bluuebunny/crossref_metadata_2025 huggingface dataset:
Gentle Perseverance Lifts the Veil on Martian Dust
Authors: Lorenz Ralph D.
Published: September 2023

Observations with sensitive photodiode detectors on the Perseverance rover (Hueso et al., 2023, https://doi.org/10.1029/2022JE007516; Vicente‐Retortillo et al., 2023, https://doi.org/10.1029/2022je007672) to detect dust devils and track formation, and movies of the Ingenuity helicopter's downwash impingement on the Martian surface (Lemmon et al., 2022a, https://doi.org/10.1029/2022je007605; Lemmon et al., 2022b, https://doi.org/10.1029/2022gl100126), together with in‐situ meteorological data, give new insights into the important problem of dust‐lifting on Mars, a phenomenon which influenced the lifetime of recent rovers and landers. These results, together with new low‐gravity wind tunnel experiments on parabolic flights and interpretation of the large blast pattern from lander retrorockets, indicate that particle motion and visible darkening on Mars can result from aerodynamic pressures of only 1–5 Pa, considerably less than previously thought.
Minnelide combined with anti-ANGPTL3-FLD monoclonal antibody completely protects mice with adriamycin nephropathy by promoting autophagy and inhibiting apoptosis
Authors: Ji Baowei , Liu Junchao , Yin Ye , Xu Hong , Shen Qian , Yu Jian
Published: September 2023

Minimal change disease (MCD) is the common type of nephrotic syndrome (NS) in children. Currently, there is an urgent need to explore new treatments because of the significant side effects of long-term use of glucocorticoids and immunosuppressive drugs and the failure to reduce proteinuria in some patients. Angiopoietin-like protein 3 (Angptl3) is an essential target of NS, and anti-ANGPTL3-FLD monoclonal antibody (mAb) significantly reduces proteinuria in mice with adriamycin nephropathy (AN). However, some proteinuria is persistent. Minnelide, a water-soluble prodrug of triptolide, has been used for the treatment of glomerular disease. Therefore, the present study aimed to investigate whether minnelide combined with mAb could further protect mice with AN and the underlying mechanisms. 8-week-old C57BL/6 female mice were injected with 25 mg/kg of Adriamycin (ADR) by tail vein to establish the AN model. A dose of 200 μg/kg of minnelide or 20 mg/kg of mAb was administered intraperitoneally for the treatment. In vitro, the podocytes were treated with 0.4 μg/mL of ADR for 24 h to induce podocyte injury, and pretreatment with 10 ng/mL of triptolide for 30 min or 100 ng/mL of mAb for 1 h before ADR exposure was used to treat. The results showed that minnelide combined with mAb almost completely ameliorates proteinuria and restores the ultrastructure of the podocytes in mice with AN. In addition, minnelide combined with mAb restores the distribution of Nephrin, Podocin, and CD2AP and reduces the level of inflammatory factors in mice with AN. Mechanistically, minnelide combined with mAb could further alleviate apoptosis and promote autophagy in mice with AN by inhibiting the mTOR signaling pathway. In vitro, triptolide combined with mAb increases the expression of Nephrin, Podocin, and CD2AP, alleviates apoptosis, and promotes autophagy. Overall, minnelide combined with mAb completely protects the mice with AN by promoting autophagy and inhibiting apoptosis.
YAP is required for prostate development, regeneration, and prostate stem cell function
Authors: Xie Hui , Guo Linpei , Ma Qianwang , Zhang Wenyi , Yang Zhao , Wang Zhun , Peng Shuanghe , Wang Keruo , Wen Simeng , Shang Zhiqun , Niu Yuanjie
Published: September 2023

Prostate development and regeneration depend on prostate stem cell function, the delicate balance of stem cell self-renewal and differentiation. However, mechanisms modulating prostate stem cell function remain poorly identified. Here, we explored the roles of Yes-associated protein 1 (YAP) in prostate stem cells, prostate development and regeneration. Using YAPfl/fl, CD133-CreER mice, we found that stem cell-specific YAP-deficient mice had compromised branching morphogenesis and epithelial differentiation, resulting in damaged prostate development. YAP inhibition also significantly affected the regeneration process of mice prostate, leading to impaired regenerated prostate. Furthermore, YAP ablation in prostate stem cells significantly reduced its self-renewal activity in vitro, and attenuated prostate regeneration of prostate grafts in vivo. Further analysis revealed a decrease in Notch and Hedgehog pathways expression in YAP inhibition cells, and treatment with exogenous Shh partially restored the self-renewal ability of prostate sphere cells. Taken together, our results revealed the roles of YAP in prostate stem cell function and prostate development and regeneration through regulation of the Notch and Hedgehog signaling pathways.
Projecting genetic associations through gene expression patterns highlights disease etiology and drug mechanisms
Authors: Pividori Milton , Lu Sumei , Li Binglan , Su Chun , Johnson Matthew E. , Wei Wei-Qi , Feng Qiping , Namjou Bahram , Kiryluk Krzysztof , Kullo Iftikhar J. , Luo Yuan , Sullivan Blair D. , Voight Benjamin F. , Skarke Carsten , Ritchie Marylyn D. , Grant Struan F. A. ,   eMERGE Consortium, Greene Casey S.
Published: September 2023

