bluuebunny/crossref_metadata_2025 huggingface dataset:
Age at onset as an index of genetic heterogeneity in major psychiatric and substance use disorders
Authors: Kendler Kenneth S. , Henrik Ohlsson , Sundquist Jan , Sundquist Kristina
Published: December 2024

Background

Robust clinical indices of etiologic heterogeneity for psychiatric disorders are rare. We investigate whether age at onset (AAO) reflects genetic heterogeneity, utilizing Genetic Risk Ratios (GRR) derived from Family Genetic Risk Scores (FGRS).

Methods

We examined, in individuals born in Sweden 1940–2003, whether AAO for five primary disorders -- drug use disorder (DUD), alcohol use disorder (AUD), major depression (MD), bipolar disorder (BD), and schizophrenia (SZ)-- was associated with varying levels of GRRs with a range of informative secondary disorders and traits.

Results

Our disorders displayed a varying pattern of change of GRRs with increasing AAO. At one end was SZ, where all GRRs rose with increasing AAO meaning that SZ became increasing genetically heterogeneous with later AAO. The most balanced disorder was AUD where, with increasing AAO, GRRs rose for AD, BD, and MD and declined for DUD, CB, and ADHD. That is, at young AAO, AUD had high levels of genetic risk for other externalizing disorders while at older AAO, high genetic risk for internalizing disorders were more prominent. MD was at the continuum's other end where all GRRs, except for AD, decreased with higher AAO, meaning that MD became increasingly genetically homogeneous with later AAO.

Conclusions

Genetic heterogeneity was robustly associated with AAO across our five primary disorders with substantial inter-disorder differences in the observed patterns. In particular, young AAO was associated with maximal genetic homogeneity for SZ and DUD while older AAO had greater genetic homogeneity for MD with AUD falling in between.
Concept Mapping: An Innovative Approach to Clinical Case Analysis in an Undergraduate Medical Education Curriculum in Social Sciences, Humanities, Ethics, and Professionalism
Authors: Berger Jeffrey T. , Ribeiro Miller Dana , Mooney Melissa
Published: December 2024

Although ethics is increasingly integrated in the curriculum of U.S. medical schools, it remains not well integrated with system issues, and social and structural contexts of illness. Moreover, ethical analysis is not often taught as a clinical skill. To address these issues, an outcomes driven course in Social Sciences, Humanities, Ethics and Professionalism (SHEP) was created. Within the course, a web-based concept mapping device, SHEP Case Analysis Tool (SCAT), was created which schematizes the structure and flow of clinical cases from diagnosis to treatment options, to shared decision making to outcome, and includes key stakeholders, influences, and structural features of the health system. In the course, each student analyzes a case in which they were directly involved using SCAT and presents their analysis to faculty and peers. This exercise 1) reinforces knowledge-based portions of the course pedagogy, 2) supports meta-cognition and critical thinking through concept mapping, 3) applies multidimensional analysis to identify ethical, social, and system issues that impact patient-care. 4) develops problem solving skills, 5) counters the hidden curriculum/support professional identity formation, and 6) develops skills in reflective discourse. This paper outlines the development and use of this concept mapping case analysis tool in an undergraduate medical education curriculum.
(In)stability in American public attitudes toward Jews: a panel analysis
Authors: Cohen Jeffrey E.
Published: December 2024

Polls for the past several decades indicate high regard for Jews in democracies in Western Europe and North American. We however have a limited understanding of the properties underlying those poll responses, for instance whether response bias or nonattitudes account for those results. The nonattitudes perspective suggests that respondents’ survey answers to questions about Jews are not true attitudes. Nonattitudes are weakly held responses to survey questions, and tend to be unstable over time, reflecting random as opposed to systematic change. This paper uses panel data from Voter Study Group surveys to test for individual-level stability in attitudes toward Jews by non-Jews in the United States in the 2010s to assess whether such attitudes are true or nonattitudes. Results suggest considerable instability especially when compared to attitudes toward Muslims, Democrats, and Republicans, suggesting a high degree of nonattitudes in non-Jews attitudes toward Jews. The conclusion offers reasons that might account for this instability in attitudes toward Jews and implications for the continuation of positive regard for Jews in western democracies.
Bullshitting and Bullibility – Conditions and Consequences
Authors: Petrocelli John V. , Li Yanying , Wang Enhui , Curran Joseph M.
Published: December 2024

Abstract: Bullshitting involves communicating with little to no regard for truth, established knowledge, or genuine evidence in a way that helps people impress, persuade, influence, or confuse others, or to embellish or explain things in an area in which their obligations to provide opinions exceed their actual knowledge in those domains. Put another way, bullshitting encompasses a set of rhetorical strategies employed to help a person sound like they know what they are talking about when they really do not. Although bullshit can be useful to individual bullshitters as a persuasive tool, it can have considerable negative consequences for learning, memory, attitudes, opinions, and beliefs about what is believed to be true. Deeper understanding of the conditions under which bullshitting and general bullibility (i.e., consistent failure to discern bullshit from nonbullshit despite social cues signaling something is bullshit) are likely to emerge should position observers with a more successful vantage point to detect this deceptive behavior in others.
ARTEMIS Observations of Lunar Crustal Field‐Solar Wind Interaction and Impact on Reflected Plasma Under Weak Radial IMF
Authors: Liu Terry Z. , Angelopoulos Vassilis , An Xin , Madanian Hadi
Published: December 2024

