bluuebunny/crossref_metadata_2025 huggingface dataset:
Catatonia in Preadolescent Children
Authors: De Stefano Lara , Palffy Alexander , Ghaziuddin Neera
Published: January 2024

Objective

The aim of the study is to describe prepubescent catatonia in very young children, which is poorly documented in the current literature and, as a result, overlooked in medical settings.

Methods

We examined a convenience sample of 10 patients at an academic center who were younger than 12 years and met criteria for catatonia. After institutional review board approval, we extracted from the electronic medical records demographic and diagnostic information, comorbidity, developmental history, and laboratory testing. Bush Francis Catatonia Rating Scales at initial presentation and other symptomatology were gathered in addition to treatment received. Fifty percent of patients in this group were seen and diagnosed with catatonia at their presentation in an outpatient clinic, whereas the remaining 50% were diagnosed upon hospitalization, by the psychiatry consultation liaison team.

Results

All patients but one was diagnosed with a comorbid condition before the diagnosis of catatonia, including 70% with a previous diagnosis of autism spectrum disorder. Three patients had concurrent anti-N-methyl-D-aspartate receptor encephalitis, and one initially presented with seizures. All patients were treated for catatonia with lorazepam, and two patients additionally received electroconvulsive therapy. Regardless of the presence of early regression invariably associated with an autism spectrum diagnosis, secondary symptoms of regression were noted in each case at the time of diagnosing catatonia.

Conclusions

Similar to previous observations in adolescents, prepubescent catatonia seems strongly associated with neurodevelopmental disorders, secondary regression, variability in presentation, and comorbidity with other neurological conditions. Delayed recognition of catatonia can hinder rapid and effective treatment in young children.
Prediction of myeloid malignant cells in Fanconi anemia using machine learning
Authors: Flores-Mejía Luis A. , Siliceo-Portugal Pablo , Figueroa Ulises Juárez , Quezada Iram García , Barcenas Martínez Bibiana T. , Sosa David , Rivera Anet , Tovar Hugo , Frías Sara , Rodríguez Alfredo
Published: January 2024

Fanconi anemia (FA) is an inherited bone marrow failure syndrome with cancer predisposition. Most FA patients develop aplastic anemia during childhood and have an extremely high cumulative risk to develop cancer during their lifespan. Myeloid malignancy is one of the main tumor risks for patients with FA, including high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Although bone marrow transplantation is the treatment of choice for FA patients that develop aplastic anemia, patients with a more stable bone marrow remain at a high risk of presenting MDS/AML and should be monitored for appearance of myeloid malignant clones. Markers for an as-early-as-possible identification of emerging myeloid malignant cells are needed for the monitoring of patients with FA, since quick medical action after detection of neoplastic transformation is needed.

In this work we have leveraged publicly available single cell RNA seq (scRNAseq) datasets of patients with MDS and AML for training deep neural networks (DNN). We have generated two machine learning models aimed to identify myeloid malignant transcriptional profiles in scRNAseq datasets from the bone marrow of patients with FA, one for detection of MDS and a second one for AML. Both predictors displayed high sensitivity, specificity, and accuracy for detection of single cell resolution myeloid malignant transcriptional profiles.

Multiple tools for analysis of single cell transcriptional data were implemented to characterize the predicted MDS and AML cells. Our analysis suggests that the predicted MDS and AML cells from FA patients are enriched in the lympho-myeloid-primed progenitor (LMPP) and the granulocyte-monocyte progenitor (GMP) populations. The predicted MDS and AML cells have gene expression and master transcriptional factor profiles that suggest malignant transformation and that differ from the rest of FA cells. Also cues of immune evasion were detected using single cell pathway analysis (SCPA) and cell-cell communication profiles. Next work will be aimed to find potential cell surface markers on the predicted MDS and AML cells as well as to assess our predictions in primary samples from FA patients.
Glutaminase as a metabolic target of choice to counter acquired resistance to Palbociclib by colorectal cancer cells
Authors: Tarrado-Castellarnau Míriam , Foguet Carles , Tarragó-Celada Josep , Palobart Marc , Hernández-Carro Claudia , Perarnau Jordi , Zodda Erika , Polat Ibrahim H. , Marin Silvia , Suarez-Bonnet Alejandro , Lozano Juan José , Yuneva Mariia , Thomson Timothy M. , Cascante Marta
Published: January 2024

