bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antagonistic role of the BTB-zinc finger transcription factors Chinmo and Broad-Complex in the juvenile/pupal transition and in growth control
Authors: Chafino Sílvia , Giannios Panagiotis , Casanova Jordi , Martín David , Franch-Marro Xavier 
Published: November 2022

AbstractDuring development, the growing organism transits through a series of temporally regulated morphological stages to generate the adult form. In humans, for example, development progresses from childhood through to puberty and then to adulthood, when sexual maturity is attained. Similarly, in holometabolous insects, immature juveniles transit to the adult form through an intermediate pupal stage when larval tissues are eliminated and the imaginal progenitor cells form the adult structures. The identity of the larval, pupal and adult stages depends on the sequential expression of the transcription factorschinmo, Br-CandE93. However, how these transcription factors determine temporal identity in developing tissues is poorly understood. Here we report on the role of the larval specifierchinmoin larval and adult progenitor cells during fly development. Interestingly,chinmopromotes growth in larval and imaginal tissues in a Br-C-independent and -dependent manner, respectively. In addition, we found that the absence ofchinmoduring metamorphosis is critical for proper adult differentiation. Importantly, we also provide evidence that, in contrast to the well-known role ofchinmoas a pro-oncogene, Br-C and E93 act as tumour suppressors. Finally, we reveal that the function ofchinmoas a juvenile specifier is conserved in hemimetabolous insects as its homolog has a similar role inBlatella germanica. Taken together, our results suggest that the sequential expression of the transcription factors Chinmo, Br-C and E93 during larva, pupa an adult respectively, coordinate the formation of the different organs that constitute the adut organism.
Network plasticity in the honey bee antennal lobe during odor presentation
Authors: Paoli Marco , Antonacci Yuri , Faes Luca , Haase Albrecht 
Published: November 2022

AbstractOdorant processing presents multiple parallels across animal species, and insects became relevant models for the study of olfactory coding because of the tractability of the underlying neural circuits. Within the insect brain, odorants are received by olfactory sensory neurons and processed by the antennal lobe network. Such a network comprises multiple nodes, named glomeruli, that receive sensory information and are interconnected by local interneurons participating in shaping the neural representation of an odorant. The study of functional connectivity between the nodes of a sensory networkin vivois a challenging task that requires simultaneous recording from multiple nodes at high temporal resolutions. Here, we used fast two-photon microscopy to follow the calcium dynamics of antennal lobe glomeruli and applied Granger causality analysis to assess the functional directed connectivity among network nodes during and after olfactory stimulation. Our findings show that there is a significant causal coupling between network nodes also in the absence of olfactory stimulation. However, connectivity patterns change upon odorant arrival, showing an increase in connection density and conveying odorant-specific information. Furthermore, we show that causal functional connectivity is unique in individual subjects, and cannot be detected upon artificial glomerular scrambling across individuals. This demonstrates that network states do not consist solely of correlations of mean glomerular responses, which are known to be conserved across bees.
Bioinformatic methods for stratification of obese patients and identification of cancer susceptibility biomarkers based on the analysis of the gut microbiome
Authors: Lacruz-Pleguezuelos Blanca , Fernández Lara P. , Ramírez de Molina Ana , Carrillo de Santa Pau Enrique , Marcos-Zambrano Laura Judith 
Published: November 2022

AbstractObesity has an impact on health by increasing the risk of various diseases. However, these risks might also depend on the metabolic health status, as it seems that metabolically healthy obese subjects are under a reduced risk of suffering comorbidities such as colorectal cancer. The gut microbiome has an effect on obesity and metabolic disorders through several integration pathways, making it a potential therapeutic target for these diseases. In this study, we characterized the gut microbiota of 356 obese and non-obese European individuals with different comorbidities associated with obesity. Using approaches based on supervised machine learning and network biology, we found a set of biomarkers of interest for differentiating metabolically healthy from unhealthy subjects. Then, we performed a linear discriminant analysis of effect size on a population of 1593 colorectal cancer, adenoma and control subjects assembled by the COST Action ML4Microbiome to investigate their role in colorectal cancer risk. Four of our biomarkers appeared in both approaches, suggesting their possible role in colorectal cancer development, prognosis and follow up:Clostridium leptum, Gordonibacter pamelaeae, Eggerthella lentaandCollinsella intestinalis. Further research via longitudinal studies or experimental validation of these microbial species would be necessary to confirm this association.
A novel fishing cat reference genome for the evaluation of potential germline risk variants
Authors: Carroll Rachel A. , Rice Edward S. , Murphy William J. , Lyons Leslie A. , Coghill Lyndon , Swanson William F. , Terio Karen A. , Boyd Tyler , Warren Wesley C. 
Published: November 2022

