bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ST131 clade and a Phylogroup A clade bearing a novel Escherichia coli O-antigen cluster predominate among bloodstream E. coli isolates from southwest Nigeria hospitals
Authors: Afolayan Ayorinde O. , Aboderin Aaron O. , Oaikhena Anderson O. , Odih Erkison Ewomazino , Ogunleye Veronica O. , Adeyemo Adeyemi T. , Adeyemo Abolaji T. , Bejide Oyeniyi S. , Underwood Anthony , Argimón Silvia , Abrudan Monica , Egwuenu Abiodun , Ihekweazu Chikwe , Aanensen David M. , Okeke Iruka N. 
Published: November 2021

AbstractEscherichia coli bloodstream infections are typically attributed to a limited number of lineages that carry virulence factors associated with invasion and, in recent years, invasive E. coli are increasingly multiply antimicrobial resistant. In Nigeria, E. coli is a common cause of bloodstream infections but the identity of circulating clones is largely unknown and surveillance of their antimicrobial resistance has been limited. We verified and whole genome-sequenced 68 bloodstream E. coli isolates recovered between 2016 and 2018 at three sentinel sites in southwestern Nigeria and susceptibility tested 67 of them. Resistance to antimicrobials commonly used in Nigeria was high, with 67(100%), 62 (92.5%), 53 (79%) and 37(55%) showing resistance to trimethoprim, ampicillin, ciprofloxacin and aminoglycosides, respectively. All the isolates were susceptible to carbapenems and colistin. The strain set included isolates from globally disseminated high risk clones including those belonging to ST12 (n=2), ST131 (n=12) and ST648 (n = 4). Twenty-three (33.82%) of the isolates clustered within two clades. The first of these consisted of ST131 strains, comprised of O16:H5 and O25:H4 sub-lineages. The second was an ST10-ST167 complex clade comprised of strains carrying capsular genes that may have originated in Klebsiella. We additionally determined that four temporally-associated ST90 strains from one sentinel were closely related enough to suggest that at least some of them represented a retrospectively detected outbreak cluster. Our data demonstrate that a broad repertoire of invasive E. coli isolates cause bloodstream infections in southwest Nigeria. In addition to pandemic lineages, particularly ST131, these include a previously undescribed lineage carrying an O-antigen cluster previously only reported from Klebsiella. Genomic surveillance is valuable for tracking these and other clones and for outbreak identification.Data SummaryPhylogenetic tree, clinical data, and epidemiological data were visualized using Microreact (https://microreact.org/project/hmj3KwxS1dmmFPCKFx6qeA-invasive-escherichia-coli-sw-nigeria-2016-2018). All the sequence data have been deposited in the ENA under the project ID PRJEB29739 (https://www.ebi.ac.uk/ena/browser/view/PRJEB29739). Accessions can be found in Table S6.
Cell Wall Biochemistry Drives Pollen Tube Mechanics and Affects Growth Rate
Authors: Vogler Hannes , Munglani Gautam , Ndinyanka Fabrice Tohnyui , Draeger Christian , Burri Jan T. , Eichenberger Christof , Knox J. Paul , Mollet Jean Claude , Nelson Bradley J. , Herrmann Hans J. , Ringli Christoph , Grossniklaus Ueli 
Published: November 2021

SUMMARYPollen tubes live a life on a razor’s edge. They must maintain cell wall integrity whilst growing towards the ovule at extraordinary speed but explosively burst at just the right moment to release the sperm cells—with fatal consequences for reproduction if things go wrong. The precisely controlled growth of the pollen tube depends on the fine-tuned balance between the expansive force of turgor pressure and the restraining effect of the cell wall. Currently, it is not well understood how the composition of the cell wall affects its mechanical properties. Using Arabidopsis mutants, we have investigated these interactions by combining experimental and simulation techniques to determine instantaneous and time-dependent mechanical parameters. This allowed, for the first time, the quantification of the effects of cell wall biochemistry on turgor pressure and cell wall elasticity and to predict their effects on growth rate. Our systems biology approach is widely applicable to study the implications of mechanical stress on growth.
A novel machine learning-based approach for the detection and analysis of spontaneous synaptic currents
Authors: Pircher Thomas , Pircher Bianca , Feigenspan Andreas 
Published: November 2021

