bluuebunny/crossref_metadata_2025_split huggingface dataset:
A window to the brain: ultrasound imaging of human neural activity through a permanent acoustic window
Authors: Rabut Claire , Norman Sumner L. , Griggs Whitney S. , Russin Jonathan J. , Jann Kay , Christopoulos Vasileios , Liu Charles , Andersen Richard A. , Shapiro Mikhail G. 
Published: June 2023

AbstractRecording human brain activity is crucial for understanding normal and aberrant brain function. However, available recording methods are either highly invasive or have relatively low sensitivity. Functional ultrasound imaging (fUSI) is an emerging technique that offers sensitive, large-scale, high-resolution neural imaging. However, fUSI cannot be performed through adult human skull. Here, we use a polymeric skull replacement material to create an acoustic window allowing ultrasound to monitor brain activity in fully intact adult humans. We design the window through experiments in phantoms and rodents, then implement it in a participant undergoing reconstructive skull surgery. Subsequently, we demonstrate fully non-invasive mapping and decoding of cortical responses to finger movement, marking the first instance of high-resolution (200 μm) and large-scale (50 mmx38 mm) brain imaging through a permanent acoustic window.
Fusion crystallization reveals the behavior of both the 1TEL crystallization chaperone and the TNK1 UBA domain
Authors: Nawarathnage Supeshala , Tseng Yi Jie , Soleimani Sara , Smith Tobin , Pedroza Romo Maria J , Abiodun Wisdom Oshireku , Egbert Christina M. , Madhusanka Deshan , Bunn Derick , Woods Bridger , Tsubaki Evan , Stewart Cameron , Brown Seth , Doukov Tzanko , Andersen Joshua L. , Moody James D. 
Published: June 2023

SummaryHuman thirty-eight-negative kinase-1 (TNK1) is implicated in cancer progression. The TNK1-UBA domain binds polyubiquitin and plays a regulatory role in TNK1 activity and stability. Sequence analysis suggests an unusual architecture for the TNK1 UBA domain, but an experimentally-validated molecular structure is undetermined. To gain insight into TNK1 regulation, we fused the UBA domain to the 1TEL crystallization chaperone and obtained crystals diffracting as far as 1.53 Å. A 1TEL search model enabled solution of the X-ray phases. GG and GSGG linkers allowed the UBA to reproducibly find a productive binding mode against its host 1TEL polymer and to crystallize at protein concentrations as low as 0.1 mg/mL. Our studies support a mechanism of TELSAM fusion crystallization and show that TELSAM fusion crystals require fewer crystal contacts than traditional protein crystals. Modeling and experimental validation suggest the UBA domain may be selective for both the length and linkages of polyubiquitin chains.
Dengue virus preferentially uses human and mosquito non-optimal codons
Authors: Castellano Luciana A , McNamara Ryan J , Pallares Horacio M , Gamarnik Andrea V , Alvarez Diego E , Bazzini Ariel A 
Published: June 2023

AbstractCodon optimality refers to the effect codon composition has on messenger RNA (mRNA) stability and translation level and implies that synonymous codons are not silent from a regulatory point of view. Here, we investigated the adaptation of virus genomes to the host optimality code using mosquito-borne dengue virus (DENV) as a model. We defined which codons are associated with unstable and stable (non-optimal and optimal codons, respectively) mRNAs in mosquito cells and showed that DENV preferentially uses non-optimal codons and avoids codons that are defined as optimal in either human or mosquito cells. Human genes enriched in the codons preferentially and frequently used by DENV are up-regulated during infection, and so is the tRNA decoding the non-optimal and DENV preferentially used codon for arginine. We found that synonymous mutations towards DENV’s preferred non-optimal codons (e.g., AGA) increase fitness of DENV during serial passaging in human or mosquito cells. Finally, our analyses revealed that hundreds of viruses preferentially use non-optimal codons, with those infecting a single host displaying an even stronger bias, suggesting that synonymous codon choice is a key aspect of host-pathogen interaction.
Aerobic denitrification as N2O source in microbial communities
Authors: Roothans Nina , Gabriëls Minke , Pabst Martin , van Loosdrecht Mark C. M. , Laureni Michele 
Published: June 2023