Genes act in concert with each other in specific contexts to perform their functions. Determining how these genes influence complex traits requires a mechanistic understanding of expression regulation across different conditions. It has been shown that this insight is critical for developing new therapies. Transcriptome-wide association studies have helped uncover the role of individual genes in disease-relevant mechanisms. However, modern models of the architecture of complex traits predict that gene-gene interactions play a crucial role in disease origin and progression. Here we introduce PhenoPLIER, a computational approach that maps gene-trait associations and pharmacological perturbation data into a common latent representation for a joint analysis. This representation is based on modules of genes with similar expression patterns across the same conditions. We observe that diseases are significantly associated with gene modules expressed in relevant cell types, and our approach is accurate in predicting known drug-disease pairs and inferring mechanisms of action. Furthermore, using a CRISPR screen to analyze lipid regulation, we find that functionally important players lack associations but are prioritized in trait-associated modules by PhenoPLIER. By incorporating groups of co-expressed genes, PhenoPLIER can contextualize genetic associations and reveal potential targets missed by single-gene strategies.
Dominance vs epistasis: the biophysical origins and plasticity of genetic interactions within and between alleles
Authors: Xie Xuan , Sun Xia , Wang Yuheng , Lehner Ben , Li Xianghua
Published: September 2023

An important challenge in genetics, evolution and biotechnology is to understand and predict how mutations combine to alter phenotypes, including molecular activities, fitness and disease. In diploids, mutations in a gene can combine on the same chromosome or on different chromosomes as a “heteroallelic combination”. However, a direct comparison of the extent, sign, and stability of the genetic interactions between variants within and between alleles is lacking. Here we use thermodynamic models of protein folding and ligand-binding to show that interactions between mutations within and between alleles are expected in even very simple biophysical systems. Protein folding alone generates within-allele interactions and a single molecular interaction is sufficient to cause between-allele interactions and dominance. These interactions change differently, quantitatively and qualitatively as a system becomes more complex. Altering the concentration of a ligand can, for example, switch alleles from dominant to recessive. Our results show that intra-molecular epistasis and dominance should be widely expected in even the simplest biological systems but also reinforce the view that they are plastic system properties and so a formidable challenge to predict. Accurate prediction of both intra-molecular epistasis and dominance will require either detailed mechanistic understanding and experimental parameterization or brute-force measurement and learning.
Transfer Learning with Kernel Methods
Authors: Radhakrishnan Adityanarayanan , Ruiz Luyten Max , Prasad Neha , Uhler Caroline
Published: September 2023

Transfer learning refers to the process of adapting a model trained on a source task to a target task. While kernel methods are conceptually and computationally simple models that are competitive on a variety of tasks, it has been unclear how to develop scalable kernel-based transfer learning methods across general source and target tasks with possibly differing label dimensions. In this work, we propose a transfer learning framework for kernel methods by projecting and translating the source model to the target task. We demonstrate the effectiveness of our framework in applications to image classification and virtual drug screening. For both applications, we identify simple scaling laws that characterize the performance of transfer-learned kernels as a function of the number of target examples. We explain this phenomenon in a simplified linear setting, where we are able to derive the exact scaling laws.
Coupled reaction equilibria enable the light-driven formation of metal-functionalized molecular vanadium oxides
Authors: Repp Stefan , Remmers Moritz , Rein Alexandra Stefanie Jessica , Sorsche Dieter , Gao Dandan , Anjass Montaha , Mondeshki Mihail , Carrella Luca M. , Rentschler Eva , Streb Carsten
Published: September 2023

The introduction of metal sites into molecular metal oxides, so-called polyoxometalates, is key for tuning their structure and reactivity. The complex mechanisms which govern metal-functionalization of polyoxometalates are still poorly understood. Here, we report a coupled set of light-dependent and light-independent reaction equilibria controlling the mono- and di-metal-functionalization of a prototype molecular vanadium oxide cluster. Comprehensive mechanistic analyses show that coordination of a Mg2+ ion to the species {(NMe2H2)2[VV12O32Cl]}3- results in formation of the mono-functionalized {(NMe2H2)[(MgCl)VV12O32Cl]}3- with simultaneous release of a NMe2H2+ placeholder cation. Irradiation of this species with visible light results in one-electron reduction of the vanadate, exchange of the second NMe2H2+ with Mg2+, and formation/crystallization of the di-metal-functionalized [(MgCl)2VIVVV11O32Cl]4-. Mechanistic studies show how stimuli such as light or competing cations affect the coupled equilibria. Transfer of this synthetic concept to other metal cations is also demonstrated, highlighting the versatility of the approach.
Cell diversity and plasticity during atrioventricular heart valve EMTs
Authors: Lotto Jeremy , Cullum Rebecca , Drissler Sibyl , Arostegui Martin , Garside Victoria C. , Fuglerud Bettina M. , Clement-Ranney Makenna , Thakur Avinash , Underhill T. Michael , Hoodless Pamela A.
Published: September 2023

Epithelial-to-mesenchymal transitions (EMTs) of both endocardium and epicardium guide atrioventricular heart valve formation, but the cellular complexity and small scale of this tissue have restricted analyses. To circumvent these issues, we analyzed over 50,000 murine single-cell transcriptomes from embryonic day (E)7.75 hearts to E12.5 atrioventricular canals. We delineate mesenchymal and endocardial bifurcation during endocardial EMT, identify a distinct, transdifferentiating epicardial population during epicardial EMT, and reveal the activation of epithelial-mesenchymal plasticity during both processes. In Sox9-deficient valves, we observe increased epithelial-mesenchymal plasticity, indicating a role for SOX9 in promoting endothelial and mesenchymal cell fate decisions. Lastly, we deconvolve cell interactions guiding the initiation and progression of cardiac valve EMTs. Overall, these data reveal mechanisms of emergence of mesenchyme from endocardium or epicardium at single-cell resolution and will serve as an atlas of EMT initiation and progression with broad implications in regenerative medicine and cancer biology.
A theory for colors of strongly correlated electronic systems
Authors: Acharya Swagata , Pashov Dimitar , Weber Cedric , van Schilfgaarde Mark , Lichtenstein Alexander I. , Katsnelson Mikhail I.
Published: September 2023

