bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure of the Commander endosomal trafficking complex linked to X-linked intellectual disability/Ritscher-Schinzel syndrome
Authors: Healy Michael D. , McNally Kerrie E. , Butkovic Rebeka , Chilton Molly , Kato Kohji , Sacharz Joanna , McConville Calum , Moody Edmund R.R. , Shaw Shrestha , Planelles-Herrero Vicente J. , Yadav Sathish K.N. , Ross Jennifer , Borucu Ufuk , Palmer Catherine S. , Chen Kai-En , Croll Tristan I. , Hall Ryan J. , Caruana Nikeisha J. , Ghai Rajesh , Nguyen Thi H.D. , Heesom Kate J. , Saitoh Shinji , Berger Imre , Schaffitzel Christiane , Williams Tom A. , Stroud David A. , Derivery Emmanuel , Collins Brett M. , Cullen Peter J. 
Published: January 2023

SUMMARYThe Commander complex is required for endosomal recycling of diverse transmembrane cargos and is mutated in Ritscher-Schinzel syndrome. It comprises two subassemblies; Retriever composed of VPS35L, VPS26C and VPS29, and the CCC complex which contains ten subunits COMMD1-COMMD10 and two coiled-coil domain-containing (CCDC) proteins CCDC22 and CCDC93. Combining X-ray crystallography, electron cryomicroscopy andin silicopredictions we have assembled a complete structural model of Commander. Retriever is distantly related to the endosomal Retromer complex but has unique features preventing the shared VPS29 subunit from interacting with Retromer-associated factors. The COMMD proteins form a distinctive hetero-decameric ring stabilised by extensive interactions with CCDC22 and CCDC93. These adopt a coiled-coil structure that connects the CCC and Retriever assemblies and recruits a sixteenth subunit, DENND10, to form the complete Commander complex. The structure allows mapping of disease-causing mutations and reveals the molecular features required for the function of this evolutionarily conserved trafficking machinery.
Distinct mechanisms underlie value-driven modulation of visual cortex by previously rewarded visual and auditory stimuli
Authors: Antono Jesssica Emily , Dang Shilpa , Auksztulewicz Ryszard , Pooresmaeili Arezoo 
Published: January 2023

AbstractPast reward associations may be signaled by stimuli from different sensory modalities, however it remains unclear how different types of reward-associated stimuli modulate perception. In this human fMRI study, we employed a paradigm involving a visual discrimination task, where a visual target was simultaneously presented with either an intra-(visual) or a cross-modal (auditory) cue that was previously associated with rewards. We hypothesized that depending on the sensory modality of the cues distinct neural pathways underlie the value-driven modulation of visual areas. Two steps of analyses were conducted: first, using a multivariate approach, we confirmed that previously reward-associated cues enhanced the target representation in the early visual areas. Then, using effective connectivity analysis, we tested three possible patterns of communication across the brain regions that could underlie the modulation of visual cortex: a direct pathway from the frontal valuation areas to the visual areas, a mediated pathway through the attention-related areas, and a mediated pathway that additionally involved distinct sensory association areas for auditory and visual rewards. We found evidence for the third model and demonstrate that reward-related information is communicated across the valuation and attention-related brain regions such as the intraparietal sulcus across for both visual and auditory cues. Additionally, the long-range communication of reward information also involved the superior temporal areas in case of auditory reward-associated stimuli. These results suggest that in the presence of previously rewarded stimuli from different sensory modalities, a combination of domain-general and domain-specific mechanisms are recruited across the brain to adjust visual processing.
Longitudinal study of functional brain networks for processing infant directed and adult directed speech during the first year
Authors: Háden Gábor P. , Tóth Brigitta , Winkler István 
Published: January 2023

