bluuebunny/crossref_metadata_2025_split huggingface dataset:
GEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program
Authors: Lewis Michael , Terré Berta , Knobel Philip A. , Cheng Tao , Lu Hao , Attolini Camille Stephan-Otto , Smak Jordann , Coyaud Etienne , Garcia-Cao Isabel , Sharma Shalu , Vineethakumari Chithran , Querol Jessica , Gil-Gómez Gabriel , Piergiovanni Gabriele , Costanzo Vincenzo , Peiró Sandra , Raught Brian , Zhao Haotian , Salvatella Xavier , Roy Sudipto , Mahjoub Moe R. , Stracker Travis H. 
Published: March 2023

AbstractMulticiliated cells (MCCs) project dozens to hundreds of motile cilia from their apical surface to promote the movement of fluids or gametes in the mammalian brain, airway or reproductive organs. Differentiation of MCCs requires the sequential action of the Geminin family transcriptional activators, GEMC1 and MCIDAS, that both interact with E2F4/5-DP1. How these factors activate transcription and the extent to which they play redundant functions remains poorly understood. Here, we demonstrate that the transcriptional targets and proximal proteomes of GEMC1 and MCIDAS are highly similar. However, we identified distinct interactions with SWI/SNF subcomplexes; GEMC1 interacts primarily with the ARID1A containing BAF complex while MCIDAS interacts primarily with BRD9 containing ncBAF complexes. Treatment with a BRD9 inhibitor impaired MCIDAS-mediated activation of several target genes and compromised the MCC differentiation program in multiple cell based models. Our data suggest that the differential engagement of distinct SWI/SNF subcomplexes by GEMC1 and MCIDAS is required for MCC-specific transcriptional regulation and mediated by their distinct C-terminal domains.
Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis
Authors: Panthagani Jesse , O’Donovan Charles , Aiyegbusi Olalekan Lee , Liu Xiaoxuan , Bayliss Susan , Calvert Melanie , Pesudovs Konrad , Denniston Alastair K. , Moore David J. , Braithwaite Tasanee 
Published: March 2023

Abstract
Objective
To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.

Methods
We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).

Results
From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.

Conclusion
There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.
Ultra-low-current driven InGaN blue micro light-emitting diodes for electrically efficient and self-heating relaxed microdisplay
Authors: Baek Woo Jin , Park Juhyuk , Shim Joonsup , Kim Bong Ho , Park Seongchong , Kim Hyun Soo , Geum Dae-Myeong , Kim Sang Hyeon 
Published: March 2023

AbstractInGaN-based micro-light-emitting diodes have a strong potential as a crucial building block for next-generation displays. However, small-size pixels suffer from efficiency degradations, which increase the power consumption of the display. We demonstrate strategies for epitaxial structure engineering carefully considering the quantum barrier layer and electron blocking layer to alleviate efficiency degradations in low current injection regime by reducing the lateral diffusion of injected carriers via reducing the tunneling rate of electrons through the barrier layer and balanced carrier injection. As a result, the fabricated micro-light-emitting diodes show a high external quantum efficiency of 3.00% at 0.1 A/cm2 for the pixel size of 10 × 10 μm2 and a negligible Jmax EQE shift during size reduction, which is challenging due to the non-radiative recombination at the sidewall. Furthermore, we verify that our epitaxy strategies can result in the relaxation of self-heating of the micro-light-emitting diodes, where the average pixel temperature was effectively reduced.
Large-scale identification of genes involved in septal pore plugging in multicellular fungi
Authors: Mamun Md. Abdulla Al , Cao Wei , Nakamura Shugo , Maruyama Jun-ichi 
Published: March 2023