AbstractSpontaneous synaptic activity is a hallmark of neural networks. A thorough description of these synaptic signals is essential for understanding neurotransmitter release and the generation of a postsynaptic response. However, the complexity of synaptic current trajectories has either precluded an in-depth analysis or it has forced human observers to resort to manual or semi-automated approaches based on subjective amplitude and area threshold settings. Both procedures are time-consuming, error-prone and likely affected by human bias. Here, we present three complimentary methods for a fully automated analysis of spontaneous excitatory postsynaptic currents measured in major cell types of the mouse retina and in a primary culture of mouse auditory cortex. Two approaches rely on classical threshold methods, while the third represents a novel machine learning-based algorithm. Comparison with frequently used existing methods demonstrates the suitability of our algorithms for an unbiased and efficient analysis of synaptic signals in the central nervous system.
Age-Dependent Formation of TMEM106B Amyloid Filaments in Human Brain
Authors: Schweighauser Manuel , Arseni Diana , Huang Melissa , Lövestam Sofia , Shi Yang , Yang Yang , Zhang Wenjuan , Kotecha Abhay , Garringer Holly J. , Vidal Ruben , Hallinan Grace I. , Newell Kathy L. , Tarutani Airi , Murayama Shigeo , Miyazaki Masayuki , Saito Yuko , Yoshida Mari , Hasegawa Kazuko , Lashley Tammaryn , Revesz Tamas , Kovacs Gabor G. , van Swieten John , Takao Masaki , Hasegawa Masato , Ghetti Bernardino , Falcon Benjamin , Murzin Alexey G. , Goedert Michel , Scheres Sjors H.W. 
Published: November 2021

SummaryMany age-dependent neurodegenerative diseases, like Alzheimer’s and Parkinson’s, are characterised by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-β (Aβ), α-synuclein and TDP-43 are the most common. Here, we used electron cryo-microscopy (cryo-EM) structure determination to show that residues 120-254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in the human brain. We solved cryo-EM structures of TMEM106B filaments from the brains of 22 individuals with neurodegenerative conditions, including sporadic and inherited tauopathies, Aβ-amyloidoses, synucleinopathies and TDP-43opathies, as well as from the brains of two neurologically normal individuals. We observed three different TMEM106B folds, with no clear relationship between folds and diseases. The presence of TMEM106B filaments correlated with that of a 29 kDa sarkosyl-insoluble fragment of the protein on Western blots. The presence of TMEM106B filaments in the brains of older, but not younger, neurologically normal individuals indicates that they form in an age-dependent manner.
A Transparent Ultrasound Array for Real-time Optical, Ultrasound and Photoacoustic Imaging
Authors: Chen Haoyang , Agrawal Sumit , Osman Mohamed , Minotto Josiah , Mirg Shubham , Liu Jinyun , Dangi Ajay , Tran Quyen , Jackson Thomas , Kothapalli Sri-Rajasekhar 
Published: November 2021

AbstractObjective and Impact StatementSimultaneous imaging of ultrasound and optical contrasts can help map structural, functional and molecular biomarkers inside living subjects with high spatial resolution. There is a need to develop a platform to facilitate this multimodal imaging capability to improve diagnostic sensitivity and specificity.IntroductionCurrently, combining ultrasound, photoacoustic and optical imaging modalities is challenging because con-ventional ultrasound transducer arrays are optically opaque. As a result, complex geometries are used to co-align both optical and ultrasound waves in the same field of view.MethodsOne elegant solution is to make the ultrasound transducer transparent to light. Here, we demonstrate a novel transparent ultrasound transducer (TUT) liner array fabricated using a transparent lithium niobate piezoelectric material for real-time multimodal imaging.ResultsThe TUT array consisted of 64 elements and centered at ∼ 6 MHz frequency. We demonstrate a quad-mode ultrasound, Doppler ultrasound, photoacoustic and fluorescence imaging in real-time using the TUT array directly coupled to the tissue mimicking phantoms.ConclusionThe TUT array successfully showed a multimodal imaging capability, and has potential applications in diagnosing cancer, neuro and vascular diseases, including image-guided endoscopy and wearable imaging.
DNA Self-Assembled Plasmonic Nanodiamonds for Biological Sensing
Authors: Liang Le , Zheng Peng , Jia Sisi , Ray Krishanu , Chen Yun , Barman Ishan 
Published: November 2021