Magnetic anomalies or crustal fields are frequently observed close to the lunar surface, yet their interaction with the ambient plasma is not fully understood. Utilizing data from the Acceleration, Reconnection, Turbulence and Electrodynamics of Moon's Interaction with the Sun (ARTEMIS) spacecraft, we perform case studies of such interactions under radial, weak interplanetary magnetic field. Our analysis shows that while the lunar crustal field direction did not directly affect the velocity and density of reflected ions, it locally increased their pitch angles, favoring growth of ultralow‐frequency waves. Additionally, we find that while the solar wind ions were demagnetized, retaining a nearly constant velocity, the magnetized electrons acquired significant perpendicular drift velocity due to the crustal field, resulting in a Hall current. This current altered the field strength near the lunar surface. The calculated loss cone angles of electrons reflected by the near‐surface field estimated from the Hall current are consistent with observations, suggesting that the crustal field was dominated by the Hall magnetic field. Our study advances our understanding of how lunar crustal fields interact with the solar wind and modify the nearby reflected plasma.
Challenges in Submarine Fiber‐Optic Earthquake Monitoring
Authors: Igel Jonas K. H. , Klaasen Sara , Noe Sebastian , Nomikou Paraskevi , Karantzalos Konstantinos , Fichtner Andreas
Published: December 2024

Utilizing existing telecommunication cables for Distributed Acoustic Sensing (DAS) experiments has eased the collection of seismological data in previously difficult‐to‐access areas such as the ocean bottom. To assess the potential of submarine DAS for monitoring seismic activity, we conducted an experiment from mid‐October to mid‐December 2021 using a 45 km long dark fiber extending from the Greek island of Santorini along the ocean bottom to the neighboring island of Ios. This region is of great geophysical and public interest because of its historical and recent seismic and volcanic activity, especially along the Kolumbo volcanic chain. Besides recording anthropogenic noise and around 1,000 seismic events, we observe the primary and secondary microseisms in the submarine section, the latter inducing Scholte waves in a sediment layer where the cable is well‐coupled. By using the spectral element wave propagation solver Salvus, we compute synthetic strains for earthquakes with varying degrees of model complexity. Despite including topography, a water layer, and a heterogeneous velocity model, we are unable to reproduce the lack of coherence in our observed earthquake waveforms. Backpropagation simulations for four observed earthquakes indicate that clear convergence of the wavefield, and thus the ability to constrain a source region, is only possible when all model complexities are considered. We conclude that, despite the promising emergence of DAS, monitoring capabilities are limited by often unfavorable cable geometries, cable coupling, and the complexity of the medium. Interrogating multiple cables simultaneously or jointly analyzing DAS and seismometer data could help improve future monitoring experiments.
Deciphering white matter microstructural alterations in catatonia according to ICD-11: replication and machine learning analysis
Authors: Peretzke Robin , Neher Peter F. , Brandt Geva A. , Fritze Stefan , Volkmer Sebastian , Daub Jonas , Northoff Georg , Bohn Jonas , Kirchhoff Yannick , Roy Saikat , Maier-Hein Klaus H. , Meyer-Lindenberg Andreas , Hirjak Dusan
Published: December 2024

Catatonia is a severe psychomotor disorder characterized by motor, affective and cognitive-behavioral abnormalities. Although previous magnetic resonance imaging (MRI) studies suggested white matter (WM) dysconnectivity in the pathogenesis of catatonia, it is unclear whether microstructural alterations of WM tracts connecting psychomotor regions might contribute to a better classification of catatonia patients. Here, diffusion-weighted MRI data were collected from two independent cohorts (whiteCAT/replication cohort) of patients with (n = 45/n = 13) and without (n = 56/n = 26) catatonia according to ICD-11 criteria. Catatonia severity was examined using the Northoff (NCRS) and Bush-Francis (BFCRS) Catatonia Rating Scales. We used tract-based spatial statistics (TBSS), tractometry (TractSeg) and machine-learning (ML) to classify catatonia patients from tractometry values as well as tractomics features generated by the newly developed tool RadTract. Catatonia patients showed fractional anisotropy (FA) alterations measured via TractSeg in different corpus callosum segments (CC_1, CC_3, CC_4, CC_5 and CC_6) compared to non-catatonia patients across both cohorts. Our classification results indicated a higher level of performance when trained on tractomics as opposed to traditional tractometry values. Moreover, in the CC_6, we successfully trained two classifiers using the tractomics features identified in the whiteCAT data. These classifiers were applied separately to the whiteCAT and replication cohorts, demonstrating comparable performance with Area Under the Receiver Operating Characteristics (AUROC) values of 0.79 for the whiteCAT cohort and 0.76 for the replication cohort. In contrast, training on FA tractometry resulted in lower AUROC values of 0.66 for the whiteCAT cohort and 0.51 for the replication cohort. In conclusion, these findings underscore the significance of CC WM microstructural alterations in the pathophysiology of catatonia. The successful use of an ML based classification model to identify catatonia patients has the potential to improve diagnostic precision.
BRAF inhibitors enhance erythropoiesis and treat anemia through paradoxical activation of MAPK signaling
Authors: Wu Shunkang , Deng Yuelin , Sun Haobo , Liu Xuewen , Zhou Shuo , Zhao Hanxi , Li Huan , Guo Fusheng , Yue Qiuyu , Wu Fan , Zhao Xinying , Li Na , Zhu Shicong , Hu Qi , Xie Si , Zheng Jie , Lv Meng , Kong Yuan , Huang Xiao-Jun , Lei Xiaoguang , Tong Xiangmin , Gao Xiaofei , Lee Hsiang-Ying
Published: December 2024

