bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paradoxical Effects of Depression on Psoriatic Arthritis Outcomes in a Combined Psoriasis-Psoriatic Arthritis Center
Authors: Haberman Rebecca H. , Um Seungha , Catron Sydney , Chen Alan , Lydon Eileen , Attur Malavika , Neimann Andrea L. , Reddy Soumya , Troxel Andrea , Adhikari Samrachana , Scher Jose U. 
Published: September 2022

AbstractPsoriatic arthritis (PsA) is a chronic, complex, inflammatory arthritis that, when left untreated, can lead to erosions, deformities and decrease in quality of life. PsA is known to be associated with multiple comorbidities, including cardiovascular, metabolic and mental health syndromes, all of which can increase its overall morbidity and mortality. Here we describe a cohort of patients with PsA from an urban, tertiary care, and followed at a combined rheumatology-dermatology center. Depression was reported in 22.8% of the population, anxiety in 18%, and attention deficit hyperactivity disorder in 4%. Depression was more common in female participants (p<.001). At baseline, individuals with PsA and concomitant depression had similar tender and swollen joint counts and RAPID3 compared to those without depression, and had lower body surface area affected by psoriasis (p=.04). At year one, all patients had improvement in clinical outcomes. However, patients with depression had a significantly higher tender joint count compared to those without depression (p=.001), despite similar swollen joint count and body surface area. These observations underscore the importance of addressing depression and psychological distress as part of PsA treatment outcomes and points towards the need to address residual pain through co-adjuvant approaches.
Microtubule-mediated GLUT4 trafficking is disrupted in insulin resistant skeletal muscle
Authors: Knudsen Jonas R. , Persson Kaspar W. , Henriquez-Olguin Carlos , Li Zhencheng , Leo Nicolas Di , Raun Steffen H. , Hingst Janne R. , Trouillon Raphaël , Wohlwend Martin , Wojtaszewski Jørgen F. P. , Gijs Martin A. M. , Jensen Thomas E. 
Published: September 2022

AbstractMicrotubules serve as tracks for long-range intracellular trafficking of glucose transporter 4 (GLUT4), but the role of this process in skeletal muscle and insulin resistance is unclear. Here, we used fixed and live-cell imaging to study microtubule-based GLUT4 trafficking in human and mouse muscle fibers and L6 rat muscle cells. We found GLUT4 localized along and on the microtubules in mouse and human muscle fibers. Pharmacological microtubule disruption using Nocodazole (Noco) prevented long-range GLUT4 trafficking and depleted GLUT4-enriched structures at microtubule nucleation sites in a fully reversible manner. Using a perfused muscle-on-a-chip system to enable real-time glucose uptake measurements in isolated mouse skeletal muscle fibers, we observed that Noco maximally disrupted the microtubule network after 5 min without affecting insulin-stimulated glucose uptake. In contrast, a 2h Noco treatment markedly decreased insulin responsiveness of glucose uptake. Insulin resistance in mouse muscle fibers induced either in vitro by C2 ceramides or in vivo by diet-induced obesity, impaired microtubule-based GLUT4 trafficking. In L6 muscle cells, pharmacological activation of the microtubule motor protein kinesin-1 increased basal and insulin-stimulated GLUT4 translocation, whereas shRNA-mediated knockdown of the kinesin-1 protein encoding gene Kif5B reduced insulin-stimulated GLUT4 translocation. Thus, in adult skeletal muscle fibers, the microtubule network is essential for intramyocellular GLUT4 movement, likely functioning to maintain an insulin-responsive cell-surface recruitable GLUT4 pool via kinesin-1 mediated trafficking.
Social problems and brain structure development following childhood mild traumatic brain injury
Authors: Dégeilh Fanny , Soest Tilmann von , Ferschmann Lia , Beer Joanne C. , Gaubert Malo , Koerte Inga K. , Tamnes Christian K. 
Published: September 2022