Many strongly correlated transition metal insulators are colored, even though they have band gaps much larger than the highest energy photons from the visible light. An adequate explanation for the color requires a theoretical approach able to compute subgap excitons in periodic crystals, reliably and without free parameters—a formidable challenge. The literature often fails to disentangle two important factors: what makes excitons form and what makes them optically bright. We pick two archetypal cases as examples: NiO with green color and MnF2 with pink color, and employ two kinds of ab initio many body Green’s function theories; the first, a perturbative theory based on low-order extensions of the GW approximation, is able to explain the color in NiO, while the same theory is unable to explain why MnF2 is pink. We show its color originates from higher order spin-flip transitions that modify the optical response, which is contained in dynamical mean-field theory (DMFT). We show that symmetry lowering mechanisms may determine how ‘bright’ these excitons are, but they are not fundamental to their existence.
Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity
Authors: Romeo Sara G. , Secco Ilaria , Schneider Edoardo , Reumiller Christina M. , Santos Celio X. C. , Zoccarato Anna , Musale Vishal , Pooni Aman , Yin Xiaoke , Theofilatos Konstantinos , Trevelin Silvia Cellone , Zeng Lingfang , Mann Giovanni E. , Pathak Varun , Harkin Kevin , Stitt Alan W. , Medina Reinhold J. , Margariti Andriana , Mayr Manuel , Shah Ajay M. , Giacca Mauro , Zampetaki Anna
Published: September 2023

The microvasculature plays a key role in tissue perfusion and exchange of gases and metabolites. In this study we use human blood vessel organoids (BVOs) as a model of the microvasculature. BVOs fully recapitulate key features of the human microvasculature, including the reliance of mature endothelial cells on glycolytic metabolism, as concluded from metabolic flux assays and mass spectrometry-based metabolomics using stable tracing of 13C-glucose. Pharmacological targeting of PFKFB3, an activator of glycolysis, using two chemical inhibitors results in rapid BVO restructuring, vessel regression with reduced pericyte coverage. PFKFB3 mutant BVOs also display similar structural remodelling. Proteomic analysis of the BVO secretome reveal remodelling of the extracellular matrix and differential expression of paracrine mediators such as CTGF. Treatment with recombinant CTGF recovers microvessel structure. In this work we demonstrate that BVOs rapidly undergo restructuring in response to metabolic changes and identify CTGF as a critical paracrine regulator of microvascular integrity.
Evidence of bifunctionality of carbons and metal atoms in catalyzed acetylene hydrochlorination
Authors: Giulimondi Vera , Ruiz-Ferrando Andrea , Giannakakis Georgios , Surin Ivan , Agrachev Mikhail , Jeschke Gunnar , Krumeich Frank , López Núria , Clark Adam H. , Pérez-Ramírez Javier
Published: September 2023

Carbon supports are ubiquitous components of heterogeneous catalysts for acetylene hydrochlorination to vinyl chloride, from commercial mercury-based systems to more sustainable metal single-atom alternatives. Their potential co-catalytic role has long been postulated but never unequivocally demonstrated. Herein, we evidence the bifunctionality of carbons and metal sites in the acetylene hydrochlorination catalytic cycle. Combining operando X-ray absorption spectroscopy with other spectroscopic and kinetic analyses, we monitor the structure of single metal atoms (Pt, Au, Ru) and carbon supports (activated, non-activated, and nitrogen-doped) from catalyst synthesis, using various procedures, to operation at different conditions. Metal atoms exclusively activate hydrogen chloride, while metal-neighboring sites in the support bind acetylene. Resolving the coordination environment of working metal atoms guides theoretical simulations in proposing potential binding sites for acetylene in the support and a viable reaction profile. Expanding from single-atom to ensemble catalysis, these results reinforce the importance of optimizing both metal and support components to leverage the distinct functions of each for advancing catalyst design.
Bayesian analyses indicate bivalves did not drive the downfall of brachiopods following the Permian-Triassic mass extinction
Authors: Guo Zhen , Flannery-Sutherland Joseph T. , Benton Michael J. , Chen Zhong-Qiang
Published: September 2023

Certain times of major biotic replacement have often been interpreted as broadly competitive, mediated by innovation in the succeeding clades. A classic example was the switch from brachiopods to bivalves as major seabed organisms following the Permian-Triassic mass extinction (PTME), ~252 million years ago. This was attributed to competitive exclusion of brachiopods by the better adapted bivalves or simply to the fact that brachiopods had been hit especially hard by the PTME. The brachiopod-bivalve switch is emblematic of the global turnover of marine faunas from Palaeozoic-type to Modern-type triggered by the PTME. Here, using Bayesian analyses, we find that unexpectedly the two clades displayed similar large-scale trends of diversification before the Jurassic. Insight from a multivariate birth-death model shows that the extinction of major brachiopod clades during the PTME set the stage for the brachiopod-bivalve switch, with differential responses to high ocean temperatures post-extinction further facilitating their displacement by bivalves. Our study strengthens evidence that brachiopods and bivalves were not competitors over macroevolutionary time scales, with extinction events and environmental stresses shaping their divergent fates.
Complex multi-fault rupture and triggering during the 2023 earthquake doublet in southeastern Türkiye
Authors: Liu Chengli , Lay Thorne , Wang Rongjiang , Taymaz Tuncay , Xie Zujun , Xiong Xiong , Irmak Tahir Serkan , Kahraman Metin , Erman Ceyhun
Published: September 2023

