bluuebunny/crossref_metadata_2025 huggingface dataset:
The Extending Ocean Drilling Pursuits (eODP) Project: Synthesizing Scientific Ocean Drilling Data
Authors: Sessa Jocelyn A. , Fraass Andrew J. , LeVay Leah J. , Jamson Katie M. , Peters Shanan E.
Published: February 2023

For over 50 years, cores recovered from ocean basins have generated fossil, lithologic, and chemical archives that have revolutionized fields within the earth sciences. Although scientific ocean drilling (SOD) data are openly available following each expedition, the formats for these data are heterogeneous. Furthermore, lithological, chronological, and paleobiological data are typically separated into different repositories, limiting researchers' abilities to discover and analyze integrated SOD data sets. Emphasis within Earth Sciences on Findable, Accessible, Interoperable, and Reusable (FAIR) Data Principles and the establishment of community‐led databases provide a pathway to unite SOD data and further harness the scientific potential of the investments made in offshore drilling. Here, we describe a workflow for compiling, cleaning, and standardizing key SOD records, and importing them into the Paleobiology Database and Macrostrat, systems with versatile, open data distribution mechanisms. These efforts are being carried out by the extending Ocean Drilling Pursuits (eODP) project. eODP has processed all of the lithological, chronological, and paleobiological data from one SOD repository, along with numerous other data sets that were never deposited in a database; these were manually transcribed from original reports. This compiled data set contains over 79,899 lithological units from 1,125 drilling holes from 422 sites. Over 26,000 fossil‐bearing samples, with 5,378 taxonomic entries from 13 biological groups, are placed within this lithologic spatiotemporal framework. All information is available via GitHub and Macrostrat's application programming interface, which renders data retrievable by a variety of parameters, including age, site, and lithology.
Contrasting Influence of Nitrogen Oxides on the Cloud Condensation Nuclei Activity of Monoterpene‐Derived Secondary Organic Aerosol in Daytime and Nighttime Oxidation
Authors: Zhang Chenqi , Guo Yindong , Shen Hongru , Luo Hao , Pullinen Iida , Schmitt Sebastian H. , Wang Mingjin , Fuchs Hendrik , Kiendler‐Scharr Astrid , Wahner Andreas , Mentel Thomas F. , Zhao Defeng
Published: February 2023

Anthropogenic nitrogen oxides may influence the cloud condensation nuclei (CCN) activity of biogenic secondary organic aerosols (SOA) in both daytime photooxidation and nighttime NO3 oxidation, which has significant implications for the climatic impact of SOA. We investigated the influence of NOx on the CCN activity of monoterpene‐derived SOA in OH oxidation and in NO3 oxidation. In OH oxidation, NOx had little influence on the hygroscopic parameter κ of organic aerosol (κOrg), which was attributed to the minor fraction of organic nitrates (ON) in SOA (<24%), resulted from the low branching ratio of RO2 + NO to form ON. In contrast, in NO3 oxidation κOrg was much reduced compared to OH/O3 oxidation due to a dominant fraction of ON. We report κ of MT‐derived ON formed in photo‐oxidation and NO3 oxidation (0.029–0.052) for the first time to our knowledge, which may be used to improve model simulations of CCN concentrations.
Biophysical Dynamics at Ocean Fronts Revealed by Bio‐Argo Floats
Authors: McKee Darren C. , Doney Scott C. , Della Penna Alice , Boss Emmanuel S. , Gaube Peter , Behrenfeld Michael J.
Published: February 2023

The straining regions of the ocean in between mesoscale eddies contain large vertical velocities that may be important in regulating phytoplankton accumulation rates. We analyze time series of variables measured by ocean Bio‐Argo floats (mixed layer depths [MLDs], chlorophyll, and carbon concentrations) in conjunction with variables derived from satellite altimetry (strain rates, Lyapunov exponents, vertical velocities) to determine the evolution of mixed layer phytoplankton biomass in response to straining by the mesoscale geostrophic flow. A Lagrangian (water parcel following) framework is justified by restricting the analysis to profiles whose value of a Quasi‐Planktonic Index—an index quantifying averaged distance between a float trajectory and a surface geostrophic trajectory over three consecutive time steps—is less than 5 km. Bin‐averaged Lagrangian derivatives of phytoplankton biomass and chlorophyll concentration are positive for elevated strain rate and upwelling quasigeostrophic vertical velocities. Lagrangian derivatives of MLD and phytoplankton carbon averaged at straining fronts (in rotated along‐ and across‐front coordinates) have features in common with submesoscale dynamics, including increasing phytoplankton carbon (and chlorophyll) and a shoaling mixed layer over the front. To elucidate a mechanism, we average time derivatives of modeled cell division rates, finding the pattern approximately matches the pattern of phytoplankton accumulation rates and is controlled primarily by the term modulating light stress, suggesting that frontal dynamics cause accelerations of division rates by increasing available light. Regions of increasing chlorophyll are also approximately co‐located with upwelling quasigeostrophic velocity, suggesting non‐Lagrangian behavior of floats causes some imprint of larger scale, more persistent mesoscale signals.
Outcome prediction by the 2022 European LeukemiaNet genetic-risk classification for adults with acute myeloid leukemia: an Alliance study
Authors: Mrózek Krzysztof , Kohlschmidt Jessica , Blachly James S. , Nicolet Deedra , Carroll Andrew J. , Archer Kellie J. , Mims Alice S. , Larkin Karilyn T. , Orwick Shelley , Oakes Christopher C. , Kolitz Jonathan E. , Powell Bayard L. , Blum William G. , Marcucci Guido , Baer Maria R. , Uy Geoffrey L. , Stock Wendy , Byrd John C. , Eisfeld Ann-Kathrin
Published: February 2023