AbstractChildhood mild traumatic brain injury (mTBI) is associated with elevated risk of developing social problems, which may be underpinned by changes in the structural developmental trajectory of the social brain, a network of cortical regions supporting social cognition and behavior. However, limited sample sizes and cross-sectional designs generally used in neuroimaging studies of pediatric TBI have prevented explorations of this hypothesis. This longitudinal retrospective study examined the development of parent-reported social problems and cortical thickness in social brain regions following childhood mTBI using data from the large population-based Adolescent Brain Cognitive Development (ABCD) Study. Two-group latent change score models revealed different developmental trajectories from ages 10 to 12 years in social problems between children with (n=345) and without (n=7,089) mTBI. Children with mTBI showed higher levels of social problems than controls at age 10. Then, social problems decreased over 2 years, but still remained higher than in controls in which they stayed stable. Both groups showed similar decreases in social brain cortical thickness between ages 10 and 12 years. Further studies providing detailed information on the injury mechanism and acute symptoms are needed to better understand individual differences in social impairment and brain development in pediatric TBI.
Prognostic value of 8q gain in relation to BAP1 and SF3B1 mutated uveal melanoma
Authors: Nguyen Josephine Q.N. , Drabarek Wojtek , Vaarwater Jolanda , Yavuzyigitoglu Serdar , Verdijk Robert M. , Paridaens Dion , Naus Nicole C. , de Klein Annelies , Brosens Erwin , Kiliç Emine 
Published: September 2022

Unstructured abstractChromosome 8q gain is associated with poor prognosis. Here, we show that the predictive value of chromosome 8q gain depends on the mutation status and is true for BAP1 but not for SF3B1-mutated tumors.
Bacillus subtilis remains translationally active after CRISPRi-mediated replication initiation arrest
Authors: Muñoz-Gutierrez Vanessa , Cornejo Fabián A. , Schmidt Katja , Frese Christian K. , Halte Manuel , Erhardt Marc , Elsholz Alexander K.W. , Turgay Kürşad , Charpentier Emmanuelle 
Published: September 2022

AbstractInitiation of bacterial DNA replication takes place at the origin of replication, a region characterized by the presence of multiple DnaA boxes that serve as the binding sites for the master initiator protein DnaA. The absence or failure of DNA replication can result in bacterial cell growth arrest or death. Here, we aimed to uncover the physiological and molecular consequences of stopping replication in the model bacterium Bacillus subtilis. For this purpose, DNA replication was blocked using a CRISPRi approach specifically targeting DnaA boxes 6 and 7, which are essential for replication initiation. We characterized the phenotype of these cells and analyzed the overall changes in the proteome using quantitative mass spectrometry. Cells with arrested replication were elongating and not dividing but showed no evidence of DNA damage response. Moreover, these cells did not cease translation over time. This study sets the ground for future research on non-replicating but translationally active B. subtilis, which might be a valuable tool for biotechnological applications.ImportanceEven though bacteria are constantly replicating under laboratory conditions, natural environments expose them to various stresses like lack of nutrients, high salinity, and pH changes, which can keep them in non-replicating states. Non-replicating states can allow bacteria to become less sensitive or tolerant to antibiotics (persisters), remain inactive in specific niches for an extended period (dormancy), and adapt to some hostile ecosystems. Non-replicating states have been studied due to the possibility of repurposing energy to produce additional metabolites or proteins. Using CRISPRi targeting bacterial replication initiation sequences, we successfully arrested the replication of B. subtilis. We observed that non-replicating cells continued growing but not dividing, and the initial arrest did not induce global stress conditions such as SOS or stringent response. Notably, these cells continued their metabolic activity and translation. This study provides comprehensive insights into the physiological response of replication initiation blockage in B. subtilis.
Carcinoma associated mesenchymal stem cells promote ovarian cancer metastasis by increasing tumor heterogeneity through direct mitochondrial transfer
Authors: Pressimone Catherine , Frisbie Leonard , Dyer Emma , Baruwal Roja , Croix Claudette St. , Watkins Simon , Calderone Michael , Gorecki Grace , Javed Zaineb , Atiya Huda I , Hempel Nadine , Pearson Alexander , Coffman Lan 
Published: September 2022

