bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three new species,Xanthomonas hawaiiensissp. nov.,Stenotrophomonas aracearumsp. nov., andStenotrophomonas oahuensissp. nov., isolated from Araceae family
Authors: Chuang Shu-Cheng , Dobhal Shefali , Alvarez Anne M. , Arif Mohammad 
Published: September 2023

AbstractXanthomonasandStenotrophomonasare closely related genera in the family Lysobacteraceae. In our previous study of aroid-associated bacterial strains, most strains isolated from anthurium, and other aroids were reclassified asX. phaseoliand otherXanthomonasspecies. However, two strains fromSpathiphyllumandColocasiawere phylogenetically distant from other strains in theXanthomonasclade and two anthurium strains clustered within theStenotrophomonasclade. Phylogenetic trees based on 16S rRNA and nine housekeeping genes placed the former strains with type strain ofX. saccharifrom sugarcane and the latter strains with type strain ofS. bentoniticafrom bentonite. In pairwise comparisons with type strains, the overall genomic relatedness indices required delineation of new species; digital DNA-DNA hybridization and average nucleotide identity values were lower than 70% and 95%, respectively. Hence, three new species are proposed:S. aracearumsp. nov. andS. oahuensissp. nov. for two anthurium strains, andX. hawaiiensissp. nov. for the spathiphyllum and colocasia strains. The genome size ofX. hawaiiensissp. nov. is ∼4.88 Mbp and higher thanS. aracearumsp. nov. (4.33 Mbp) andS. oahuensissp. nov. (4.68 Mbp). Pan and core-genome analyses revealed 426 and 576 core genes present in 40 xanthomonads and 25 stenotrophomonads, respectively. The average number of unique genes inStenotrophomonasspp. was higher than inXanthomonasspp. implying higher genetic diversity inStenotrophomonas.
Bridging Neurons and Behavior in a Convolutional Neural Network with Emergent Human-like Covert Attention
Authors: Srivastava Sudhanshu , Wang William Yang , Eckstein Miguel P. 
Published: September 2023

ABSTRACTCovert visual attention allows the brain to select different regions of the visual world without eye movements. Cues predictive of a target location orient covert attention and improve perceptual performance. How entire neuronal populations represent and integrate target, cues, and location information to result in behavioral signatures of covert attention is not understood. We analyze 1.8M neurons of feedforward Convolutional Neural Networks (CNNs) that show human-like attentional cueing effects. Consistent with neurophysiology, we show early layers with retinotopic neurons separately tuned to target or cue, and later layers with neurons with joint tuning and increased influence of the cue on target responses. We show cue-inhibitory and location-opponent neurons that are unreported by neurophysiologists and identify the neuronal circuits that result in neuronal cueing effects. The cue influences the mean neuronal responses and changes target sensitivity through three mechanisms: cue-weighted summation and opponency across locations, and interaction with the thresholding Rectified Linear Unit (ReLU). Some CNN computational stages mirror a Bayesian ideal observer (BIO), but with more gradual transitions, while the opponency and ReLU interaction are distinct from the BIO. Together, the findings establish a likely system-wide characterization of the brain computations that mediate the behavioral signatures of covert attention.
Anterolateral temporal lobe localization of dysnomia after temporal lobe epilepsy surgery
Authors: Mhanna Asmaa , Bruss Joel , Sullivan Alyssa W. , Howard Matthew A. , Tranel Daniel , Boes Aaron D. 
Published: September 2023