Two major earthquakes (MW 7.8 and MW 7.7) ruptured left-lateral strike-slip faults of the East Anatolian Fault Zone (EAFZ) on February 6, 2023, causing >59,000 fatalities and ~$119B in damage in southeastern Türkiye and northwestern Syria. Here we derived kinematic rupture models for the two events by inverting extensive seismic and geodetic observations using complex 5-6 segment fault models constrained by satellite observations and relocated aftershocks. The larger event nucleated on a splay fault, and then propagated bilaterally ~350 km along the main EAFZ strand. The rupture speed varied from 2.5-4.5 km/s, and peak slip was ~8.1 m. 9-h later, the second event ruptured ~160 km along the curved northern EAFZ strand, with early bilateral supershear rupture velocity (>4 km/s) followed by a slower rupture speed (~3 km/s). Coulomb Failure stress increase imparted by the first event indicates plausible triggering of the doublet aftershock, along with loading of neighboring faults.
Quantum key distribution in a packet-switched network
Authors: Mandil Reem , DiAdamo Stephen , Qi Bing , Shabani Alireza
Published: September 2023

Packet switching revolutionized the Internet by allowing the efficient use of network resources for data transmission. In a previous work, we introduced packet switching in quantum networks as a path to the Quantum Internet and presented a proof-of-concept for its application to quantum key distribution (QKD). In this paper, we outline a three-step approach for key rate optimization in a packet-switched network. Our simulated results show that practical key rates may be achieved in a sixteen-user network with no optical storage capacity. Under certain network conditions, we may improve the key rate by using an ultra-low-loss fiber delay line to store packets during network delays. We also find that implementing cut-off storage times in a strategy analogous to real-time selection in free-space QKD can significantly enhance performance. Our work demonstrates that packet switching is imminently suitable as a platform for QKD, an important step towards developing large-scale and integrated quantum networks.
Ontology for the Avida digital evolution platform
Authors: Ortega Raúl , Wulff Enrique , Fortuna Miguel A.
Published: September 2023

The Ontology for Avida (OntoAvida) aims to develop an integrated vocabulary for the description of Avida, the most widely used computational approach for performing experimental evolution using digital organisms–self-replicating computer programs that evolve within a user-defined computational environment. The lack of a clearly defined vocabulary makes some biologists feel reluctant to embrace the field of digital evolution. This integrated framework empowers biologists by equipping them with the necessary tools to explore and analyze the field of digital evolution more effectively. By leveraging the vocabulary of Avida, researchers can gain deeper insights into the evolutionary processes and dynamics of digital organisms. In addition, OntoAvida allows researchers to make inference based on certain rules and constraints, facilitate the reproducibility of in silico evolution experiments and trace the provenance of the data stored in avidaDB–an RDF database containing the genomes, transcriptomes, and phenotypes of more than a million digital organisms. OntoAvida is part of the Open Biological and Biomedical Ontologies (OBO Foundry) and is available at http://www.obofoundry.org/ontology/ontoavida.html.
The first high-quality chromosome-level genome of Eretmochelys imbricata using HiFi and Hi-C data
Authors: Guo Yusong , Tang Jiao , Zhuo Zixuan , Huang Jingru , Fu Zhenli , Song Jiahao , Liu Min , Dong Zhongdian , Wang Zhongduo
Published: September 2023

Eretmochelys imbricata, a critically endangered sea turtle inhabiting tropical oceans and protected across the world, had an unknown genome sequence until now. In this study, we used HiFi reads and Hi-C technology to assemble a high-quality, chromosome-level genome of E. imbricata. The genome size was 2,138.26 Mb, with contig N50 length of 123.49 Mb and scaffold N50 of 137.21 Mb. Approximately 97.52% of the genome sequence was anchored to 28 chromosomes. A total of 20,206 protein-coding genes were predicted. We also analyzed the evolutionary relationships, gene family expansions, and positive selection of E. imbricata. Our results revealed that E. imbricata diverged from Chelonia mydas 38 million years ago and had enriched olfactory receptors and aging-related genes. Our genome will be useful for studying E. imbricata and its conservation.
High throughput compound screening in neuronal cells identifies statins as activators of ataxin 3 expression
Authors: Stahl Fabian , Schmitt Ina , Denner Philip , de Boni Laura , Wüllner Ullrich , Breuer Peter
Published: September 2023

The spinocerebellar ataxias (SCA) comprise a group of inherited neurodegenerative diseases. SCA3 is the most common form, caused by the expansion of CAG repeats within the ataxin 3 (ATXN3) gene. The mutation results in the expression of an abnormal protein, containing long polyglutamine (polyQ) stretches. The polyQ stretch confers a toxic gain of function and leads to misfolding and aggregation of ATXN3 in neurons. Thus, modulators of ATXN3 expression could potentially ameliorate the pathology in SCA3 patients. Therefore, we generated a CRISPR/Cas9 modified ATXN3-Exon4-Luciferase (ATXN3-LUC) genomic fusion- and control cell lines to perform a reporter cell line-based high-throughput screen comprising 2640 bioactive compounds, including the FDA approved drugs. We found no unequivocal inhibitors of, but identified statins as activators of the LUC signal in the ATXN3-LUC screening cell line. We further confirmed that Simvastatin treatment of wild type SK-N-SH cells increases ATXN3 mRNA and protein levels which likely results from direct binding of the activated sterol regulatory element binding protein 1 (SREBP1) to the ATXN3 promotor. Finally, we observed an increase of normal and expanded ATXN3 protein levels in a patient-derived cell line upon Simvastatin treatment, underscoring the potential medical relevance of our findings.
Experimental study of erodible bed scoured by the debris flow in the narrow-steep gully
Authors: Wu Yu , Ji Jiejie , Qi Shunchao , Wang Xiekang , Li Dong , Li Hongtao , Yang Xingguo , Yao Qiang
Published: September 2023