AbstractOvarian cancer is characterized by early, diffuse metastatic spread with most women presenting with extensive abdominal metastasis at the time of diagnosis. Prior work demonstrated carcinoma-associated mesenchymal stem cells (CA-MSCs) enhance ovarian cancer metastasis through a process of direct cellular interaction and formation of heterocellular CA-MSC and tumor cell complexes. In this study, we demonstrated that CA-MSCs enhance metastasis by increasing tumor cell heterogeneity through mitochondrial donation. We showed that CA-MSCs directly interacted with ovarian cancer cells via tunneling nanotubules (TNTs), and CA-MSCs used these TNTs to transfer live mitochondria to adjacent ovarian cancer cells. This mitochondrial donation preferentially occurred with ovarian cancer cells that had the lowest mitochondrial mass, as quantified using live, actively respiring mitochondrial labeling. These ‘mito poor’ cancer cells demonstrated decreased proliferation, increased sensitivity to chemotherapy, and decreased oxidative phosphorylation compared to ‘mito rich’ cancer cells. CA-MSCs rescued the phenotypes of mito poor cancer cells, restoring their proliferative capacity, increasing chemotherapy resistance, and increasing oxidative phosphorylation. We validated these findings in a fully autologous system using CA-MSCs and cancer cells derived from the same patient to prevent confounding effects of cellular response to foreign organelle/DNA. Using a knockdown of the mitochondrial motor protein, MIRO1, in CA-MSCs, we demonstrated that mitochondrial transfer is necessary for the CA-MSC-mediated rescue of ‘mito poor’ cancer cells. Mitochondria of CA-MSC origin persisted in tumor cells over multiple passages. Importantly, CA-MSC mitochondrial donation occurred in vivo, significantly enhanced tumor cell heterogeneity and decreased survival in an orthotopic ovarian cancer mouse model. Collectively, this work identified CA-MSC mitochondrial transfer as a critical mediator of ovarian cancer cell survival, heterogeneity, and metastasis, and blocking CA-MSC mitochondrial transfer represents a unique therapeutic target in ovarian cancer.
Experimental Parameters-Based Monte-Carlo Simulation of Single-Molecule Localization Microscopy of Nuclear Pore Complex to Evaluate Clustering Algorithms
Authors: Yeo Wei-Hong , Zhang Yang , Neely Amy E. , Bao Xiaomin , Sun Cheng , Zhang Hao F. 
Published: September 2022

AbstractSingle-molecule localization microscopy (SMLM) enables the detailed visualization of nuclear pore complexes (NPC) in vitro with sub-20 nm resolution. However, it is challenging to translate the localized coordinates in SMLM images to NPC functions because different algorithms to cluster localizations as individual NPCs can be biased without ground truth for validation. We developed a Monte-Carlo simulation to generate synthetic SMLM images of NPC and used the simulated NPC images as the ground truth to evaluate the performance of six clustering algorithms. We identified HDBSCAN as the optimal clustering algorithm for NPC counting and sizing. Furthermore, we compared the clustering results between the experimental and synthetic data for NUP133, a subunit in the NPC, and found them to be in good agreement.
Massively-parallel Microbial mRNA Sequencing (M3-Seq) reveals heterogeneous behaviors in bacteria at single-cell resolution
Authors: Wang Bruce , Lin Aaron E. , Yuan Jiayi , Koch Matthias D. , Adamson Britt , Wingreen Ned S. , Gitai Zemer 
Published: September 2022

AbstractBacterial populations are highly adaptive. They can respond to stress and survive in shifting environments. How the behaviors of individual bacteria vary during stress, however, is poorly understood. To identify and characterize rare bacterial subpopulations, technologies for single-cell transcriptional profiling have been developed. Existing approaches, though, are all limited in some technical capacity (e.g., number of cells or transcripts that can be profiled). Due in part to these limitations, few conditions have yet been studied with these tools. Here, we developMassively-parallelMicrobialmRNA sequencing (M3-Seq), a single-cell RNA-sequencing platform for bacteria that pairs combinatorial cell indexing withpost hocrRNA depletion. We show that M3-Seq can profile hundreds of thousands of bacterial cells from different species under a range of conditions in single experiments. We then apply M3-Seq to reveal rare populations, insights into bet hedging strategies during stress responses, and host responses to phage infection.
A chromosome-assigned Mongolian gerbil genome with sequenced centromeres provides evidence of a new chromosome
Authors: Brekke Thomas D. , Papadopulos Alexander S. T. , Julià Eva , Fornas Oscar , Fu Beiyuan , Yang Fengtang , de la Fuente Roberto , Page Jesus , Baril Tobias , Hayward Alexander , Mulley John F. 
Published: September 2022