AbstractObjectivesTo evaluate what factors influence naming ability after temporal lobectomy in patients with drug-resistant epilepsy.Methods85 participants with drug-resistant epilepsy who underwent temporal lobe (TL) resective surgery were retrospectively identified (49 left TL and 36 right TL). Naming ability was assessed before and >3 months post-surgery using the Boston Naming Test (BNT).Multivariate lesion-symptom mapping was performed to evaluate whether lesion location related to naming deficits. Multiple regression analyses were conducted to examine if other patient characteristics were significantly associated with pre-to post-surgery changes in naming ability.ResultsLesion laterality and location were important predictors of post-surgical naming performance. Naming performance significantly improved after right temporal lobectomy (p= 0.015) while a decrement in performance was observed following left temporal lobectomy (p= 0.002). Lesion-symptom mapping showed the decline in naming performance was associated with surgical resection of the anterior left middle temporal gyrus (Brodmann area 21,r=0.41,p= <.001). For left hemisphere surgery, later onset of epilepsy was associated with a greater reduction in post-surgical naming performance (p= 0.01).SignificanceThere is a wide range of variability in outcomes for naming ability after temporal lobectomy, from significant improvements to decrements observed. If future studies support the association of left anterior middle temporal gyrus resection and impaired naming this may help in surgical planning and discussions of prognosis.
Deep learning-based prediction of one-year mortality in the entire Finnish population is an accurate but unfair digital marker of aging
Authors: Vabalas Andrius , Hartonen Tuomo , Vartiainen Pekka , Jukarainen Sakari , Viippola Essi , Rodosthenous Rodosthenis S. , Liu Aoxing , Hägg Sara , Perola Markus , Ganna Andrea 
Published: September 2023

AbstractBackgroundAccurately predicting short-term mortality is important for optimizing healthcare resource allocation, developing risk-reducing interventions, and improving end-of-life care. Moreover, short-term mortality risk reflects individual frailty and can serve as digital aging marker. Previous studies have focused on specific, high-risk populations. Predicting all-cause mortality in an unselected population incorporating both health and socioeconomic factors has direct public health relevance but requires careful fairness considerations.MethodsWe developed a deep learning model to predict 1-year mortality using nationwide longitudinal data from the Finnish population (N= 5.4 million), including >8,000 features and spanning back up to 50 years. We used the area under the receiver operating characteristic curve (AUC) as a primary metric to assess model performance and fairness.FindingsThe model achieved an AUC of 0.944 with strong calibration, outperforming a baseline model that only included age and sex (AUC = 0.897). The model generalized well to different causes of death (AUC > 0.800 for 45 out of 50 causes), including COVID-19 which was not present in the training data. The model performed best among young females and worst in older males (AUC = 0.910 vs. AUC = 0.718). Extensive fairness analyses revealed that individuals belonging to multiple disadvantaged groups had the worst model performance, not explained by age and sex differences, reduced healthcare contact, or smaller training set sizes within these groups.ConclusionA deep learning model based on nationwide longitudinal multi-modal data accurately identified short-term mortality risk holding the potential for developing a population-wide in-silico aging marker. Unfairness in model predictions represents a major challenge to the equitable integration of these approaches in public health interventions.
Direct and indirect responses of the Arabidopsis transcriptome to an induced increase in trehalose 6-phosphate
Authors: Avidan Omri , Martins Marina C. M. , Feil Regina , Lohse Marc , Giorgi Federico M. , Schlereth Armin , Lunn John E. , Stitt Mark 
Published: September 2023

AbstractTrehalose 6-phosphate (Tre6P) is an essential signal metabolite that reports and regulates the level of sucrose, linking growth and development to the metabolic status. We hypothesized that Tre6P plays a role in mediating the regulation of gene expression by sucrose. To test this, we performed transcriptomic profiling on Arabidopsis plants that expressed a bacterial trehalose-6-phosphate synthase (TPS) under the control of an ethanol-inducible promoter. Induction led to a 4-fold rise in Tre6P levels, a concomitant decrease in sucrose, and significant changes of over 13,000 transcripts and two-fold or larger changes of over 5000 transcripts. Comparison with nine published responses to sugar availability allowed some of these changes to be linked to the rise in Tre6P, while others were probably due to lower sucrose or other indirect effects. Changes linked to Tre6P included repression of photosynthesis and induction of many growth-related processes including ribosome biogenesis. About 500 starvation-related genes are known to be induced by SUCROSE-NON-FERMENTING-1-RELATED KINASE 1 (SnRK1). They were largely repressed by Tre6P in a manner consistent with Tre6P acting to inhibit SnRK1. SnRK1 also represses many genes that are involved in biosynthesis and growth. These responded to Tre6P in a more complex manner, pointing to Tre6P also interacting with further C-signaling pathways. In addition, elevated Tre6P modified expression of genes encoding regulatory subunits of the SnRK1 complex and TPS class II and FLZ proteins that are thought to modulate SnRK1 function, and genes involved in the circadian clock and in TOR, light, abscisic acid and other hormone signaling.One sentence summaryAn induced increase in trehalose 6-phosphate levels has direct effects on gene expression via inhibition of SUCROSE-NON-FERMENTING-1-RELATED KINASE 1 and interactions with light, circadian clock and phytohormone signaling, and widespread indirect effects on gene expression from reciprocal changes in sucrose levels.
KlebsiellaPneumoniae turns more virulent under flow stresses in capillary like microchannels
Authors: Jain Siddhant , Singh Anmol , Tiwari Nivedita , Naik Aparna , Chatterjee Ritika , Chakravortty Dipshikha , Basu Saptarshi 
Published: September 2023

