bluuebunny/crossref_metadata_2025_split huggingface dataset:
The transcriptional response to low temperature is weakly conserved across theEnterobacteriaceae
Authors: Hoang Johnson , Stoebel Daniel M 
Published: June 2024

AbstractBacteria respond to changes in their external environment, such as temperature, by changing the transcription of their genes. We know little about how these regulatory patterns evolve. We used RNA-seq to study the transcriptional response to a shift from 37°C to 15°C in wild-typeEscherichia coli, Salmonella enterica, Citrobacter rodentium, Enterobacter cloacae, Klebsiella pneumoniae,andSerratia marcescens, as well as ΔrpoSstrains ofE. coliandS. enterica.We found that these species change the transcription of between 626 and 1057 genes in response to the temperature shift, but there were only 16 differentially expressed genes in common among the six species. Species-specific transcriptional patterns of shared genes were a prominent cause of this lack of conservation. GO enrichment of regulated genes suggested many species-specific phenotypic responses to temperature changes, but enriched terms associated with iron metabolism, central metabolism, and biofilm formation were implicated in at least half of the species. The alternative sigma factor RpoS regulated about 200 genes between 37°C and 15°C in bothE. coliandS. enterica, with only 83 genes in common between the two species. Overall, there was limited conservation of the response to low temperature generally, or the RpoS-regulated part of the response specifically. This study suggests that species-specific patterns of transcription of shared genes, rather than horizontal acquisition of unique genes, are the major reason for the lack of conservation of the transcriptomic response to low temperature.ImportanceWe studied how different species of bacteria from the same Family (Enterobacteriacae) change the expression of their genes in response to a decrease in temperature. Using de novo-generated parallel RNA-seq datasets, we found that the six species in this study change the level of expression of many of their genes in response to a shift from human body temperature (37°C) to a temperature that might be found out of doors (15°C). Surprisingly, there were very few genes that change expression in all six species. This was due in part to differences in gene content, and in part due to shared genes with distinct expression profiles between the species. This study is important to the field because it illustrates that closely related species can share many genes but not use those genes in the same way in response to the same environmental change.
Exploring aggregation genes in aP. aeruginosachronic infection model
Authors: Gannon Alexa D. , Matlack Jenet , Darch Sophie E. 
Published: June 2024

AbstractBacterial aggregates are observed in both natural and artificial environments. In the context of disease, aggregates have been isolated from both chronic and acute infections.Pseudomonas aeruginosa(Pa) aggregates contribute significantly to chronic infections, particularly in the lungs of people with cystic fibrosis (CF). Unlike the large biofilm structures observedin vitro, Pain CF sputum forms smaller aggregates (∼10-1000 cells), and the mechanisms behind their formation remain underexplored. This study aims to identify genes essential and unique toPaaggregate formation in a synthetic CF sputum media (SCFM2). We culturedPastrain PAO1 in SCFM2 and LB, both with and without mucin, and used RNA sequencing (RNA-seq) to identify differentially expressed genes. The presence of mucin revealed hundreds of significantly differentially expressed (DE) genes, predominantly downregulated, with 40% encoding hypothetical proteins unique to aggregates. Using high-resolution microscopy, we assessed the ability of mutants to form aggregates and identified 13 that were unable to form WT aggregates. Notably, no mutant exhibited a completely planktonic phenotype. Instead, we identified multiple spatial phenotypes described as ‘normal,’ ‘entropic,’ or ‘impaired.’ Entropic mutants displayed tightly packed, raft-like structures, while impaired mutants had loosely packed cells. Predictive modeling linked the prioritized genes to metabolic shifts, iron acquisition, surface modification, and quorum sensing. Co-culture experiments with wild-type PAO1 revealed further spatial heterogeneity and the ability to ‘rescue’ some mutant phenotypes, suggesting cooperative interactions during growth. This study enhances our understanding ofPaaggregate biology, specifically the genes and pathways unique to aggregation in CF-like environments. Importantly, it provides insights for developing therapeutic strategies targeting aggregate-specific pathways.ImportanceThis study identifies genes essential for the formation ofPseudomonas aeruginosa(Pa) aggregates in cystic fibrosis (CF) sputum, filling a critical gap in understanding their specific biology. Using a synthetic CF sputum model (SCFM2) and RNA sequencing, 13 key genes were identified, whose disruption led to distinct spatial phenotypes observed through high-resolution microscopy. The addition of wild-type cells either rescued the mutant phenotype or increased spatial heterogeneity, suggesting cooperative interactions are involved in aggregate formation. This research advances our knowledge ofPaaggregate biology, particularly the unique genes and pathways involved in CF-like environments, offering valuable insights for developing targeted therapeutic strategies against aggregate-specific pathways.
Bred for affection: The canine anterior ectosylvian gyrus responds selectively to social reinforcement
Authors: Miller Kai J. , Lampert Frederik , Mivalt Filip , Kim Inyong , Ince Nuri , Kim Jiwon , Kremen Vaclav , Baker Matthew R. , Van den Boom Max A. , Hermes Dora , Coenen Volker A. , Schalk Gerwin , Brunner Peter , Worrell Gregory A. 
Published: June 2024