Several mechanisms of resistance of cancer cells to cyclin-dependent kinase inhibitors (CDKi) have been identified, including the upregulation of metabolic regulators such as glutaminase. However, whether such mechanisms and targets are optimal has not been determined. Here, we have systematically analyzed metabolic reprogramming in colorectal cancer cells exposed to Palbociclib, a CDKi selectively targeting CDK4/6, or Telaglenestat, a selective glutaminase inhibitor. Through multiple approaches, we show that Palbociclib and Telaglenestat elicit complementary metabolic responses and are thus uniquely suited to counter the metabolic reprogramming induced by the reciprocal drug. As such, while Palbociclib induced reduced tumor growthin vivo, and Telaglenestat did not show a significant effect, the drug combination displayed a strong synergistic effect on tumor growth. Likewise, initial responses to Palbociclib were followed by signs of adaptation and resistance, which were prevented by combining Palbociclib with Telaglenestat. In conclusion, combination with Telaglenestat optimally forestalls acquired resistance to Palbociclib in cancer cells.
Bio-electricity production from Fibroblasts and their cultivation media
Authors: Shlosberg Yaniv , Lesman Ayelet
Published: January 2024

The recent understanding of the critical future damage that might happen on earth by climate change has urged scientists to initiate new creative ideas for clean energy technologies that will reduce carbon emissions. A promising approach is the utilization of living cells as electron donors in bio-electrochemical cells (BECs). This concept has been intensively studied for micro-organisms such as non-photosynthetic bacteria, cyanobacteria, and microalgae, but not for mammalian cells. In this work, we report for the first-time integrating live fibroblast cells in a BEC to produce electrical current that is about 3 times higher than intact micro-organisms. Furthermore, we apply 2D-fluorescence and electrochemical measurements to show that like in micro-organisms based BECs, NADH and flavins play a role in the electron mediation between the cells and the anode. Finally, we show that the cultivation medium of fibroblasts also consists of redox species that may produce dark and photocurrent.
Efficient value encoding through convergence of tactile and visual value information in the primate putamen
Authors: Hwang Seong-Hwan , Park Doyoung , Lee Ji-Woo , Lee Sue-Hyun , Kim Hyoung F.
Published: January 2024

The processing of diverse sensory values by a limited number of basal ganglia neurons raises the question of whether each value is processed independently or combined as the number of neurons decreases from the cortex to downstream structures. Here, we discovered that tactile and visual values were partially converged in the primate putamen, enhancing its efficiency in encoding values while preserving modality information. Humans and monkeys performed tactile and visual value discrimination tasks. Notably, the human putamen selectively represented both tactile and visual values in fMRI scans. Single-unit electrophysiology further revealed that half of the individual neurons in the macaque putamen encoded both tactile and visual values, and the other half encoded each value separately. The bimodal value neurons enable more efficient value encoding using fewer neurons than the modality-selective value neurons. Our data suggest that the basal ganglia system uses modality convergence to efficiently encode values with limited resources.
Reconstructing fresh green leaf spectra in the SWIR-2 region (2001–2500 nm) collected in a humid environment by referring to publicly available green leaf spectral databases
Authors: Denaro Lino Garda , Li Hsin-Ju , Chong Jie-Yun , Huang Cho-ying
Published: January 2024