Erythropoiesis is a crucial process in hematopoiesis, yet it remains highly susceptible to disruption by various diseases, which significantly contribute to the global challenges of anemia and blood shortages. Current treatments like erythropoietin (EPO) or glucocorticoids often fall short, especially for hereditary anemias such as Diamond-Blackfan anemia (DBA). To uncover new erythropoiesis-stimulating agents, we devised a screening system using primary human hematopoietic stem and progenitor cells (HSPCs). We discovered that BRAF inhibitors (BRAFi), commonly used to treat BRAFV600E melanoma, can unexpectedly and effectively promote progenitor cell proliferation by temporarily delaying erythroid differentiation. Notably, these inhibitors exhibited pronounced efficacy even under cytokine-restricted conditions and in patient samples of DBA. Mechanistically, although these BRAFi inhibit the MAPK cascade in BRAFV600E mutant cells, they paradoxically act as amplifiers in wild-type BRAF cells, potently enhancing the cascade. Furthermore, we found that while the oncogenic BRAFV600E mutation disrupts hematopoiesis and erythropoiesis through AP-1 hyperactivation, BRAFi minimally impact HSPC self-renewal and differentiation. In vivo studies have shown that BRAFi can enhance human hematopoiesis and erythropoiesis in severe immunodeficient mouse models and alleviate anemia in the Rpl11 haploinsufficiency DBA model, as well as other relevant anemia models. This discovery underscores the role of the MAPK pathway in hematopoiesis and positions BRAFi as a promising therapeutic option for improving hematopoietic reconstitution and treating anemias, including DBA.
Influenza A(H5N1) shedding in air corresponds to transmissibility in mammals
Authors: Tosheva Ilona I. , Filaire Fabien , Rijnink Willemijn F. , de Meulder Dennis , van Kekem Bianca , Bestebroer Theo M. , Funk Mathis , Spronken Monique I. , Cáceres C. Joaquin , Perez Daniel R. , Richard Mathilde , Koopmans Marion P. G. , Fraaij Pieter L. A. , Fouchier Ron A. M. , Herfst Sander
Published: December 2024

An increase in spillover events of highly pathogenic avian influenza A(H5N1) viruses to mammals suggests selection of viruses that transmit well in mammals. Here we use air-sampling devices to continuously sample infectious influenza viruses expelled by experimentally infected ferrets. The resulting quantitative virus shedding kinetics data resembled ferret-to-ferret transmission studies and indicated that the absence of transmission observed for earlier A(H5N1) viruses was due to a lack of infectious virus shedding in the air, rather than the absence of necessary mammalian adaptation mutations. Whereas infectious human A(H1N1pdm) virus was efficiently shed in the air, infectious 2005 zoonotic and 2024 bovine A(H5N1) viruses were not detected in the air. By contrast, shedding of infectious virus was observed for 1 out of 4 ferrets infected with a 2022 European polecat A(H5N1) virus and a 2024 A(H5N1) virus isolated from a dairy farm worker.
Membrane mechanics dictate axonal pearls-on-a-string morphology and function
Authors: Griswold Jacqueline M. , Bonilla-Quintana Mayte , Pepper Renee , Lee Christopher T. , Raychaudhuri Sumana , Ma Siyi , Gan Quan , Syed Sarah , Zhu Cuncheng , Bell Miriam , Suga Mitsuo , Yamaguchi Yuuki , Chéreau Ronan , Nägerl U. Valentin , Knott Graham , Rangamani Padmini , Watanabe Shigeki
Published: December 2024

Axons are ultrathin membrane cables that are specialized for the conduction of action potentials. Although their diameter is variable along their length, how their morphology is determined is unclear. Here, we demonstrate that unmyelinated axons of the mouse central nervous system have nonsynaptic, nanoscopic varicosities ~200 nm in diameter repeatedly along their length interspersed with a thin cable ~60 nm in diameter like pearls-on-a-string. In silico modeling suggests that this axon nanopearling can be explained by membrane mechanical properties. Treatments disrupting membrane properties, such as hyper- or hypotonic solutions, cholesterol removal and nonmuscle myosin II inhibition, alter axon nanopearling, confirming the role of membrane mechanics in determining axon morphology. Furthermore, neuronal activity modulates plasma membrane cholesterol concentration, leading to changes in axon nanopearls and causing slowing of action potential conduction velocity. These data reveal that biophysical forces dictate axon morphology and function, and modulation of membrane mechanics likely underlies unmyelinated axonal plasticity.
Nanomechanical detection to empower robust monitoring of sepsis and microbial adaptive immune system-mediated proinflammatory disease
Authors: Thanapirom Kessarin , Al-Akkad Walid , Pelut Aylin , Sadouki Zahra , Finkel Jemima B. , Nardi-Hiebl Stefan , Vogt Wieland , Vojnar Benjamin , Wulf Hinnerk , Eberhart Leopold , McHugh Timothy D , Rombouts Krista , Pinzani Massimo , Tsochatzis Emmanouil , Ndieyira Joseph W.
Published: December 2024

The correlation between circulating microbes and sepsis as well as proinflammatory diseases is increasingly gaining recognition. However, the detection of microbes’ cell-free DNA (cfDNA), which exist at concentrations of a billion times lower than blood proteins, poses a significant challenge for early disease detection. Here, we present Nano mechanics combined with highly sensitive readout sequences to address the challenges of ultralow counts of disease biomarkers, thus enabling robust quantitative monitoring of chronic medical conditions at different stages of human disease progression. To showcase the effectiveness of our approach, we employ fragments of cfDNA and human cell secretory proteins as models with predictive capabilities for human diseases. Notably, our method reveals a reliable representation over an impressive three to four orders of magnitude in the detection limit and dynamic range, surpassing commercially available quantitative polymerase chain reaction (qPCR) commonly used in routine clinical practice. This concept underpins a highly sensitive and selective medical device designed for the early detection of circulating microbes in patients undergoing intensive cancer therapy. This will help pinpoint individuals at risk of complications, including damage to the intestinal barrier and development of neutropenic fever/Sirsa/Sepsis. Moreover, this approach introduces new avenues for stratifying antibiotic prophylaxis in proinflammatory diseases.
Modification of glass screen printed electrodes with graphene quantum dots for enhanced power output in miniaturized microbial fuel cells
Authors: Mao Yuvraj Maphrio , Amreen Khairunnisa , Calay Rajnish Kaur , Banerjee Aritro , Goel Sanket
Published: December 2024