ABSTRACTStudying mammalian brain function aids our understanding of human brain evolution. We implanted a beagle with a prototype human neuromodulation platform that measures activity from the brain surface. One year later, a set of simple sensory tasks was performed, finding visual and somatosensory representation in the canine homologs of the expected areas in humans. Surprisingly, the canine anterior ectosylvian gyrus, which is anatomically homologous to human receptive speech areas, was selectively active during independent social reinforcement tasks. This suggests that human speech understanding may have evolved from more general mammalian brain structures that are specialized for social reinforcement.
Lack of Oncomodulin Increases ATP-Dependent Calcium Signaling and Susceptibility to Noise in Adult Mice
Authors: Yang Yang , Jeng Jing-Yi , Murtha Kaitlin , Climer Leslie K. , Ceriani Federico , Sese Weintari D. , Hornak Aubrey J. , Liberman M. Charles , Marcotti Walter , Simmons Dwayne D. 
Published: June 2024

AbstractTight regulation of Ca2+is crucial for the function of cochlear outer hair cells (OHCs). Dysregulation of Ca2+homeostasis in OHCs is associated with impaired hearing function and contributes to increased vulnerability to environmental insults, such as noise exposure. Ca2+signaling in developing OHCs can be modulated by oncomodulin (OCM), an EF-hand calcium-binding protein. Here, we investigated whether the lack of OCM disrupts the control of intracellular Ca2+in mature OHCs, and influences vulnerability to noise. Using young adult CBA/CaJ mice, we found that OHCs fromOcm-knockout (Ocm-/-) mice exhibited normal biophysical profiles and electromotile responses compared to littermate control OHCs. Moderate noise exposure (95 dB SPL, 2 hrs) caused temporary hearing threshold shifts inOcm+/+andOcm-/-mice but the loss of hearing was permanent forOcm-/-mice. However, whileOcm+/+fully recovered their hearing 2 weeks after noise exposure,Ocm-/-mice showed permanent threshold shifts. Using a genetically encoded Ca2+sensor (GCaMP6s) expressed inOcm+/+andOcm-/-OHCs, we found that chronic noise exposure (95 dB SPL, 9 hrs) increased ATP-induced Ca2+signaling inOcm-/-OHCs compared toOcm+/+OHCs. Chronic noise exposures also caused higher hearing threshold shifts inOcm-/-mice. Prior to noise exposure, P2X2 expression was already upregulated inOcm-/-mice compared toOcm+/+mice. Following chronic noise, P2X2 receptors were upregulated in theOcm+/+cochlea but not in theOcm-/-cochlea, which retains their pre-noise high expression level. We propose that the lack of OCM increases susceptibility to noise. Increased purinergic signaling and dysregulation of cytosolic Ca2+homeostasis could contribute to early onset hearing loss in theOcm-/-mice.
Tool skill impacts the archaeological evidence across technological primates
Authors: Luncz Lydia V. , Slania Nora E. , Almeida-Warren Katarina , Carvalho Susana , Falótico Tiago , Malaivijitnond Suchinda , Arroyo Adrián , de la Torre Ignacio , Proffitt Tomos 
Published: June 2024