In recent years, debris flows have frequently erupted in the narrow-steep gully of the earthquake-hit Wenchuan region, displaying high flow velocities and powerful scouring abilities. However, few scouring studies in the narrow-steep gully have been conducted. A model experiment simulated the debris flow scouring process in a narrow-steep flume, in which several important physical parameters, including the debris flow density (ρ), flume slope (θ), and grain size of the sediment (D), were varied to investigate their influences on the erodible strength. The experimental flows were composed of 50 L of water and grains, which scoured 2.3 m of erodible bed down a steeply inclined flume. A high-speed camera photographed the scouring processes, while a 3D laser device captured the final bed shapes. The experiments show that the debris flow first collides with the sediment at the head of the gully to form a pit, which is enlarged by continuous impact; the velocity of the debris flow out of the pit is significantly reduced due to the change in flow direction, resulting in a much lesser scouring effect after the pit; and finally, the gully bed presents the shape of a pit at the entrance and a groove in the middle and rear. The critical scour slope, where the gully bed shows scouring, increases with increasing debris flow density but decreases with increasing grain size of sediment. Following scouring, the maximum scouring depth is further positively correlated with the flume slope. In narrow-steep gullies, the gully bed is extremely susceptible to scouring by debris flow with a low density, and even headward erosion appears, at which the maximum scouring depth only increased from 148.04 to 149.97 mm, but the erosion amount had a significant increase of 36.9%. The research results have an important significance for revealing the disaster-causing phenomena and mechanisms of debris flows in the narrow-steep gully.
Cellular shortening and calcium dynamics are improved by noisy stimulus in a model of cardiomyopathy
Authors: Morales-Rubio Russell , Bernal-Ramírez Judith , Rubio-Infante Nestor , Luévano-Martínez Luis A. , Ríos Amelia , Escalante Bruno A. , García-Rivas Gerardo , Rodríguez González Jesús
Published: September 2023

Noise is present in cell biology. The capability of cells to respond to noisy environment have become essential. This study aimed to investigate whether noise can enhance the contractile response and Ca2+ handling in cardiomyocytes from a cardiomyopathy model. Experiments were conducted in an experimental setup with Gaussian white noise, frequency, and amplitude control to stimulate myocytes. Cell shortening, maximal shortening velocity, time to peak shortening, and time to half relaxation variables were recorded to cell shortening. Ca2+ transient amplitude and raise rate variables were registered to measure Ca2+ transients. Our results for cell shortening, Ca2+ transient amplitude, and raise rate suggest that cell response improve when myocytes are noise stimulated. Also, cell shortening, maximal shortening velocity, Ca2+ transient amplitude, and raise improves in control cells. Altogether, these findings suggest novel characteristics in how cells improve their response in a noisy environment.
A novel retinoic acid receptor-γ agonist antagonizes immune checkpoint resistance in lung cancers by altering the tumor immune microenvironment
Authors: Wei Cheng-Hsin , Huang Lu , Kreh Blair , Liu Xiuxia , Tyutyunyk-Massey Liliya , Kawakami Masanori , Chen Zibo , Shi Mi , Kozlov Serguei , Chan King C. , Andresson Thorkell , Carrington Mary , Vuligonda Vidyasagar , Sanders Martin E. , Horowitz Amir , Hwu Patrick , Peng Weiyi , Dmitrovsky Ethan , Liu Xi
Published: September 2023

All-trans-retinoic acid (ATRA), the retinoic acid receptors (RARs) agonist, regulates cell growth, differentiation, immunity, and survival. We report that ATRA-treatment repressed cancer growth in syngeneic immunocompetent, but not immunodeficient mice. The tumor microenvironment was implicated: CD8+ T cell depletion antagonized ATRA’s anti-tumorigenic effects in syngeneic mice. ATRA-treatment with checkpoint blockade did not cooperatively inhibit murine lung cancer growth. To augment ATRA’s anti-tumorigenicity without promoting its pro-tumorigenic potential, an RARγ agonist (IRX4647) was used since it regulates T cell biology. Treating with IRX4647 in combination with an immune checkpoint (anti-PD-L1) inhibitor resulted in a statistically significant suppression of syngeneic 344SQ lung cancers in mice—a model known for its resistance to checkpoints and characterized by low basal T cell and PD-L1 expression. This combined treatment notably elevated CD4+ T-cell presence within the tumor microenvironment and increased IL-5 and IL-13 tumor levels, while simultaneously decreasing CD38 in the tumor stroma. IL-5 and/or IL-13 treatments increased CD4+ more than CD8+ T-cells in mice. IRX4647-treatment did not appreciably affect in vitro lung cancer growth, despite RARγ expression. Pharmacokinetic analysis found IRX4647 plasma half-life was 6 h in mice. Yet, RARα antagonist (IRX6696)-treatment with anti-PD-L1 did not repress syngeneic lung cancer growth. Together, these findings provide a rationale for a clinical trial investigating an RARγ agonist to augment check point blockade response in cancers.
Inferring the diurnal variability of OH radical concentrations over the Amazon from BVOC measurements
Authors: Ringsdorf A. , Edtbauer A. , Vilà-Guerau de Arellano J. , Pfannerstill E. Y. , Gromov S. , Kumar V. , Pozzer A. , Wolff S. , Tsokankunku A. , Soergel M. , Sá M. O. , Araújo A. , Ditas F. , Poehlker C. , Lelieveld J. , Williams J.
Published: September 2023