This paper demonstrates screen-printing technique, Glass Screen printed (GSP) on glass layer with Graphene Quantum Dots (GQDs) via drop casting approach to manufacture electrodes for Miniaturized Microbial Fuel Cells (MMFCs). MMFCs are viable options to sustainably operate low-power devices such as sensors, implantable medical devices, etc. However, the technology is still not fully mature for practical applications due to limitations of output power. Materials and design improvements are required for decreasing internal resistance for better electron transfer and improving overall performance. In this work the electrodes manufactured by GSP technique, and anode modified by GQD was tested in MMFC using RO wastewater. It was found that the GQDs increased the surface area to improve electron transfer kinetics at the anode. As a result, GQDs-based GSPEs showed 7.4 times higher power output 332 nW/cm2 compared to its unaltered electrode which displayed a power output of 44.8 nW/cm2. Electrodes made by GSP technique are more durable and less susceptible to biofouling and corrosion compared to conventional methods. The modified anodes further showed sustained output for long term operation.
Spontaneous nanosized liposome formation from crude dried lecithin upon addition of glycerol
Authors: Marangoni Alejandro G. , Pensini Erica
Published: December 2024

Nanosized liposomal vesicles (NLV) were successfully prepared using natural sunflower lecithin without the use of high-pressure homogenization or filtration. Upon glycerol addition to dispersions of lecithin multilamellar vesicles (MLVs), these broke down spontaneously to liposomes with diameters in the range of 100–200 nm. Static light scattering demonstrated that glycerol addition above 30% (w/w) induced the complete transformation of MLVs into NLVs. Langmuir trough compression experiments showed a two-region compressional behavior. Upon 62% (w/w) glycerol addition, the compressional modulus of the liposomes decreased from 18.5 to 8.13 mN/m. Water activity and pulse NMR measurements also showed a divergence in behavior above 30% (w/w) glycerol. Liposomes were not birefringent in water but became strongly birefringent at and above 30% (w/w) glycerol, as determined by polarized light microscopy, and lost all birefringence above 80% (w/w). This was interpreted as the induction of stress-birefringence in the phospholipid bilayers above 30% (w/w) glycerol, and a relaxation of such stress above 80% (w/w) glycerol. We hypothesize that the mixture of phospholipids in the lecithin results in an effective non-zero intrinsic curvature for the molecular mixture, which lowers the bending energy of the bilayer, allowing for an easier break-up upon mixing. Secondly, glycerol addition decreases attractive van der Waals’ interaction between lamellae in an MLV, thus weakening the multilamellar liposome walls. Glycerol also affects bilayer stability by strengthening the hydrogen bond network of water, which will affect phospholipid headgroup hydration. All these factors result in the spontaneous breakdown of MLVs into NLVs.
Seismic performance of the replaceable steel links with different short length ratios
Authors: Xiong Liquan , Guo Zhengchao , Cai Jun , Jiang Kaiyu , Li Linyan
Published: December 2024

Compared with the traditional frame structures, the novel composite frame with replaceable steel links can realize the rapid recovery of building occupancy after seismic actions to provide the capacity of reducing structural damage and ensure the reuse of a structure. In this system, plastic deformation and damage mainly concentrated in the steel links serving as the structural fuses and other structural members still remained elastic or minor plastic, and then the damaged steel links can be easy for replace. In order to study the seismic performance of the replaceable steel links, a total of four test specimens with different short length ratios were designed. A low-cycle reversed loading test was carried out in terms of failure characteristic, hysteretic response and shear strength. The results indicated that all tested specimens presented a stable and full hysteretic response while the steel links especially exhibited a large inelastic deformation capacity and fully developed shear strength as the structural fuses. Besides, failure modes of steel links included two types of shear failure and bending-shear failure, followed by two types of damage features, including web-to-stiffener weld tear, web buckling, flange-to-end plate weld tear and flange buckling, respectively. Finally, nonlinear finite element models (FEMs) of test specimens were implemented by the Abaqus software. The numerical results were in good agreement with the experimental results in terms of load-deformation curves, initial stiffness, the development of Von Mises stress and cumulative plastic equivalent strain (PEEQ) indexes to facilitate design practice.
Gating-spring stiffness increases outer-hair-cell bundle stiffness, damping, and receptor current
Authors: Zhu Zenghao , Reid Wisam , Ó Maoiléidigh Dáibhid
Published: December 2024

In our ears, outer-hair-cell bundles (OHBs) convert sound-induced forces into receptor currents that drive cochlear amplification, the process responsible for the micropascal-scale threshold and million-fold dynamic range of hearing. OHBs rely on gating springs to open mechanoelectrical-transduction (MET) ion channels, through which the receptor current flows. OHBs have larger gating-spring stiffnesses than other types of hair bundles, but we have a poor understanding of how gating-spring stiffness contributes to OHB mechanics and receptor-current regulation. Using experimentally-constrained mathematical models of the OHB, we show that the increased gating-spring stiffness in an OHB increases its stiffness and damping. The OHB’s 3D morphology reduces the contribution of gating-spring stiffness to OHB stiffness, reduces the contribution of MET-channel gating to OHB stiffness and damping, but causes additional OHB damping that rises with gating-spring stiffness. Gating-spring stiffness increases the OHB’s receptor current but decreases its displacement-current dynamic range. Strikingly, the OHB’s 3D morphology causes its force-current dynamic range to decrease with gating-spring stiffness. Our results suggest a trade-off between threshold and dynamic range regulated by OHB gating-spring stiffness.
Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer
Authors: Rhinehart Dena P. , Lai Jiaying , Sanin David E. , Vakkala Varsha , Mendes Adrianna , Bailey Christopher , Antonarakis Emmanuel S. , Paller Channing J. , Wu Xiaojun , Lotan Tamara L. , Karchin Rachel , Sena Laura A.
Published: December 2024