Recently, the European LeukemiaNet (ELN) revised its genetic-risk classification of acute myeloid leukemia (AML). We categorized 1637 adults with AML treated with cytarabine/anthracycline regimens according to the 2022 and 2017 ELN classifications. Compared with the 2017 ELN classification, 2022 favorable group decreased from 40% to 35% and adverse group increased from 37% to 41% of patients. The 2022 genetic-risk groups seemed to accurately reflect treatment outcomes in all patients and patients aged <60 years, but in patients aged ≥60 years, relapse rates, disease-free (DFS) and overall (OS) survival were not significantly different between intermediate and adverse groups. In younger African-American patients, DFS and OS did not differ between intermediate-risk and adverse-risk patients nor did DFS between favorable and intermediate groups. In Hispanic patients, DFS and OS did not differ between favorable and intermediate groups. Outcome prediction abilities of 2022 and 2017 ELN classifications were similar. Among favorable-risk patients, myelodysplasia-related mutations did not affect patients with CEBPAbZIP mutations or core-binding factor AML, but changed risk assignment of NPM1-mutated/FLT3-ITD-negative patients to intermediate. NPM1-mutated patients with adverse-risk cytogenetic abnormalities were closer prognostically to the intermediate than adverse group. Our analyses both confirm and challenge prognostic significance of some of the newly added markers.
Retinoid homeostasis in major depressive disorder
Authors: Otto Lisa Rebecca , Clemens Vera , Üsekes Berk , Cosma Nicoleta Carmen , Regen Francesca , Hellmann-Regen Julian
Published: February 2023

The small, hormone-like molecule retinoic acid (RA) is a vital regulator in several neurobiological processes that are affected in depression. Next to its involvement in dopaminergic signal transduction, neuroinflammation, and neuroendocrine regulation, recent studies highlight the role of RA in homeostatic synaptic plasticity and its link to neuropsychiatric disorders. Furthermore, experimental studies and epidemiological evidence point to the dysregulation of retinoid homeostasis in depression. Based on this evidence, the present study investigated the putative link between retinoid homeostasis and depression in a cohort of 109 patients with major depressive disorder (MDD) and healthy controls. Retinoid homeostasis was defined by several parameters. Serum concentrations of the biologically most active Vitamin A metabolite, all-trans RA (at-RA), and its precursor retinol (ROL) were quantified and the individual in vitro at-RA synthesis and degradation activity was assessed in microsomes of peripheral blood-derived mononuclear cells (PBMC). Additionally, the mRNA expression of enzymes relevant to retinoid signaling, transport, and metabolism were assessed. Patients with MDD had significantly higher ROL serum levels and greater at-RA synthesis activity than healthy controls providing evidence of altered retinoid homeostasis in MDD. Furthermore, MDD-associated alterations in retinoid homeostasis differed between men and women. This study is the first to investigate peripheral retinoid homeostasis in a well-matched cohort of MDD patients and healthy controls, complementing a wealth of preclinical and epidemiological findings that point to a central role of the retinoid system in depression.
The HLA ligandome of oropharyngeal squamous cell carcinomas reveals shared tumour-exclusive peptides for semi-personalised vaccination
Authors: Mühlenbruch Lena , Abou-Kors Tsima , Dubbelaar Marissa L. , Bichmann Leon , Kohlbacher Oliver , Bens Martin , Thomas Jaya , Ezić Jasmin , Kraus Johann M. , Kestler Hans A. , von Witzleben Adrian , Mytilineos Joannis , Fürst Daniel , Engelhardt Daphne , Doescher Johannes , Greve Jens , Schuler Patrick J. , Theodoraki Marie-Nicole , Brunner Cornelia , Hoffmann Thomas K. , Rammensee Hans-Georg , Walz Juliane S. , Laban Simon
Published: February 2023

Background

The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy of immune checkpoint inhibitors such as PD1/PD-L1 antibodies.

Methods

Mapping of the OPSCC HLA ligandome was performed by mass spectrometry (MS) based analysis of naturally presented HLA ligands isolated from tumour tissue samples (n = 40) using immunoaffinity purification. The cohort included 22 HPV-positive (primarily HPV-16) and 18 HPV-negative samples. A benign reference dataset comprised of the HLA ligandomes of benign haematological and tissue datasets was used to identify tumour-associated antigens.

Results

MS analysis led to the identification of naturally HLA-presented peptides in OPSCC tumour tissue. In total, 22,769 peptides from 9485 source proteins were detected on HLA class I. For HLA class II, 15,203 peptides from 4634 source proteins were discovered. By comparative profiling against the benign HLA ligandomic datasets, 29 OPSCC-associated HLA class I ligands covering 11 different HLA allotypes and nine HLA class II ligands were selected to create a peptide warehouse.