AbstractFluidic habitats are very common to bacterial life, however, very little is known about the effect of the flow stresses on the virulence of the bacteria. In the present work, we conduct microfluidic experiments to understand the consequence of stresses generated by flowing fluid on the bacterial morphology and virulence. We considerKlebsiella pneumoniae(KP), an ESKAPE pathogen as the model bacteria that are responsible for blood stream infections like bacteremia apart from pneumonia, urinary tract infections and more. We generate four different stress conditions by changing the flow rate and channel geometry subsequently altering the shear rate and stressing time (τ). We observe significant changes in the structural aspects of the stressed bacteria. With an increase in stressing parameters, the viability of the bacterial sample deteriorated. Most importantly, these stressed samples proliferate much more than unstressed samples inside the RAW264.7 murine macrophages. The results shed light on the complex relationship between flow stresses and bacterial virulence. Furthermore, we challenge the bacterial samples with ciprofloxacin to see how they behave under different stress conditions. The present study can be extended to model deadly diseases like bacteremia using organ-on-a-chip technology and help understand bacterial pathogenicity under realistic environments.Figure:A schematic representation of the present work. Figure created with BioRender (www.biorender.com)
Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets
Authors: Stylianou Maria , Kisby Thomas , Despotopoulou Despoina , Parker Helen , Thawley Alexandra , Arashvand Kiana , Lozano Neus , MacDonald Andrew S. , Kostarelos Kostas 
Published: September 2023

AbstractThe glioblastoma (GBM) microenvironment is characterised as immunologically ‘cold’, with immunosuppressive components that compromise the efficacy of current immunotherapies. Tumour associated macrophages and microglia (TAMMs) that are activated towards an immunosuppressive, pro-tumoral state have been identified as major contributing factors to the ‘coldness’ of GBM, while further promoting tumour progression and resistance to therapy. Based on this understanding, strategies such as macrophage reprogramming have been explored but have so far been limited by poor delivery and retention of reprogramming agents to the target cell populations within the GBM microenvironment. Consequently, clinical efficacy of such approaches has thus far shown limited success. Two-dimensional, graphene oxide (GO) nanosheets have been demonstrated to spread readily throughout the entire tumour microenvironment following a single intratumoral injection, interacting primarily with TAMMs. The current study aimed to investigate whether the immunosuppressive character of TAMMs in GBM can be ameliorated using GO sheets as a vector system to selectively deliver a TLR7/8 agonist (Resiquimod, R848), into these populations. GO enhanced the activity of R848 and induced the expression of M1-like markers on bone marrow derived macrophagesin vitro. Using multi-parameter flow cytometry and histological analysis in a syngeneic, orthotopic mouse model of GBM, we observed that a single intratumoral injection of GO:R848 complex significantly elevated the proportion of macrophages and microglia expressing MHCII, TNFα and CD86 (associated with a pro-inflammatory, anti-tumoral state), while downregulating their expression of the M2 markers ARG1 and YM1 (associated with an anti-inflammatory, pro-tumoral state). This local complex administration inhibited tumour progression and significantly reduced tumour burden. These data illustrate that immunomodulatory GO nanosheets can effectively alter the immune landscape of GBM and modulate the wider GBM microenvironment.ToC Image
Allelic variants confer Arabidopsis adaptation to small regional environmental differences
Authors: Wijfjes Raúl Y. , Boesten René , Becker Frank F. M. , Theeuwen Tom P. J. M. , Snoek Basten L. , Mastoraki Maria , Verheijen Jelle J. , Güvencli Nuri , Denkers Lissy-Anne M. , Koornneef Maarten , van Eeuwijk Fred A. , Smit Sandra , de Ridder Dick , Aarts Mark G.M. 
Published: September 2023