AbstractIn most cultures infant directed speech (IDS) is used to communicate with young children. The main role IDS plays in parent-child interactions appears to change over time from conveying emotion to facilitating language acquisition. There is EEG evidence for the discrimination of IDS form adult directed speech (ADS) at birth, however, less is known about the development of brain networks responsible for differentially processing IDS and ADS. The current study compared topological characteristics of functional brain networks obtained from 49 healthy infants at the age of 0, 6, and 9 months listening to the same fairy tale presented by the same speaker in IDS and ADS speech. Brain connectivity was assessed by the phase lag synchronization index in 6 frequency bands (delta, theta, low alpha, high alpha, beta, gamma). The topology of the large scale network organization was quantified using minimum spanning tree graphs, separately for each band. The delta band cortical network’s organization was found to be significantly more hierarchical and had a more cost-efficient organization during listening to ID compared to listening to AD. This network organization changes with age as nodes over the frontal cortex become more central within the network. The general picture emerging from the results is that with development the speech processing network becomes more integrated and its focus is shifting towards the left hemisphere. Our results suggest that ID speech specific differences in network topology are related to changes in the role of IDS during the first year of life.Highlights-Multiple stages of maturation are reflected by different EEG bands, occurring in parallel, but with different timing.-Networks processing infant directed speech changes during the first year of life reflecting the change in the role infant directed speech plays in development.-Speech processing networks are shifting towards the left hemisphere with age.-Longitudinal study of speech perception using functional networks on a large sample
A Distinct Phenotype of Polarized Memory B cell holds IgE Memory
Authors: Koenig Joshua F.E. , Knudsen Niels Peter H , Phelps Allyssa , Bruton Kelly , Hoof Ilka , Lund Gitte , Libera Danielle Della , Lund Anders , Christensen Lars Harder , Glass David R. , Walker Tina , Fang Allison , Waserman Susan , Jordana Manel , Andersen Peter S 
Published: January 2023

AbstractAllergen-specific IgE antibodies mediate allergic pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. We report a population of type 2 polarized MBCs defined as CD23hi, IL-4Rαhi, CD32lowat the transcriptional and surface protein levels. These “MBC2s” are enriched in IgG1 and IgG4-expressing cells, while constitutively expressing germline transcripts for IgE. Allergen-specific B cells from patients with allergic rhinitis and food allergy were enriched in MBC2s. MBC2s generated allergen specific-IgE during sublingual immunotherapy, thereby identifying these cells as the primary reservoir of IgE. The identification of MBC2s provides insights into the maintenance of IgE memory, which is detrimental in allergic diseases, but which could be beneficial in protection against venoms and helminths.One-Sentence SummaryIdentification of a novel memory B cell subset which holds allergen specific IgE memory.
The worldwide invasion history of a pest ambrosia beetle inferred using population genomics
Authors: Urvois T. , Perrier C. , Roques A. , Sauné L. , Courtin C. , Kajimura H. , Hulcr J. , Cognato A.I. , Auger-Rozenberg M.-A. , Kerdelhué C. 
Published: January 2023

AbstractXylosandrus crassiusculus, a fungus-farming wood borer native to Southeastern Asia, is the most rapidly spreading invasive ambrosia species worldwide. Previous studies focusing on its genetic structure suggested the existence of cryptic genetic variation in this species. Yet, these studies used different genetic markers, focused on different geographical areas, and did not include Europe. Our first goal was to determine the worldwide genetic structure of this species based on both mitochondrial and genomic markers. Our second goal was to studyX. crassiusculus’ invasion history on a global level and identify the origins of the invasion in Europe. We used a COI and RAD sequencing design to characterize 188 and 206 specimens worldwide, building the most comprehensive genetic dataset for any ambrosia beetle to date. The results were largely consistent between markers. Two differentiated genetic clusters were invasive, albeit in different regions of the world. The two markers were inconsistent only for a few specimens found exclusively in Japan. Mainland USA could have acted as a source for further expansion to Canada and Argentina through stepping-stone expansion and bridgehead events. We showed that Europe was only colonized by Cluster 2 through a complex invasion history including several arrivals from multiple origins in the native area, and possibly including bridgehead from the USA. Our results also suggested that Spain was colonized directly from Italy through intracontinental dispersion. It is unclear whether the mutually exclusive allopatric distribution of the two Clusters is due to neutral effects or due to different ecological requirements.
In-situ metagenomics: A platform for rapid sequencing and analysis of metagenomes in less than one day
Authors: Tamames Javier , Jiménez Diego , Redondo Álvaro , Martínez-García Sandra , de los Rios Asunción 
Published: January 2023