AbstractNitrous oxide (N2O) is a potent greenhouse gas of primarily microbial origin. Aerobic and anoxic emissions are commonly ascribed to nitrification and denitrification, respectively. Beyond this established dichotomy, we quantitatively prove that heterotrophic denitrification can significantly contribute to aerobic nitrogen turnover and N2O emissions in complex microbiomes exposed to frequent oxic/anoxic transitions. Planktonic, nitrification-inhibited denitrifying enrichments respired over a third of the influent organic substrate with nitrate at high oxygen concentrations. N2O accounted for up to one quarter of the aerobically respired nitrate. The constitutive detection of all denitrification enzymes in both anoxic and oxic periods highlight the selective advantage offered by metabolic preparedness in dynamic environments. We posit that aerobic denitrification and associated N2O formation is currently underestimated in dynamic microbial ecosystems.
Hexokinase regulates Mondo-mediated longevity via the PPP and organellar dynamics
Authors: Laboy Raymond , Ndoci Marjana , Vonolfen Maximilian , Ballhysa Eugen , Syed Shamsh Tabrez , Droth Tim , Schilling Klara , Löhrke Anna , Atanassov Ilian , Antebi Adam 
Published: June 2023

AbstractThe transcriptional complex Mondo/Max-like, MML-1/MXL-2, acts as a convergent transcriptional regulatory output of multiple longevity pathways inCaenorhabditis elegans. These transcription factors coordinate nutrient sensing with carbohydrate and lipid metabolism across the evolutionary spectrum. While most studies have focused on the downstream outputs, little is known about the upstream inputs that regulate these transcription factors in a live organism. Here, we found that knockdown of various glucose metabolic enzymes decreases MML-1 localization in the nucleus and identified two hexokinase isozymes,hxk-1andhxk-2,as the most vigorous regulators of MML-1 function. Upon hexokinase knockdown, MML-1 redistributes to mitochondria and lipid droplets (LD) and concomitantly, transcriptional targets are downregulated and germline longevity is abolished. Further, we found thathxk-1regulates MML-1 through mitochondrial β-oxidation, whilehxk-2regulates MML-1 by modulating the pentose phosphate pathway (PPP) and its coordinated association with lipid droplets. Similarly, inhibition of the PPP rescues mammalian MondoA nuclear translocation and transcriptional function upon starvation. These studies reveal how metabolic signals and organellar communication regulate a key convergent metabolic transcription factor to promote longevity.
AutoRNC: an automated modeling program for building atomic models of ribosome-nascent chain complexes
Authors: McDonnell Robert T. , Elcock Adrian H. 
Published: June 2023

AbstractThe interpretation of experimental studies of co-translational protein folding often benefits from the use of computational methods that seek to model the nascent chain and its interactions with the ribosome. Ribosome-nascent chain (RNC) constructs studied experimentally can vary significantly in size and the extent to which they contain secondary and tertiary structure, and building realistic 3D models of them therefore often requires expert knowledge. To circumvent this issue, we describe here AutoRNC, an automated modeling program capable of constructing large numbers of plausible atomic models of RNCs within minutes. AutoRNC takes input from the user specifying any regions of the nascent chain that contain secondary or tertiary structure and attempts to build conformations compatible with those specifications – and with the constraints imposed by the ribosome – by sampling and progressively piecing together dipeptide conformations extracted from the RCSB. We first show that conformations of completely unfolded proteins built by AutoRNC in the absence of the ribosome have radii of gyration that match well with the corresponding experimental data. We then show that AutoRNC can build plausible conformations for a wide range of RNC constructs for which experimental data have already been reported. Since AutoRNC requires only modest computational resources, we anticipate that it will prove to be a useful hypothesis generator for experimental studies, for example, in providing indications of whether designed constructs are likely to be capable of folding, as well as providing useful starting points for downstream atomic or coarse-grained simulations of the conformational dynamics of RNCs.
Hyperglycosylation of prosaposin in tumor DCs promotes immune escape in cancer
Authors: Sharma Pankaj , Zhang Xiaolong , Ly Kevin , Kim Ji Hyung , Wan Qi , Kim Jessica , Lou Mumeng , Kain Lisa , Teyton Luc , Winau Florian 
Published: June 2023