Leaf spectra (reflectance and transmittance) are key parameters for land surface physical and biogeochemical modeling and are commonly measured using a portable spectroradiometer and an integrating sphere or contact probe with an artificial light source. However, spectral data may be obscured mainly because of water vapor and low signal-to-noise ratios, especially in the shortwave infrared-2 region (SWIR-2, 2001–2500 nm). This erroneous pattern is particularly pronounced in humid conditions, such as in many tropical and subtropical regions, making data unusable in SWIR-2. In this study, we proposed a statistical/mathematical spectral reconstruction approach to retrieve noise-free SWIR-2 fresh green leaf spectra by referring to the available previously published quality-controlled fresh green leaf reflectance and transmittance reference databases. We processed 896 pairs of fresh tea (Camellia sinensisvar.sinensis) leaf reflectance and transmittance data from Alishan in central Taiwan. The spectral data were acquired by a field spectroradiometer with an integrating sphere. We selected a subset (500–1900 nm) of the spectra in the visible, near-infrared, and SWIR-1 regions (VNS-1) that was relatively insensitive to atmospheric conditions. Then, we applied a Gaussian fitting function to smooth the spectral profile. We matched those spectra with publicly available, quality-controlled, and Gaussian fitting function smoothed reference green leaf spectral databases obtained from Italy (LOPEX), Panama (SLZ), and Puerto Rico (G-LiHT) (1694 reflectance and 997 transmittance samples) and selected the one that was most similar (yielding the highest correlation coefficient) to each smoothed Alishan VNS-1 spectrum. We then used multivariable linear regression, linear parameter multiplication, and spectral reversion to reconstruct SWIR-2 spectra based on VNS-1 spectra. To assess the validity of the proposed SWIR-2 reconstruction method, we acquired an independent set of green leaf spectral databases from France (Angers) with SWIR-2 of 2001– 2450 nm. We found that the performance of the SWIR-2 reconstruction approach was satisfactory, with mean (± standard deviation) root-mean-square errors (RMSEs) of 0.0041 ± 0.0019 (reflectance, 3.0% of the mean SWIR-2 of the test data) and 0.0054 ± 0.0027 (transmittance, 2.5%) for each spectrum and RMSEs of 0.0058 ± 0.0027 (reflectance, 4.2%) and 0.0055 ± 0.0043 (transmittance, 2.5%) for each SWIR-2 band. The proposed approach successfully modeled SWIR-2 of the test spectra, which could be further improved with the availability of a more comprehensive set of green leaf reference spectral databases.
Hormetic effect induced byBeauveria bassianainMyzus persicae
Authors: Arinanto Leonhard Satrio , Hoffmann Ary Anthony , Ross Perran Albert , Gu Xinyue
Published: January 2024

Myzus persicae, a serious sap-sucking pest of a large variety of host plants in agriculture, is traditionally controlled using chemical insecticides but there is interest in using biopesticides as restrictions are increasingly placed on the use of broad-spectrum pesticides. Here we show that in petri dish experiments high concentrations of the fungal entomopathogenBeauveria bassiana(strain PRRI 5336) lead to rapid mortality ofM. persicaebut at a low concentration (1 × 104conidia mL−1) there is a hormetic effect where longevity and fecundity are enhanced. Hormetic effects persisted across a generation with reduced development times and increased fecundity in the offspring ofM. persicaeexposed toB. bassiana. Whole plant experiments point to a hormetic effect being detected in two out of three tested lines. The impact of these effects might also depend on whetherM. persicaewas transinfected with the endosymbiontRickettsiella viridis, which decreases fecundity and survival compared to aphids lacking this endosymbiont. This fecundity cost was ameliorated in the generation following exposure to the entomopathogen. WhileB. bassianais effective in controllingM. persicaeespecially at higher spore concentrations, utilization of this entomopathogen requires careful consideration of hormetic effects at lower spore concentrations, and further research to optimize its application for sustainable agriculture is recommended.

AUTHOR SUMMARY

Biopesticides such asBeauveria bassianacan be effective alternatives to chemical insecticides to control insect pests. We tested the efficacy of this biopesticide against the important agricultural pest aphidMyzus persicaein laboratory experiments. We also tested whether the potential biological control agent and endosymbiontRickettsiella viridiscould provide protection against mortality caused byB. bassiana. While high doses ofB. bassianacaused rapid mortality in aphids, low doses enhanced aphid fecundity and survival. This enhancement persisted into the next generation, with shortened development times and increased fecundity regardless, even when high doses were used in the previous generation. The endosymbiontR. viridisdid not provide clear protection againstB. bassiana, in contrast to previous studies in other aphid species, but beneficial effects at low doses also occurred in this aphid line. We also observed hormesis on experiments on whole plants, but only for some aphid genotypes. To a lesser extent, we also observed beneficial effects of low doses ofB. bassianain experiments on whole plants, but only in some aphid genotypes. Fitness enhancement by biopesticides at low doses raises concerns for field applications but further research is required to understand its underlying mechanisms.
Detailed mechanisms for unintended large DNA deletions with CRISPR, base editors, and prime editors
Authors: Hwang Gue-ho , Lee Seok-Hoon , Oh Minsik , Kim Segi , Habib Omer , Jang Hyeon-Ki , Kim Heon Seok , Kim Chan Hyuk , Kim Sun , Bae Sangsu
Published: January 2024