Conclusion

Tumour-associated peptides are HLA-presented on the cell surfaces of OPSCCs. The established warehouse of OPSCC-associated peptides can be used for downstream immunogenicity testing and peptide-based immunotherapy in (semi)personalised strategies.
Snake venom-defined fibrin architecture dictates fibroblast survival and differentiation
Authors: Wang Zhao , Lauko Jan , Kijas Amanda W. , Gilbert Elliot P. , Turunen Petri , Yegappan Ramanathan , Zou Dongxiu , Mata Jitendra , Rowan Alan E.
Published: February 2023

Fibrin is the provisional matrix formed after injury, setting the trajectory for the subsequent stages of wound healing. It is commonly used as a wound sealant and a natural hydrogel for three-dimensional (3D) biophysical studies. However, the traditional thrombin-driven fibrin systems are poorly controlled. Therefore, the precise roles of fibrin’s biophysical properties on fibroblast functions, which underlie healing outcomes, are unknown. Here, we establish a snake venom-controlled fibrin system with precisely and independently tuned architectural and mechanical properties. Employing this defined system, we show that fibrin architecture influences fibroblast survival, spreading phenotype, and differentiation. A fine fibrin architecture is a key prerequisite for fibroblast differentiation, while a coarse architecture induces cell loss and disengages fibroblast’s sensitivity towards TGF-β1. Our results demonstrate that snake venom-controlled fibrin can precisely control fibroblast differentiation. Applying these biophysical principles to fibrin sealants has translational significance in regenerative medicine and tissue engineering.
Tetraspanin 4 stabilizes membrane swellings and facilitates their maturation into migrasomes
Authors: Dharan Raviv , Huang Yuwei , Cheppali Sudheer Kumar , Goren Shahar , Shendrik Petr , Wang Weisi , Qiao Jiamei , Kozlov Michael M. , Yu Li , Sorkin Raya
Published: February 2023

Migrasomes are newly discovered cell organelles forming by local swelling of retraction fibers. The migrasome formation critically depends on tetraspanin proteins present in the retraction fiber membranes and is modulated by the membrane tension and bending rigidity. It remained unknown how and in which time sequence these factors are involved in migrasome nucleation, growth, and stabilization, and what are the possible intermediate stages of migrasome biogenesis. Here using live cell imaging and a biomimetic system for migrasomes and retraction fibers, we reveal that migrasome formation is a two-stage process. At the first stage, which in biomimetic system is mediated by membrane tension, local swellings largely devoid of tetraspanin 4 form on the retraction fibers. At the second stage, tetraspanin 4 molecules migrate toward and onto these swellings, which grow up to several microns in size and transform into migrasomes. This tetraspanin 4 recruitment to the swellings is essential for migrasome growth and stabilization. Based on these findings we propose that the major role of tetraspanin proteins is in stabilizing the migrasome structure, while the migrasome nucleation and initial growth stages can be driven by membrane mechanical stresses.
Twisted bilayer zigzag-graphene nanoribbon junctions with tunable edge states
Authors: Wang Dongfei , Bao De-Liang , Zheng Qi , Wang Chang-Tian , Wang Shiyong , Fan Peng , Mishra Shantanu , Tao Lei , Xiao Yao , Huang Li , Feng Xinliang , Müllen Klaus , Zhang Yu-Yang , Fasel Roman , Ruffieux Pascal , Du Shixuan , Gao Hong-Jun
Published: February 2023

Stacking two-dimensional layered materials such as graphene and transitional metal dichalcogenides with nonzero interlayer twist angles has recently become attractive because of the emergence of novel physical properties. Stacking of one-dimensional nanomaterials offers the lateral stacking offset as an additional parameter for modulating the resulting material properties. Here, we report that the edge states of twisted bilayer zigzag graphene nanoribbons (TBZGNRs) can be tuned with both the twist angle and the stacking offset. Strong edge state variations in the stacking region are first revealed by density functional theory (DFT) calculations. We construct and characterize twisted bilayer zigzag graphene nanoribbon (TBZGNR) systems on a Au(111) surface using scanning tunneling microscopy. A detailed analysis of three prototypical orthogonal TBZGNR junctions exhibiting different stacking offsets by means of scanning tunneling spectroscopy reveals emergent near-zero-energy states. From a comparison with DFT calculations, we conclude that the emergent edge states originate from the formation of flat bands whose energy and spin degeneracy are highly tunable with the stacking offset. Our work highlights fundamental differences between 2D and 1D twistronics and spurs further investigation of twisted one-dimensional systems.
Negative-mass exciton polaritons induced by dissipative light-matter coupling in an atomically thin semiconductor
Authors: Wurdack M. , Yun T. , Katzer M. , Truscott A. G. , Knorr A. , Selig M. , Ostrovskaya E. A. , Estrecho E.
Published: February 2023

Dispersion engineering is a powerful and versatile tool that can vary the speed of light signals and induce negative-mass effects in the dynamics of particles and quasiparticles. Here, we show that dissipative coupling between bound electron-hole pairs (excitons) and photons in an optical microcavity can lead to the formation of exciton polaritons with an inverted dispersion of the lower polariton branch and hence, a negative mass. We perform direct measurements of the anomalous dispersion in atomically thin (monolayer) WS2 crystals embedded in planar microcavities and demonstrate that the propagation direction of the negative-mass polaritons is opposite to their momentum. Our study introduces the concept of non-Hermitian dispersion engineering for exciton polaritons and opens a pathway for realising new phases of quantum matter in a solid state.
Metallic glass-based triboelectric nanogenerators
Authors: Xia Xin , Zhou Ziqing , Shang Yinghui , Yang Yong , Zi Yunlong
Published: February 2023