Tumors develop strategies to evade immunity by suppressing antigen presentation. Here, we show that prosaposin drives CD8 T cell-mediated tumor immunity and that its hyperglycosylation in tumor DCs leads to cancer immune escape. We found that lysosomal prosaposin and its single saposin cognates mediated disintegration of tumor cell-derived apoptotic bodies to facilitate presentation of membrane-associated antigen and T cell activation. In the tumor microenvironment, TGF-β induced hyperglycosylation of prosaposin and its subsequent secretion, which ultimately caused depletion of lysosomal saposins. In melanoma patients, we found similar prosaposin hyperglycosylation in tumor-associated DCs, and reconstitution with prosaposin rescued activation of tumor-infiltrating T cells. Targeting tumor DCs with recombinant prosaposin triggered cancer protection and enhanced immune checkpoint therapy. Our studies demonstrate a critical function of prosaposin in tumor immunity and escape and introduce a novel principle of prosaposin-based cancer immunotherapy.One Sentence SummaryProsaposin facilitates antigen cross-presentation and tumor immunity and its hyperglycosylation leads to immune evasion.
Functional Sexual Dimorphism in Human Nociceptors
Authors: Stratton Harrison , Dolatyari Mahdi , Dumaire Nicolas , Moutal Aubin , Ghetti Andre , Cotta Tamara , Mitchell Stefanie , Yue Xu , Navratilova Edita , Porreca Frank 
Published: June 2023

AbstractThe recent demonstration of differences in transcript expression in human post-mortem sensory neurons suggests the possibility of sexually dimorphic pain mechanisms. To date, however, the concept of “male” and “female” nociceptors has not been demonstrated at a functional level. We now report sensitization of female, but not male, human nociceptors by prolactin revealing a female-selective mechanism that can be exploited to improve the treatment of pain in women.
Predicting T cell activation based on intracellular calcium fluctuations
Authors: This Sébastien , Costantino Santiago , Melichar Heather J. 
Published: June 2023

AbstractAdoptive T cell therapies rely on the transduction of T cells with a predetermined antigen receptor which redirects their specificity towards tumor-specific antigens. Despite the development of multiple platforms for tumor-specific T cell receptor (TCR) discovery, this process remains time consuming and skewed toward high-affinity TCRs. Specifically, the methods for identifying therapeutically-relevant TCR sequences, predominantly achieved through the enrichment of antigen-specific T cells, represents a major bottleneck for the broader application of TCR-engineered cell therapies. Fluctuation of intracellular calcium levels in T cells is a well described, proximal readout of TCR signaling. Hence, it is an attractive candidate marker for identifying antigen-specific T cells that does not requirein vitroantigen-specific T cell expansion. However, calcium fluctuations downstream of TCR engagement with antigen are highly variable; we propose that appropriately-trained machine learning algorithms may allow for T cell classification from complex datasets such as those related to polyclonal T cell signaling events. Using deep learning tools, we demonstrate efficient and accurate prediction of antigen-specificity based on intracellular Ca2+fluctuations ofin vitro-stimulated CD8+T cells. Using a simple co-culture assay to activate monoclonal TCR transgenic T cells of known specificity, we trained a convolutional neural network to predict T cell reactivity, and we test the algorithm against T cells bearing a distinct TCR transgene as well as a polyclonal T cell response. This approach provides the foundation for a new pipeline to fast-track antigen specific TCR sequence identification for use in adoptive T cell therapy.Significance StatementWhile T cells engineered to express a cancer-specific T cell receptor (TCR) are emerging as a viable approach for personalized therapies, the platforms for identifying clinically-relevant TCR sequences are often limited in the breadth of antigen receptors they identify or are cumbersome to implement on a personalized basis. Here, we show that imaging of intracellular calcium fluctuations downstream of TCR engagement with antigen can be used, in combination with artificial intelligence approaches, to accurately and efficiently predict T cell specificity. The development of cancer-specific T cell isolation methods based on early calcium fluctuations may avoid the biases of current methodologies for the isolation of patient-specific TCR sequences in the context of adoptive T cell therapy.
Myosin 10 uses its MyTH4 and FERM domains differentially to support two aspects of spindle pole biology required for mitotic spindle bipolarity
Authors: Yim Yang-In , Pedrosa Antonio , Wu Xufeng , Chinthalapudi Krishna , Cheney Richard E. , Hammer John A. 
Published: June 2023