AbstractThe fishing cat,Prionailurus viverrinus, displays a fish hunting behavior uncommon among most other cats. Estimated population declines in the wild increase the significance of its existing zoo populations, particularly with a recent high prevalence of transitional cell carcinoma (TCC), a form of bladder cancer. We hypothesize that its small captive population may harbor TCC risk variants at the germline level. To aid conservation efforts and investigate the genetics of TCC, we present a new fishing cat chromosomescale assembly, reaffirm its close genetic relationship with the Asian leopard cat (Prionailurus bengalensis), and identify and characterize single nucleotide variants (SNVs) from whole genome sequencing (WGS) data of healthy and TCC cats. Among genes previously associated with bladder cancer risk in humanBRCA2was found to have the highest number of missense mutations in fishing cats, with only two variants exhibiting a predominance in TCC cats. These new fishing cat genomic resources will aid efforts to improve their genetic fitness and enhance the comparative study of feline genomes.
Evaluation of Renal Markers in Systemic Autoimmune Diseases
Authors: Krishnamurthy Hari , Yang Yuanyuan , Song Qi , Krishna Karthik , Jayaraman Vasanth , Wang Tianhao , Bei Kang , Rajasekaran John J. 
Published: November 2022

ABSTRACTRenal involvement is a common occurrence in subjects with systemic autoimmune diseases. The renal manifestation and its severity depend on the underlying condition and may reversely complicate the clinical course of autoimmune diseases. Renal function markers have been widely used in the assessment of normal functioning of kidneys including glomerular filtration rate and concentrating and diluting capacity of the kidney. An increase or decrease in the values of these markers may indicate kidney dysfunction. In this study, a number of critical renal markers were examined in seropositive autoimmune diseases including systemic lupus erythematosus (SLE), connective tissue disorder (CTD), and rheumatoid arthritis (RA). The data from three cohorts of subjects enrolled in renal markers and autoimmune antibody testing between January 2015 to August 2019 were retrospectively studied. The prevalence of renal markers that were out of the reference range and their average levels in female and male subgroups across SLE, CTD, and RA cohorts were compared and analyzed. The levels of renal markers are significantly affected by the presence of autoantibodies, in particular eGFR, cystatin C, and albumin. Autoantibodies were also more frequent in subjects with severe renal function damage. Close follow-up of both renal markers and autoantibodies may potentially assist in the early diagnosis of kidney diseases and improve the survival and life expectancy of autoimmune patients.
The fission yeast cell size control system integrates pathways measuring cell surface area, volume, and time
Authors: Miller Kristi E. , Vargas-Garcia Cesar , Singh Abhyudai , Moseley James B. 
Published: November 2022

SUMMARYEukaryotic cells tightly control their size, but the relevant aspect of size is unknown in most cases. Fission yeast divide at a threshold cell surface area due in part to the protein kinase Cdr2. We find that fission yeast cells only divide by surface area under a size threshold but shift to volume-based divisions when they reach a larger size. The size threshold for changing from surface area to volume-based control is set by ploidy. Within this size control system, we identified the mitotic activator Cdc25 as a volume-based sizer molecule, while the mitotic cyclin Cdc13 accumulates as a timer. We propose an integrated model for cell size control based on multiple signaling pathways that report on distinct aspects of cell size and growth, including cell surface area (Cdr2), cell volume (Cdc25), and time (Cdc13). Combined modeling and experiments show how this system can generate both sizer and adder-like properties.HIGHLIGHTSFission yeast use surface area or volume-based cell size control depending on overall size and ploidyMitotic activator Cdc25 exhibits properties of a volume-based sizer moleculeMitotic cyclin Cdc13 accumulates in the nucleus dependent on time, not sizeCombined modeling and experiments identify conditions for sizer versus adder behavior
Standardization of Data Analysis for RT-QuIC-based Detection of Chronic Wasting Disease
Authors: Rowden Gage R. , Picasso-Risso Catalina , Li Manci , Schwabenlander Marc D. , Wolf Tiffany , Larsen Peter 
Published: November 2022