Surface wear is a major hindrance in the solid/solid interface of triboelectric nanogenerators (TENG), severely affecting their output performance and stability. To reduce the mechanical input and surface wear, solid/liquid-interface alternatives have been investigated; however, charge generation capability is still lower than that in previously reported solid/solid-interface TENGs. Thus, achieving triboelectric interface with high surface charge generation capability and low surface wear remains a technological challenge. Here, we employ metallic glass as one triboelectric interface and show it can enhance the triboelectrification efficiency by up to 339.2%, with improved output performance. Through mechanical and electrical characterizations, we show that metallic glass presents a lower friction coefficient and better wear resistance, as compared with copper. Attributed to their low atomic density and the absence of grain boundaries, all samples show a higher triboelectrification efficiency than copper. Additionally, the devices demonstrate excellent humidity resistance. Under different gas pressures, we also show that metallic glass-based triboelectric nanogenerators can approach the theoretical limit of charge generation, exceeding that of Cu-based TENG by 35.2%. A peak power density of 15 MW·m-2 is achieved. In short, this work demonstrates a humidity- and wear-resistant metallic glass-based TENG with high triboelectrification efficiency.
The cytomegalovirus gB/MF59 vaccine candidate induces antibodies against an antigenic domain controlling cell-to-cell spread
Authors: Gomes A. C. , Baraniak I. A. , Lankina A. , Moulder Z. , Holenya P. , Atkinson C. , Tang G. , Mahungu T. , Kern F. , Griffiths P. D. , Reeves M. B.
Published: February 2023

Vaccination against human cytomegalovirus (CMV) infection remains high priority. A recombinant form of a protein essential for CMV entry, glycoprotein B (gB), demonstrated partial protection in a clinical trial (NCT00299260) when delivered with the MF59 adjuvant. Although the antibody titre against gB correlated with protection poor neutralising responses against the 5 known antigenic domains (AD) of gB were evident. Here, we show that vaccination of CMV seronegative patients induces an antibody response against a region of gB we term AD-6. Responses to the polypeptide AD-6 are detected in >70% of vaccine recipients yet in <5% of naturally infected people. An AD-6 antibody binds to gB and to infected cells but not the virion directly. Consistent with this, the AD-6 antibody is non-neutralising but, instead, prevents cell-cell spread of CMV in vitro. The discovery of AD-6 responses has the potential to explain part of the protection mediated by gB vaccines against CMV following transplantation.
Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas
Authors: Ren Yanming , Huang Zongyao , Zhou Lingling , Xiao Peng , Song Junwei , He Ping , Xie Chuanxing , Zhou Ran , Li Menghan , Dong Xiangqun , Mao Qing , You Chao , Xu Jianguo , Liu Yanhui , Lan Zhigang , Zhang Tiejun , Gan Qi , Yang Yuan , Chen Tengyun , Huang Bowen , Yang Xiang , Xiao Anqi , Ou Yun , Su Zhengzheng , Chen Lu , Zhang Yan , Ju Yan , Zhang Yuekang , Wang Yuan
Published: February 2023

Diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) are the most lethal brain tumors that primarily occur in pediatric and adult patients, respectively. Both tumors exhibit significant heterogeneity, shaped by distinct genetic/epigenetic drivers, transcriptional programs including RNA splicing, and microenvironmental cues in glioma niches. However, the spatial organization of cellular states and niche-specific regulatory programs remain to be investigated. Here, we perform a spatial profiling of DMG and GBM combining short- and long-read spatial transcriptomics, and single-cell transcriptomic datasets. We identify clinically relevant transcriptional programs, RNA isoform diversity, and multi-cellular ecosystems across different glioma niches. We find that while the tumor core enriches for oligodendrocyte precursor-like cells, radial glial stem-like (RG-like) cells are enriched in the neuron-rich invasive niche in both DMG and GBM. Further, we identify niche-specific regulatory programs for RG-like cells, and functionally confirm that FAM20C mediates invasive growth of RG-like cells in a neuron-rich microenvironment in a human neural stem cell derived orthotopic DMG model. Together, our results provide a blueprint for understanding the spatial architecture and niche-specific vulnerabilities of DMG and GBM.
Wafer-scale and universal van der Waals metal semiconductor contact
Authors: Kong Lingan , Wu Ruixia , Chen Yang , Huangfu Ying , Liu Liting , Li Wei , Lu Donglin , Tao Quanyang , Song Wenjing , Li Wanying , Lu Zheyi , Liu Xiao , Li Yunxin , Li Zhiwei , Tong Wei , Ding Shuimei , Liu Songlong , Ma Likuan , Ren Liwang , Wang Yiliu , Liao Lei , Duan Xidong , Liu Yuan
Published: February 2023

Van der Waals (vdW) metallic contacts have been demonstrated as a promising approach to reduce the contact resistance and minimize the Fermi level pinning at the interface of two-dimensional (2D) semiconductors. However, only a limited number of metals can be mechanically peeled and laminated to fabricate vdW contacts, and the required manual transfer process is not scalable. Here, we report a wafer-scale and universal vdW metal integration strategy readily applicable to a wide range of metals and semiconductors. By utilizing a thermally decomposable polymer as the buffer layer, different metals were directly deposited without damaging the underlying 2D semiconductor channels. The polymer buffer could be dry-removed through thermal annealing. With this technique, various metals could be vdW integrated as the contact of 2D transistors, including Ag, Al, Ti, Cr, Ni, Cu, Co, Au, Pd. Finally, we demonstrate that this vdW integration strategy can be extended to bulk semiconductors with reduced Fermi level pinning effect.
Emergence of high piezoelectricity from competing local polar order-disorder in relaxor ferroelectrics
Authors: Liu Hui , Shi Xiaoming , Yao Yonghao , Luo Huajie , Li Qiang , Huang Houbing , Qi He , Zhang Yuanpeng , Ren Yang , Kelly Shelly D. , Roleder Krystian , Neuefeind Joerg C. , Chen Long-Qing , Xing Xianran , Chen Jun
Published: February 2023