AbstractThe archaeological record offers insights into our evolutionary past by revealing ancient behaviour through stone and fossil remains. Percussive foraging is suggested to be particularly relevant for the emergence of tool-use in our lineage, yet early hominin percussive behaviours remain largely understudied compared to flaked technology. Stone tool-use of extant primates allows the simultaneous investigation of their artefacts and the associated behaviours. This is important for understanding the development of tool surface modification, and crucial for interpreting damage patterns in the archaeological record. Here, we compare the behaviour and the resulting material record across stone tool-using primates. We investigate the relationship of nut-cracking technique and stone tool modification across chimpanzees, capuchins, and long-tailed macaques by conducting standardized field experiments with comparable raw materials. We show that different techniques likely emerged in response to diverse nut hardness, leading to variation in foraging success across species. Our experiments further demonstrate a correlation between techniques and the intensity of visible percussive damage on the tools. Tools used with more precision and efficiency as demonstrated by macaques, show fewer use wear traces. This suggests that some percussive techniques may be less readily identified in the archaeological record.
Direct Genome-Scale Screening ofGluconobacter oxydansB58 for Rare Earth Element Bioleaching
Authors: Marecos Sabrina , Pian Brooke , Medin Sean A. , Schmitz Alexa , Wu Mingming , Balta J. Brian , Gazel Esteban , Holycross Megan , Reid Matthew C. , Barstow Buz 
Published: June 2024

AbstractThe transition to a sustainable energy economy will require an enormous increase in the supply of rare earth elements (REE). Bioleaching offers a promising alternative to conventional hydrometallurgical methods for REE extraction from low-grade ores. However, exploiting this potential remains challenging due to large gaps in our understanding of the genetics involved, and inadequate biological tools to address them. We generated a highly non-redundant whole genome knockout collection for the bioleaching microbeGluconobacter oxydansB58, reducing redundancy by 85% compared to the previous best collection. This new collection was directly screened for bioleaching neodymium from a synthetic monazite powder, identifying 89 genes important for bioleaching, 68 of which have not previously been associated with this mechanism. We conducted bench-scale experiments to validate the extraction efficiency of promising strains: 8 demonstrated significant increases in bioleaching by up to 111% (G. oxydansδGO_1598, a disruption of the gene encoding the orotate phosphoribosyltransferase enzyme PyrE), and one strain significantly reduced it by 97% (δGO_1096, a disruption of the gene encoding the GTP-binding protein TypA). Notable changes in biolixiviant pH were only observed for 3 strains, suggesting an important role for non-acid mechanisms in bioleaching. These findings provide valuable insights into further enhancing REE-bioleaching byG. oxydans’ through targeted genetic engineering.
Targeted mutagenesis of specific genomic DNA sequences in animals for thein vivogeneration of variant libraries
Authors: Falo-Sanjuan Julia , Diaz-Tirado Yuliana , Turner Meghan A. , Rourke Olivia , Davis Julian , Medrano Claudia , Haines Jenna , McKenna Joey , Karshenas Arman , Eisen Michael B. , Garcia Hernan G. 
Published: June 2024

AbstractUnderstanding how the number, placement and affinity of transcription factor binding sites dictates gene regulatory programs remains a major unsolved challenge in biology, particularly in the context of multicellular organisms. To uncover these rules, it is first necessary to find the binding sites within a regulatory region with high precision, and then to systematically modulate this binding site arrangement while simultaneously measuring the effect of this modulation on output gene expression. Massively parallel reporter assays (MPRAs), where the gene expression stemming from 10,000s of in vitro-generated regulatory sequences is measured, have made this feat possible in high-throughput in single cells in culture. However, because of lack of technologies to incorporate DNA libraries, MPRAs are limited in whole organisms. To enable MPRAs in multicellular organisms, we generated tools to create a high degree of mutagenesis in specific genomic lociin vivousing base editing. Targeting GFP integrated in the genome ofDrosophilacell culture and whole animals as a case study, we show that the base editor AIDevoCDA1stemming from sea lamprey fused to nCas9 is highly mutagenic. Surprisingly, longer gRNAs increase mutation efficiency and expand the mutating window, which can allow the introduction of mutations in previously untargetable sequences. Finally, we demonstrate arrays of >20 gRNAs that can efficiently introduce mutations along a 200bp sequence, making it a promising tool to test enhancer functionin vivoin a high throughput manner.
Immunity and bacterial recruitment in plant leaves are parallel processes whose link shapes sensitivity to temperature stress
Authors: Jose Jisna , Teutloff Erik , Naseem Simrat , Barth Emanuel , Halitschke Rayko , Marz Manja , Agler Matthew T. 
Published: June 2024

