bluuebunny/crossref_metadata_2025_split huggingface dataset:
A heterogeneously expressed gene family modulates biofilm architecture and hypoxic growth ofAspergillus fumigatus
Authors: Kowalski Caitlin H. , Morelli Kaesi A. , Stajich Jason E. , Nadell Carey D. , Cramer Robert A. 
Published: December 2020

AbstractThe genusAspergillusencompasses human pathogens such asAspergillus fumigatusand industrial powerhouses such asAspergillus niger.In both cases,Aspergillusbiofilms have consequences for infection outcomes and yields of economically important products. Yet, the molecular components influencing filamentous fungal biofilm development, structure, and function remain ill-defined. Macroscopic colony morphology is an indicator of underlying biofilm architecture and fungal physiology. A hypoxia-locked colony morphotype ofA. fumigatushas abundant colony furrows that coincide with a reduction in vertically-oriented hyphae within biofilms and increased low oxygen growth and virulence. Investigation of this morphotype has led to the identification of the causative gene,biofilm architecture factor A (bafA),a small cryptic open reading frame within a subtelomeric gene cluster. BafA is sufficient to induce the hypoxia-locked colony morphology and biofilm architecture inA. fumigatus.Analysis across a large population ofA. fumigatusisolates identified a larger family ofbafgenes, all of which have the capacity to modulate hyphal architecture, biofilm development, and hypoxic growth. Furthermore, introduction ofA. fumigatus bafAintoA. nigeris sufficient to generate the hypoxia-locked colony morphology, biofilm architecture, and increased hypoxic growth. Together these data indicate the potential broad impacts of this previously uncharacterized family of small genes to modulate biofilm architecture and function in clinical and industrial settings.ImportanceThe manipulation of microbial biofilms in industrial and clinical applications remains a difficult task. The problem is particularly acute with regard to filamentous fungal biofilms for which molecular mechanisms of biofilm formation, maintenance, and function are only just being elucidated. Here we describe a family of small genes heterogeneously expressed acrossAspergillus fumigatusstrains that are capable of modifying colony biofilm morphology and microscopic hyphal architecture. Specifically, these genes are implicated in the formation of a hypoxia-locked colony morphotype that is associated with increased virulence ofA.fumigatus. Synthetic introduction of these gene family members, here referred to as biofilm architecture factors, in bothA. fumigatusandA. nigeradditionally modulates low oxygen growth and surface adherence. Thus, these genes are candidates for genetic manipulation of biofilm development in Aspergilli.
Biofilm development on urinary catheters promotes the appearance of viable but non-culturable (VBNC) bacteria
Authors: Wilks Sandra A. , Koerfer Verena V. , Prieto Jacqui A. , Fader Mandy , Keevil C. William 
Published: December 2020

ABSTRACTCatheter-associated urinary tract infections have serious consequences, both for patients and in impacting on healthcare resources. Much work has been carried out to develop an antimicrobial catheter. Although such developments have shown promise under laboratory conditions, none have demonstrated a clear advantage in clinical trials.Using a range of microbiological and advanced microscopy techniques, a detailed laboratory study comparing biofilm development on silicone, hydrogel latex and silver alloy coated hydrogel latex catheters was carried out. Biofilm development byEscherichia coli, Pseudomonas aeruginosaandProteus mirabilison three commercially available catheters was tracked over time. Samples were examined with episcopic differential interference contrast (EDIC) microscopy, culture analysis and staining techniques to quantify viable but non-culturable (VBNC) bacteria.Both qualitative and quantitative assessment found biofilms to develop rapidly on all three materials. EDIC microscopy revealed the rough surface topography of the materials. Differences between culture counts and quantification of total and dead cells demonstrated the presence of VBNC populations, where bacteria retain viability but are not metabolically active.The use of non-culture based techniques showed the development of widespread VBNC populations. These VBNC populations were more evident on silver alloy coated hydrogel latex catheters, indicating a bacteriostatic effect at best. The laboratory tests reported here, that detect VBNC bacteria, allow more rigorous assessment of antimicrobial catheters offering an explanation for why there is often minimal benefit to patients.IMPORTANCESeveral antimicrobial urinary catheter materials have been developed but, although laboratory studies may show a benefit, none have significantly improved clinical outcomes. The use of poorly designed laboratory testing and lack of consideration to the impact of VBNC populations may be responsible. While the presence of VBNC populations is becoming more widely reported, there remains a lack of understanding of the clinical impact or influence of exposure to antimicrobial products. This is the first study to investigate the impact of antimicrobial surface materials and the appearance of VBNC populations. This demonstrates how improved testing is needed prior to clinical trials uptake.
Inter-breeder differences in prepulse inhibition deficits of C57BL/6J mice in a maternal infection model for schizophrenia
Authors: Kobayashi Yutaro , Inaba Hiroyoshi , Iwakura Yuriko , Namba Hisaaki , Sotoyama Hidekazu , Murata Yui , Iwamoto Kazuya , Nawa Hiroyuki 
Published: December 2020