AbstractChronic wasting disease (CWD) is a disease affecting cervids and is caused by prions accumulating as pathogenic fibrils in lymphoid tissue and the central nervous system. Approaches for detecting CWD prions historically relied on antibody-based assays. However, recent advancements in protein amplification technology provided the foundation for a new class of CWD diagnostic tools. In particular, real-time quaking-induced conversion (RT-QuIC) has rapidly become a feasible option for CWD diagnosis. Despite its increased usage for CWD-focused research, there lacks consensus regarding the interpretation of RT-QuIC data for diagnostic purposes. It is imperative then to identify a standardized and replicable method for determining CWD status from RT-QuIC data. Here, we assessed variables that could impact RT-QuIC results and explored the use of maxpoint ratios (maximumRFU/backgroundRFU) to improve the consistency of RT-QuIC analysis. We examined a variety of statistical analyses to retrospectively analyze CWD status based on RT-QuIC and ELISA results from 668 white-tailed deer lymph nodes. Our results revealed an MPR threshold of 2.0 for determining the rate of amyloid formation, and MPR analysis showed excellent agreement with independent ELISA results. These findings suggest that the use of MPR is a statistically viable option for normalizing between RT-QuIC experiments and defining CWD status.
Integrated single cell analysis reveals co-evolution of malignant B cells and the tumor microenvironment in transformed follicular lymphoma
Authors: Sarkozy Clémentine , Wu Shaocheng , Takata Katsuyoshi , Aoki Tomohiro , Neriah Susana B , Milne Katy , Goodyear Talia , Strong Celia , Rastogi Tashi , Lai Daniel , Sehn Laurie H , Farinha Pedro , Nelson Brad H , Weng Andrew , Scott David W , Craig Jeffrey W , Steidl Christian , Roth Andrew 
Published: November 2022

AbstractFollicular lymphoma (FL) is the most common indolent form of non-Hodgkin lymphoma. Histological transformation of FL to a more aggressive form of lymphoma occurs with a linear incidence of 2-3% per year and is associated with poor outcome. Divergent clonal evolution and an altered tumour microenvironment (TME) have both been implicated in the transformation process. However, the phenotypic consequences of this evolution and its implication in reshaping the TME remain unknown. To address this knowledge gap we performed single cell whole genome (scWGS) and single cell whole transcriptome sequencing (scWTS) of paired pre/post transformation samples of 11 FL patients. We further performed scWTS analysis of additional 11 FL samples from patients that had not undergone transformation within 7 years. Our comprehensive single cell analysis revealed the evolutionary dynamics of transformation at unprecedented resolution. Computational integration of scWGS and scWTS allowed us to identify gene programs upregulated and positively selected during evolution. Furthermore, our scWTS analysis revealed a shifting TME landscape, with an exhausted CD8 T cell signature emerging during transformation. Using multi-color immunofluorescence we transferred these findings to a novel TME based biomarker of transformation, subsequently validated in 2 independent cohorts of pretreatment FL samples. Taken together, our results provide a comprehensive view of the combined genomic and phenotypic evolution of malignant cells during transformation, and the shifting cross-talk between malignant cells and the TME.Graphical abstract
Integration of event experiences to build relational knowledge in the human brain
Authors: Leshinskaya Anna , Nguyen Mitchell , Ranganath Charan 
Published: November 2022

SUMMARYWe investigated how the human brain integrates experiences of specific events to build general knowledge about typical event structure. We examined an episodic area important for temporal relations, anterior-lateral entorhinal cortex (alEC), and a semantic area important for action concepts, middle temporal gyrus (MTG). Participants underwent fMRI while watching sequences of novel events and recalling their temporal relations over two sessions one week apart. Across different contexts, the roles of these events could either be consistent, or conflict; integrative representations should weaken in the conflicting condition. We found integrative representations that emerged quickly in alEC, and only subsequently in MTG, which showed a significant change across sessions. Thus, alEC is important in building integrative representations early in learning and may be a gateway to semantic knowledge in MTG. We suggest that both episodic and semantic systems participate in integrating new information when it is aligned with their content specializations.
Adaptive coding across visual features during free-viewing and fixation conditions
Authors: Nigam Sunny , Milton Russell , Pojoga Sorin , Dragoi Valentin 
Published: November 2022