Metastatic prostate cancer (PCa) is not curable due to its ability to acquire therapy resistance. Theoretically, acquired therapy resistance can be driven by changes to previously sensitive cancer cells or their environment and/or by outgrowth of a subpopulation of cancer cells with primary resistance. Direct demonstration of the latter mechanism in patients with PCa is lacking. Here we present a case report as proof-of-principle that outgrowth of a subpopulation of cancer cells lacking the genomic target and present prior to therapy initiation can drive acquired resistance to targeted therapy and threaten survival in patients with PCa.
Identification of responsible sequences which mutations cause maternal H19-ICR hypermethylation with Beckwith–Wiedemann syndrome-like overgrowth
Authors: Hara Satoshi , Matsuhisa Fumikazu , Kitajima Shuji , Yatsuki Hitomi , Kubiura-Ichimaru Musashi , Higashimoto Ken , Soejima Hidenobu
Published: December 2024

Beckwith-Wiedemann syndrome (BWS) is caused by a gain of methylation (GOM) at the imprinting control region within the Igf2-H19 domain on the maternal allele (H19-ICR GOM). Mutations in the binding sites of several transcription factors are involved in H19-ICR GOM and BWS. However, the responsible sequence(s) for H19-ICR GOM with BWS-like overgrowth has not been identified in mice. Here, we report that a mutation in the SOX-OCT binding site (SOBS) causes partial H19-ICR GOM, which does not extend beyond CTCF binding site 3 (CTS3). Moreover, simultaneously mutating both SOBS and CTS3 causes complete GOM of the entire H19-ICR, leading to the misexpression of the imprinted genes, and frequent BWS-like overgrowth. In addition, CTS3 is critical for CTCF/cohesin-mediated chromatin conformation. These results indicate that SOBS and CTS3 are the sequences in which mutations cause H19-ICR GOM leading to BWS-like overgrowth and are essential for maintaining the unmethylated state of maternal H19-ICR.
Mechanisms of axoneme and centriole elimination in Naegleria gruberi
Authors: Woglar Alexander , Busso Coralie , Garcia-Rodriguez Gabriela , Douma Friso , Croisier Marie , Knott Graham , Gönczy Pierre
Published: December 2024

The early branching eukaryote Naegleria gruberi can transform transiently from an amoeboid life form lacking centrioles and flagella to a flagellate life form where these elements are present, followed by reversion to the amoeboid state. The mechanisms imparting elimination of axonemes and centrioles during this reversion process are not known. Here, we uncover that flagella primarily fold onto the cell surface and fuse within milliseconds with the plasma membrane. Once internalized, axonemes are severed by Spastin into similarly-sized fragments that are then enclosed by membranes, before their contents are eliminated through the lysosomal pathway. Moreover, we discovered that centrioles undergo progressive K63 autophagy-linked poly-ubiquitination and K48 proteasome-promoting poly-ubiquitination, and that such ubiquitination occurs next to centriolar microtubules. Most centrioles are eliminated in either lysosomes or the cytoplasm in a lysosomal- and proteasome-dependent manner. Strikingly, we uncover in addition that centrioles can be shed in the extracellular milieu and taken up by other cells. Collectively, these findings reveal fundamental mechanisms governing the elimination of essential cellular constituents in Naegleria that may operate broadly in eukaryotic systems.
Coordination of cytochrome bc1 complex assembly at MICOS
Authors: Zerbes Ralf M , Colina-Tenorio Lilia , Bohnert Maria , von der Malsburg Karina , Peikert Christian D , Mehnert Carola S , Perschil Inge , Klar Rhena F U , de Boer Rinse , Kram Anita , van der Klei Ida , Oeljeklaus Silke , Warscheid Bettina , Rampelt Heike , van der Laan Martin
Published: December 2024

The boundary and cristae domains of the mitochondrial inner membrane are connected by crista junctions. Most cristae membrane proteins are nuclear-encoded and inserted by the mitochondrial protein import machinery into the inner boundary membrane. Thus, they must overcome the diffusion barrier imposed by crista junctions to reach their final location. Here, we show that respiratory chain complexes and assembly intermediates are physically connected to the mitochondrial contact site and cristae organizing system (MICOS) that is essential for the formation and stability of crista junctions. We identify the inner membrane protein Mar26 (Fmp10) as a determinant in the biogenesis of the cytochrome bc
1 complex (complex III). Mar26 couples a Rieske Fe/S protein-containing assembly intermediate to MICOS. Our data indicate that Mar26 maintains an assembly-competent Rip1 pool at crista junctions where complex III maturation likely occurs. MICOS facilitates efficient Rip1 assembly by recruiting complex III assembly intermediates to crista junctions. We propose that MICOS, via interaction with assembly factors such as Mar26, contributes to the spatial and temporal coordination of respiratory chain biogenesis.
Controlling chemical interface damping by removing aromatic monothiol and dithiol groups from gold nanorods using sodium borohydride solution
Authors: Kim Ji Min , Ha Ji Won
Published: December 2024

This study provides insights into the removal of aromatic thiol molecules using NaBH4, as well as the direct control of CID in individual AuNRs.
Harnessing concerted functions in confined environments: cascading enzymatic reactions in nanofluidic biosensors for sensitive detection of arginine
Authors: Gramajo Marcos E. , Otero Maffoni Lautaro , Hernández Parra L. Miguel , Marmisollé Waldemar A. , Cortez M. Lorena , Toimil-Molares M. Eugenia , Peinetti Ana S. , Azzaroni Omar
Published: December 2024

