bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunomodulatory Extracellular Matrix Hydrogel Mitigates Scar Formation in a Model of Tongue Fibrosis
Authors: Zelus EI , Panduro A , Alperin M , Vahabzadeh-Hagh AM , Christman KL 
Published: May 2022

AbstractBackgroundWhile head and neck cancer treatment regimens, including surgical resection, irradiation, and chemotherapy, are effective at removing tumors, they lead to muscle atrophy, denervation, and fibrosis, contributing to the pathogenesis of tongue dysphagia – difficulty swallowing. Current standard of care is ineffective; we propose an alternative approach utilizing an acellular and minimally invasive biomaterial to preserve muscle content and reduce fibrosis of the tongue after injury. Here, we investigate a decellularized extracellular matrix hydrogel for the treatment of tongue fibrosis in a partial glossectomy injury model.MethodsSkeletal muscle extracellular matrix (SKM) hydrogel was fabricated by decellularizing porcine skeletal muscle tissue through established protocols. A partial glossectomy injury in the rat was used as a model of tongue fibrois, and SKM hydrogels along with saline controls were injected to the site of scarring two weeks after injury. Tissues were harvested at 3 and 7 days post-injection for gene expression analysis of immune and myogenic pathways, and at 4 weeks post-injection to evaluate histomorphological changes in skeletal muscle and scar formation.ResultsSKM hydrogel reduced scar formation and improved muscle fiber cross-sectional area in the region of injury compared to saline controls. SKM upregulated pro-regenerative immune response while downregulating pro-inflammatory response and further promoted angiogenic gene expression.ConclusionThis study demonstrates the immunomodulatory and tissue-regenerative capacity of an acellular and minimally invasive biomaterial in a rodent model of tongue fibrosis.
Assessing PDB Macromolecular Crystal Structure Confidence at the Individual Amino Acid Residue Level
Authors: Shao Chenghua , Wang Sijian , Burley Stephen K. 
Published: May 2022

SummaryApproximately 87% of the more than 190,000 atomic-level, (three-dimensional) 3D biostructures in the Protein Data Bank (PDB) were determined using macromolecular crystallography (MX). Agreement between 3D atomic coordinates and experimental data for >100 million individual amino acid residues occurring within ∼150,000 PDB MX structures was analyzed in detail. The Real-Space-Correlation-Coefficient (RSCC) calculated using the 3D atomic coordinates for each residue and experimental electron density enables outlier detection of unreliable atomic coordinates (particularly important for poorly-resolved sidechain atoms) and ready evaluation of local structure quality by PDB users. For human protein MX structures in PDB, comparisons of per-residue RSCC experimental-agreement metric with AlphaFold2 computed structure model confidence (pLDDT-predicted local distance difference test) document (i) that RSCC values and pLDDT scores are correlated (median correlation coefficient∼0.41), and (ii) that experimentally-determined MX structures (3.5 Å resolution or better) are more reliable than AlphaFold2 computed structure models and should be used preferentially whenever possible.
Cosmopolitan Scolytinae: strong common drivers but too many singularities for accurate prediction
Authors: Grégoire Jean-Claude , Jactel Hervé , Hulcr Jiri , Battisti Andrea , Inward Daegan , Petter Françoise , Grousset Fabienne 
Published: May 2022