AbstractMulticellular filamentous fungi have septal pores that allow cytoplasmic exchange, and thus connectivity, between neighboring cells in the filament. Hyphal wounding and other stress conditions induce septal pore closure to minimize cytoplasmic loss. However, the composition of the septal pore and the mechanisms underlying its function are not well understood. Here, we set out to identify new septal components by determining the subcellular localization of 776 uncharacterized proteins in a multicellular ascomycete,Aspergillus oryzae. The set of 776 uncharacterized proteins was selected on the basis that their genes were present in the genomes of multicellular, septal pore-bearing ascomycetes (threeAspergillusspecies, in subdivision Pezizomycotina) and absent/divergent in the genomes of septal pore-lacking ascomycetes (yeasts). Upon determining their subcellular localization, 62 proteins were found to localize to the septum or septal pore. Deletion of the encoding genes revealed that 23 proteins are involved in regulating septal pore plugging upon hyphal wounding. Thus, this study determines the subcellular localization of many uncharacterized proteins inA. oryzaeand, in particular, identifies a set of proteins involved in septal pore function.
Structural basis for antibody recognition of vulnerable epitopes on Nipah virus F protein
Authors: Byrne Patrick O. , Fisher Brian E. , Ambrozak David R. , Blade Elizabeth G. , Tsybovsky Yaroslav , Graham Barney S. , McLellan Jason S. , Loomis Rebecca J. 
Published: March 2023

AbstractNipah virus (NiV) is a pathogenic paramyxovirus that causes fatal encephalitis in humans. Two envelope glycoproteins, the attachment protein (G/RBP) and fusion protein (F), facilitate entry into host cells. Due to its vital role, NiV F presents an attractive target for developing vaccines and therapeutics. Several neutralization-sensitive epitopes on the NiV F apex have been described, however the antigenicity of most of the F protein’s surface remains uncharacterized. Here, we immunize mice with prefusion-stabilized NiV F and isolate ten monoclonal antibodies that neutralize pseudotyped virus. Cryo-electron microscopy reveals eight neutralization-sensitive epitopes on NiV F, four of which have not previously been described. Novel sites span the lateral and basal faces of NiV F, expanding the known library of vulnerable epitopes. Seven of ten antibodies bind the Hendra virus (HeV) F protein. Multiple sequence alignment suggests that some of these newly identified neutralizing antibodies may also bind F proteins across the Henipavirus genus. This work identifies new epitopes as targets for therapeutics, provides a molecular basis for NiV neutralization, and lays a foundation for development of new cross-reactive antibodies targeting Henipavirus F proteins.
Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve split-hand/foot malformation type 3
Authors: Cova Giulia , Glaser Juliane , Schöpflin Robert , Prada-Medina Cesar Augusto , Ali Salaheddine , Franke Martin , Falcone Rita , Federer Miriam , Ponzi Emanuela , Ficarella Romina , Novara Francesca , Wittler Lars , Timmermann Bernd , Gentile Mattia , Zuffardi Orsetta , Spielmann Malte , Mundlos Stefan 
Published: March 2023

AbstractSplit-Hand/Foot Malformation type 3 (SHFM3) is a congenital limb malformation associated with tandem duplications at the LBX1/FGF8 locus. Yet, the disease patho-mechanism remains unsolved. Here we investigate the functional consequences of SHFM3-associated rearrangements on chromatin conformation and gene expression in vivo in transgenic mice. We show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. Re-engineering of a SHFM3-associated duplication and a newly reported inversion in mice results in restructuring of the chromatin architecture. This leads to ectopic activation of the Lbx1 and Btrc genes in the apical ectodermal ridge (AER) in an Fgf8-like pattern induced by AER-specific enhancers of Fgf8. We provide evidence that the SHFM3 phenotype is the result of a combinatorial effect on gene misexpression in the developing limb. Our results reveal insights into the molecular mechanism underlying SHFM3 and provide conceptual framework for how genomic rearrangements can cause gene misexpression and disease.
Poly(heptazine imide) ligand exchange enables remarkable low catalyst loadings in heterogeneous metallaphotocatalysis
Authors: Xing Liuzhuang , Yang Qian , Zhu Chen , Bai Yilian , Tang Yurong , Rueping Magnus , Cai Yunfei 
Published: March 2023