AbstractRising global temperatures necessitate developing climate-resilient crops with better adaptability to changing climates. Under elevated temperatures, plant immunity is downregulated, putting them at risk of foliar pathogen attack. Manipulating plant defense hormones is one way to mitigate this detrimental effect. However, it is unclear how plant immunity interacts with plant microbiome assembly and how temperature will thus affect overall plant health and stability. We used chemical mutagenesis to identify a phenotypically healthy genotype ofA. thaliana, “CLLF”,that compared to the wild type naturally recruits an altered leaf bacteriome, including unusually high bacteria loads. Simultaneously, CLLF hyperaccumulates salicylic acid (SA) and jasmonates, has constitutively upregulated systemic and innate defenses, and has increased resistance to necrotrophic fungal and hemi-biotrophic bacterial pathogens, indicating that pathogen immunity and non-pathogen recruitment function in parallel. Growth of specific non-pathogenic leaf bacteria on SA as a carbon source suggests the same hormones may even link the two processes. CLLF also showed high tolerance to heat stress in comparison to the wild type, but SA-associated defense processes are not downregulated under heat. Synthetic community (SynCom) experiments showed that when the taxonomic diversity of bacteria available to CLLF is artificially reduced, resilience to heat stress is compromised, leading to dysbiosis, but this does not occur with the full SynCom or in the wild type with any SynCom. Thus, the downregulation of defenses in response to heat may contribute to avoidance of dysbiosis caused by some leaf bacteria, but full bacteriome taxonomic diversity can restore balance.Significance StatementPlants are living ecosystems colonized by diverse microorganisms who strongly shape host health. Understanding how balance arises in host-associated microbiomes is a key step to understanding how to preserve, manage and possibly optimize these complex ecosystems, especially in a changing climate. Using a random mutagenesis approach in a naturalA. thalianaecotype, we find that constitutively upregulated defenses are associated with both tolerance to (a)biotic threats and healthy recruitment of leaf bacteria, very likely in a direct manner. Thus, immunity and bacterial recruitment in leaves operate in parallel. Synthetic community experiments show further that this link plays important roles in shaping plant resilience to heat stress, an important consideration in developing plants more stable to climate change.
Induction of a Müller glial-specific protective pathway safeguards the retina from diabetes induced damage
Authors: Lin Cheng-Hui , Wu Man-Ru , Tanasa Bogdan , Prakhar Praveen , Davis Alexander E. , Li Liang , Xia Alexander , Shan Yang , Fort Patrice E. , Wang Sui 
Published: June 2024

AbstractDiabetes can lead to cell-type-specific responses in the retina, including vascular lesions, glial dysfunction and neurodegeneration, all of which contribute to retinopathy. However, the molecular mechanisms underlying these cell type-specific responses, and the cell types that are sensitive to diabetes have not been fully elucidated. Employing single cell transcriptomic analyses, we profiled the transcriptional changes induced by diabetes in different retinal cell types in diabetic rat models as the disease progressed. Rod photoreceptors, a subtype of amacrine interneurons, and Müller glial cells exhibited rapid responses to diabetes at the transcript levels. Genes associated with ion regulation were upregulated in all three cell types, suggesting a common response to diabetes. Furthermore, focused studies revealed that while Müller glial cells initially increased the expression of genes playing protective roles, they cannot sustain this beneficial effect as the disease progressed. We explored one of the candidate protective genes, Zinc finger protein 36 homolog (Zfp36), and observed that depletingZfp36in rat Müller glial cells in vivo using AAV-based tools exacerbated early diabetes-induced phenotypes, including gliosis, neurodegeneration, and vascular defects. Notably, the over-expression ofZfp36slowed the development of phenotypes associated with diabetic retinopathy. In summary, this work unveiled retinal cell types that are sensitive to diabetes and demonstrated that Müller glial cells can mount protective responses throughZfp36. The failure to maintainZfp36levels contributes to the development of diabetic retinopathy.
Association between APOE genotypes and Metabolic Syndrome in a Middle Aged and Elderly Urban Indian Population
Authors: Azhuvalappil Shilna , Prasad Raghav , Sahadevan Pravin , Chatterjee Priya , Pradhan Hitesh , Rai Pooja , Gupta Anant , Kommaddi Reddy Peera , Issac Thomas G. , Sundarakumar Jonas S. 
Published: June 2024