Cascading enzymatic reactions within nanochannels enable rapid (<5 min) and highly sensitive detection of arginine by leveraging cooperative functions in a confined environment.
Atomically thin 2D materials for solution-processable emerging photovoltaics
Authors: Stroyuk Oleksandr , Raievska Oleksandra , Hauch Jens , Brabec Christoph J.
Published: December 2024

This Feature highlights the most prominent features of atomically thin 2D materials and their potential for emerging photovoltaics.
Dielectric barrier discharge-mediated one-pot rapid synthesis of platinum nanoclusters for fluorescent sensing of malachite green
Authors: Ma Bingxin , Wang Bodong , Li Yuqi , Jiang Lianshuang , Hou Xiandeng , Xu Kailai
Published: December 2024

Water-soluble and green-fluorescent GSH@PtNCs were rapidly synthesized by a DBD-mediated one-pot method, and successfully applied to fluorescence sensing of malachite green based on the inner filter effect.
Visible light-induced cascade annulation of sulfoxonium ylides with azides for the synthesis of 2-trifluoromethyl indoles
Authors: Cui Jia-Huan , Chen Qian-Yu , Zhang Jun , He Yan , Li Xingguang , Liu Pei-Nian
Published: December 2024

An efficient protocol was reported for the synthesis of 2-trifluoromethyl indoles through visible-light-promoted intermolecular cyclization of sulfoxonium ylides with azides, without the need for external photocatalysts, transition metals, or bases.
19F-PCS measurements on proteins in live mammalian cells
Authors: Guo Shu-Li , Pan Bin-Bin , Li Xia-Yan , Xiao Yu-Hao , Su Xun-Cheng
Published: December 2024

We exploited the difference in activity between two cysteine residues to sequentially introduce paramagnetic and 19F tags at specific sites in a single protein, and sizable 19F-PCS was determined in live mammalian cells.
Macrocyclic catalysis mediated by water: opportunities and challenges
Authors: Zhang Dejun , Wang Lingyun , Wu Wanqing , Cao Derong , Tang Hao
Published: December 2024

This work summarizes macrocyclic catalysis strategies for overcoming aqueous-phase reactivity challenges, product inhibition, and catalyst compatibility in “one-pot” reactions.
Molecular acceptor engineering to precisely design a NIR type I photosensitizer for efficient PDT-based synergistic therapy
Authors: Zou Ziqi , Xie Yili , Wan Jiaxing , Wan Qing , Tian Jianwen , Zhang Xiaoyong , Wei Yen
Published: December 2024

Three near-infrared red type I PSs (named TP1, TP2, and TP3) were synthesized by adjusting their electron acceptors. TP3 can achieve efficient PDT-based synergistic therapy in cells via glutathione depletion.
Tailoring the coordination microenvironment of Zn(ii) in a light-responsive coordination polymer system for molecular sensing and photodegradation performance
Authors: Zhao Yan , Zhou Xing , Liu Zheng-Yu , Wang Jia-Jun , Ding Bo , Liu Gui-Xi , Yang En-Cui
Published: December 2024

Three semi-conductive CPs with skilfully tuned coordination surroundings exhibited highly efficient sensing of bilirubin and photodegradation of methylene blue due to the bandgap-dominated movements of the photogenerated charge carriers.
Cocrystals of [1,2,5]oxadiazolo[3,4-c]cinnoline 5-oxides and 1,5-dioxides: step-by-step development of crystal engineering of energetic materials
Authors: Baraboshkin N. M. , Zelenov V. P. , Fedyanin I. V. , Samigullina A. I. , Klenov M. S.
Published: December 2024

Using crystal structure prediction methods, cocrystal packings for BTF and FTDO with FCO/FCDO were simulated. New cocrystals of BTF and FTDO with FCDO were obtained, their crystal structures determined and the main interactions analyzed.
Ammonia electro-oxidation on nickel hydroxide: phases, pH and poisoning
Authors: Offen-Polak Inbal , Ayali Aviram Hilla , Hijaze Adan , Slot Thierry K. , Eisenberg David
Published: December 2024

The disordered α phase of nickel hydroxide is a better catalysts for ammonia electro-oxidation than the β phase, but is also poisoned more strongly at high ammonia concentrations.
Theoretical insights into the effect of metal co-substituted CeO2(111) surfaces on oxygen vacancy formation and chemical looping CO2 assisted CH4 conversion to synthesis gas
Authors: Wang Zeshan , Li Yuelun , Wang Yuxin , Li Tao , Zheng Jiahao , Huang LiNan , Zuo Huicong , Tian Dong , Wang Hua , Li Kongzhai
Published: December 2024

Chemical looping CO2 assisted CH4 conversion to synthesis gas with Zn and Nd co-substituted on CeO2 (111) surface as oxygen carrier.
Impact of grain boundaries on the electronic properties and Schottky barrier height in MoS2@Au heterojunctions
Authors: Sorkin Viacheslav , Zhou Hangbo , Yu Zhi Gen , Ang Kah-Wee , Zhang Yong-Wei
Published: December 2024

This work explores GB impact on MoS2@Au SBH. DFT shows GBs significantly reduce SBH in defect-free MoS2. Our findings emphasize the importance of GB control for high-performance MoS2-based neuromorphic devices.
Non-convergence of the blinking timescale of twelve-faceted perovskite nanocrystals observed through an advanced fluorescence correlation spectroscopy study
Authors: Acharjee Debopam , Mahato Asit Baran , Panda Mrinal Kanti , Ghosh Subhadip
Published: December 2024