AbstractChromosome-scale genome assemblies based on ultra-long read sequencing technologies are able to illuminate previously intractable aspects of genome biology such as fine-scale centromere structure and large-scale variation in genome features such as heterochromatin, GC content, recombination rate, and gene content. We present here a new chromosome-scale genome of the Mongolian gerbil (Meriones unguiculatus) which includes the complete sequence of all centromeres. Gerbil centromeres are composed of four different repeats of length 6pb, 37bp, 127bp, or 1747bp which occur in simple alternating arrays and span 1-6Mb. Gerbil genomes have both an extensive set of GC-rich genes and chromosomes strikingly enriched for constitutive heterochromatin. We sought to determine if there was a link between these two phenomena and found that the two heterochromatic chromosomes of the Mongolian gerbil have distinct underpinnings: Chromosome 5 has a large block of intra-arm heterochromatin as the result of a massive expansion of centromeric repeats, while chromosome 13 is comprised of extremely large (>150kb) repeated sequences. In addition to characterizing centromeres, our results demonstrate the importance of including karyotypic features such as chromosome number and the locations of centromeres in the interpretation of genome sequence data, and highlight novel patterns involved in the evolution of chromosomes.
Efficient estimation of time-dependent functional connectivity using Structural Connectivity constraints
Authors: Hernandez Larzabal Hernan , Araya David , Gonzalez Rodriguez Lazara Liset , Roman Claudio , Trujillo-Barreto Nelson , Guevara Pamela , El-Deredy Wael 
Published: September 2022

ABSTRACTMultivariate autoregressive models [MAR] allows estimating effective brain connectivity by considering both power and phase fluctuations of the signals involved. A MAR models brain activity in one region as a linear combination of past activations in all other regions. A Hidden Markov model, HMM, whose states’ emisions are drawn from state-specific MARs, can then be used to model fast switching of effective brain connectivity over time. However, the large number of MAR parameters, impede the accurate and efficient estimation of such models from neuroimaging timeseries with limited length.We propose a new model for inferring time-dependent effective brain connectivity by using a sparse MAR parameterisation to model the states’ emisions of a Hidden Semi-Markov Model, HsMM-MAR-AC. The sparse MAR model parameters are restricted by Anatomical Connectivity information in two ways: direct effective connectivity between two regions is only considered if the corresponding structural link/connection exists; and the time-lag associated with each direct connection is computed based on the average fibre length between the two regions, such that only one lag per connection is estimated.We simulated ground truth time-dependent brain connectivity states by generating time-series of 4 to 10 minutes sampled at 5ms, from switching Resting State Networks with a reference structural connectivity, and evaluated the accuracy of the new model in recovering the simulated Brain connectivity States against different levels of connectivity thresholding above and below the reference.We show that even when restricting the MAR to half of the reference connections, the model was able to recover the number of brain states, the associated connectivity features and their dynamics, with as little data as 4 mins. More relaxed structural connectivity thresholds required longer data to estimate the model accurately, and became computationally unfeasible without anatomical restrictions.HsMM-MAR-AC offers an efficient algorithm for estimating time-depend Effective Connectivity (tdEC) from neuroimaging data, that exploits the advantages of MAR without identifiability problems, excessive demand on data collection, or unnecessary computational complexity.
Thalamic regulation of a visual critical period and motor behavior
Authors: Hageter John , Starkey Jacob , Horstick Eric J 
Published: September 2022

SummaryDuring the visual critical period, sensory experience refines the structure and function of visual circuits. The basis of this plasticity was long thought to be limited to cortical circuits, yet recently described thalamic ocular dominance plasticity challenges this dogma and demonstrates greater complexity underlying visual plasticity. Yet how visual experience modulates responses of thalamic neurons or how the thalamus modulates CP timing is incompletely understood. Using a novel larval zebrafish, thalamus-centric ocular dominance model, we show functional changes in the thalamus and a role of inhibitory signaling to establish critical period timing using a combination of functional imaging, optogenetics, and pharmacology. Moreover, hemisphere-specific functional changes in genetically defined thalamic neurons correlate with changes in visuomotor behavior, establishing a role of thalamic plasticity in modulating motor performance. Together, our work demonstrates that visual plasticity is more broadly conserved and shows that visual experience leads to neuron-level functional changes in the thalamus that require inhibitory signaling to establish critical period timing.
A conserved ribosomal protein has entirely dissimilar structures in different organisms
Authors: Schierholz Léon , Brown Charlotte R. , Helena-Bueno Karla , Uversky Vladimir N. , Hirt Robert P. , Barandun Jonas , Melnikov Sergey V. 
Published: September 2022