AbstractThe development of heterogeneous metallaphotocatalysis is of great interest for sustainable organic synthesis. The rational design and controllable preparation of well-defined (site-isolated) metal/photo bifunctional solid catalysts to meet such goal remains a critical challenge. Herein, we demonstrate the incorporation of privileged homogeneous bipyridyl-based Ni-catalysts into highly ordered and crystalline potassium poly(heptazine imide) (K-PHI). A variety of PHI-supported cationic bipyridyl-based Ni-catalysts (LnNi-PHI) have been prepared and fully characterized by various techniques including NMR, ICP-OES, XPS, HAADF-STEM and XAS. The LnNi-PHI catalysts exhibit exceptional chemical stability and recyclability in diverse C−P, C−S, C−O and C−N cross-coupling reactions. The proximity and cooperativity effects in LnNi-PHI significantly enhances the photo/Ni dual catalytic activity, thus resulting in low catalyst loadings and high turnover numbers.
Scale dependence in hydrodynamic regime for jumping on water
Authors: Gwon Minseok , Kim Dongjin , Kim Baekgyeom , Han Seungyong , Kang Daeshik , Koh Je-Sung 
Published: March 2023

AbstractMomentum transfer from the water surface is strongly related to the dynamical scale and morphology of jumping animals. Here, we investigate the scale-dependent momentum transfer of various jumping organisms and engineered systems at an air-water interface. A simplified analytical model for calculating the maximum momentum transfer identifies an intermediate dynamical scale region highly disadvantageous for jumping on water. The Weber number of the systems should be designed far from 1 to achieve high jumping performance on water. We design a relatively large water-jumping robot in the drag-dominant scale range, having a high Weber number, for maximum jumping height and distance. The jumping robot, around 10 times larger than water striders, has a take-off speed of 3.6 m/s facilitated by drag-based propulsion, which is the highest value reported thus far. The scale-dependent hydrodynamics of water jumpers provides a useful framework for understanding nature and robotic system interacting with the water surface.
A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination
Authors: Qiang Lihua , Zhang Yong , Lei Zehui , Lu Zhe , Tan Shasha , Ge Pupu , Chai Qiyao , Zhao Mengyuan , Zhang Xinwen , Li Bingxi , Pang Yu , Zhang Lingqiang , Liu Cui Hua , Wang Jing 
Published: March 2023

AbstractFerroptosis is a lipid peroxidation-driven and iron-dependent programmed cell death involved in multiple physical processes and various diseases. Emerging evidence suggests that several pathogens manipulate ferroptosis for their pathogenicity and dissemination, but the underlying molecular mechanisms remain elusive. Here, we identify that protein tyrosine phosphatase A (PtpA), an effector secreted by tuberculosis (TB)-causing pathogen Mycobacterium tuberculosis (Mtb), triggers ferroptosis to promote Mtb pathogenicity and dissemination. Mechanistically, PtpA, through its Cys11 site, interacts with host RanGDP to enter host cell nucleus. Then, the nuclear PtpA enhances asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a) via targeting protein arginine methyltransferase 6 (PRMT6), thus inhibiting glutathione peroxidase 4 (GPX4) expression, eventually inducing ferroptosis to promote Mtb pathogenicity and dissemination. Taken together, our findings provide insights into molecular mechanisms of pathogen-induced ferroptosis, indicating a potential TB treatment via blocking Mtb PtpA-host PRMT6 interface to target GPX4-dependent ferroptosis.
Data integration across conditions improves turnover number estimates and metabolic predictions
Authors: Wendering Philipp , Arend Marius , Razaghi-Moghadam Zahra , Nikoloski Zoran 
Published: March 2023

AbstractTurnover numbers characterize a key property of enzymes, and their usage in constraint-based metabolic modeling is expected to increase the prediction accuracy of diverse cellular phenotypes. In vivo turnover numbers can be obtained by integrating reaction rate and enzyme abundance measurements from individual experiments. Yet, their contribution to improving predictions of condition-specific cellular phenotypes remains elusive. Here, we show that available in vitro and in vivo turnover numbers lead to poor prediction of condition-specific growth rates with protein-constrained models ofEscherichia coliandSaccharomyces cerevisiae, particularly when protein abundances are considered. We demonstrate that correction of turnover numbers by simultaneous consideration of proteomics and physiological data leads to improved predictions of condition-specific growth rates. Moreover, the obtained estimates are more precise than corresponding in vitro turnover numbers. Therefore, our approach provides the means to correct turnover numbers and paves the way towards cataloguing kcatomes of other organisms.
Modeling of three-dimensional innervated epidermal like-layer in a microfluidic chip-based coculture system
Authors: Ahn Jinchul , Ohk Kyungeun , Won Jihee , Choi Dong-Hee , Jung Yong Hun , Yang Ji Hun , Jun Yesl , Kim Jin-A , Chung Seok , Lee Sang-Hoon 
Published: March 2023

