presents an intriguing concept for preparing Hg0 adsorbents and could pave the way for the biomimetic remediation of diverse pollutants.
Sonic hedgehog-heat shock protein 90β axis promotes the development of nonalcoholic steatohepatitis in mice
Authors: Zhang Weitao , Lu Junfeng , Feng Lianshun , Xue Hanyue , Shen Shiyang , Lai Shuiqing , Li PingPing , Li Ping , Kuang Jian , Yang Zhiwei , Xu Xiaojun
Published: February 2024

Sonic hedgehog (SHH) and heat shock protein 90β (HSP90β) have been implicated in nonalcoholic steatohepatitis (NASH) but their molecular mechanisms of action remain elusive. We find that HSP90β is a key SHH downstream molecule for promoting NASH process. In hepatocytes, SHH reduces HSP90β ubiquitylation through deubiquitylase USP31, thus preventing HSP90β degradation and promoting hepatic lipid synthesis. HSP90β significantly increases in NASH mouse model, leading to secretion of exosomes enriched with miR-28-5p. miR-28-5p directly targetes and decreases Rap1b levels, which in turn promotes NF-κB transcriptional activity in macrophages and stimulates the expression of inflammatory factors. Genetic deletion, pharmacological inhibition of the SHH-HSP90β axis, or delivery of miR-28-5p to macrophages in the male mice liver, impairs NASH symptomatic development. Importantly, there is a markedly higher abundance of miR-28-5p in NASH patient sera. Taken together, the SHH-HSP90β-miR-28-5p axis offers promising therapeutic targets against NASH, and serum miR-28-5p may serve as a NASH diagnostic biomarker.
EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death
Authors: Wu Jiacheng , Xu Xiaoqing , Duan Jiaqi , Chai Yangyang , Song Jiaying , Gong Dongsheng , Wang Bingjing , Hu Ye , Han Taotao , Ding Yuanyuan , Liu Yin , Li Jingnan , Cao Xuetao
Published: February 2024

TNF acts as one pathogenic driver for inducing intestinal epithelial cell (IEC) death and substantial intestinal inflammation. How the IEC death is regulated to physiologically prevent intestinal inflammation needs further investigation. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects intestinal epithelium from TNF-induced IEC apoptosis. EFHD2 inhibits TNF-induced apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin and suppresses Cofilin phosphorylation, thus blocking TNF receptor I (TNFR1) internalization to inhibit IEC apoptosis and consequently protecting intestine from inflammation. Our findings deepen the understanding of EFHD2 as the key regulator of membrane receptor trafficking, providing insight into death receptor signals and autoinflammatory diseases.
Chromatin attachment to the nuclear matrix represses hypocotyl elongation in Arabidopsis thaliana
Authors: Xu Linhao , Zheng Shiwei , Witzel Katja , Van De Slijke Eveline , Baekelandt Alexandra , Mylle Evelien , Van Damme Daniel , Cheng Jinping , De Jaeger Geert , Inzé Dirk , Jiang Hua
Published: February 2024

The nuclear matrix is a nuclear compartment that has diverse functions in chromatin regulation and transcription. However, how this structure influences epigenetic modifications and gene expression in plants is largely unknown. In this study, we show that a nuclear matrix binding protein, AHL22, together with the two transcriptional repressors FRS7 and FRS12, regulates hypocotyl elongation by suppressing the expression of a group of genes known as SMALL AUXIN UP RNAs (SAURs) in Arabidopsis thaliana. The transcriptional repression of SAURs depends on their attachment to the nuclear matrix. The AHL22 complex not only brings these SAURs, which contain matrix attachment regions (MARs), to the nuclear matrix, but it also recruits the histone deacetylase HDA15 to the SAUR loci. This leads to the removal of H3 acetylation at the SAUR loci and the suppression of hypocotyl elongation. Taken together, our results indicate that MAR-binding proteins act as a hub for chromatin and epigenetic regulators. Moreover, we present a mechanism by which nuclear matrix attachment to chromatin regulates histone modifications, transcription, and hypocotyl elongation.
Palmitic acid in type 2 diabetes mellitus promotes atherosclerotic plaque vulnerability via macrophage Dll4 signaling
Authors: Wang Xiqiang , Zhu Ling , Liu Jing , Ma Yanpeng , Qiu Chuan , Liu Chengfeng , Gong Yangchao , Yuwen Ya , Guan Gongchang , Zhang Yong , Pan Shuo , Wang Junkui , Liu Zhongwei
Published: February 2024