Relaxor ferroelectrics are known for outstanding piezoelectric properties, finding a broad range of applications in advanced electromechanical devices. Decoding the origins of the enhanced properties, however, have long been complicated by the heterogeneous local structures. Here, we employ the advanced big-box refinement method by fitting neutron-, X-ray-based total scattering, and X-ray absorption spectrum simultaneously, to extract local atomic polar displacements and construct 3D polar configurations in the classical relaxor ferroelectric Pb(Mg1/3Nb2/3)O3–PbTiO3. Our results demonstrate that prevailing order-disorder character accompanied by the continuous rotation of local polar displacements commands the composition-driven global structure evolution. The omnidirectional local polar disordering appears as an indication of macroscopic relaxor characteristics. Combined with phase-field simulations, it demonstrates that the competing local polar order-disorder between different states with balanced local polar length and direction randomness leads to a flattening free-energy profile over a wide polar length, thus giving rise to high piezoelectricity. Our work clarifies that the critical structural feature required for high piezoelectricity is the competition states of local polar rather than relaxor.
Electrohydrodynamic atomization of CNT on PTFE membrane for scaling resistant membranes in membrane distillation
Authors: Francis Lijo , Hilal Nidal
Published: February 2023

In this study, an electrohydrodynamic atomization or electrospraying technique is used for the uniform deposition of carbon nanotubes (CNT) on a commercially available PTFE membrane and employed for Membrane Distillation (MD) process. Modified PTFE-CNT membrane was characterized for water contact angle, liquid entry pressure (LEP), pore size distribution, and surface morphology. The electrospray coating of CNT on the PTFE membrane enhances the turbulence and thereby the temperature polarization coefficient (TPC). The pore size of the micropatterned PTFE-CNT membrane has been reduced and pore size distribution has been narrowed compared to the PTFE membrane. Field-effect scanning electron microscopy images of the membranes were observed before and after the MD process. Functionally graded PTFE-CNT membrane showed superior desalination performance compared to the PTFE membrane with less amount of cake layer formation on the membrane surface. Water vapor flux remained constant during 24-h continuous MD process operation with 99.99% rejection of inorganic salts.
Cross-national analysis of attitudes towards fossil fuel subsidy removal
Authors: Harring Niklas , Jönsson Erik , Matti Simon , Mundaca Gabriela , Jagers Sverker C.
Published: February 2023

In 2021, governments of 51 countries spent US$697 billion on subsidizing fossil fuels. Removing fossil fuel subsidies is crucial not only for reducing CO2 emissions and making carbon pricing more effective, but also for making more valuable use of government funds. Currently, however, scientific evidence on the scale and scope of public attitudes towards fossil fuel subsidy-removal policies is lacking, yet it is instrumental for gauging political feasibility. Furthermore, previous studies tend to focus on carbon pricing in the developed world only. Here we present a comparative analysis of attitudes towards both carbon taxation and fossil fuel subsidy removal, focusing on five developing countries across four continents. It is found that (1) removing fossil fuel subsidies is not more undesirable than introducing carbon taxation and (2) the public has more-positive attitudes towards subsidy removal if optimal use of the saved fiscal revenues is specified.
Retrospective analysis of enhancer activity and transcriptome history
Authors: Boers Ruben , Boers Joachim , Tan Beatrice , van Leeuwen Marieke E. , Wassenaar Evelyne , Sanchez Erlantz Gonzalez , Sleddens Esther , Tenhagen Yasha , Mulugeta Eskeatnaf , Laven Joop , Creyghton Menno , Baarends Willy , van IJcken Wilfred F. J. , Gribnau Joost
Published: February 2023

Cell state changes in development and disease are controlled by gene regulatory networks, the dynamics of which are difficult to track in real time. In this study, we used an inducible DCM–RNA polymerase subunit b fusion protein which labels active genes and enhancers with a bacterial methylation mark that does not affect gene transcription and is propagated in S-phase. This DCM–RNA polymerase fusion protein enables transcribed genes and active enhancers to be tagged and then examined at later stages of development or differentiation. We apply this DCM-time machine (DCM-TM) technology to study intestinal homeostasis, revealing rapid and coordinated activation of enhancers and nearby genes during enterocyte differentiation. We provide new insights in absorptive–secretory lineage decision-making in intestinal stem cell (ISC) differentiation and show that ISCs retain a unique chromatin landscape required to maintain ISC identity and delineate future expression of differentiation-associated genes. DCM-TM has wide applicability in tracking cell states, providing new insights in the regulatory networks underlying cell state changes.
The amniotic fluid proteome changes with term labor and informs biomarker discovery in maternal plasma
Authors: Bhatti Gaurav , Romero Roberto , Gomez-Lopez Nardhy , Chaiworapongsa Tinnakorn , Than Nandor Gabor , Theis Kevin R. , Galaz Jose , Gotsch Francesca , Pique-Regi Roger , Berry Stanley M. , Kavdia Mahendra , Tarca Adi L.
Published: February 2023