AbstractAimMany scolytine beetle species have been expanding their range in new territories across geographic barriers, traveling with wood, wood products and plants for planting, sometimes with a high impact on plant health. Here we attempt to quantify the mobility of these cosmopolitan species and to identify the biological drivers of mobility and impact.LocationWorldMajor taxa studiedColeoptera; Curculionidae; ScolytinaeMethodsMobility was estimated by counting the numbers of landmasses (contiguous pieces of land, surrounded by ocean or sea) colonized by each species. A series of potential drivers (taxonomic tribes; feeding habits; polyphagy; reproductive strategy; host taxa; pheromones and primary attractants) as well as impact on host health were recorded.Results163 species were identified, out of 5546 counted in the whole subfamily. Four tribes (Xyleborini; Ipini; Crypturgini; Hylastini) were significantly over-represented, and two others (Corthylini; Hexacolini) were under-represented. 53% of the 163 species are inbreeding, a very significant excess as compared to the whole subfamily (29%). The inbreeders colonized more landmasses than the outbreeders. There is a significant relationship between the number of host families attacked by a species and the number of colonized landmasses. Species restricted to conifers colonized fewer landmasses than hardwood generalists. Species attacking both types of hosts are the most mobile. Most of the invasive species respond to host primary attractants, only one quarter respond to pheromones. All very mobile species respond to primary attractants, and none responds to pheromones. Very mobile species are all associated with a high or moderate impact.Main conclusionsThe most mobile species belong for a large part to a limited number of subtribes. They are often inbreeding, polyphagous and respond to primary attractants but do not produce pheromones. However, many species that do not, or only partly, belong to these categories, have established in several landmasses, sometimes with a high impact. For example, the outbreeding Scolytus multistriatus, that attacks only 3 host families and produces aggregation pheromones, has established in thirteen landmasses, with a high impact. Therefore, risk prediction needs to assess diversity of species-specific biological traits beyond the few routinely analyzed in literature.
Striosomes constrain locomotor vigor with respect to an innate valence differential
Authors: Hawes Sarah , Liang Bo , Oldham Braden , Song Bin , Chang Lisa , Lin Da-Ting , Cai Huaibin 
Published: May 2022

SummarySurvival demands that safe and unsafe contexts are met with different locomotor profiles, yet whether striatal microcircuitry links contextual valence to spontaneous locomotor vigor is unresolved. Here we test for striosome contributions to spontaneous locomotion using ablation, calcium imaging and chemogenetics in the context of a modified Light/Dark box test. We found that locomotor speed reflects the unlearned, external valence differential present in this test, and that striosomes gate valence-oriented speed selection. Our data suggest that striosomes dampen motor vigor associated with lesser valence, or elevated anxiety.HighlightsMice explore the light and dark zones in Light/Dark box with different walk speedStriosome ablation reduces restful slowing and elevates speed relative to zoneMany striosome neurons exhibit light-zone preference and speed related activityStriosome enhancement slows mice and blunts zone discrimination by speed
Highly Dynamic Gene Family Evolution Suggests Changing Roles for PON Genes Within Metazoa
Authors: Lucas Sarah A.M. , Graham Allie M , Presnell Jason S , Clark Nathan L 
Published: May 2022

AbstractChange in gene family size has been shown to facilitate adaptation to different selective pressures. This includes gene duplication to increase dosage or diversification of enzymatic substrates and gene deletion due to relaxed selection. We recently found that the PON1 gene, an enzyme with arylesterase and lactonase activity, was lost repeatedly in different aquatic mammalian lineages, suggesting that the PON gene family is responsive to environmental change. We further investigated if these fluctuations in gene family size were restricted to mammals and approximately when this gene family was expanded within mammals. Using 112 metazoan protein models, we explored the evolutionary history of the PON family to characterize the dynamic evolution of this gene family. We found that there have been multiple, independent expansion events in tardigrades, cephalochordates, and echinoderms. In addition, there have been partial gene loss events in monotremes and sea cucumbers and what appears to be complete loss in arthropods, urochordates, platyhelminths, ctenophores, and placozoans. In addition, we show the mammalian expansion to three PON paralogs occurred in the ancestor of all mammals after the divergence of sauropsida but before the divergence of monotremes from therians. We also provide evidence of a novel PON expansion within the brushtail possum. In the face of repeated expansions and deletions in the context of changing environments, we suggest a range of selective pressures, including pathogen infection and mitigation of oxidative damage, are likely influencing the diversification of this dynamic gene family across metazoa.
Microglia maintain homeostatic conditions in the developing rostral migratory stream
Authors: Meller Sarah J. , Hernandez Lexie , Martin-Lopez Eduardo , Liberia Teresa , Greer Charles A. 
Published: May 2022