AbstractWe present here a complete system for metagenomic analysis that allows performing the sequencing and analysis of a medium-size metagenome in less than one day. This unprecedented development was possible due to the conjunction of state-of-the art experimental and computational advances: a portable laboratory suitable for DNA extraction and sequencing with nanopore technology; the powerful metagenomic analysis pipeline SqueezeMeta, capable to provide a complete analysis in a few hours and using scarce computational resources; and tools for the automatic inspection of the results via a graphical user interface, that can be coupled to a web server to allow remote visualization of data (SQMtools and SQMxplore). We have tested the feasibility of our approach in the sequencing of the microbiota associated to volcanic rocks in La Palma, Canary Islands. Also, we did a two-day sampling campaign of marine waters in which the results obtained the first day guided the experimental design of the second day. This system offers the possibility of prospecting any habitat in a quick way, obtaining both taxonomic and functional information about the target microbiome.
Predicted and Experimental NMR Chemical Shifts at Variable Temperatures: The Effect of Protein Conformational Dynamics
Authors: Yi Xu , Zhang Lichirui , Friesner Richard A. , McDermott Ann 
Published: January 2023

AbstractNMR chemical shifts provide a sensitive probe of protein structure and dynamics. Prediction of shifts, and therefore interpretation of shifts, particularly for the frequently measured amidic15N sites, remains a tall challenge. We demonstrate that protein15N chemical shift prediction from QM/MM predictions can be improved if conformational variation is included via MD sampling, focusing on the antibiotic target,E. coliDihydrofolate reductase (DHFR). Variations of up to 25 ppm in predicted15N chemical shifts are observed over the trajectory. For solution shifts the average of fluctuations on the low picosecond timescale results in a superior prediction to a single optimal conformation. For low temperature solid state measurements, the histogram of predicted shifts for locally minimized snapshots with specific solvent arrangements sampled from the trajectory explains the heterogeneous linewidths; in other words, the conformations and associated solvent are ‘frozen out’ at low temperatures and result in inhomogeneously broadened NMR peaks. We identified conformational degrees of freedom that contribute to chemical shift variation. Backbone torsion angles show high amplitude fluctuations during the trajectory on the low picosecond timescale. For a number of residues, including I60, ψ varies by up to 60º within a conformational basin during the MD simulations, despite the fact that I60 (and other sites studied) are in a secondary structure element and remain well folded during the trajectory. Fluctuations in ψ appear to be compensated by other degrees of freedom in the protein, including φ of the succeeding residue, resulting in “rocking” of the amide plane with changes in hydrogen bonding interactions. Good agreement for both room temperature and low temperature NMR spectra provides strong support for the specific approach to conformational averaging of computed chemical shifts.
Hydrogels with stiffness-degradation spatial patterns control anisotropic 3D cell response
Authors: Garrido Claudia A. , Garske Daniela S. , Thiele Mario , Amini Shahrouz , Real Samik , Duda Georg N. , Schmidt-Bleek Katharina , Cipitria Amaia 
Published: January 2023