AbstractReconstruction of skin equivalents with physiologically relevant cellular and matrix architecture is indispensable for basic research and industrial applications. As skin-nerve crosstalk is increasingly recognized as a major element of skin physiological pathology, the development of reliable in vitro models to evaluate the selective communication between epidermal keratinocytes and sensory neurons is being demanded. In this study, we present a three-dimensional innervated epidermal keratinocyte layer as a sensory neuron-epidermal keratinocyte co-culture model on a microfluidic chip using the slope-based air-liquid interfacing culture and spatial compartmentalization. Our co-culture model recapitulates a more organized basal-suprabasal stratification, enhanced barrier function, and physiologically relevant anatomical innervation and demonstrated the feasibility of in situ imaging and functional analysis in a cell-type-specific manner, thereby improving the structural and functional limitations of previous coculture models. This system has the potential as an improved surrogate model and platform for biomedical and pharmaceutical research.
Ribozyme-mediated RNA synthesis and replication in a model Hadean microenvironment
Authors: Salditt Annalena , Karr Leonie , Salibi Elia , Le Vay Kristian , Braun Dieter , Mutschler Hannes 
Published: March 2023

AbstractEnzyme-catalyzed replication of nucleic acid sequences is a prerequisite for the survival and evolution of biological entities. Before the advent of protein synthesis, genetic information was most likely stored in and replicated by RNA. However, experimental systems for sustained RNA-dependent RNA-replication are difficult to realise, in part due to the high thermodynamic stability of duplex products and the low chemical stability of catalytic RNAs. Using a derivative of a group I intron as a model for an RNA replicase, we show that heated air-water interfaces that are exposed to a plausible CO2-rich atmosphere enable sense and antisense RNA replication as well as template-dependent synthesis and catalysis of a functional ribozyme in a one-pot reaction. Both reactions are driven by autonomous oscillations in salt concentrations and pH, resulting from precipitation of acidified dew droplets, which transiently destabilise RNA duplexes. Our results suggest that an abundant Hadean microenvironment may have promoted both replication and synthesis of functional RNAs.
Multiphoton non-local quantum interference controlled by an undetected photon
Authors: Qian Kaiyi , Wang Kai , Chen Leizhen , Hou Zhaohua , Krenn Mario , Zhu Shining , Ma Xiao-song 
Published: March 2023

AbstractThe interference of quanta lies at the heart of quantum physics. The multipartite generalization of single-quanta interference creates entanglement, the coherent superposition of states shared by several quanta. Entanglement allows non-local correlations between many quanta and hence is a key resource for quantum information technology. Entanglement is typically considered to be essential for creating non-local quantum interference. Here, we show that this is not the case and demonstrate multiphoton non-local quantum interference that does not require entanglement of any intrinsic properties of the photons. We harness the superposition of the physical origin of a four-photon product state, which leads to constructive and destructive interference with the photons’ mere existence. With the intrinsic indistinguishability in the generation process of photons, we realize four-photon frustrated quantum interference. This allows us to observe the following noteworthy difference to quantum entanglement: We control the non-local multipartite quantum interference with a photon that we never detect, which does not require quantum entanglement. These non-local properties pave the way for the studies of foundations of quantum physics and potential applications in quantum technologies.
Sustainable application of calcium carbide residue as a filler for 3D printing materials
Authors: Samoylenko Dmitriy E. , Rodygin Konstantin S. , Ananikov Valentine P. 
Published: March 2023