Patients with Type 2 Diabetes Mellitus are increasingly susceptible to atherosclerotic plaque vulnerability, leading to severe cardiovascular events. In this study, we demonstrate that elevated serum levels of palmitic acid, a type of saturated fatty acid, are significantly linked to this enhanced vulnerability in patients with Type 2 Diabetes Mellitus. Through a combination of human cohort studies and animal models, our research identifies a key mechanistic pathway: palmitic acid induces macrophage Delta-like ligand 4 signaling, which in turn triggers senescence in vascular smooth muscle cells. This process is critical for plaque instability due to reduced collagen synthesis and deposition. Importantly, our findings reveal that macrophage-specific knockout of Delta-like ligand 4 in atherosclerotic mice leads to reduced plaque burden and improved stability, highlighting the potential of targeting this pathway. These insights offer a promising direction for developing therapeutic strategies to mitigate cardiovascular risks in patients with Type 2 Diabetes Mellitus.
Electric control of optically-induced magnetization dynamics in a van der Waals ferromagnetic semiconductor
Authors: Hendriks Freddie , Rojas-Lopez Rafael R. , Koopmans Bert , Guimarães Marcos H. D.
Published: February 2024

Electric control of magnetization dynamics in two-dimensional (2D) magnetic materials is an essential step for the development of novel spintronic nanodevices. Electrostatic gating has been shown to greatly affect the static magnetic properties of some van der Waals magnets, but the control over their magnetization dynamics is still largely unexplored. Here we show that the optically-induced magnetization dynamics in the van der Waals ferromagnet Cr2Ge2Te6 can be effectively controlled by electrostatic gates, with a one order of magnitude change in the precession amplitude and over 10% change in the internal effective field. In contrast to the purely thermally-induced mechanisms previously reported for 2D magnets, we find that coherent opto-magnetic phenomena play a major role in the excitation of magnetization dynamics in Cr2Ge2Te6. Our work sets the first steps towards electric control over the magnetization dynamics in 2D ferromagnetic semiconductors, demonstrating their potential for applications in ultrafast opto-magnonic devices.
Poly-γ-glutamylation of biomolecules
Authors: Bashiri Ghader , Bulloch Esther M. M. , Bramley William R. , Davidson Madison , Stuteley Stephanie M. , Young Paul G. , Harris Paul W. R. , Naqvi Muhammad S. H. , Middleditch Martin J. , Schmitz Michael , Chang Wei-Chen , Baker Edward N. , Squire Christopher J.
Published: February 2024

Poly-γ-glutamate tails are a distinctive feature of archaeal, bacterial, and eukaryotic cofactors, including the folates and F420. Despite decades of research, key mechanistic questions remain as to how enzymes successively add glutamates to poly-γ-glutamate chains while maintaining cofactor specificity. Here, we show how poly-γ-glutamylation of folate and F420 by folylpolyglutamate synthases and γ-glutamyl ligases, non-homologous enzymes, occurs via processive addition of L-glutamate onto growing γ-glutamyl chain termini. We further reveal structural snapshots of the archaeal γ-glutamyl ligase (CofE) in action, crucially including a bulged-chain product that shows how the cofactor is retained while successive glutamates are added to the chain terminus. This bulging substrate model of processive poly-γ-glutamylation by terminal extension is arguably ubiquitous in such biopolymerisation reactions, including addition to folates, and demonstrates convergent evolution in diverse species from archaea to humans.
Liquid crystalline inverted lipid phases encapsulating siRNA enhance lipid nanoparticle mediated transfection
Authors: Pattipeiluhu Roy , Zeng Ye , Hendrix Marco M.R.M. , Voets Ilja K. , Kros Alexander , Sharp Thomas H.
Published: February 2024