The atmospheric oxidation of biogenic volatile organic compounds (BVOC) by OH radicals over tropical rainforests impacts local particle production and the lifetime of globally distributed chemically and radiatively active gases. For the pristine Amazon rainforest during the dry season, we empirically determined the diurnal OH radical variability at the forest-atmosphere interface region between 80 and 325 m from 07:00 to 15:00 LT using BVOC measurements. A dynamic time warping approach was applied showing that median averaged mixing times between 80 to 325 m decrease from 105 to 15 min over this time period. The inferred OH concentrations show evidence for an early morning OH peak (07:00–08:00 LT) and an OH maximum (14:00 LT) reaching 2.2 (0.2, 3.8) × 106 molecules cm−3 controlled by the coupling between BVOC emission fluxes, nocturnal NOx accumulation, convective turbulence, air chemistry and photolysis rates. The results were evaluated with a turbulence resolving transport (DALES), a regional scale (WRF-Chem) and a global (EMAC) atmospheric chemistry model.
Two new species of Trichocomaceae (Eurotiales), accommodated in Rasamsonia and Talaromyces section Bacillispori, from the Czech Republic
Authors: Špetík Milan , Eichmeier Aleš , Burgová Jana , Houbraken Jos
Published: September 2023

During a previous study on microfungi associated with clematis roots, Penicillium-like fungi were isolated and identified based on morphology. In this study, we subjected those strains to a detailed examination which led to the proposal of two taxonomic novelties, named Rasamsonia chlamydospora and Talaromyces clematidis. The first taxon is characterized by rough-walled mycelium, acerose to flask shaped phialides, cylindrical conidia and by production of chlamydospore-like structures. The four-loci-based phylogeny analysis delineated the taxon as a taxonomic novelty in Rasamsonia. Talaromyces clematidis is characterized by restricted growth on Czapek yeast extract agar, dichloran 18% glycerol agar and yeast extract sucrose agar, and production of yellow ascomata on oatmeal agar. Phylogenetic analyses placed this taxon as a taxonomic novelty in Talaromyces sect. Bacillispori. Both taxa are introduced here with detailed descriptions, photoplates and information on their phylogenetic relationship with related species.
Differential regulatory control of curli (csg) gene expression in Salmonella enterica serovar Typhi requires more than a functional CsgD regulator
Authors: Ou Camille , Dozois Charles M. , Daigle France
Published: September 2023

The human-specific Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a systemic disease with no known reservoir. Curli fimbriae are major components of biofilm produced by Salmonella and are encoded by the csg gene cluster (csgBAC and csgDEFG). The role of curli in S. Typhi is unknown, although detection of anti-curli antibodies suggests they are produced during host infection. In this study, we investigated curli gene expression in S. Typhi. We demonstrated that the CsgD regulatory protein binds weakly to the csgB promoter. Yet, replacing S. Typhi csgD with the csgD allele from S. Typhimurium did not modify the curli negative phenotype on Congo Red medium suggesting that differential regulation of curli gene expression in S. Typhi is not dependent on modification of the CsgD regulator. The entire csg gene cluster from S. Typhimurium was also cloned into S. Typhi, but again, despite introduction of a fully functional csg gene cluster from S. Typhimurium, curli were still not detected in S. Typhi. Thus, in addition to intrinsic genomic differences in the csg gene cluster that have resulted in production of a modified CsgD protein, S. Typhi has likely undergone other changes independent of the csg gene cluster that have led to distinctive regulation of csg genes compared to other Salmonella serovars.
Soil moisture controls the partitioning of carbon stocks across a managed boreal forest landscape
Authors: Larson Johannes , Wallerman Jörgen , Peichl Matthias , Laudon Hjalmar
Published: September 2023

Boreal forests sequester and store vast carbon (C) pools that may be subject to significant feedback effects induced by climatic warming. The boreal landscape consists of a mosaic of forests and peatlands with wide variation in total C stocks, making it important to understand the factors controlling C pool sizes in different ecosystems. We therefore quantified the total C stocks in the organic layer, mineral soil, and tree biomass in 430 plots across a 68 km2 boreal catchment. The organic layer held the largest C pool, accounting for 39% of the total C storage; tree and mineral C pools accounted for 38% and 23%, respectively. The size of the soil C pool was positively related to modelled soil moisture conditions, especially in the organic soil layer (R2 = 0.50). Conversely, the tree C pool exhibited a unimodal relationship: storage was highest under intermediate wetness conditions. The magnitude and variation in the total soil C stocks observed in this work were comparable to those found at the national level in Sweden, suggesting that C accumulation in boreal landscapes is more sensitive to local variation resulting primarily from differences in soil moisture conditions than to regional differences in climate, nitrogen deposition, and parent material.
Low concentrations of acetamiprid, deltamethrin, and sulfoxaflor, three commonly used insecticides, adversely affect ant queen survival and egg laying
Authors: Svoboda Jakub , Pech Pavel , Heneberg Petr
Published: September 2023