ABSTRACTMicroglia invade the neuroblast migratory corridor of the rostral migratory stream (RMS) early in development. This work examines how microglia maintain the homeostatic conditions permissive to neuroblast migration in the RMS during the early postnatal period. GFP labeled microglia in CX3CR-1GFP/+ mice assemble primarily along the outer borders of the RMS during the first postnatal week, where they exhibit predominantly an ameboid morphology and associate with migrating neuroblasts. Microglia ablation for 3 days postnatally does not impact the density of pulse labeled BrdU+ neuroblasts nor the distance migrated by tdTomato electroporated neuroblasts in the RMS. However, microglia wrap DsRed-labeled neuroblasts in the RMS of P7 CX3CR-1GFP/+;DCXDsRed/+ mice and express the phagocytic markers CD68, CLEC7A and MERTK, suggesting active phagocytosis of neuroblasts in the developing RMS. Microglia depletion for 14 days postnatally further induced an accumulation of DCX+ neuroblasts and CC3+ apoptotic cells in the RMS, a wider RMS and extended patency of the lateral ventricle extension in the olfactory bulb. These findings illustrate the importance of microglia phagocytosis in maintaining the homeostasis of the early postnatal RMS.SIGNIFICANCE STATEMENTMicroglia are brain-resident immune cells responsible for both maintaining homeostatic conditions necessary for normal neurodevelopment as well as orchestrating the brain’s response to environmental insults. The effects of microglia-mediated immune response during development may be of special relevance to the olfactory system, which is unique in both its vulnerability to environmental insults as well as its extended period of neurogenesis and neuronal migration. The work presented here examines how microglia maintain homeostatic conditions in the neuroblast migratory corridor of the rostral migratory stream (RMS) in the olfactory system during early postnatal development. Our findings illustrate the importance of microglia phagocytosis in the early postnatal RMS and provides insights into microglia function during periods of neurogenesis and neuronal migration.
Inferring Neural Activity Before Plasticity: A Foundation for Learning Beyond Backpropagation
Authors: Song Yuhang , Millidge Beren , Salvatori Tommaso , Lukasiewicz Thomas , Xu Zhenghua , Bogacz Rafal 
Published: May 2022

AbstractFor both humans and machines, the essence of learning is to pinpoint which components in its information processing pipeline are responsible for an error in its output — a challenge that is known ascredit assignment. How the brain solves credit assignment is a key question in neuroscience, and also of significant importance for artificial intelligence. It has long been assumed that credit assignment is best solved by backpropagation, which is also the foundation of modern machine learning. However, it has been questioned whether it is possible for the brain to implement backpropagation and learning in the brain may actually be more efficient and effective than backpropagation. Here, we set out a fundamentally different principle on credit assignment, calledprospective configuration. In prospective configuration, the network first infers the pattern of neural activity that should result from learning, and then the synaptic weights are modified to consolidate the change in neural activity. We demonstrate that this distinct mechanism, in contrast to backpropagation, (1) underlies learning in a well-established family of models of cortical circuits, (2) enables learning that is more efficient and effective in many contexts faced by biological organisms, and (3) reproduces surprising patterns of neural activity and behaviour observed in diverse human and animal learning experiments. Our findings establish a new foundation for learning beyond backpropagation, for both understanding biological learning and building artificial intelligence.
Fruitful female fecundity after feedingGryllodes sigillatusroyal jelly
Authors: Muzzatti MJ , McConnell E , Neave S , MacMillan HA , Bertram SM 
Published: May 2022

AbstractDietary honey bee royal jelly increases insect growth rates and adult body size. Royal jelly could enhance mass insect production as a dietary supplement, but it is costly to produce. The mechanisms underlying the effects of royal jelly on growth remain unclear, and so it is valuable to understand the effects of royal jelly on a mass reared model species to try and augment body size in a more cost-effective manner. To determine the effect of royal jelly on a cricket species (Gryllodes sigillatus) farmed on mass for human consumption, we ran two experiments. In one experiment we tested the dose-dependent response ofGryllodes sigillatusto royal jelly using a range of diets across 0-30% w/w royal jelly. In another experiment we measured the individual-level life history responses ofGryllodes sigillatusto royal jelly over time by individually rearing freshly-hatchedGryllodes sigillatuson two separate diets: half were fed a commercially available cricket diet, while the other half were fed the same diet mixed with 15% w/w fresh royal jelly. Body size and mass measurements were recorded weekly for five weeks. We found the effects of royal jelly to be sex-dependent within crickets: females fed the royal jelly diet grew to be 30% heavier, and this effect was driven by significantly longer abdomens containing 67% more eggs compared to those fed the basal diet. There was a higher probability of crickets reaching adulthood after 35 days when fed royal jelly, and female mass was optimised at approximately 17% w/w royal jelly. Our results reveal that while a royal jelly dietary supplement can increase the yield of mass-reared insects, the life-history responses are species- and sex-specific.
Plasticity of threespine stickleback nuptial signals: laboratory manipulation of ambient light causes a shift in male reflectance patterns
Authors: Scott Robert J. 
Published: May 2022