Efficient cytosolic delivery of RNA molecules remains a formidable barrier for RNA therapeutic strategies. Lipid nanoparticles (LNPs) serve as state-of-the-art carriers that can deliver RNA molecules intracellularly, as exemplified by the recent implementation of several vaccines against SARS-CoV-2. Using a bottom-up rational design approach, we assemble LNPs that contain programmable lipid phases encapsulating small interfering RNA (siRNA). A combination of cryogenic transmission electron microscopy, cryogenic electron tomography and small-angle X-ray scattering reveals that we can form inverse hexagonal structures, which are present in a liquid crystalline nature within the LNP core. Comparison with lamellar LNPs reveals that the presence of inverse hexagonal phases enhances the intracellular silencing efficiency over lamellar structures. We then demonstrate that lamellar LNPs exhibit an in situ transition from a lamellar to inverse hexagonal phase upon interaction with anionic membranes, whereas LNPs containing pre-programmed liquid crystalline hexagonal phases bypass this transition for a more efficient one-step delivery mechanism, explaining the increased silencing effect. This rational design of LNPs with defined lipid structures aids in the understanding of the nano-bio interface and adds substantial value for LNP design, optimization and use.
The transcriptional regulatory network modulating human trophoblast stem cells to extravillous trophoblast differentiation
Authors: Kim Mijeong , Jang Yu Jin , Lee Muyoung , Guo Qingqing , Son Albert J. , Kakkad Nikita A. , Roland Abigail B. , Lee Bum-Kyu , Kim Jonghwan
Published: February 2024

During human pregnancy, extravillous trophoblasts play crucial roles in placental invasion into the maternal decidua and spiral artery remodeling. However, regulatory factors and their action mechanisms modulating human extravillous trophoblast specification have been unknown. By analyzing dynamic changes in transcriptome and enhancer profile during human trophoblast stem cell to extravillous trophoblast differentiation, we define stage-specific regulators, including an early-stage transcription factor, TFAP2C, and multiple late-stage transcription factors. Loss-of-function studies confirm the requirement of all transcription factors identified for adequate differentiation, and we reveal that the dynamic changes in the levels of TFAP2C are essential. Notably, TFAP2C pre-occupies the regulatory elements of the inactive extravillous trophoblast-active genes during the early stage of differentiation, and the late-stage transcription factors directly activate extravillous trophoblast-active genes, including themselves as differentiation further progresses, suggesting sequential actions of transcription factors assuring differentiation. Our results reveal stage-specific transcription factors and their inter-connected regulatory mechanisms modulating extravillous trophoblast differentiation, providing a framework for understanding early human placentation and placenta-related complications.
Predicting proximal tubule failed repair drivers through regularized regression analysis of single cell multiomic sequencing
Authors: Ledru Nicolas , Wilson Parker C. , Muto Yoshiharu , Yoshimura Yasuhiro , Wu Haojia , Li Dian , Asthana Amish , Tullius Stefan G. , Waikar Sushrut S. , Orlando Giuseppe , Humphreys Benjamin D.
Published: February 2024

Renal proximal tubule epithelial cells have considerable intrinsic repair capacity following injury. However, a fraction of injured proximal tubule cells fails to undergo normal repair and assumes a proinflammatory and profibrotic phenotype that may promote fibrosis and chronic kidney disease. The healthy to failed repair change is marked by cell state-specific transcriptomic and epigenomic changes. Single nucleus joint RNA- and ATAC-seq sequencing offers an opportunity to study the gene regulatory networks underpinning these changes in order to identify key regulatory drivers. We develop a regularized regression approach to construct genome-wide parametric gene regulatory networks using multiomic datasets. We generate a single nucleus multiomic dataset from seven adult human kidney samples and apply our method to study drivers of a failed injury response associated with kidney disease. We demonstrate that our approach is a highly effective tool for predicting key cis- and trans-regulatory elements underpinning the healthy to failed repair transition and use it to identify NFAT5 as a driver of the maladaptive proximal tubule state.
The secondary somatosensory cortex gates mechanical and heat sensitivity
Authors: Taub Daniel G. , Jiang Qiufen , Pietrafesa Francesca , Su Junfeng , Carroll Aloe , Greene Caitlin , Blanchard Michael R. , Jain Aakanksha , El-Rifai Mahmoud , Callen Alexis , Yager Katherine , Chung Clara , He Zhigang , Chen Chinfei , Woolf Clifford J.
Published: February 2024