ABSTRACTRibosomes from different species can markedly differ in their composition by including dozens of ribosomal proteins that are unique to specific lineages but absent in others. However, it remains unknown how ribosomes acquire and specialize new proteins throughout evolution. Here, to help answer this question, we describe the evolution of the ribosomal protein msL1/msL2 that was recently found in ribosomes from the parasitic microorganism clade, microsporidia. We first show that this protein has a conserved location in the ribosome but entirely dissimilar structures in different organisms: in each of the analyzed species, msL1/msL2 exhibits an altered secondary structure, an inverted orientation of the N- and C-termini on the ribosomal binding surface, and a completely transformed three-dimensional fold. We then show that this evolutionary fold switching is likely caused by changes in the msL1/msL2-binding site in the ribosome; specifically, by variations in microsporidian rRNA. These observations allow us to infer an evolutionary scenario in which a small, positively-charged,de novo-born unfolded protein was first captured by rRNA to become part of the ribosome and subsequently underwent complete fold switching to optimize its binding to its evolving ribosomal binding site. Overall, our work provides a striking example of how a protein can switch its fold in the context of a complex biological assembly while retaining its specificity for its molecular partner. This finding will help us better understand the origin and evolution of new protein components of complex molecular assemblies – thereby enhancing our ability to engineer biological molecules, identify protein homologs, and peer into the history of life on Earth.
Repetitive mild traumatic brain injury impairs resting state fMRI connectivity and alters protein profile signaling networks
Authors: Ravi Sakthivel , Criado-Marrero Marangelie , Barroso Daylin , Braga Isadora M , Bolen Mackenzie , Rubinovich Uriel , Hery Gabriela P. , Grudny Matteo M , Koren John , Prokop Stefan , Febo Marcelo , Abisambra Jose Francisco 
Published: September 2022

AbstractRepetitive mild traumatic brain injury (rmTBI) is a leading and severe threat to cognition that often goes undiagnosed. A major challenge in developing diagnostics and treatments for the consequences of rmTBI is the fundamental knowledge gaps that explain how rmTBI promotes brain dysfunction. It is both critical and urgent to understand the neuropathological and functional consequences of rmTBI to develop effective therapeutic strategies. In this study, we sought to define the extent of altered brain functional connectivity (FC) and expression of neuropathological markers after rmTBI. We performed two rmTBI (2x 0.6□J impacts 24□h apart) in male and female C57BL/6J wild-type (WT) (~2.5-3mo) mice using closed head injury model of engineered rotational acceleration (CHIMERA) or sham procedures. At 5-6 days post-injury (dpi), we measured changes in brain volume and FC using T2-weighted images, resting-state functional MRI (rsfMRI), and graph theory analyses. We used diffusion tensor imaging (DTI) to assess microstructural changes in white matter tracts. In addition, at 7dpi, we measured changes in Iba1 and GFAP to determine the extent of gliosis. The expression of disease-associated protein markers in grey and white matter regions were evaluated using the NanoString-GeoMx digital spatial protein profiling (DSP) platform. The rsfMRI data revealed aberrant changes in connectivity such as node clustering coefficient, global and local efficiency, participation coefficient, eigenvector centrality, and betweenness centrality in thalamus and other key brain regions that process visual, auditory, and somatosensory information. In addition, DTI revealed significantly decreased fractional anisotropy (FA) and axial diffusivity in the optic tract. Also, mean, radial, and axial diffusivity (L1) were significantly increased in the hippocampus. DSP revealed that phospho-serine 199 tau (pS199) as well as glial markers such as GFAP, cathepsin-D, and Iba1 were significantly increased in the optic tract. In thalamic nuclei, the neuroinflammatory marker GPNMB was increased significantly, and the cell proliferation marker Ki-67 was decreased in the rmTBI group. Our data suggest that rmTBI significantly alters brain functional connectivity and causes a profound inflammatory response in gray matter regions, beyond chronic white matter damage.