ABSTRACTGenetic and environmental factors interact with each other to influence the risk of various psychiatric diseases; however, the intensity and nature of their interactions remain to be elucidated. We used a maternal infection model using polyinosinic-polycytidylic acid (Poly(I:C)) to determine the relationship between the maternal breeding environment and behavioral changes in the offspring. We purchased pregnant C57BL/6J mice from three breeders and administered Poly(I:C) (2 mg/kg) intravenously in their tail vein on gestation day 15. The offspring were raised to 8-12 weeks old and subjected to the acoustic startle tests to measure their startle response intensity, prepulse inhibition levels, and degree of the adaptation of the startle response. No statistical interaction between Poly(I:C) administration and sex was observed for prepulse inhibition; thus, male and female mice were analyzed together. The Poly(I:C) challenge significantly decreased prepulse inhibition levels of the offspring born to the pregnant dams from Breeder A but not those from the other breeders. However, there were no significant inter-breeder differences in Poly(I:C) effects on startle response and on startle adaptation. The rearing environment of mouse dams has a prominent impact on the Poly(I:C)-induced prepulse inhibition deficits in this maternal infection model.
Nanowires unravel a time-correlated stochastic vectorial process in cells
Authors: Nair Vishnu , Seebald Matthew 
Published: December 2020

AbstractA cell uses its cytoskeletal machinery to control its membrane projections to seek and obtain cargo from its microenvironment. Though this process has been studied extensively using spherical cargo, it remains largely unknown how the process operates with vectorial ones, which are non-spheroid rigid objects with an aspect ratio. In this study, a vectorial cargo, silicon nanowire, was observed to have multiple modes of initial contact and to realign along a membrane projection or on a lamella. Using a qualitative theoretical approach, we demonstrate how membrane energy fluctuations potentially drive this realignment of a vectorial cargo. This was understood by calculations which establish how aspect ratio controls the energy landscape in a vectorial object and its influence on relative energy stability of nanowire-membrane contacts. A study of the realignment transport of vectorial cargoes and their comparison with Ornstein-Uhlenbeck process simulations revealed how one-dimensional time-correlated noise manifested in the transport process. Furthermore, a comparison between sliding of nanowires on cell membrane contacts versus rotational realignment with the same model revealed identical characteristics behind both. The understanding that one-dimensional time-correlated noise underlies both sliding and rotation of a vectorial cargo establishes how cytoskeletal dynamics effectively couples their realignment with subsequent transport for phagocytosis. This work establishes the significance of vectorial cargoes and the nature of underlying vectorial processes that enable their cellular processing.
Overlapping Definitive Progenitor Waves Divide and Conquer to Build a Layered Hematopoietic System
Authors: Freyer Laina , Iturri Lorea , Biton Anne , Perdiguero Elisa Gomez 
Published: December 2020