ABSTRACTTheoretical studies have long proposed that adaptation allows the brain to effectively use the limited response range of sensory neurons to encode widely varying natural inputs. However, despite this influential view, experimental studies have exclusively focused on how the neural code adapts to a range of stimuli lying along a single feature axis, such as orientation or contrast. Here, we performed electrical recordings in macaque visual cortex (area V4) to reveal significant adaptive changes in the neural code of single cells and populations across multiple feature axes. Both during free viewing and passive fixation, populations of cells improved their ability to encode image features after rapid exposure to stimuli lying on orthogonal feature axes even in the absence of initial tuning to these stimuli. These results reveal a remarkable adaptive capacity of visual cortical populations to improve network computations relevant for natural viewing despite the modularity of the functional cortical architecture.
Semaphorin7A patterns neural circuitry in the lateral line of the zebrafish
Authors: Dasgupta Agnik , Reagor Caleb C. , Paik Sang P. , Snow Lauren M. , Jacobo Adrian , Hudspeth A. J. 
Published: November 2022

AbstractIn a developing nervous system, axonal arbors often undergo complex rearrangements before neural circuits attain their final innervation topology. In the lateral line sensory system of the zebrafish, developing sensory axons reorganize their terminal arborization patterns to establish precise neural microcircuits around the mechanosensory hair cells. However, a quantitative understanding of the changes in the sensory arbor morphology and the regulators behind the microcircuit assembly remain enigmatic. Here, we report that Semaphorin7A (Sema7A) acts as an important mediator of these processes. Utilizing a semi-automated three-dimensional neurite tracing methodology and computational techniques, we have identified and quantitatively analyzed distinct topological features that shape the network in wild-type and Sema7A loss-of-function mutants. In contrast to those of wild-type animals, the sensory axons in Sema7A mutants display aberrant arborizations with disorganized network topology and diminished contacts to hair cells. Moreover, ectopic expression of a secreted form of Sema7A by non-hair cells induces chemotropic guidance of sensory axons. Our findings propose that Sema7A likely functions both as a juxtracrine and as a secreted cue to pattern neural circuitry during sensory organ development.
Esr1+ hypothalamic-habenula neurons shape aversive states
Authors: Calvigioni Daniela , Fuzik Janos , Le Merre Pierre , Slashcheva Marina , Jung Felix , Ortiz Cantin , Lentini Antonio , Csillag Veronika , Graziano Marta , Nikolakopoulou Ifigeneia , Weglage Moritz , Lazaridis Iakovos , Kim Hoseok , Lenzi Irene , Park Hyunsoo , Reinius Björn , Carlén Marie , Meletis Konstantinos 
Published: November 2022

AbstractExcitatory projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) drive aversive responses. We used Patch-seq guided multimodal classification to define the structural and functional heterogeneity of the LHA-LHb pathway. Our classification identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles, and projection patterns. We found that genetically-defined LHA-LHb neurons signal distinct aspects of emotional or naturalistic behaviors: Esr1+ LHA-LHb neurons induce aversion, whereas Npy+ LHA-LHb neurons control rearing behavior. Repeated optogenetic drive of Esr1+ LHA-LHb neurons induces a behaviorally persistent aversive state, and large-scale recordings showed a region-specific neural representation of the aversive state in the prelimbic region of the prefrontal cortex. We further found that exposure to unpredictable mild shocks induced a sex-specific sensitivity to develop a stress state in female mice, which was associated with a specific shift in the intrinsic properties of bursting-type Esr1+ LHA-LHb neurons. In summary, we describe the diversity of LHA-LHb neuron types, and provide evidence for the role of Esr1+ neurons in aversion and sexually dimorphic stress sensitivity.
Rab11 is essential to pancreas morphogenesis, lumen formation and endocrine mass
Authors: Barlow Haley R. , Htike Yadanar , Fassetta Luke , Ahuja Neha , Bierschenk Tyler , Azizoglu D. Berfin , Flores Juan , Gao Nan , Marciano Denise , Cleaver Ondine 
Published: November 2022