CRISPR-Cas9 nucleases are versatile tools for genetic engineering cells and function by producing targeted double-strand breaks (DSBs) in the DNA sequence. However, the unintended production of large deletions (>100 bp) represents a challenge to the effective application of this genome-editing system. We optimized a long-range amplicon sequencing system and developed a k-mer sequence-alignment algorithm to simultaneously detect small DNA alteration events and large DNA deletions. With this workflow, we determined that CRISPR-Cas9 induced large deletions at varying frequencies in cancer cell lines, stem cells, and primary T cells. With CRISPR interference screening, we determined that end resection and the subsequent TMEJ [DNA polymerase theta-mediated end joining] repair process produce most large deletions. Furthermore, base editors and prime editors also generated large deletions despite employing mutated Cas9 “nickases” that produce single-strand breaks. Our findings reveal an important limitation of current genome-editing tools and identify strategies for mitigating unwanted large deletion events.
Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19
Authors: Ashok Deepthi , Liu Ting , Criscione Joseph , Prakash Meghana , Kim Byunggik , Chow Julian , Craney Morgan , Papanicolaou Kyriakos N. , Sidor Agnieszka , Brian Foster D. , Pekosz Andrew , Villano Jason , Kim Deok-Ho , O’Rourke Brian
Published: January 2024

Background

Cardiac risk rises during acute SARS-CoV-2 infection and in long COVID syndrome in humans, but the mechanisms behind COVID-19-linked arrhythmias are unknown. This study explores the acute and long term effects of SARS-CoV-2 on the cardiac conduction system (CCS) in a hamster model of COVID-19.

Methods

Radiotelemetry in conscious animals was used to non-invasively record electrocardiograms and subpleural pressures after intranasal SARS-CoV-2 infection. Cardiac cytokines, interferon-stimulated gene expression, and macrophage infiltration of the CCS, were assessed at 4 days and 4 weeks post-infection. A double-stranded RNA mimetic, polyinosinic:polycytidylic acid (PIC), was used in vivo and in vitro to activate viral pattern recognition receptors in the absence of SARS-CoV-2 infection.

Results

COVID-19 induced pronounced tachypnea and severe cardiac conduction system (CCS) dysfunction, spanning from bradycardia to persistent atrioventricular block, although no viral protein expression was detected in the heart. Arrhythmias developed rapidly, partially reversed, and then redeveloped after the pulmonary infection was resolved, indicating persistent CCS injury. Increased cardiac cytokines, interferon-stimulated gene expression, and macrophage remodeling in the CCS accompanied the electrophysiological abnormalities. Interestingly, the arrhythmia phenotype was reproduced by cardiac injection of PIC in the absence of virus, indicating that innate immune activation was sufficient to drive the response. PIC also strongly induced cytokine secretion and robust interferon signaling in hearts, human iPSC-derived cardiomyocytes (hiPSC-CMs), and engineered heart tissues, accompanied by alterations in electrical and Ca2+handling properties. Importantly, the pulmonary and cardiac effects of COVID-19 were blunted by in vivo inhibition of JAK/STAT signaling or by a mitochondrially-targeted antioxidant.

Conclusions

The findings indicate that long term dysfunction and immune cell remodeling of the CCS is induced by COVID-19, arising indirectly from oxidative stress and excessive activation of cardiac innate immune responses during infection, with implications for long COVID Syndrome.
Distinct causes underlie double-peaked trilobite morphological disparity
Authors: Drage Harriet B. , Pates Stephen
Published: January 2024

Trilobite cephalic morphology impacted the autecology of individuals, and is critical for high- and low-level taxonomic assignments. Disparity in trilobite cephalon shape varied through time and was integral to the occupation of a diversity of ecological niches. To fully appreciate trilobite cephalic evolution, we must understand how this disparity varies, and what factors control cephalon morphometry. We explore the disparity of trilobite cephala through the Palaeozoic, and analyse the associations between cephalic morphometry and taxonomic assignment and geological Period, using a dataset of 983 2D trilobite cephalon outlines. Elliptical Fourier transformation visualised as a Principal Components Analysis suggests significant differences in morphospace occupation for order and Period groups, and comparisons of disparity measures also suggest significantly different disparities between the groups. Trilobite cephalic disparity peaks in the Ordovician and Devonian. The Cambrian–Ordovician expansion of morphospace occupation appears a result of radiation to new niches, and thus all trilobite orders were established by the late Ordovician. In comparison, the morphospace expansion from the Silurian to Devonian seems solely a result of within-niche diversification rather than novel niche occupation. However, analyses interrogating the regions of morphospace occupied, including centroid distances, average pairwise shape comparisons and Linear Discriminant Analysis demonstrate that, except for the order Harpida and the Cambrian and Ordovician Periods, order and geological Period could not be robustly predicted for an unknown trilobite. Further, Kmeans clustering analyses suggest the total dataset naturally subdivides into only seven groups that do not correspond with taxonomic orders, though Kmeans clusters do decrease in number through the Palaeozoic, aligning with findings of decreasing disparity.
Phenylketonuria: modelling cerebral amino acid and neurotransmitter metabolism
Authors: Wegrzyn Agnieszka B. , van Vliet Danique , van Eunen Karen , Heiner-Fokkema M. Rebecca , van der Zee Eddy A. , van Spronsen Francjan J. , Bakker Barbara M.
Published: January 2024