Scanning FCS, distinct from traditional FCS, explores charge carrier dynamics in 12-faceted perovskite nanocrystals across a broad range of timescales, uncovering their non-converging blinking behaviour.
Revising exciton diffusion lengths in polymer dot photocatalysts
Authors: Brnovic Andjela , Hunt Leigh Anna , Tian Haining , Hammarström Leif
Published: December 2024

The study reveals that an intrinsic diffusion length of PFBT Pdots exceeds previously reported values and a quenching volume comparable to the particle core size, suggesting that efficient exciton migration to the surface is viable.
Searching the chemical space of hetero-atom bridged norbornadienes
Authors: Oberhof Nils , Hillers-Bendtsen Andreas Erbs , Obel Oscar Berlin , Schjelde Karoline , Mikkelsen Kurt V. , Dreuw Andreas
Published: December 2024

Substituted hetero-atom bridged norbornadienes has been screened for suitable molecular solar thermal systems exploiting an efficient computational design strategy. Five new substitution patterns have been identified as particularly promising.
Superconductivity in hexagonal Ce0.5La0.5H9 under high pressure
Authors: Pinsook Udomsilp , Tsuppayakorn-aek Prutthipong , Bovornratanaraks Thiti
Published: December 2024

Our calculations support the experimental finding that Ce0.5La0.5H9 is a stable compound and clearly indicate that it achieves a high-Tc of approximately 127 K at 120 GPa.
Black phosphorus-based nanoplatforms for cancer therapy: chemistry, design, biological and therapeutic behaviors
Authors: Bigham Ashkan , Serrano-Ruiz Manuel , Caporali Maria , Fasolino Ines , Peruzzini Maurizio , Ambrosio Luigi , Raucci Maria Grazia
Published: December 2024

Black phosphorus nanomaterials have opened new doors to cancer therapy. They can induce anticancer activities intrinsically (selectively) and/or with external stimuli (PTT, PDT, SDT, etc.) and are highly suitable for drug/gene delivery.
Nanomaterial-enabled metabolic reprogramming strategies for boosting antitumor immunity
Authors: Ma Muye , Zhang Yongliang , Pu Kanyi , Tang Wei
Published: December 2024

We discuss the recent advances in nanomaterial design strategies for immunometabolic modulatory platforms and their applications in targeting the cancer-immunity cycle to enhance therapeutic outcomes.
Operando X-ray absorption spectroscopic flow cell for electrochemical CO2 reduction: new insight into the role of copper species
Authors: Matam Santhosh K. , Sharma P. K. , Yu E. H. , Drivas C. , Khan M. D. , Wilding M. , Ramanan N. , Gianolio D. , Isaacs M. A. , Guan S. , Davies P. R. , Catlow C. Richard A.
Published: December 2024

We report a novel operando X-ray absorption spectroscopic (XAS) flow cell that enables to probe Cu-GDE thoroughly from surface to bulk during electrochemical CO2 reduction, providing information on copper oxidation and coordination states.
Quantitative elemental analysis of human leukemia K562 single cells by inductively coupled plasma mass spectrometry in combination with a microdroplet generator
Authors: Tanaka Yu-ki , Katayama Hinano , Iida Risako , Ogra Yasumitsu
Published: December 2024

A μDG was installed into a sample introduction system of scICP-MS to achieve efficient and quantitative elemental analysis of cultured mammalian cells at the single-cell level.
A 3D-printed multi-compartment organ-on-chip platform with a tubing-free pump models communication with the lymph node
Authors: Cook Sophie R. , Ball Alexander G. , Mohammad Anwaruddin , Pompano Rebecca R.
Published: December 2024

We developed a user-friendly multi-compartment chip and impeller pump to model the acute response to vaccine within a lymph node.
Correction: A comprehensive apoptotic assessment of niloticin in cervical cancer cells: a tirucallane-type triterpenoid from Aphanamixis polystachya (Wall.) Parker
Authors: Joseph Anuja Gracy , Biji Mohanan , Murali Vishnu Priya , Sherin Daisy R. , Valsan Alisha , Sukumaran Vimalkumar P. , Radhakrishnan Kokkuvayil Vasu , Maiti Kaustabh Kumar
Published: December 2024

Correction for ‘A comprehensive apoptotic assessment of niloticin in cervical cancer cells: a tirucallane-type triterpenoid from Aphanamixis polystachya (Wall.) Parker’ by Anuja Gracy Joseph et al., RSC Med. Chem., 2024, 15, 3444–3459, https://doi.org/10.1039/D4MD00318G.
Optimizing dielectric, mechanical, and thermal properties of epoxy resin through molecular design for multifunctional performance
Authors: Deng Yuheng , Wong Yen Wen , Teh Letitia Kai Yue , Wang Qi , Sun Weifeng , Chern Wen Kwang , Oh Joo Tien , Chen Zhong
Published: December 2024

Epoxy resins are widely used as dielectric materials in electrical and electronic systems. This study demonstrates that small amounts of chemical modifiers can significantly enhance epoxy resin performance.
Solid-state self carbo-passivation for refurbishing colloidal dispersity of catalytic silica nanoreactors
Authors: Choi Jeong Hun , Kumari Nitee , Acharya Anubhab , Kumar Amit , Park Sanghwang , Ro Dongyeon , Seo Jongcheol , Lee Eunhye , Bae Jee Hwan , Chun Dong Won , Oh Kyungtaek , Ryu Sunmin , Lee In Su
Published: December 2024

A self-carbo-passivation strategy tackles the agglomeration issue in silica nanostructures by thermally forming carbonaceous skin patches on the nanoparticle surface.
An efficient visible light-driven double-well-based Pt/CdS/3D-graphene heterostructure for electrocatalytic and photo-electrocatalytic methanol oxidation
Authors: Ullah Habib , Mumtaz Muqaddas Fatima , Mumtaz Asad , Sajid Hina , Zahra Sani , Sardar Sabahat , Naz Uzma , Niazi Qamir Ullah , Iqbal Shahid , Adil Syed Farooq , Hatshan Mohammad Rafe , Khan Mujeeb , Ambreen Jaweria , Irshad Muhammad Imran , Ahmad Muhammad
Published: December 2024