AbstractIn nature, tissues are patterned, but most biomaterials used in human applications are not. Patterned biomaterials offer the opportunity to mimic spatially segregating biophysical and biochemical properties found in nature. Engineering such properties allows to study cell-matrix interactions in anisotropic matrices in great detail. Here, we developed alginate-based hydrogels with patterns in stiffness and degradation, composed of distinct areas of soft non-degradable (Soft-NoDeg) and stiff degradable (Stiff-Deg) material properties. The hydrogels exhibit emerging patterns in stiffness and degradability over time, taking advantage of dual Diels-Alder covalent crosslinking and UV-mediated peptide crosslinking. The materials were mechanically characterized using rheology for single-phase and surface micro-indentation for patterned materials. 3D encapsulated mouse embryonic fibroblasts (MEFs) allowed to characterize the anisotropic cell-matrix interaction in terms of cell morphology by employing a novel image-based quantification tool. Live/dead staining showed no differences in cell viability but distinct patterns in proliferation, with higher cell number in Stiff-Deg materials at day 14. Patterns of projected cell area became visible already at day 1, with larger values in Soft-NoDeg materials. This was inverted at day 14, when larger projected cell areas were identified in Stiff-Deg. This shift was accompanied by a significant decrease in cell circularity in Stiff-Deg. The control of anisotropic cell morphology by the material patterns was also confirmed by a significant increase in filopodia number and length in Stiff-Deg materials. The novel image-based quantification tool was useful to spatially visualize and quantify the anisotropic cell response in 3D hydrogels with stiffness-degradation spatial patterns. Our results show that patterning of stiffness and degradability allows to control cell anisotropic response in 3D and can be quantified by image-based strategies. This allows a deeper understanding of cell-matrix interactions in a multicomponent material.
Unlocking the Power of R: A High-Accuracy Method for Measuring DAB Staining on Immunohistochemical Slides
Authors: Amine Fares Mohamed , Tarek Khenenou , Eddine Rahmoun Djallal 
Published: January 2023

AbstractThe current research aimed to establish a method for measuring the percentage of diaminobenzidine (DAB) staining on immunohistochemical slides with high accuracy and efficiency. The R programming language was utilized in this endeavor. A total of 50 slides were collected from various types of tissue, and were stained using an anti-cytokeratin antibody and the DAB detection method. These slides were then scanned using a high-resolution scanner, and the resulting images were analyzed using R, a custom script was specifically developed to segment the tissue and DAB-positive areas, and calculate the percentage of DAB staining on the slide. The results were then compared to manual measurements of DAB staining performed by a trained technician. The R-based method was found to be highly accurate, with a mean absolute error of only 0.76 % compared to manual measurements, this study provides evidence that the use of R for DAB quantification is a fast and reliable alternative to manual methods, enabling the analysis of large numbers of slides in a short period of time. It offers a valuable tool for researchers and technicians in the field of histopathology, enabling them to quickly and accurately analyze DAB staining on immunohistochemical slides, which is essential for the diagnosis and treatment of various diseases.
Engineering synthetic CopT/A-based genetic circuits for miRNA imaging and functional gene regulation
Authors: Zhang Chuanxian , Shi Xiaorui , Tang Chu , Du Yarong , Shu Wenjie , Wang Fu 
Published: January 2023

AbstractSynthetic genetic circuits that can operate at the transcriptional and translation levels have been widely applied in the control of cellular behaviors and functions. However, the regulation of genetic circuits is often accompanied by the introduction of exogenous substances or the endogenous generation of inhibitory products, which would bring uncontrollable hazards for biological safety and reduce the efficiency of the system. Here, we described a miRNA-responsive CopT-CopA (miCop) genetic circuit system to realize real-time monitoring the intracellular expression of miRNA-124a during neurogenesis or miRNA-122 under the stimulation of extracellular drugs in living cells and animals. Furthermore, to prove the modularity of the system, we engineered this mipCop to tune the expression of DTA (diphtheria toxin A) gene, and showed the powerful capacity of killing cancer cells by inducing apoptosis and cell cycle arrest based on miRNA response. This study provides an effective means to couple miRNA sensing with miRNA-responsive gene modulation, which may open up new diagnostic or therapeutic applications.
The Evolution of Local Energetic Frustration in Protein Families
Authors: Freiberger Maria I. , Ruiz-Serra Victoria I. , Pontes Camila , Romero-Durana Miguel , Galaz-Davison Pablo , Ramírez-Sarmiento Cesar , Schuster Claudio D. , Marti Marcelo A. , Wolynes Peter G. , Ferreiro Diego U. , Parra R. Gonzalo , Valencia Alfonso 
Published: January 2023