Ants are key ecosystem service providers and can serve as important biological control agents in pest management. However, the effects of insecticides on common farmland ant species are poorly understood. We tested the effects of three commonly used insecticides on ants (Hymenoptera, Formicidae). The tested insecticides were acetamiprid (neonicotinoid; formulated as Mospilan 20 SP), deltamethrin (pyrethroid; formulated as Sanium Ultra), and sulfoxaflor (sulfilimine; formulated as Gondola). We tested two ant (Hymenoptera: Formicidae) species with different colony founding strategies,Lasius niger(Linnaeus, 1758) andMyrmica rubra(Linnaeus, 1758). We sprayed their queens with insecticides at concentrations recommended for use in foliar applications in agriculture, i.e., at 1.25 g L−1(acetamiprid), 0.6 g L−1(sulfoxaflor), and 0.875 g L−1(deltamethrin). Further, we diluted the compounds in distilled water and tested them at 10%, 1%, and 0.1% of the field-recommended concentrations, and used distilled water as a control. We monitored the survival of the queens and the number of eggs laid. All three tested insecticides caused severe lethal and sublethal concentration-dependent effects. Even at concentrations three orders of magnitudes lower than recommended for field applications, significantly lower numbers of eggs were found in the queens’ nests. The extent of the sublethal effects of acetamiprid and sulfoxaflor was concentration-dependent and differed between the two ant species. Besides bees and bumblebees, ants represent an important group of hymenopterans that are severely affected even by low concentrations of the tested compounds and therefore should be included in risk assessment schemes.
Knowledge of lactation amenorrhea method among postpartum women in Ethiopia: a facility-based cross-sectional study
Authors: Eticha Tadesse Gure , Girma Sagni , Mamo Galana , Asefa Fekede , Birhanu Abdi , Taye Bedasa , Alemu Addisu , Niguse Kabtamu , Gedefaw Abel , Genet Tinsae , Amenu Demesew , Mekuria Thomas , Tura Abera Kenay
Published: September 2023

While the importance of knowledge about contraceptives in improving their utilization and thereby reducing the risk of unintended pregnancies is well documented, there are limited studies documented about the Lactational Amenorrhea Method (LAM). Thus, understanding the knowledge of postpartum mothers about LAM is essential for designing tailored interventions. This study assessed the level of knowledge about LAM and its associated factors among postpartum mothers in Ethiopia. A facility-based cross-sectional study was conducted among 3148 randomly selected postpartum participants. The study utilized multistage sampling approach in hospitals located across five regions and one city administration in Ethiopia. Data were collected using face-to-face interviews at discharge. A participant was categorized as having knowledge of LAM if she correctly answered the three LAM criteria: amenorrhea, the first 6 months, and exclusive breast feeding. A binary logistic regression model was used to identify factors associated with knowledge of LAM. Variables with p < 0.25 in the binary logistic regression were included in the multiple logistic regression. Then, associations were described using the adjusted odds ratio (AOR) along with the 95% confidence interval (CI), and statistical significance was declared at p < 0.05. Only four in 10 participants (40.6%; 95% CI 38.9–42.3) had knowledge of LAM. Participants who attended college or above educational level (AOR = 2.1, 95% CI 1.5–2.8), those with parity of two (AOR = 2.3; 95% CI 1.6–3.6) or more than two (AOR = 2.4; 95% CI 1.5–4.0), those who expressed a desire for further fertility (AOR = 1.3; 95% CI 1.1–1.5), individuals who received counselling on LAM (AOR = 3.0; 95% CI 2.6–3.7), and those who gave birth in hospital (AOR = 2.6; 95% CI 1.4–2.6) had higher odds of knowledge about LAM, compared to their counter parts. In contrary, participants resided far away from health facilities had 30% lower odd of knowledge about LAM compared to those resided near the health facilities (AOR = 0.70; 95% CI 0.6–0.8). The proportion of participants who had knowledge of LAM was low. Strengthening counseling about LAM during antenatal care and delivery with due attention to women with limited access to health facilities should be considered for increasing their level of knowledge on LAM.
Comprehensive prediction of urolithiasis based on clinical factors, blood chemistry and urinalysis: UROLITHIASIS score
Authors: Kim Hyo Joon , Oh Sang Hoon
Published: September 2023

Comprehensive prediction of urolithiasis using available factors obtained in the emergency department may aid in patient-centered diagnostic imaging decisions. This retrospective study analyzed the clinical factors, blood chemistry and urine parameters of patients who underwent nonenhanced urinary computed tomography for suspected urolithiasis. A scoring system was developed from a logistic regression model and was tested using the area under the curve (AUC). The prevalence of urolithiasis and important possible causes in the three risk subgroups were determined. Finally, the scoring model was validated. In the derivation cohort (n = 673), 566 patients were diagnosed with urolithiasis. Age > 35 years, history of urolithiasis, pain duration < 8 h, nausea/vomiting, costovertebral angle tenderness, serum creatinine ≥ 0.92 mg/dL, erythrocytes ≥ 10/high power field, no leukocytes ≤  + , and any crystalluria were retained in the final multivariable model and became part of the score. This scoring model demonstrated good discrimination (AUC 0.808 [95% CI, 0.776–0.837]). In the validation cohort (n = 336), the performance was similar (AUC 0.803 [95% CI, 0.756–0.844]), surpassing that of the STONE score (AUC 0.654 [95% CI, 0.601–0.705], P < 0.001). This scoring model successfully stratified patients according to the probability of urolithiasis. Further validation in various settings is needed.
Transparent wood composite prepared from two commercially important tropical timber species
Authors: Anish M. C. , Pandey Krishna K. , Kumar Rakesh
Published: September 2023