AbstractI caught courting male threespine stickleback (Gasterosteus aculeatus) in Hotel Lake, BC, Canada, and transferred them to one of three experimental lighting environments. Male signal reflectance was measured upon capture from the lake, at one-day post transfer to the experimental light, and at onset of courtship behaviour under artificial light. Male signals responded rapidly to the change in lighting environment following transfer from the wild to the artificial lighting environments and in different ways dependent upon the artificial light composition. Males under red-shifted light had higher signal reflectance in the short wavelength range of the spectrum and less reflectance in the medium and long wavelength range of the spectrum relative to the males in blue-green shifted and full-spectrum lighting. Given the relative prominence of the male stickleback nuptial signal in the behavioural ecology literature, the increasing evidence for the signal’s ambient light dependent expression, and the large body of literature based on experiments conducted under artificial light, it would be prudent to repeat some of the classic mate choice experiments under more realistic lighting conditions.
Pdx1 expression in hematopoietic cells activates Kras-mutation to drive leukemia in KC (Pdx1-Cre ; LSL-KrasG12D/+) mice
Authors: Walcheck Morgan T. , Nukaya Manabu , Ranheim Erik A. , Matkowskyj Kristina A. , Ronnekleiv-Kelly Sean 
Published: May 2022

ABSTRACTBackgroundPdx1 expression in pancreatic lineage cells underlies the utility of the KC mouse model (Pdx1-Cre; LSL-KrasG12D/+) for understanding how KrasG12D-mutation drives formation of pancreas cancer precursor lesions and carcinoma. The highly utilized KC model has a reported mortality rate of about 30%, which has been attributed to pancreas cancer, despite lack of substantive evidence. This study describes a novel cause of the early deaths, in which KC mice develop Kras-driven T-cell acute lymphoblastic leukemia (T-ALL).MethodsKC mice and control mice underwent histopathologic examination including thymus, liver, spleen, bone marrow and pancreas, and immunohistochemistry (IHC) was used to confirm leukemia development. A reporter strain (Ai14) was used to identify location of Pdx1-Cre expression and concomitant mutant-Kras activation, which was confirmed using flow cytometry, IHC, immunofluorescence, mRNA analysis, and bone marrow transplant studies.ResultsPdx1 expression in the hematopoietic compartment of KC mice resulted in Cre-recombinase mediated excision of lox-stop and activation of mutant-Kras gene (KrasG12D/+) in the multipotent progenitor cells (MPP), and subsequent development of Kras-mutant T-ALL creating thymic tumors in a subset of mice. Overall, 20% (5/25) of KC mice developed a large thymic tumor due to T-ALL by 9 months of age. Moreover, through isolation and transplantation of pooled bone marrow from KC mice into CD45 congenic mice, 100% of recipient mice were found to develop T-ALL. These results further confirm mutant-Kras expression in the hematologic compartment is driving the development of T-ALL in the KC mouse model.ConclusionsThese results are an essential consideration for investigators while utilizing this model in pancreas cancer studies, particularly when evaluating factors that may coincidentally enhance the formation of KrasG12D-driven T-ALL (e.g. transcription factors impacting hematopoietic cells). Finally, the lower penetrance of T-ALL development in KC mice (compared to existing leukemia models) suggest that the KC mouse could be considered as an alternative research model to evaluate onset and factors that exacerbate development of T-ALL.
Physical Obstacles Constrain Behavioral Parameter Space of Successful Localization in Honey Bee Swarms
Authors: Nguyen Dieu My T. , Iuzzolino Michael L. , Peleg Orit 
Published: May 2022