AbstractNitrogen-vacancy (NV) centers in diamonds are promising solid-state quantum emitters for developing superior biological imaging modalities. They possess desired bio-compatibility, photostability and electronic spin-related photophysical properties that are optically accessible at room temperature. Yet, bare nanodiamond-based imaging modalities are limited by the brightness and temporal resolution due to the intrinsically long lifetime of NV centers. Moreover, it remains a technological challenge using top-down fabrication to create freestanding hybrid nanodiamond imaging probes with enhanced performance. In this study, we leverage the bottom-up DNA self-assembly to develop a hybrid plasmonic nanodiamond construct, which we coin as the plasmon-enhanced nanodiamond (PEN), for biological imaging. The PEN nano-assembly features a closed plasmonic nanocavity that completely encapsulates a single nanodiamond, thus enabling the largest possible plasmonic enhancement to accelerate the emission dynamics of NV centers. Creation of the PEN nano-assembly is size-independent, so is its broadband scattering spectrum that is optimally overlapped with the emission spectrum of NV centers. Study of the structure-property correlation reveals that the optimal condition for emission dynamics modification is causally linked to that for a plasmonic nanocavity. The cellular internalization and cytotoxicity studies further confirm the delivery efficiency and biological safety of PEN nano-assemblies. Collectively, the PEN nano-assembly provides a promising approach for manipulating photophysical properties of solid-state quantum emitters and could serve as a versatile platform to uncover non-trivial quantum effects in biological systems.
PBPK modelling of dexamethasone in patients with COVID-19 and liver disease
Authors: Montanha Maiara Camotti , Cottura Nicolas , Booth Michael , Hodge Daryl , Bunglawala Fazila , Kinvig Hannah , Grañana-Castillo Sandra , Lloyd Andrew , Khoo Saye , Siccardi Marco 
Published: November 2021

AbstractThe aim of the study was to apply Physiologically-Based Pharmacokinetic (PBPK) modelling to predict the effect of liver disease (LD) on the pharmacokinetics (PK) of dexamethasone (DEX) in the treatment of COVID-19. A whole-body PBPK model was created to simulate 100 adult individuals aged 18-60 years. Physiological changes (e.g., plasma protein concentration, liver size, CP450 expression, hepatic blood flow) and portal vein shunt were incorporated into the LD model. The changes were implemented by using the Child-Pugh (CP) classification system. DEX was qualified using clinical data in healthy adults for both oral (PO) and intravenous (IV) administrations and similarly propranolol (PRO) and midazolam (MDZ) were qualified with PO and IV clinical data in healthy and LD adults. The qualified model was subsequently used to simulate a 6 mg PO and 20 mg IV dose of DEX in patients with varying degrees of LD, with and without shunting. The PBPK model was successfully qualified across DEX, MDZ and PRO. In contrast to healthy adults, the simulated systemic clearance of DEX decreased (35% - 60%) and the plasma concentrations increased (170% - 400%) in patients with LD. Moreover, at higher doses of DEX, the AUC ratio between healthy/LD individuals remained comparable to lower doses. The exposure of DEX in different stages of LD was predicted through PBPK modelling, providing a rational framework to predict PK in complex clinical scenarios related to COVID-19. Model simulations suggest dose adjustments of DEX in LD patients are not necessary considering the low dose administered in the COVID-19 protocol.
Pathogens detected using a syndromic molecular diagnostic platform in patients hospitalized with severe respiratory illness in South Africa in 2017
Authors: Moleleki Malefu , du Plessis Mignon , Ndlangisa Kedibone , Reddy Cayla , von Gottberg Anne , Hellferscee Orienka , Mekgoe Omphe , McMorrow Meredith , Walaza Sibongile , Cohen Cheryl , Tempia Stefano , Variava Ebrahim , Wolter Nicole 
Published: November 2021

AbstractBackgroundPneumonia continues to be a leading cause of death globally; however, in >50% of cases, an etiological agent is not identified. We describe the use of a multi-pathogen platform, TaqMan array card (TAC) real-time PCR, for the detection of pathogens in patients hospitalized with severe respiratory illness (SRI).MethodsWe conducted prospective hospital-based surveillance for SRI among patients at two sentinel sites in South Africa between January and December 2017. Patients were included in this study if a blood specimen and at least one respiratory specimen (naso- and oro-pharyngeal (NP/OP) swabs and/or sputum) were available for testing. We tested respiratory specimens for 21 respiratory pathogens and blood samples for nine bacteria using TAC. Pathogen detection was compared by age group and HIV status using the chi-squared test.ResultsDuring 2017, 956 patients were enrolled in SRI surveillance, and of these, 637 (67%) patients were included in this study (637 blood, 487 NP/OP and 411 sputum specimens tested). At least one pathogen was detected in 83% (527/637) of patients. Common pathogens detected includedH. influenzae(225/637; 35%),S. pneumoniae(224/637; 35%), rhinovirus (144/637; 23%),S. aureus(129/637; 20%),K. pneumoniae(85/637; 13%),M. tuberculosis(75/637; 12%), and respiratory syncytial virus (57/637; 9%). Multiple pathogens (≥2) were co-detected in 57% (364/637) of patients.ConclusionWhile use of a multi-pathogen platform was useful in the detection of a pathogen in the majority of the patients, pathogen co-detections were common and would need clinical assessment for usefulness in individual-level treatment and management decisions.
What happened when? Brain and behavioral responses to modified structure and content in episodic cueing
Authors: Siestrup Sophie , Jainta Benjamin , El-Sourani Nadiya , Trempler Ima , Wolf Oliver T. , Cheng Sen , Schubotz Ricarda I. 
Published: November 2021