AbstractEnergetic local frustration offers a biophysical perspective to interpret the effects of sequence variability on protein families. Here we present a methodology to analyze local frustration patterns within protein families that allows us to uncover constraints related to stability and function, and identify differential frustration patterns in families with a common ancestry. We have analyzed these signals in very well studied cases such as PDZ, SH3,αandβglobins and RAS families. Recent advances in protein structure prediction make it possible to analyze a vast majority of the protein space. An automatic and unsupervised proteome-wide analysis on the SARS-CoV-2 virus demonstrates the potential of our approach to enhance our understanding of the natural phenotypic diversity of protein families beyond single protein instances. We have applied our method to modify biophysical properties of natural proteins based on their family properties, as well as perform unsupervised analysis of large datasets to shed light on the physicochemical signatures of poorly characterized proteins such as emergent pathogens.
Genome Skimming with Nanopore Sequencing Precisely Determines Global and Transposon DNA Methylation in Vertebrates
Authors: Faulk Christopher 
Published: January 2023

AbstractGenome skimming is defined as low-pass sequencing below 0.05X coverage and is typically used for mitochondrial genome recovery and species identification. Long read nanopore sequencers enable simultaneous reading of both DNA sequence and methylation and can multiplex samples for low-cost genome skimming. Here I present nanopore sequencing as a highly precise platform for global DNA methylation and transposon assessment. At coverage of just 0.001X, or 30 Mb of reads, accuracy is sub-1%. Biological and technical replicates validate high precision. Skimming 40 vertebrate species reveals conserved patterns of global methylation consistent with whole genome bisulfite sequencing and an average mapping rate above 97%. Genome size directly correlates to global DNA methylation, explaining 44% of its variance. Accurate SINE and LINE transposon methylation in both mouse and primates can be obtained with just 0.0001X coverage, or 3 Mb of reads. Sample multiplexing, field portability, and the low price of this instrument combine to make genome skimming for DNA methylation an accessible method for epigenetic assessment from ecology to epidemiology, and by low resource groups.
LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2
Authors: Mar Katrina B. , Van Dyke Marley C. , Lopez Alexandra H. , Eitson Jennifer L. , Fan Wenchun , Hanners Natasha W. , Evers Bret M. , Shelton John M. , Schoggins John W. 
Published: January 2023

AbstractLY6E is an antiviral protein that inhibits coronavirus entry. Its expression in immune cells allows mice to control murine coronavirus infection. However, it is not known which immune cell subsets mediate this control or whether LY6E protects mice from SARS-CoV-2. In this study, we used tissue-specific Cre recombinase expression to ablateLy6ein distinct immune compartments or in all epiblast-derived cells, and bone marrow chimeras to target Ly6e in a subset of radioresistant cells. Mice lackingLy6einLyz2-expressing cells and radioresistantVav1-expressing cells were more susceptible to lethal murine coronavirus infection. Mice lackingLy6eglobally developed clinical disease when challenged with the Gamma (P.1) variant of SARS-CoV-2. By contrast, wildtype mice and mice lacking type I and type III interferon signaling had no clinical symptoms after SARS-CoV-2 infection. Transcriptomic profiling of lungs from SARS-CoV-2-infected wildtype andLy6eknockout mice revealed a striking reduction of secretory cell-associated genes in infected knockout mice, includingMuc5b, an airway mucin-encoding gene that may protect against SARS-CoV-2-inflicted respiratory disease. Collectively, our study reveals distinct cellular compartments in which Ly6e confers cell intrinsic antiviral effects, thereby conferring resistance to disease caused by murine coronavirus and SARS-CoV-2.