AbstractHoney bees (Apis mellifera L.) localize the queen and aggregate into a swarm by forming a collective scenting network to directionally propagate volatile pheromone signals. Previous experiments show the robustness of this communication strategy in the presence of physical obstacles that partially block pheromone flow and the path to the queen. Specifically, there is a delay in the formation of the scenting network and aggregation compared to a simple environment without perturbations. To better understand the effect of obstacles beyond temporal dynamics, we use the experimental results as inspiration to explore how the behavioral parameter space of collective scenting responds to obstacle. We extend an agent-based model previously developed for a simple environment to account for the presence of physical obstacles. We study how individual agents with simple behavioral rules for scenting and following concentration gradients can give rise to collective localization and swarming. We show that the bees are capable of navigating the more complex environment with a physical obstacle to localize the queen and aggregate around her, but their range of behavioral parameters is more limited and less flexible as a result of the spatial density heterogeneity in the bees imposed by the obstacle.
Bacteroides muris sp. nov. isolated from the cecum of wild-derived house mice
Authors: Fokt Hanna , Unni Rahul , Repnik Urska , Schmitz Ruth A , Bramkamp Marc , Baines John F. , Unterweger Daniel 
Published: May 2022

AbstractTwo bacterial strains, KH365_2T and KH569_7, were isolated from the cecum contents of wild-derived house mice. The strains were characterized as Gram-negative, rod-shaped, strictly anaerobic, and non-motile. Phylogenetic analysis based on 16S rRNA gene sequences revealed that both strains were most closely related to Bacteroides uniformis ATCC 8492T. Whole genome sequences of KH365_2T and KH569_7 strains have a DNA G+C content of 46.02% and 46.03% mol, respectively. Most morphological and biochemical characteristics did not differ between the newly isolated strains and classified Bacteroides strains. However, the average nucleotide identity (ANI) and dDNA-DNA hybridization (dDDH) values clearly distinguished the two strains from described members of the genus Bacteroides. Here, we present the phylogeny, morphology, and physiology of a novel species of the genus Bacteroides and propose the name Bacteroides muris sp. nov., with KH365_2T (DSM XXX = CCUG XXX) as type strain.
Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice
Authors: Engler-Chiurazzi EB , Russel AE , Povroznik JM , McDonald K , Porter K , Wang DS , Billig BK , Felton CC , Hammock J , Schreurs BG , O’Callaghan JD , Zwezdaryk KJ , Simpkins JW 
Published: May 2022

AbstractAge-related cognitive decline, a common component of the brain aging process, is associated with significant impairment in daily functioning and quality of life among geriatric adults. While the complexity of mechanisms underlying cognitive aging are still being elucidated, microbial exposure and the multifactorial inflammatory cascades associated with systemic infections is emerging as a potential driver of neurological senescence. The negative cognitive and neurobiological consequences of a single pathogen-associated inflammatory experience, such as that modeled through treatment with lipopolysaccharide (LPS), are well documented. Yet, the brain aging impacts of repeated, intermittent inflammatory challenges are less well studied. To extend the emerging literature assessing the impact of infection burden on cognitive function among normally aging mice, here, we repeatedly exposed adult mice to intermittent LPS challenges during the aging period. Male 10-month-old C57BL6 mice were systemically administered escalating doses of LPS once every two weeks for 2.5 months. We evaluated cognitive consequences using the non-spatial step-through inhibitory avoidance task and both spatial working and reference memory versions of the Morris water maze. We also probed several potential mechanisms, including cortical and hippocampal cytokine/chemokine gene expression as well as hippocampal neuronal function via extracellular field potential recordings. Though there was limited evidence for an ongoing inflammatory state in cortex and hippocampus, we observed impaired learning and memory and a disruption of hippocampal long-term potentiation. These data suggest that a history of intermittent exposure to LPS-induced inflammation is associated with a subtle but significantly accelerated trajectory of cognitive decline. The broader impact of these findings may have important implications for standard of care involving infections in aging individuals or populations at-risk for dementia.