The intra-uterine components of labor, namely, myometrial contractility, cervical ripening, and decidua/membrane activation, have been extensively characterized and involve a local pro-inflammatory milieu of cellular and soluble immune mediators. Targeted profiling has demonstrated that such processes extend to the intra-amniotic space, yet unbiased analyses of the proteome of human amniotic fluid during labor are lacking. Herein, we utilized an aptamer-based platform to characterize 1,310 amniotic fluid proteins and found that the proteome undergoes substantial changes with term labor (251 proteins with differential abundance, q < 0.1, and fold change > 1.25). Proteins with increased abundance in labor are enriched for immune and inflammatory processes, consistent with prior reports of labor-associated changes in the intra-uterine space. By integrating the amniotic fluid proteome with previously generated placental-derived single-cell RNA-seq data, we demonstrated the labor-driven upregulation of signatures corresponding to stromal-3 and decidual cells. We also determined that changes in amniotic fluid protein abundance are reflected in the maternal plasma proteome. Collectively, these findings provide novel insights into the amniotic fluid proteome in term labor and support its potential use as a source of biomarkers to distinguish between true and false labor by using maternal blood samples.
Evaluation of polyhydroxyalkanoate (PHA) synthesis by Pichia sp. TSLS24 yeast isolated in Vietnam
Authors: Thu Nguyen Thi Tam , Hoang Le Huy , Cuong Pham Kien , Viet-Linh Nguyen , Nga Tran Thi Huyen , Kim Dang Dinh , Leong Yoong Kit , Nhi-Cong Le Thi
Published: February 2023

Following the rising concern on environmental issues caused by conventional fossil-based plastics and depleting crude oil resources, polyhydroxyalkanoates (PHAs) are of great interest by scientists and biodegradable polymer market due to their outstanding properties which include high biodegradability in various conditions and processing flexibility. Many polyhydroxyalkanoate-synthesizing microorganisms, including normal and halophilic bacteria, as well as algae, have been investigated for their performance in polyhydroxyalkanoate production. However, to the best of our knowledge, there is still limited studies on PHAs-producing marine yeast. In the present study, a halophilic yeast strain isolated from Spratly Island in Vietnam were investigated for its potential in polyhydroxyalkanoate biosynthesis by growing the yeast in Zobell marine agar medium (ZMA) containing Nile red dye. The strain was identified by 26S rDNA analysis as Pichia kudriavzevii TSLS24 and registered at Genbank database under code OL757724. The amount of polyhydroxyalkanoates synthesized was quantified by measuring the intracellular materials (predicted as poly(3-hydroxybutyrate) -PHB) by gravimetric method and subsequently confirmed by Fourier transform infrared (FTIR) spectroscopic and nuclear magnetic resonance (NMR) spectroscopic analyses. Under optimal growth conditions of 35 °C and pH 7 with supplementation of glucose and yeast extract at 20 and 10 gL−1, the isolated strain achieved poly(3-hydroxybutyrate) content and concentration of 43.4% and 1.8 gL−1 after 7 days of cultivation. The poly(3-hydroxybutyrate) produced demonstrated excellent biodegradability with degradation rate of 28% after 28 days of incubation in sea water.
A CRISPR-Cas9-mediated F0 screen to identify pro-regenerative genes in the zebrafish retinal pigment epithelium
Authors: Lu Fangfang , Leach Lyndsay L. , Gross Jeffrey M.
Published: February 2023

Ocular diseases resulting in death of the retinal pigment epithelium (RPE) lead to vision loss and blindness. There are currently no FDA-approved strategies to restore damaged RPE cells. Stimulating intrinsic regenerative responses within damaged tissues has gained traction as a possible mechanism for tissue repair. Zebrafish possess remarkable regenerative abilities, including within the RPE; however, our understanding of the underlying mechanisms remains limited. Here, we conducted an F0 in vivo CRISPR-Cas9-mediated screen of 27 candidate RPE regeneration genes. The screen involved injection of a ribonucleoprotein complex containing three highly mutagenic guide RNAs per target gene followed by PCR-based genotyping to identify large intragenic deletions and MATLAB-based automated quantification of RPE regeneration. Through this F0 screening pipeline, eight positive and seven negative regulators of RPE regeneration were identified. Further characterization of one candidate, cldn7b, revealed novel roles in regulating macrophage/microglia infiltration after RPE injury and in clearing RPE/pigment debris during late-phase RPE regeneration. Taken together, these data support the utility of targeted F0 screens for validating pro-regenerative factors and reveal novel factors that could regulate regenerative responses within the zebrafish RPE.
Novel insights into plant defensin ingestion induced metabolic responses in the polyphagous insect pest Helicoverpa armigera
Authors: Mulla Javed A. , Tamhane Vaijayanti A.
Published: February 2023

Lepidopteran insect pest Helicoverpa armigera is one of the most destructive pests of crop plants and several biotechnological approaches are being developed for its control. Plant defensins are small cationic and cysteine-rich peptides that play a role in plant defense. Ingestion of a defensin from Capsicum annuum (CanDef-20) induced a dose-dependent reduction in larval and pupal mass, delayed metamorphosis and also severely reduced fecundity and fertility in H. armigera. To understand the molecular mechanisms of CanDef-20 ingestion-mediated antibiosis in H. armigera larvae, a comparative transcriptomics analysis was carried out. Predominant downregulation of GOs represents serine-type endopeptidases, structural constituents of ribosomes and integral membrane components and differential upregulation of ATP binding, nucleus and translation, while up-regulation of nucleic acid binding represented by transposable elements, were detected. Different isoforms of lipase, serine endopeptidase, glutathione S-transferase, cadherin, alkaline phosphatase and aminopeptidases were found to be upregulated as a compensatory response to CanDef-20 ingestion. In vitro enzyme assays and qPCR analysis of some representative genes associated with vital cellular processes like metamorphosis, food digestion and gut membrane indicated adaptive differential regulations in CanDef-20 fed H. armigera larvae. We conclude that CanDef-20 ingestion affects insect metabolism in a number of ways through its interaction with cell membrane, enzymes, cytoplasmic proteins and triggering transposon mobilization which are linked to growth retardation and adaptive strategies in H. armigera.
Brown bear skin-borne secretions display evidence of individuality and age-sex variation
Authors: Clapham Melanie , Wilson Abbey E. , Williams Candace L. , Sergiel Agnieszka
Published: February 2023