The proposed charge transfer mechanism of a double-well-based Pt/CdS/3D-graphene heterostructure and its efficient visible light-driven photo-electrocatalytic methanol oxidation.
The intrinsic piezoelectricity of monoclinic Pb(Zr1−xTix)O3
Authors: Niu Junyu , Li Chong , Xi Zengzhe
Published: December 2024

The Cm(MB) structure of PZT was confirmed by DFT as a stable phase via phonon and covalent bonding analysis. Given its lower piezoelectric, the intrinsic piezoelectricity of low-symmetry phase was confirmed not the major contributor to MPB effect.
High-resolution in situ photo-irradiation MAS NMR: application to the UV-polymerization of n-butyl acrylate
Authors: Hooper Thomas J. N. , de Oliveira-Silva Rodrigo , Sakellariou Dimitrios
Published: December 2024

An in situ irradiation MAS NMR setup is demonstrated via high-resolution 1H and 13C NMR of the UV-polymerization of n-butyl acrylate.
Highly dispersed copper-based nanocomposite synthesis via spray pyrolysis: towards waste-to-hydrogen production through the water-gas shift reaction
Authors: Jeon I-Jeong , Lee Jae Seob , Baek Kun Woo , Kim Chang-Hyeon , Gong Ji-Hyeon , Jang Won-Jun , Cho Jung Sang , Shim Jae-Oh
Published: December 2024

In this study, we synthesized a Cu–ZrCeO2 catalyst using spray pyrolysis, which exhibited high activity, stability, and reusability at high temperatures.
Gα12 and Gα13 proteins are required for transforming growth factor-β-induced myofibroblast differentiation
Authors: Reed Eleanor B. , Sitikov Albert , Shin Kun Woo D. , Hamanaka Robert B. , Cetin-Atalay Rengül , Mutlu Gökhan M. , Mongin Alexander A. , Dulin Nickolai O.
Published: December 2024

Myofibroblast differentiation, characterized by accumulation of cytoskeletal and extracellular matrix proteins by fibroblasts, is a key process in wound healing and pathogenesis of tissue fibrosis. Transforming growth factor-β (TGF-β) is the most powerful known driver of myofibroblast differentiation. TGF-β signals through transmembrane receptor serine/threonine kinases that phosphorylate Smad transcription factors (Smad2/3) leading to activation of transcription of target genes. Heterotrimeric G proteins mediate distinct signaling from seven-transmembrane G protein coupled receptors, which are not known to be linked to Smad activation. We tested whether G protein signaling plays any role in TGF-β-induced myofibroblast differentiation, using primary cultured human lung fibroblasts. Activation of Gαs by cholera toxin blocked TGF-β-induced myofibroblast differentiation without affecting Smad2/3 phosphorylation. Neither inhibition of Gαi by pertussis toxin nor siRNA-mediated combined knockdown of Gαq and Gα11 had a significant effect on TGF-β-induced myofibroblast differentiation. In contrast, combined knockdown of Gα12 and Gα13 significantly inhibited TGF-β-stimulated expression of myofibroblast marker proteins (collagen-1, fibronectin, smooth-muscle α-actin), with siGα12 being significantly more potent than siGα13. Mechanistically, combined knockdown of Gα12 and Gα13 resulted in substantially reduced phosphorylation of Smad2 and Smad3 in response to TGF-β, which was accompanied by a significant decrease in the expression of TGF-β receptors (TGFBR1, TGFBR2) and of Smad3. Thus, our study uncovers a novel role of Gα12/13 proteins in the control of TGF-β signaling and myofibroblast differentiation.
Opposing regulation of endoplasmic reticulum retention under stress by ERp44 and PDIA6
Authors: Yassin Olaya , Praveen Bellam , Darawshi Odai , LaFramboise Thomas , Shmuel Miriam , Pattanayak Shakti P. , Law Brian K. , Hatzoglou Maria , Tirosh Boaz
Published: December 2024

Conditions of endoplasmic reticulum (ER) stress reduce protein synthesis by provoking translation regulation, governed by the eIF2α kinase PERK. When PERK is inhibited during ER stress, retention of a selective subset of glycoproteins occurs, a phenomenon we termed selective ER retention (sERr). sERr clients are enriched with tyrosine kinase receptors (RTKs), which form large molecular weight disulfide bonded complexes in the ER. The protein disulfide isomerase ERp44 promotes sERr and increases the size of sERr complexes. Here we show that sERr is reversible upon washout. Pulse chase analyses show that upon recovery, only a small fraction of the sERr complexes disintegrates and contributes to the matured proteins, while most are newly synthesized. Sequential inductions of sERr and washouts demonstrate an accelerated recovery that is dependent on the unfolded protein response transducer IRE1. Since IRE1 regulates the expression level PDIA6, we analyzed its contribution to sERr. We found that PDIA6 and ERp44 constitutively interact by disulfides and have opposite effects on resumed recovery of trafficking following removal of sERr conditions. Deletion of ERp44 accelerates, while deletion of PDIA6 slows down recovery with a minimal effect on total protein synthesis. ERp44 is a primary interactor with sERr clients. When missing, PDIA6 partitions more into sERr complexes. Deletion of the tumor suppressor PTEN, which induces RTK signaling, promoted sERr formation kinetics, and accelerated the recovery, suggesting feedback between RTKs signaling and sERr. This study suggests that sERr, should develop physiologically or pathologically, is counteracted by adaptation responses that involve IRE1 and PDIA6.