ABSTRACTEpisodic memories are not static but can be modified on the basis of new experiences, potentially allowing us to make valid predictions in the face of an ever-changing environment. Recent research has identified prediction errors during retrieval as a possible trigger for such changes. In the present study, we used modified episodic cues to investigate whether different types of mnemonic prediction errors modulate brain activity and subsequent memory performance. Participants encoded different episodes which consisted of short toy stories. During a subsequent functional magnetic resonance imaging (fMRI) session, participants were then presented videos showing the original episodes, or modified versions thereof. In modified videos, either the order of two subsequent action steps was changed or an object was exchanged for another. Content modifications recruited inferior frontal, parietal, and temporo-occipital areas reflecting the processing of the new object information, while brain responses to structure modifications in right dorsal premotor and inferior frontal areas remained subthreshold. In a post-fMRI memory test, the participants’ tendency to accept modified episodes as originally encoded increased significantly when they had been presented modified versions already during the fMRI session. Our study provides valuable initial insights into the neural processing of different types of episodic prediction errors and their influence on subsequent memory.
Determining the architecture of nuclear ring of Xenopus laevis nuclear pore complex using integrated approaches
Authors: Ren He , Tai Linhua , Zhu Yun , Chan Chun , Zhao Qun , Xu Jiashu , Wang Xiangyang , Ma Xinyao , Zhao Lili , Huang Xiaojun , Yin Guoliang , Jia Mingkang , Zhu Xiaohong , An Yuxin , Zhao Gan , Huang Changxiong , Zhang Lihua , Fan Jun , Sun Fei , Zhang Chuanmao 
Published: November 2021

ABSTRACTThe nuclear pore complexes (NPCs) are large protein assemblies as a physical gate to regulate nucleocytoplasmic transport. Here, using integrated approaches including cryo-electron microscopy, hybrid homology modeling and cell experiment, we determined the architecture of the nuclear ring (NR) from Xenopus laevis oocytes NPC at subnanometer resolution. In addition to the improvement of the Y complex model, eight copies of Nup205 and ELYS were assigned in NR. Nup205 connects the inner and outer Y complexes and contributes to the assembly and stability of the NR. By interacting with both the inner Nup160 and the nuclear envelope (NE), the N-terminal β-propeller and α-solenoid domains of ELYS were found to be essential for accurate assembly of the NPC on the NE.
Deciphering the language of antibodies using self-supervised learning
Authors: Leem Jinwoo , Mitchell Laura S. , Farmery James H.R. , Barton Justin , Galson Jacob D. 
Published: November 2021

AbstractAn individual’s B cell receptor (BCR) repertoire encodes information about past immune responses, and potential for future disease protection. Deciphering the information stored in BCR sequence datasets will transform our fundamental understanding of disease and enable discovery of novel diagnostics and antibody therapeutics. One of the grand challenges of BCR sequence analysis is the prediction of BCR properties from their amino acid sequence alone. Here we present an antibody-specific language model, AntiBERTa, which provides a contextualised representation of BCR sequences. Following pre-training, we show that AntiBERTa embeddings learn biologically relevant information, generalizable to a range of applications. As a case study, we demonstrate how AntiBERTa can be fine-tuned to predict paratope positions from an antibody sequence, outperforming public tools across multiple metrics. To our knowledge, AntiBERTa is the deepest protein family-specific language model, providing a rich representation of BCRs. AntiBERTa embeddings are primed for multiple downstream tasks and can improve our understanding of the language of antibodies.
Non-canonical Function of a Hif-1α Splice Variant Contributes to the Sustained Flight of Locusts
Authors: Ding Ding , Zhang Jie , Du Baozhen , Wang Xuanzhao , Hou Li , Guo Siyuan , Chen Bing , Kang Le 
Published: November 2021