Scent originates from excretions and secretions, and its chemical complexity in mammals translates into a diverse mode of signalling. Identifying how information is encoded can help to establish the mechanisms of olfactory communication and the use of odours as chemical signals. Building upon existing behavioural and histological literature, we examined the chemical profile of secretions used for scent marking by a solitary, non-territorial carnivore, the brown bear (Ursus arctos). We investigated the incidence, abundance, and uniqueness of volatile organic compounds (VOCs) from cutaneous glandular secretions of 12 wild brown bears collected during late and post-breeding season, and assessed whether age-sex class, body site, and individual identity explained profile variation. VOC profiles varied in the average number of compounds, compound incidence, and compound abundance by age-sex class and individual identity (when individuals were grouped by sex), but not by body site. Mature males differed from other age-sex classes, secreting fewer compounds on average with the least variance between individuals. Compound uniqueness varied by body site and age for both males and females and across individuals. Our results indicate that brown bear skin-borne secretions may facilitate age-sex class and individual recognition, which can contribute towards further understanding of mating systems and social behaviour.
The role of tracheal wall injury in the development of benign airway stenosis in rabbits
Authors: Zhang Jie , Liu Yue hong , Yang Zhen yu , Liu Zi yi , Wang Chang guo , Zeng Da xiong , Jiang Jun hong
Published: February 2023

To investigate the role of tracheal wall injury in the development of benign airway stenosis in rabbits. Prospective study. We injured the tracheal walls of 28 New Zealand white rabbits using four different methods. Experimental group: Group A (n = 7, mild injury of tracheal mucosa by ordinary brush under bronchoscopy); Group B (n = 7, severe injury of tracheal mucosa by nylon brush under tracheotomy); Group C (n = 7, tracheal cartilage was injured by vascular clamp after tracheotomy); Group D (n = 7, the tracheal cartilage was injured with vascular forceps and the tracheal mucosa was injured with a nylon brush after tracheotomy). Bronchoscopy was performed on each experimental rabbit at 1, 2, 3 and 4 weeks after operation. High-resolution computed tomography (HRCT) and endobronchial optical coherence tomography (EB-OCT) were performed at 4 weeks, and the rabbits were sacrificed after the examination. Their gross and histological findings were comparatively determined whether the experimental rabbit stenosis was established. No airway stenosis was observed in group A. In group B, 28.57% of experimental rabbits developed tracheal stenosis (granulation tissue proliferation was observed in rabbits No. 2 and No. 6 at 1, 2 and 3 weeks after operation, and the tracheal scar contracture was observed in No.6 rabbit at 4 weeks after operation). Fourteen rabbits in group C and group D had tracheal stenosis caused by granulation tissue proliferation at 1, 2 and 3 weeks after operation. At the fourth week after operation, 71.43% of experimental rabbits had tracheal stenosis due to granulation tissue hyperplasia, 7.14% of experimental rabbits had tracheal stenosis due to scar contracture and granulation hyperplasia, and 21.43% of experimental rabbits had tracheal stenosis due to scar contracture. EB-OCT scan showed that the cartilage layer with low signal reflection band was discontinuous. The injury of cartilage is the key factor of benign airway stenosis. Acute injury of airway mucosa alone is unlikely to cause airway stenosis, but combined with cartilage injury may aggravate airway stenosis. EB-OCT can clearly identify the airway layers of rabbits, which is helpful to evaluate the damage of tracheal cartilage and mucosa. The diagnostic potential of this technique makes EB-OCT a promising approach for the study and monitoring of airway diseases.
ERP and attachment dimensions as predictors of seeking care or food comfort in stressful situations
Authors: Uccula Arcangelo , Mercante Beniamina , Pozzati Caterina , Deriu Franca , Enrico Paolo
Published: February 2023

In this study, we aimed to test the association of the Late Positive Potential (LPP) response and attachment dimensions in the choice of care/food pictures and its reaction time (RT) in threatening versus neutral conditions. Fifty-two participants (38 females, Mage22.62) responded to the ECR questionnaire and were exposed to adequate visual stimuli, during EEG recording. Results showed that threatening stimuli increase the choice of care, decrease RT, and increase LPP magnitude in centro-parietal areas (Cpz, Pz, P3 and P4). Food choice was lower, with increased RT. Furthermore, larger LPP magnitude in centro-parietal cluster was associated with increased RT in the choice of care. Considering the dimensions of attachment, in threatening conditions, while anxiety was not associated with RT and care/food choice, avoidance was associated with an increase in care choice and RT. In conclusion, the specific association of increased RT in care choice with high LPP magnitude centro-parietal cluster may be explained in terms of a functional interference of these areas in the choice of care, but not of food. Further, we postulate that the increased RT of avoidant individuals may reflect a more articulated choice process.
Modeling present and future distribution of plankton populations in a coastal upwelling zone: the copepod Calanus chilensis as a study case
Authors: Rivera Reinaldo , Escribano Rubén , González Carolina E. , Pérez-Aragón Manuela
Published: February 2023