ABSTRACTThe molecular links between tissue-level morphogenesis and the differentiation of cell lineages in the pancreas remain elusive despite a decade of studies. We previously showed that in pancreas both these processes depend on proper lumenogenesis. The Rab GTPase Rab11 has been shown to be essential to epithelial lumen formationin vitro, however few studies have addressed its functionsin vivoand none have tested its requirement in pancreas. Here, we show that Rab11 is critical to proper pancreas development. Co-deletion of the Rab11 isoformsRab11AandRab11Bin the developing pancreatic epithelium (Rab11pancDKO) results in ~50% neonatal lethality, and surviving adult Rab11pancDKOmice exhibit defective endocrine function. Loss of Rab11 in the embryonic pancreas results in morphogenetic defects of the epithelium linked to defective lumen formation and interconnection. In contrast to wildtype cells, Rab11pancDKOcells attempt to form multiple lumens, resulting in a failure to coordinate a single apical membrane initiation site (AMIS) between groups of cells. We show that these defects are due to failures in vesicle trafficking, as apical components remain trapped within Rab11pancDKOcells. Together, these observations suggest Rab11 directly regulates epithelial lumen formation and morphogenesis. Our report links intracellular trafficking to organ morphogenesisin vivo, and presents a novel framework for decoding pancreatic development.HIGHLIGHTSRab11Af/f;Rab11B-/-;Pdx1-Cre pancreas displays disruption of epithelial organization and reduction of endocrine cell mass.Loss of Rab11 results in disruption of pancreatic lumen continuity due to a failure of lumen formation.Epithelial cells lacking Rab11 display abnormal polarity.
Amyloid-beta peptides 40 and 42 employ distinct molecular pathways for cell entry and intracellular transit at the BBB endothelium
Authors: Wang Zengtao , Sharda Nidhi , Omtri Rajesh S. , Li Ling , Kandimalla Karunya K. 
Published: November 2022

ABSTRACTBlood-brain barrier (BBB) is a critical portal regulating the bidirectional transport of amyloid beta (Aβ) proteins between blood and brain. Disrupted trafficking at the BBB may not only promote the build-up of Aβ plaques in the brain parenchyma, but also facilitate Aβ accumulation within the BBB endothelium, which aggravates BBB dysfunction. Soluble Aβ42:Aβ40 ratios in plasma and cerebrospinal fluid have been reported to decrease during Alzheimer’s disease (AD) progression. Our previous publications demonstrated that trafficking of Aβ42 and Aβ40 at the BBB is distinct and is disrupted under various pathophysiological conditions. However, the intracellular mechanisms that allow BBB endothelium to differentially handle Aβ40 and Aβ42 have not been clearly elucidated. In this study, we identified mechanisms of fluorescently labeled Aβ (F-Aβ) endocytosis in polarized human cerebral microvascular endothelial (hCMEC/D3) cell monolayers using pharmacological inhibition and siRNA knock-down approaches. Further, intracellular transit of F-Aβ following endocytosis was tracked using live cell imaging. Our studies demonstrated that both F-Aβ peptides were internalized by BBB endothelial cells via energy, dynamin and actin dependent endocytosis. Interestingly, endocytosis of F-Aβ40 is found to be clathrin-mediated, whereas F-Aβ42 endocytosis is caveolae-mediated. Following endocytosis, both isoforms were sorted by the endo-lysosomal system. While Aβ42 was shown to accumulate more in the lysosome which could lead to its higher degradation and/or aggregation at lower lysosomal pH, Aβ40 demonstrated robust accumulation in recycling endosomes which may facilitate its transcytosis across the BBB. These results provide a mechanistic insight into the selective ability of BBB endothelium to transport Aβ40 versus Aβ42. This knowledge contributes to the understanding of molecular pathways underlying Aβ accumulation in the BBB endothelium and associated cerebrovascular dysfunction as well as amyloid deposition in the brain parenchyma which are implicated in AD pathogenesis.