AbstractNatural populations ofArabidopsis thalianaprovide powerful systems to study adaptation of wild plant species. Previous research has predominantly focused on global populations or accessions collected from regions with diverse climates. However, little is known about the genetics underlying adaptation in regions with mild environmental clines. We have examined a diversity panel consisting of 192A. thalianaaccessions collected from the Netherlands, a region with limited climatic variation. Despite the relatively uniform climate, we identified compelling evidence of local adaptation within this population. Notably, semidwarf accessions, due to mutation of theGIBBERELLIC ACID REQUIRING 5(GA5) gene, occur at a relatively high frequency near the coast and these displayed enhanced tolerance to high wind velocities. Additionally, we evaluated the performance of the population under iron deficiency conditions and found that allelic variation in theFE SUPEROXIDE DISMUTASE 3(FSD3) gene affects tolerance to low iron levels. Moreover, we explored patterns of local adaptation to environmental clines in temperature and precipitation, observing that allelic variation atLA RELATED PROTEIN 1C(LARP1c) likely affects drought tolerance. Not only is the genetic variation observed in a diversity panel ofA. thalianacollected in a region with mild environmental clines comparable to that in collections sampled over larger geographic ranges, it is also sufficiently rich to elucidate the genetic and environmental factors underlying natural plant adaptation.
Phenotypic characterization ofHAM1, a novel mating regulator of the fungal pathogenCryptococcus neoformans
Authors: Yee Elizabeth Arsenault , Ross Robbi L. , Santiago-Tirado Felipe H. 
Published: September 2023

AbstractCryptococcus neoformansis a fungal pathogen responsible for >200,000 yearly cases with a mortality as high as 81%. This burden results, in part, from an incomplete understanding of its pathogenesis and ineffective antifungal treatments; hence, there is a pressing need to understand the biology and host interactions of this yeast to develop improved treatments. Protein palmitoylation is important for cryptococcal virulence, and we previously identified the substrates of its main palmitoyl transferase. One of them was encoded by the uncharacterized gene CNAG_02129. In the filamentous fungusNeurospora crassa, a homolog of this gene named HAM-13 plays a role in proper cellular communication and filament fusion. InCryptococcus, cellular communication is essential during mating, therefore we hypothesized that CNAG_02129, which we namedHAM1,may play a role in mating. We found thatham1Δ mutants produce more fusion products during mating, filament more robustly, and exhibit competitive fitness defects under mating and non-mating conditions. Additionally, we found several differences with the major virulence factor, the polysaccharide capsule, that may affect virulence, consistent with prior studies linking virulence to mating. We observed thatham1Δ mutants have decreased capsule attachment and transfer but exhibit higher amounts of exopolysaccharide shedding and biofilm production. Lastly,HAM1expression is significantly lower in mating media relative to non-mating conditions, consistent with it acting as a negative regulator of mating. Understanding the connection between mating and virulence inC. neoformansmay open new avenues of investigation into ways to improve the treatment of this disease.ImportanceFungal mating is a vital part of the lifecycle of the pathogenic yeastCryptococcus neoformans. More than just ensuring the propagation of the species, mating allows for sexual reproduction to occur and generates genetic diversity as well as infectious propagules that can invade mammalian hosts. Despite its importance in the biology of this pathogen, we still do not know all of the major players regulating the mating process and if they are involved or impact its pathogenesis. Here we identified a novel negative regulator of mating that also affects certain cellular characteristics known to be important for virulence. This gene, which we callHAM1, is widely conserved across the cryptococcal family as well as in many pathogenic fungal species. This study will open new avenues of exploration regarding the function of uncharacterized but conserved genes in a variety of pathogenic fungal species, and specifically in serotype A ofC. neoformans.
Ventromedial Frontoinsular Connectivity is Associated with Long-term Smoking Behavior Change in Aging
Authors: Thovinakere Nagashree , Ai Meishan , Noriega de la Colina Adrián E. , Walker Caitlin , Baracchini Giulia , Tremblay-Mercier Jennifer , Villeneuve Sylvia ,   The PREVENT-AD Research Group, Nathan Spreng R. , Geddes Maiya R. 
Published: September 2023