Predicting species distribution in the ocean has become a crucial task to assess marine ecosystem responses to ongoing climate change. In the Humboldt Current System (HCS), the endemic copepodCalanus chilensisis one of the key species bioindicator of productivity and water masses. Here we modeled the geographic distribution ofCalanus chilensisfor two bathymetric ranges, 0–200 and 200–400 m. For the 0–200 m layer, we used the Bayesian Additive Regression Trees (BART) method, whereas, for the 200–400 m layer, we used the Ensembles of Small Models (ESMs) method and then projected the models into two future scenarios to assess changes in geographic distribution patterns. The models were evaluated using the multi-metric approach. We identified that chlorophyll-a (0.34), Mixed Layer Depth (0.302) and salinity (0.36) explained the distribution ofC. chilensis. The geographic prediction of the BART model revealed a continuous distribution from Ecuador to the southernmost area of South America for the 0–200 m depth range, whereas the ESM model indicated a discontinuous distribution with greater suitability for the coast of Chile for the 200–400 m depth range. A reduction of the distribution range ofC. chilensisis projected in the future. Our study suggests that the distribution ofC. chilensisis conditioned by productivity and mesoscale processes, with both processes closely related to upwelling intensity. These models serve as a tool for proposing indicators of changes in the ocean. We further propose that the speciesC. chilensisis a high productivity and low salinity indicator at the HCS. We recommend further examining multiple spatial and temporal scales for stronger inference.
Feasibility of an inertial measurement unit sensor-based guiding system for benign paroxysmal positional vertigo treatment: A pilot study
Authors: Pastor Cecilia A. Callejas , Kwon Chiheon , Joo Jung Sook , Kim Hee Chan , Shim Dae Bo , Ku Yunseo , Suh Myung-Whan
Published: February 2023

Performing an accurate canalith repositioning procedure (CRP) is important for treating benign paroxysmal positional vertigo, because inadequate rotational head angles can result in ineffective otolith mobilization and consequent treatment failure. Specialists-guided Epley maneuver reportedly had mean errors of 13.7°–24.4° while they were significantly larger (40.0°–51.5°) when self-administered. Similar results were obtained for the Barbeque maneuver: mean errors were 9.2°–13.0° by the specialists while they were significantly larger (22.9°–28.6°) when self-administered. Our study aimed to validate the feasibility of an inertial measurement unit sensor-based CRP (IMU-CRP) by analyzing the differences in accuracy in the rotational angles, comparing them with education-based conventional CRP (EDU-CRP). A pilot validation was also performed by analyzing the treatment success rate of IMU-CRP in patients with BPPV. This single-institution prospective, comparative effectiveness study examined 19 participants without active vertigo or prior knowledge of benign paroxysmal positional vertigo and CRP. Participants conducted the Epley and Barbeque roll maneuvers without and with auditory guidance (EDU-CRP vs. IMU-CRP, respectively) twice, and head rotation accuracies were compared. Differences in target angles based on the American Academy of Otolaryngology-Head and Neck Surgery guidelines were considered errors. For BPPV participants, treatment success was assessed based on the presence or absence of nystagmus, vertigo, and dizziness. For all the Epley and Barbeque roll maneuvers steps, the absolute errors were smaller for IMU- than for EDU-CRPs, with significant differences in steps 2–4 and 3–6 of the Epley and Barbeque roll maneuvers, respectively. A learning effect was found in steps 4 and 5 of the Barbeque roll maneuver but not in the Epley maneuver. The treatment success rates after 1 h were 71.4% and 100% for the Epley and Barbeque roll maneuvers, respectively. Real-time feedback on head rotation angles induced more appropriate movements in the Epley and Barbeque roll maneuvers. A guiding device based on head monitoring providing real-time auditory feedback may increase the self-administered CRP success rates in treating benign paroxysmal positional vertigo.
Scaling-up strategies for controllable biosynthetic ZnO NPs using cell free-extract of endophytic Streptomyces albus: characterization, statistical optimization, and biomedical activities evaluation
Authors: EL-Moslamy Shahira H. , Elnouby Mohamed S. , Rezk Ahmed H. , El-Fakharany Esmail M.
Published: February 2023

In this study, we identified a suitable precursor and good cellular compartmentalization for enhancing bioactive metabolites to produce biosynthetic zinc oxide nanoparticles (ZnO NPs). An effective medium for cultivating endophyticStreptomycesalbusstrain E56 was selected using several optimized approaches in order to maximize the yield of biosynthetic ZnO NPs. The highest biosynthetic ZnO NPs yield (4.63 g/L) was obtained when pipetting the mixed cell-free fractions with 100 mM of zinc sulfate as a precursor. The generation of biosynthetic ZnO NPs was quickly verified using a colored solution (white color) and UV–Visible spectroscopy (maximum peak, at 320 nm). On a small scale, the Taguchi method was applied to improve the culture medium for culturing the strain E56. As a result, its cell-dry weight was 3.85 times that of the control condition. And then the biosynthesis of ZnO NPs (7.59 g/L) was increased by 1.6 times. Furthermore, by using the Plackett–Burman design to improve the utilized biogenesis pathway, the biosynthesis of ZnO NPs (18.76 g/L) was increased by 4.3 times. To find the best growth production line, we used batch and fed batch fermentation modes to gradually scale up biomass output. All kinetics of studied cell growth were evaluated during fed-batch fermentation as follows: biomass yield was 271.45 g/L, yield coefficient was 94.25 g/g, and ZnO NPs yield was 345.32 g/L. In vitro, the effects of various dosages of the controllable biosynthetic ZnO NPs as antimicrobial and anticancer agents were also investigated. The treatments with controllable biosynthetic ZnO NPs had a significant impact on all the examined multidrug-resistant human pathogens as well as cancer cells.