AbstractMyosin 10 (Myo10) has the ability to link actin filaments to integrin-based adhesions and to microtubules by virtue of its integrin-binding FERM domain and microtubule-binding MyTH4 domain, respectively. Here we used Myo10 knockout cells to define Myo10’s contribution to the maintenance of spindle bipolarity, and complementation to quantitate the relative contributions of its MyTH4 and FERM domains. Myo10 knockout HeLa cells and mouse embryo fibroblasts (MEFs) both exhibit a pronounced increase in the frequency of multipolar spindles. Staining of unsynchronized metaphase cells showed that the primary driver of spindle multipolarity in knockout MEFs and knockout HeLa cells lacking supernumerary centrosomes is pericentriolar material (PCM) fragmentation, which creates y-tubulin-positive acentriolar foci that serve as additional spindle poles. For HeLa cells possessing supernumerary centrosomes, Myo10 depletion further accentuates spindle multipolarity by impairing the clustering of the extra spindle poles. Complementation experiments show that Myo10 must interact with both integrins and microtubules to promote PCM/pole integrity. Conversely, Myo10’s ability to promote the clustering of supernumerary centrosomes only requires that it interact with integrins. Importantly, images of Halo-Myo10 knock-in cells show that the myosin localizes exclusively within adhesive retraction fibers during mitosis. Based on these and other results, we conclude that Myo10 promotes PCM/pole integrity at a distance, and that it facilitates supernumerary centrosome clustering by promoting retraction fiber-based cell adhesion, which likely provides an anchor for the microtubule-based forces driving pole focusing.
Lego-like Mixing and Matching of Engineered Bacteria Configure Full Subtractor and Adder Through an Artificial Neural Network Type Architecture
Authors: Bonnerjee Deepro , Chakraborty Saswata , Bagh Sangram 
Published: June 2023

AbstractOne of the long-term goals of synthetic bioengineering is to create configurable and programmable biological systems by just mixing and matching "LEGO"-like bio-modules. Here, we introduce a configurable and modular multi-cellular system where, from a small library of nine discrete engineered bacterial cells, a full subtractor and a full adder can be built on demand by just mixing and matching seven appropriate cell types in a culture. Here, each set of engineered bacteria was modelled as an ‘artificial neuro-synapse’ that, in a co-culture, formed a single layer artificial neural network (ANN) type architecture that worked as a biochemical full subtractor or full adder. The system is configurable with interchangeable cellular modules, whereby through simply interchanging two cell types in the subtractor culture, a full adder can be built and vice versa. This Lego-like mix and match system is mathematically predictive, and provide a flexible and scalable means to build complex cellular functions. This work may have significance in biocomputer technology development, multi-cellular synthetic biology, and cellular hardware for ANN.
Structure of a heteropolymeric type 4 pilus from a monoderm bacterium
Authors: Anger Robin , Pieulle Laetitia , Shahin Meriam , Valette Odile , Le Guenno Hugo , Kosta Artemis , Pelicic Vladimir , Fronzes Rémi 
Published: June 2023

AbstractType 4 pili (T4P) are important virulence factors, which belong to a superfamily of nanomachines ubiquitous in prokaryotes, called type 4 filaments (T4F). T4F are defined as helical polymers of type 4 pilins. Recent advances in cryo-electron microscopy (cryo-EM) led to structures of several T4F. This revealed that the long N-terminal α-helix, the trademark of pilins, packs in the centre of the filaments to form a hydrophobic core, which in bacteria is accompanied by the melting (unfolding) of a portion of α1. Since all available bacterial T4F structures are from diderm species, we tested whether this architecture is conserved in phylogenetically distant species by determining the structure of the T4P of the monodermStreptococcus sanguinis. Our 3.7 A resolution cryo-EM structure of this heteropolymeric T4P, and the resulting full atomic model including all minor pilins, highlight universal features of bacterial T4F and have widespread implications in understanding their biology.
Neuromechanical Justification of Lower-Limb Functional Tests for a Return to Running: A Muscle Coordination Analysis
Authors: Saito Hiroki , Yamano Ayu , Suzuki Nanae , Matsushita Kazuya , Yokoyama Hikaru , Sasaki Atsushi , Takahashi Tatsuya , Nakazawa Kimitaka 
Published: June 2023