AbstractA central question in the field of cognitive aging and behavioral neuroscience is what enables some individuals to successfully change their behavior more than others? Smoking is a significant risk factor for cognitive decline, particularly in vulnerable populations, including those who are at an elevated risk for Alzheimer’s disease (AD). Developing effective smoking reduction strategies is therefore a public health priority. The goal of the current study is to better understand the brain mechanisms underlying long-term smoking behavior change in cognitively normal, but at-risk, older adults. Neuroimaging and human lesional studies have implicated the insula and its functional network in subjective interoceptive awareness of cigarette craving and smoking-cue reactivity. We sought to characterize the extent to which anterior insular resting-state functional connectivity MRI predicted long-term smoking reduction (mean: 2.7 years, range 8 months – 4 years) using a seed-to-voxel approach. Twenty-three (18 women; 26%APOE4carriers; 61.5 years, SD = 3.7) cognitively unimpaired older individuals who smoked cigarettes at their baseline visit and have a first-degree family history of AD (at least one parent or multiple siblings affected) were included from a prospective longitudinal cohort, PREVENT-AD (Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease) in the current study. We found that reduced long-term smoking behavior was associated with diminished functional connectivity between bilateral anterior insula and ventromedial prefrontal cortex (vmPFC). In a second pre-registered replication study within a larger, independent sample of one hundred and eighteen cognitively normal older adults who smoked cigarettes at baseline from the UK Biobank (73 women; 27.9 %APOE4carriers; 60.3 years, SD = 2.7), we found that baseline diminished resting-state functional connectivity between anterior insula and vmPFC predicted long-term smoking reduction (mean 5.2 years; ranging from 3 years to 7 years). To our knowledge, this is the largest study to examine the neural substrates of long-term smoking cessation in human aging. Our results suggest that frontoinsular circuits may be a therapeutic target for smoking reduction and disease prevention in older adults at risk for AD.
Brain organoid-on-a-chip to create multiple domains in forebrain organoids
Authors: Tsai Yuan-Chen , Ozaki Hajime , Morikawa Ango , Shiraiwa Kaori , Pin Andy Prosvey , Salem Aya Galal , Phommahasay Kenneth Akady , Sugita Bret Kiyoshi , Vu Christine Hein , Mamoun Hammad Saba , Kamei Ken-ichiro , Watanabe Momoko 
Published: September 2023

AbstractBrain organoids are three-dimensionally reconstructed brain tissue derived from pluripotent stem cells in vitro. 3D tissue cultures have opened new avenues for exploring development and disease modeling. However, some physiological conditions, including signaling gradients in 3D cultures, have not yet been easily achieved. Here, we introduce Brain Organoid-on-a-Chip platforms that generate signaling gradients that in turn enable the induction of topographic forebrain organoids. This creates a more continuous spectrum of brain regions and provides a more complete mimic of the human brain for evaluating neurodevelopment and disease in unprecedented detail.
Investigation ofTrypanosoma-induced vascular damage sheds insights intoTrypanosoma vivaxsequestration
Authors: Pereira Sara Silva , Brás Daniela , Porqueddu Teresa , Nascimento Ana M. , De Niz Mariana 
Published: September 2023

AbstractMultiple blood-borne pathogens infecting mammals establish close interactions with the host vascular endothelium as part of their life cycles. In this work, we investigate differences in the interactions of threeTrypanosomaspecies:T. brucei, T. congolenseandT. vivaxwith the blood vasculature. Infection with these species results in vastly different pathologies, including different effects on vascular homeostasis, such as changes in vascular permeability and microhemorrhages. While all three species are extracellular parasites,T. congolenseis strictly intravascular, whileT. bruceiis capable of surviving both extra- and intravascularly. Our knowledge regardingT. vivaxtropism and its capacity of migration across the vascular endothelium is unknown. In this work, we show for the first time thatT. vivaxparasites sequester to the vascular endothelium of most organs, and that, likeT. congolense, T. vivaxY486 is largely incapable of extravasation. Infection with this parasite species results in a unique effect on vascular endothelium receptors including general downregulation of ICAM1 and ESAM, and upregulation of VCAM1, CD36 and E-selectin. Our findings on the differences between the two sequestering species (T. congolenseandT. vivax) and the non-sequestering, but extravasating,T. bruceiraise important questions on the relevance of sequestration to the parasite’s survival in the mammalian host, and the evolutionary relevance of both sequestration and extravasation.