AbstractIndustrial activity results in ton-scale production of calcium carbide and generation of a significant amount of calcium carbide residue (CCR), which is often disposed of in the environment as waste. CCR is an active chemical, and rain washes away alkali from sludge, changing the pH of soils and water and damaging the environment. In this work, we explored new opportunities for the utilization of CCR in view of the coming industrial uptake of digital design and additive technologies. Amazingly, CCR can be successfully used as a filler for the modification of 3D printed materials towards the introduction of hybrid organic/inorganic frameworks. A series of commercially available plastics (PLA, ABS, Nylon, PETG, SBS) were successfully used as matrices for CCR-based composite production with high CCR contents up to 28%. Tensile analyses showed increases in tensile strength and Young’s modulus of 9% and 60%, respectively. Moreover, in comparison with the pure plastics, the CCR-based materials better maintained the digitally designed shape (lower shrinkage). Importantly, CCR-filled materials are 3D printable, making them very promising components in the building sector. Considering the amount of already available CCR stored in the environment, this material is available in large quantities in the near future for hybrid materials, and anticipated opportunities exist in the additive manufacturing sector. The involvement of CCR in practical composite materials is equally important for environmental protection and reuse of already available multiple-ton wastes.
Evaluation of pre-processing methods for tear fluid proteomics using proximity extension assays
Authors: Vergouwen Daphne P. C. , Schotting Amber J. , Endermann Tanja , van de Werken Harmen J. G. , Grashof Dwin G. B. , Arumugam Sinthuja , Nuijts Rudy M. M. A. , ten Berge Josianne C. , Rothova Aniki , Schreurs Marco W. J. , Gijs Marlies 
Published: March 2023

AbstractTear fluid forms a potential source for biomarker identification, and can be minimal invasively collected via Schirmer strips. The lack of knowledge on the processing of Schirmer strips however complicates the analysis and between-study comparisons. We studied two different pre-processing methods, specifically the use of punches of the strip versus elution of the strip in a buffer. Tear fluid filled Schirmer strips were collected from 5 healthy participants, and divided into two halves over the length of the strip. In either part, punches or eluates were obtained from 4 different locations, from the first part touching the eye (head) to the end, to assess the protein distribution along the strips. The levels of 92 inflammatory proteins were measured in the punches/eluates using proximity extension assays. The punch method yielded higher protein detectability compared to the elution method (76% vs 66%; p ≤ 0.001). Protein expression level was found to be slightly higher in the head of the strip, however, 3 out of 5 punches from the head failed quality control. Protein expression levels over the remaining parts of the strips were similar. Our study showed beneficial use of punches of any part of the strip except the head in future biomarker research.
The cytotoxic activity of carfilzomib together with nelfinavir is superior to the bortezomib/nelfinavir combination in non-small cell lung carcinoma
Authors: Besse Lenka , Kraus Marianne , Besse Andrej , Driessen Christoph , Tarantino Ignazio 
Published: March 2023

AbstractChemotherapy resistance is still a major problem in the treatment of patients with non-small-cell-lung carcinoma (NSCLC), and novel concepts for the induction of cytotoxicity in NSCLC are highly warranted. Proteotoxicity, the induction of cytotoxicity by targeting the ubiquitin proteasome system, represents an appealing innovative strategy. The combination of the proteasome inhibitor bortezomib (BTZ) and the proteotoxic stress-inducing HIV drug nelfinavir (NFV) synergistically induces proteotoxicity and shows encouraging preclinical efficacy in NSCLC. The second-generation proteasome inhibitor carfilzomib (CFZ) is superior to BTZ and overcomes BTZ resistance in multiple myeloma patients. Here, we show that CFZ together with NFV is superior to the BTZ + NFV combination in inducing endoplasmic reticulum stress and proteotoxicity through the accumulation of excess proteasomal substrate protein in NSCLC in vitro and ex vivo. Interestingly, NFV increases the intracellular availability of CFZ through inhibition of CFZ export from NSCLC cells that express multidrug resistance (MDR) protein. Combining CFZ with NFV may therefore represent a future treatment option for NSCLC, which warrants further investigation.