Transparent wood (TW) has garnered significant global attention due to its unique properties. In this study, TW composites were fabricated using two timber species of different density classes: Ailanthus triphysa (common name: Ailanthus wood) and Hevea brasiliensis (common name: Rubberwood). Sodium hydroxide (NaOH) and Hydrogen peroxide-based alkali method was used to modify the lignin in these veneer samples, producing a white cellulose template with a fully intact hierarchical cell structure. Subsequently, a cost-effective thermosetting unsaturated polyester resin (UPR) was infiltrated into the redesigned framework and polymerized to create rigid nanostructured transparent composites. High optical haze (of 94% and 89%) and favourable light transmittance of 59 and 55 percent were exhibited by the UPR-TW composites made from rubberwood and ailanthus wood, respectively. TW was characterised using Scanning electron microscopy and Fourier-transform infrared spectroscopy. The mechanical properties of TW were measured and compared with those of natural wood and pure-polymer. Furthermore, the anisotropic light diffusion behaviour displayed by TW in accordance with the fibre orientation indicates the utility of material as a potential light shaping device. Therefore, a cost-effective and commercially viable strategy to fabricate multipurpose TW composites using a combination of lesser-known timber species (LKTS) and UPR resin was successfully demonstrated.
Evidence of two differentially regulated elongasomes in Salmonella
Authors: Castanheira Sónia , García-del Portillo Francisco
Published: September 2023

Cell shape is genetically inherited by all forms of life. Some unicellular microbes increase niche adaptation altering shape whereas most show invariant morphology. A universal system of peptidoglycan synthases guided by cytoskeletal scaffolds defines bacterial shape. In rod-shaped bacteria, this system consists of two supramolecular complexes, the elongasome and divisome, which insert cell wall material along major and minor axes. Microbes with invariant shape are thought to use a single morphogenetic system irrespective of the occupied niche. Here, we provide evidence for two elongasomes that generate (rod) shape in the same bacterium. This phenomenon was unveiled in Salmonella, a pathogen that switches between extra- and intracellular lifestyles. The two elongasomes can be purified independently, respond to different environmental cues, and are directed by distinct peptidoglycan synthases: the canonical PBP2 and the pathogen-specific homologue PBP2SAL. The PBP2-elongasome responds to neutral pH whereas that directed by PBP2SAL assembles in acidic conditions. Moreover, the PBP2SAL-elongasome moves at a lower speed. Besides Salmonella, other human, animal, and plant pathogens encode alternative PBPs with predicted morphogenetic functions. Therefore, contrasting the view of morphological plasticity facilitating niche adaptation, some pathogens may have acquired alternative systems to preserve their shape in the host.
Cerebellar climbing fibers multiplex movement and reward signals during a voluntary movement task in mice
Authors: Ikezoe Koji , Hidaka Naoki , Manita Satoshi , Murakami Masayoshi , Tsutsumi Shinichiro , Isomura Yoshikazu , Kano Masanobu , Kitamura Kazuo
Published: September 2023

Cerebellar climbing fibers convey sensorimotor information and their errors, which are used for motor control and learning. Furthermore, they represent reward-related information. Despite such functional diversity of climbing fiber signals, it is still unclear whether each climbing fiber conveys the information of single or multiple modalities and how the climbing fibers conveying different information are distributed over the cerebellar cortex. Here we perform two-photon calcium imaging from cerebellar Purkinje cells in mice engaged in a voluntary forelimb lever-pull task and demonstrate that climbing fiber responses in 68% of Purkinje cells can be explained by the combination of multiple behavioral variables such as lever movement, licking, and reward delivery. Neighboring Purkinje cells exhibit similar climbing fiber response properties, form functional clusters, and share noise fluctuations of responses. Taken together, individual climbing fibers convey behavioral information on multiplex variables and are spatially organized into the functional modules of the cerebellar cortex.
Complex strike-slip faulting during the 2021 Mw7.4 Maduo earthquake
Authors: Wei Guoguang , Chen Kejie , Lyu Mingzhe , Gong Wenzheng , Dal Zilio Luca , Ye Lingling , Tu Hongwei
Published: September 2023

Fault geometry is an essential component for understanding earthquake genesis and dynamic rupture propagation. Here we employed space-based geodetic observations and geological survey, adopting a fully Bayesian approach, to probabilistically estimate the fault geometry of the 2021 Mw7.4 Maduo earthquake. The fault is predominantly characterized by strike-slip motions with three main geometry irregularities, reflecting the segmented pattern of the earthquake rupture. On the west side of the epicenter, the fault exhibits north-dipping angles (75–81°), whereas on the east side, it shows sub-vertical angles (82–87°). For the southeast branch, geodetic inversion reveals an overall shallow-dipping (44 ± 5°) faulting, yet further segmentation of the branch in the model and analysis of aftershock mechnism indicate that the dip of the branch faults may vary between vertical and shallow angles. This finding warrants confirmation through future underground observation data.These results suggest that strike-slip faulting could occur on unsuitably orientated planes during any seismic event.
Carbonized polyacrylonitrile array as a sensitive, biocompatible, and durable substrate for surface-enhanced Raman spectroscopy
Authors: Zhang Tingting , Bao Juan , Wu Shiying , Huang Xianhuai , Li Weihua , Liu Chang , Wang Lingling , Sun Xiuyun , Li Jiansheng , Lu Rui
Published: September 2023

A carbonized PAN array was designed and applied as an effective SERS substrate. It provided a significant signal enhancement (∼105) with its strong broadband charge-transfer resonance and high reproducibility and consistency in the SERS spectrum.