ABSTRACTIntroductionThis study aimed to explore the shared muscle synergies between running and functional tests that are commonly used when considering the return to running (RTR) after sports-related injuries. We hypothesized that shared muscle synergies would differ among tasks, providing insights into prioritizing functional tests in the context of RTR.MethodsTen healthy male participants were recruited to perform running and 9 functional tasks and their 16 lower limb and trunk muscle activities were recorded using electromyography (EMG). Non-negative matrix factorization (NMF) was applied to the collected EMG data to explore shared muscle synergies between running and the functional tasks. We compared the percentages of shared synergies and temporal patterns between running and each functional test.ResultsAlthough all functional tests exhibited shared muscle synergies with running, the walk (75% [40%-100%]), single leg hops with 30% of maximum distance (SLH30) (60% [20%-100%]), and stepup (63% [0%-100%]) tasks displayed significantly higher percentages of shared synergies compared to other tests. However, significant differences in temporal patternss were observed between running and all functional tasks, indicating varying activation profiles of shared muscle synergies.ConclusionAlthough all functional tests shared muscle synergies with running, variations in the degree of shared synergies and temporal patterns imply that walking, SLH30, and step-up tests may be the most beneficial in predicting running behavior post-ACL injuries. However, functional tests cannot fully replicate running dynamics, suggesting the need for a careful interpretation when assessing readiness for RTR.
Employee–customer interaction and emotional intelligence to impact emotional labor: does interaction type play any role?
Authors: Shagirbasha Shameem , Madhan Kumar , Iqbal Juman 
Published: June 2023

PurposeGrounded in emotional dissonance and social presence theories, this study examines whether the characteristics of employee–customer interaction (frequency, routineness and duration) and emotional intelligence (EI) have an impact on emotional labor (surface acting (SA), deep acting and naturally felt emotions (NFE)) and whether the type of interaction (face to face, voice to voice and online) moderates this relationship.Design/methodology/approachA survey method was employed to collect data from employees working in hotels, customer care and e-booking services (n = 604). The model was tested using structural equation modeling (SEM).FindingsThe study showed that EI was positively linked to deep acting and NFE but negatively associated with SA. Frequency of interaction had a negative relationship with deep acting and NFE but a positive association with SA. Duration of interaction (DOI) had a positive relationship with deep acting and NFE but a negative association with NFE. Routineness of interaction had a negative relationship with deep acting and NFE but surprisingly had a negative relationship with SA. Online interaction moderated the relationship between EI and deep acting.Originality/valueThis pioneering study examines the relationship between EI and characteristics of employee–customer interaction with emotional labor in the Indian hospitality context. While the association between EI and emotional labor has been studied, this study is unique in substantiating the moderating effects of interaction type and is among the first to do so empirically.
Reliability analysis of repairable multistate phased mission systems with Markov approach based on states
Authors: Yılmaz Sibel , Elmastaş Gültekin Özge 
Published: June 2023

PurposeThe purpose of this study is to find the reliability of the three-component three-phased mission system, which can be repaired by considering the exponential distribution for repair and failure rates in the transitions between the phases based on states with Markov approach. Also, multilevel-phased mission systems are calculated based on states for partially working states.Design/methodology/approachThe reliabilities of the repairable two-level and three-level three-component three-phased mission systems based on states are calculated with the Markov approach. The structure functions are obtained for each phase of the systems, and differential equations are created by the failure and repair of each working state component. These equations are solved using Laplace method.FindingsReliability values of two-level and three-level three-component three-phased systems with different failure, repair, and time intervals are calculated and compared. The intermediate states that multilevel systems handle differently from two-level systems provide a better investigation of the systems. So, these repairable systems offer transparent information in complex systems like transportation and energy, ensuring appropriate timing and cost for repair operations.Originality/valueThis study is original in terms of calculating the reliability of the repairable phased mission system based on the states using Markov method. It is also important in calculating the reliability of the repairable multilevel phased mission system based on states and making reliability comparisons according to different repair and failure rates, equal and different time intervals.