The cerebral cortex is vital for the processing and perception of sensory stimuli. In the somatosensory axis, information is received primarily by two distinct regions, the primary (S1) and secondary (S2) somatosensory cortices. Top-down circuits stemming from S1 can modulate mechanical and cooling but not heat stimuli such that circuit inhibition causes blunted perception. This suggests that responsiveness to particular somatosensory stimuli occurs in a modality specific fashion and we sought to determine additional cortical substrates. In this work, we identify in a mouse model that inhibition of S2 output increases mechanical and heat, but not cooling sensitivity, in contrast to S1. Combining 2-photon anatomical reconstruction with chemogenetic inhibition of specific S2 circuits, we discover that S2 projections to the secondary motor cortex (M2) govern mechanical and heat sensitivity without affecting motor performance or anxiety. Taken together, we show that S2 is an essential cortical structure that governs mechanical and heat sensitivity.
Tomography-based digital twin of Nd-Fe-B permanent magnets
Authors: Bolyachkin Anton , Dengina Ekaterina , Kulesh Nikita , Tang Xin , Sepehri-Amin Hossein , Ohkubo Tadakatsu , Hono Kazuhiro
Published: February 2024

Many functional materials have been designed at the multiscale level. To properly simulate their physical properties, large and sophisticated computer models that can replicate microstructural features with nanometer-scale accuracy are required. This is the case for permanent magnets, which exhibit a long-standing problem of a significant offset between the simulated and experimental coercivities. To overcome this problem and resolve the Brown paradox, we propose an approach to construct large-scale finite element models based on the tomographic data from scanning electron microscopy. Our approach reconstructs a polycrystalline microstructure with actual shape, size, and packing of the grains as well as the individual regions of thin intergranular phase separated by triple junctions. Such a micromagnetic model can reproduce the experimental coercivity of ultrafine-grained Nd-Fe-B magnets along with its mechanism according to the angular dependence of coercivity. Furthermore, a remarkable role of thin triple junctions as nucleation centers for magnetization reversal is revealed. The developed digital twins of Nd-Fe-B permanent magnets can assist their optimization toward the ultimate coercivity, while the proposed tomography-based approach can be applied to a wide range of polycrystalline materials.
Dysfunctional attributions of success as a distinct feature of amotivation
Authors: Schormann Alisa L. A. , Butschbach Katja , Lincoln Tania M. , Riehle Marcel
Published: February 2024

We examined the association between causal attributions and self-reported motivational negative symptoms (amotivation) in a German online community sample (n = 251). Bivariate correlations revealed significant associations between amotivation and attribution of success to external, variable, and specific causes. No associations between amotivation and failure attributions were found. Our data suggest that demotivational causal attributions of success could be a feature of amotivation and a promising target for research and intervention.
Crop-GPA: an integrated platform of crop gene-phenotype associations
Authors: Gao Yujia , Zhou Qian , Luo Jiaxin , Xia Chuan , Zhang Youhua , Yue Zhenyu
Published: February 2024

With the increasing availability of large-scale biology data in crop plants, there is an urgent demand for a versatile platform that fully mines and utilizes the data for modern molecular breeding. We present Crop-GPA (https://crop-gpa.aielab.net), a comprehensive and functional open-source platform for crop gene-phenotype association data. The current Crop-GPA provides well-curated information on genes, phenotypes, and their associations (GPAs) to researchers through an intuitive interface, dynamic graphical visualizations, and efficient online tools. Two computational tools, GPA-BERT and GPA-GCN, are specifically developed and integrated into Crop-GPA, facilitating the automatic extraction of gene-phenotype associations from bio-crop literature and predicting unknown relations based on known associations. Through usage examples, we demonstrate how our platform enables the exploration of complex correlations between genes and phenotypes in crop plants. In summary, Crop-GPA serves as a valuable multi-functional resource, empowering the crop research community to gain deeper insights into the biological mechanisms of interest.