ABSTRACTAdult innate immune cells are part of a layered hematopoietic system constructed from definitive hematopoietic stem and progenitor cells (HSPC) with diverse origins during development. One source of HSPC are fetal hematopoietic stem cells (HSC) that provide long-term reconstitution throughout life. However, the extent to which HSC produce mature cellsin uterois only recently being uncovered. This is in part due to the added complexity of an overlapping wave of definitive progenitors that derive from yolk sac erythro-myeloid progenitors (EMP). HSC and EMP are generated from spatiotemporally distinct hemogenic endothelia, yet they both migrate to the fetal liver niche where they co-habitate and are presumed to reach their full potential. Delineation of the respective HSC and EMP pathways towards developmental immune cell differentiation has been confounded by challenges in ontogeny-specific cell labeling. In this study,in vivoinducible pulse chase labeling revealed that HSC contribute little to fetal myelopoiesis and that EMP are the predominant source of mature myeloid cells until birth. This is similar to what has been reported for the erythroid branch of hematopoiesis thereby establishing a developmentally-restricted privilege for erythro-myeloid differentiation from EMP compared to HSC. Tracing the origins of mature cells to the progenitor level by immunophenotyping and single cell RNA sequencing uncovered a dichotomy in the allocation of fetal liver EMP and HSC to myeloid progenitor subsets, both in timing and lineage bias. This has exposed an uncoupling between developmental granulopoiesis and monopoiesis from EMP and HSC pathways, and provides a framework for future studies of HSC-dependent and -independent hematopoiesis.HIGHLIGHTSEMP-to-HSC switch in fetal liver myelopoiesis occurs late in gestationEMP are efficient at producing early transit amplifying erythroid and myeloid intermediatesscRNA-seq reveals three trajectories of EMP myelopoiesisMyeloid lineage commitment during development is cell type and ontogeny specific
Role of hypothalamic MAPK/ERK signaling in diabetes remission induced by the central action of fibroblast growth factor 1
Authors: Brown Jenny M. , Bentsen Marie A. , Rausch Dylan M. , Phan Bao Anh , Wieck Danielle , Wasanwala Huzaifa , Matsen Miles E. , Acharya Nikhil , Richardson Nicole E. , Zhao Xin , Zhai Peng , Secher Anna , Morton Gregory J. , Pers Tune H. , Schwartz Michael W. , Scarlett Jarrad M. 
Published: December 2020

SummaryThe capacity of the brain to elicit sustained remission of hyperglycemia in rodent models of type 2 diabetes following intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) is well established. Here, we show that following icv FGF1 injection, hypothalamic signaling by extracellular signal-regulated kinases 1 and 2 (ERK1/2), members of the mitogen-activated protein kinase (MAPK) family is induced for at least 24h. Further, we show that in diabetic Lepob/obmice, this prolonged response is required for the sustained antidiabetic action of FGF1, since it is abolished by sustained (but not acute) pharmacologic blockade of hypothalamic MAPK/ERK signaling. We also demonstrate that FGF1 R50E, a FGF1 mutant that activates FGF receptors but induces only transient hypothalamic MAPK/ERK signaling, fails to mimic the sustained glucose lowering induced by FGF1. These data identify sustained activation of hypothalamic MAPK/ERK signaling as playing an essential role in the mechanism underlying diabetes remission induced by icv FGF1 administration.
Cortical stroke produces secondary injury and long-lasting gliosis in the ipsilateral thalamus
Authors: Kim Gab Seok , Stephenson Jessica M. , Al Mamun Abdullah , Wu Ting , Goss Monica G. , Min Jia-Wei , Li Jun , Liu Fudong , Marrelli Sean P. 
Published: December 2020

AbstractRemote secondary injury in the thalamus has been observed following cortical infarct, however the mechanisms are not well understood. We used the distal MCAO stroke model (pdMCAO) to explore the cellular and temporal gliosis response in secondary thalamic injury in mice. At 3 days post-stroke (PSD3), primary infarct was limited to the cortex, with no infarct in the thalamus. However, at 2 weeks after stroke (PSD14), the ipsilateral thalamus demonstrated degenerating and severely damaged neurons. Staining for GFAP (astrogliosis) or IBA-1 (microgliosis) was first apparent in the ipsilateral thalamus by PSD3, and showed a progressive increase through PSD14. The number of activated microglia was increased within the thalamus at PSD14, reflecting proliferation of resident microglia as well as infiltration of peripheral monocytes. Interestingly, astrogliosis within the thalamus was enduring, as it was still evident at two years post-stroke. Furthermore, the astrogliosis at two years (but not at 6 weeks) demonstrated glial scar-like characteristics. Lastly, we demonstrated that post-stroke treatment with an NMDA receptor antagonist (memantine) reduces gliosis in the thalamus at PSD14. These findings highlight the development of lasting secondary injury in the thalamus following cortical stroke and support the value of memantine treatment in the mitigation of this injury.
The IRE1 Inhibitor Kira6 Curtails The Inflammatory Trait Of Immunogenic Anticancer Treatments By Targeting Hsp60 Independent Of IRE1
Authors: Nicole Rufo , Dimitris Korovesis , Sofie Van Eygen , Derua Rita , Garg Abhishek D , Francesca Finotello , Monica Vara-Perez , Jan Rožanc , Michael Dewaele , de Witte Peter A , Alexopoulos Leonidas G , Janssens Sophie , Lasse Sinkkonen , Thomas Sauter , Verhelst Steven HL , Patrizia Agostinis 
Published: December 2020