AbstractThe hypoxia inducible factor (Hif) pathway is functionally conserved across metazoans in modulating cellular adaptations to hypoxia. However, the functions of this pathway under aerobic physiological conditions are rarely investigated. Here, we show that Hif-1α2, a locust Hif-1α isoform, does not induce canonical hypoxic responses but functions as a specific regulator of locust flight, which is a completely aerobic physiological process. Two Hif-1α splice variants were identified in locusts, a ubiquitously expressed Hif-1α1 and a muscle-predominantly expressed Hif-1α2. Hif-1α1 that induces typical hypoxic responses upon hypoxia exposure, remains inactive during flight. By contrast, the expression of Hif-1α2, which lacks C-terminal transactivation domain, is less sensitive to oxygen-tension but induced extensively by flying. Hif-1α2 sustains flight endurance by promoting glucose oxidation while simultaneously maintaining redox homeostasis by upregulating the production of a reactive oxygen species (ROS) quencher, DJ-1. Overall, this study reveals a novel Hif-mediated mechanism underlying prolonged aerobic physiological activity.
Mining the microbiota to identify gut commensals modulating neuroinflammation in a mouse model of multiple sclerosis
Authors: Bianchimano Paola , Britton Graham J. , Wallach David S. , Smith Emma M. , Cox Laura M. , Liu Shirong , Iwanowski Kacper , Weiner Howard L. , Faith Jeremiah J. , Clemente Jose C. , Tankou Stephanie K. 
Published: November 2021

AbstractBackgroundThe gut microbiome plays an important role in autoimmunity including multiple sclerosis and its mouse model called experimental autoimmune encephalomyelitis (EAE). Prior studies have demonstrated that the multiple sclerosis gut microbiota can contribute to disease hence making it a potential therapeutic target. In addition, antibiotic treatment has been shown to ameliorate disease in the EAE mouse model of multiple sclerosis. Yet, to this date, the mechanisms mediating these antibiotics effects are not understood. Furthermore, there is no consensus on the gut derived bacterial strains that drive neuroinflammation in multiple sclerosis.ResultsHere we characterized the gut microbiome of untreated and vancomycin treated EAE mice over time to identify bacteria with neuroimmunomodulatory potential. We observed alterations in the gut microbiota composition following EAE induction. We found that vancomycin treatment ameliorates EAE and that this protective effect is mediated via the microbiota. Notably, we observed increased abundance of bacteria known to be strong inducers of regulatory T cells, including members of Clostridium clusters XIVa and XVIII in vancomycin-treated mice during the presymptomatic phase of EAE, as well as at disease peak. We identified 50 bacterial taxa that correlate with EAE severity. Interestingly, several of these taxa exist in the human gut and some of them have been implicated in multiple sclerosis includingAnaerotruncus colihominis, a butyrate producer, which had a positive correlation with disease severity. We found thatAnaerotruncus colihominisameliorates EAE and this is associated with induction of RORγt+regulatory T cells in the mesenteric lymph nodes.ConclusionsWe identified vancomycin as a potent modulator of the gut-brain axis by promoting the proliferation of bacterial species that induce regulatory T cells. In addition, our findings reveal 50 gut commensals as regulator of the gut-brain axis that can be used to further characterize pathogenic and beneficial host-microbiota interactions in multiple sclerosis patients. Our findings suggest that elevatedAnaerotruncus colihominisin multiple sclerosis patients may represent a protective mechanism associated with recovery from the disease.
Learning enhances behaviorally relevant representations in apical dendrites
Authors: Benezra Sam E. , Patel Kripa B. , Campos Citlali Pérez , Hillman Elizabeth M.C. , Bruno Randy M. 
Published: November 2021

SUMMARYLearning alters cortical representations and improves perception. Apical tuft dendrites in Layer 1, which are unique in their connectivity and biophysical properties, may be a key site of learning-induced plasticity. We used both two-photon and SCAPE microscopy to longitudinally track tuft-wide calcium spikes in apical dendrites of Layer 5 pyramidal neurons in barrel cortex as mice learned a tactile behavior. Mice were trained to discriminate two orthogonal directions of whisker stimulation. Reinforcement learning, but not repeated stimulus exposure, enhanced tuft selectivity for both directions equally, even though only one was associated with reward. Selective tufts emerged from initially unresponsive or low-selectivity populations. Animal movement and choice did not account for changes in stimulus selectivity. Enhanced selectivity persisted even after rewards were removed and animals ceased performing the task. We conclude that learning produces long-lasting realignment of apical dendrite tuft responses to behaviorally relevant dimensions of a task.