AbstractBackgroundThis study examines the association between apolipoprotein E (APOE) genotypes and metabolic syndrome (MetS) in an older urban population in South India, as part of the Tata Longitudinal Study on Aging.MethodsA total of 618 participants aged 45 and above were analyzed cross-sectionally for the association between APOE carrier status and MetS (based on both NCEP ATP III and Consensus criteria).ResultsDespite the high prevalence of MetS observed in this cohort (51.62% by NCEP-ATP III and 61.33% by Consensus criteria), multivariable logistic regression revealed no significant association between APOE genotypes and MetS under both criteria. However, specific associations were noted in age and sex-stratified analyses; notably, E2 carriers under 60 showed 0.42-fold decreased odds (95%CI:0.20,0.89, p-value-0.023) for an increased waist circumference, and E4 carriers above 60 were at 1.85 times increased odds (95% CI:1.04,3.28, p-value<0.05) for decreased HDL.ConclusionThese findings suggest that while APOE genotypes influence certain metabolic parameters, their impact on MetS may be limited in this urban setting, possibly overshadowed by environmental factors and lifestyle influences which was highlighted by the differences seen in its sister rural cohort.
Health impacts of takeaway management zones around schools in six different local authorities across England: a public health modelling study using PRIMEtime
Authors: Rogers Nina Trivedy , Amies-Cull Ben , Adams Jean , Chang Michael , Cummins Steven , Derbyshire Daniel , Hassan Suzan , Keeble Matthew , Liu Bochu , Medina-Lara Antonieta , Savory Bea , Rahilly John , Smith Richard , Thompson Clare , White Martin , Mytton Oliver , Burgoine Thomas 
Published: June 2024

AbstractBackgroundIn England, the number of takeaway food outlets (‘takeaways’) has been increasing for over two decades. Takeaway management zones around schools are an effective way to restrict the growth of new takeaways but their impacts on population health have not been estimated.MethodsTo model the impact of takeaway management zones on health, we used estimates of change in and exposure to takeaway outlets (across home, work, and commuting buffers) based on a previous evaluation suggesting that 50% of new outlets were prevented from opening because of management zones. Based on previous cross-sectional findings, we used changes in takeaway exposure to estimate changes in BMI, from 2018 to 2040. Finally, we used PRIMEtime, a proportional multistate lifetable model, and BMI change to estimate the impact of the intervention, in a closed-cohort of adults (25-64 years), in terms of incidence of 12 non-communicable diseases, obesity prevalence, quality-adjusted life years (QALYs) and healthcare costs saved by 2040 in six selected local authorities across the rural-urban spectrum in England (Wandsworth, Manchester, Blackburn with Darwen, Sheffield, North Somerset, and Fenland).ResultsBy 2031, compared to no intervention, reductions in outlet exposure ranged from 3 outlets/person in Fenland to 28 outlets/person in Manchester. This corresponded to per person reductions in BMI of 0.68 and 0.08 kg/m2, respectively. Relative to no intervention, obesity prevalence was estimated to be reduced in both sexes in all LAs, including by 2.3 percentage points (PP) (95% uncertainty interval:2.9PP, 1.7PP) to 1.5PP (95%UI:1.9PP, 1.1PP) in males living in Manchester and Wandsworth by 2040, respectively. Model estimates showed reductions in incidence of disease, including type II diabetes (eg: 964 (95%UI:1565, 870) fewer cases /100,000 population for males in Manchester)), cardiovascular diseases, asthma, certain cancers and low back pain. Savings in healthcare costs (millions(£)) ranged from £0.90 (95%UI: £1,23, £0.54) in Fenland to £5.44 (95%UI:£3.87, £7.45) in Manchester. Gains in QALYs/100,000 person were broadly similar across local authorities.ConclusionsTakeaway management zones in England have the potential to meaningfully contribute towards reducing obesity prevalence and associated healthcare burden in the adult population, both at the local level and across the rural-urban spectrum.