ABSTRACTCellular stress evoked by immunogenic anticancer treatments engaging the unfolded protein response (UPR) can elicit inflammation with conflicting therapeutic outcomes. To define cell-autonomous mechanisms coupling the UPR to molecular mediators of inflammation, we profiled the transcriptome of cancer cells responding to immunogenic or weakly immunogenic-treatments. Bioinformatics-driven pathway analysis indicated that immunogenic treatments instigated NF-κB/AP-1-inflammatory pathways, which were abolished by the IRE1α-kinase inhibitor KIRA6. Cell-free fractions of chemotherapy and KIRA6 co-treated cancer cells were deprived of pro-inflammatory/chemoattractant factors and failed to mobilize innate immune cells. Strikingly, these potent KIRA6 anti-inflammatory effects were found to be independent of IRE1α. Generation of a KIRA6-clickable photoaffinity probe, mass spectrometry and co-immunoprecipitation analysis identified cytosolic HSP60 as a KIRA6 off-target in the NF-κB pathway. In sum, our study unravels that inflammation evoked by immunogenic treatments is curtailed by KIRA6 independently of IRE1α and further suggests great caution in interpreting the anti-inflammatory action of IRE1α chemical inhibitors.
Potential mammalian species for investigating the past connections between Amazonia and the Atlantic Forest
Authors: Fabrício Machado Arielli , Ritter Camila Duarte , Miranda Cleuton Lima , Pereira Maria João Ramos , Duarte Leandro 
Published: December 2020

AbstractMuch evidence suggests that Amazonia and the Atlantic Forest were connected through at least three dispersion routes in the past: the northeast route, the central route, and the southeast-northwest route. According to previous studies, the southeast-northwest route would have been the most frequently used. However, few studies have assessed the use of these routes based on multiple species. Here we present a compilation of potential mammal species that could have dispersed between the two forest regions to investigate these connections. We evaluate the geographic distributions of mammals occurring in both Amazonia and the Atlantic Forest and the likely connective routes between these forests. We classified the species per habitat occupancy (strict forest specialists, species that prefer forest, or generalists) and compiled the genetic data available for each species to evaluate their potential for phylogeographic studies focusing on genetic exchange between the two forest regions. We found 127 mammalian species occurring in both Amazonia and the Atlantic Forest for which significant genetic data was available. Hence, highlighting their potential for phylogeographic studies investigating the past connections between the two forests. Differently from what was previously proposed, the northeast route showed evidence of past use by more mammal species than the remaining two routes. The central route would have been the second most important in terms of species. Our results show the potential of using mammal species to investigate and bring new insights about the past connections between Amazonia and the Atlantic Forest.
Constructing neural network models from brain data reveals representational transformations underlying adaptive behavior
Authors: Ito Takuya , Yang Guangyu Robert , Laurent Patryk , Schultz Douglas H. , Cole Michael W. 
Published: December 2020

AbstractThe human ability to adaptively implement a wide variety of tasks is thought to emerge from the dynamic transformation of cognitive information. We hypothesized that these transformations are implemented via conjunctive activations in conjunction hubs – brain regions that selectively integrate sensory, cognitive, and motor activations. We used recent advances in using functional connectivity to map the flow of activity between brain regions to construct a task-performing neural network model from fMRI data during a cognitive control task. We verified the importance of conjunction hubs in cognitive computations by simulating neural activity flow over this empirically-estimated functional connectivity model. These empirically-specified simulations produced above-chance task performance (motor responses) by integrating sensory and task rule activations in conjunction hubs. These findings reveal the role of conjunction hubs in supporting flexible cognitive computations, while demonstrating the feasibility of using empirically-estimated neural network models to gain insight into cognitive computations in the human brain.
Evaluating performance of existing computational models in predicting CD8+ T cell pathogenic epitopes and cancer neoantigens
Authors: Buckley Paul R. , Lee Chloe H. , Ma Ruichong , Woodhouse Isaac , Woo Jeongmin , Tsvetkov Vasily O , Shcherbinin Dmitrii S , Antanaviciute Agne , Shughay Mikhail , Rei Margarida , Simmons Alison , Koohy Hashem 
Published: December 2020

AbstractT cell recognition of a cognate peptide-MHC complex (pMHC) presented on the surface of infected or malignant cells, is of utmost importance for mediating robust and long-term immune responses. Accurate predictions of cognate pMHC targets for T Cell Receptors (TCR) would greatly facilitate identification of vaccine targets for both pathogenic diseases as well as personalized cancer immunotherapies. Predicting immunogenic peptides therefore has been at the centre of intensive research for the past decades but has proven challenging. Although numerous models have been proposed, performance of these models has not been systematically evaluated and their success rate in predicting epitopes in the context of human pathology, has not been measured and compared. In this study, we evaluated the performance of several publicly available models, in identifying immunogenic CD8+ T cell targets in the context of pathogens and cancers. We found that for predicting immunogenic peptides from an emerging virus such as SARS-CoV-2, none of the models perform substantially better than random or offer considerable improvement beyond HLA ligand prediction. We also observed suboptimal performance for predicting cancer neoantigens. Through investigation of potential factors associated with ill performance of models, we highlight several data- and model-associated issues. In particular, we observed that cross-HLA variation in the distribution of immunogenic and non-immunogenic peptides in training data of the models seem to substantially confound the predictions. We additionally compared key parameters associated with immunogenicity between pathogenic peptides and cancer neoantigens and observed evidence for differences in the thresholds of binding affinity and stability, which suggested the need to modulate different features in identifying immunogenic pathogen vs. cancer peptides. Overall, we demonstrate that accurate and reliable prediction of immunogenic CD8+ T cell targets remains unsolved, thus we hope our work will guide users and model developers regarding potential pitfalls and unsettled questions in existing immunogenicity predictors.
Assessment of age‐related morphological changes in the testes of post‐hatch light ecotype Nigerian indigenous chicken
Authors: Udoumoh Anietie Francis , Igwebuike Udensi Maduabuchi , Okoye Chidozie Nwabuisi , Ugwu Ugochukwu Michael , Oguejiofor Chike Fidelis 
Published: December 2020

AbstractThe age‐related morphological changes of the testes in light ecotype Nigerian indigenous chicken were evaluated in this study using gross anatomical, histological and histomorphometric techniques. The results showed that the testes of 3‐ to 9‐month‐old birds were light pink while testes of sexually mature chicken were creamy white in colour. The left and right testicular weight, length, diameter, circumference and the organosomatic indices increased significantly (p < .05) with increasing age across the groups. Although the mean tubular diameter and epithelial height of the left and right seminiferous tubules increased significantly (p < .05) with age, the tubular diameter, epithelial height and luminal diameter did not vary significantly (p > .05) between the left and right testes of all the groups. The one‐cell layer thick germinal epithelium of the left testes at 3 to 6 months old showed islands of cell proliferation that contained spermatogonia and spermatocytes. At 6 to 9 months, the left testes exhibited numerous early spermatids with occasional occurrence of late stage spermatids while the right testes showed scanty early stage spermatids. At 12 to 18 months, the germinal epithelia of both left and right testes were characterized by the presence of Sertoli cells, spermatogonia, primary spermatocytes, numerous early and late stage spermatids as well as spermatozoa. In conclusion, the morphological features highlighted in the present study show that at pre‐pubertal periods, the left testes may develop faster than the right testes. However, both left and right testes may participate actively in the production of spermatozoa during the post‐pubertal life.