Abstract

Objective

Phenylketonuria (PKU) is caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase, which primarily converts phenylalanine into tyrosine. Despite a phenylalanine-deprived diet, many adult PKU patients display deficits in executive functions. These are hypothesised to be caused by high cerebral phenylalanine and a shortage of monoaminergic neurotransmitters.

Method

To better understand the relationship between plasma and brain amino acid levels and monoaminergic neurotransmitter biochemistry, we constructed a computational model. The model comprises the transport of large neutral amino acids (LNAA) across the blood-brain barrier as well as cerebral amino acid and monoaminergic neurotransmitter metabolism and was validated by direct measurements of brain amino acid concentrations in PKU mice on various diets.

Results

The model predicts that brain amino acids are positively controlled by the concentrations of the corresponding amino acids in the blood, and to a lesser extent negatively by other amino acids competing for the transport systems. The model suggests that brain levels of monoaminergic neurotransmitters are controlled more by phenylalanine, probably through non-competitive inhibition of the hydroxylases rather than by their precursor amino acids. Therefore, the model predicts that the decrease of neurotransmitters in PKU cannot be fully rescued by the addition of tyrosine and tryptophan alone, but also benefits from a reduction of the phenylalanine level. Thereby, the model substantiates the experimental data of the synergistic effect of both brain phenylalanine reduction and increased precursor amino acid availability to improve brain neurotransmitters in PKU mice.

Conclusion

We present the first complete model of the LNAA transport through the blood-brain barrier and subsequent brain neurotransmitter metabolism in PKU. The model leads to a better understanding of the pathophysiological mechanisms and the influence of individual amino acids in the diet on the underlying brain dysfunction in PKU. Moreover, it identifies gaps in our current knowledge about the LNAA transport across the blood-brain barrier. Furthermore, the model can be readily applied in studies of other neurological disorders in which the relation between diet, gene activities, brain amino acids, and neurotransmitters is important.
CREB activation drives acinar to ductal reprogramming and promote pancreatic cancer progression in animal models of alcoholic chronic pancreatitis
Authors: Srinivasan Supriya , Mehra Siddharth , Bianchi Anna , Singh Samara , Dosch Austin R. , Amirian Haleh , Jinka Sudhakar , Krishnamoorthy Varunkumar , Silva Iago De Castro , Box Edmond Worley , Garrido Vanessa , Totiger Tulasigeri M. , Zhou Zhiqun , Ban Yuguang , Datta Jashodeep , VanSaun Michael , Merchant Nipun , Nagathihalli Nagaraj S.
Published: January 2024

BACKGROUND AND AIMS

In vivoinduction of alcoholic chronic pancreatitis (ACP) causes significant acinar damage, increased fibroinflammatory response, and heightened activation of cyclic response element binding protein 1 (CREB) when compared with alcohol (A) or chronic pancreatitis (CP) mediated pancreatic damage. However, the study elucidating the cooperative interaction between CREB and the oncogenicKrasG12D/+(Kras*) in promoting pancreatic cancer progression with ACP remains unexplored.

METHODS

Experimental ACP induction was established in multiple mouse models, followed by euthanization of the animals at various time intervals during the recovery periods. Tumor latency was determined in these mice cohorts. Here, we established CREB deletion (Crebfl/fl) inPtf1aCreERTM/+;LSL-KrasG12D+/−(KC) genetic mouse models (KCC−/−). Western blot, phosphokinase array, and qPCR were used to analyze the pancreata ofPtf1aCreERTM+/−,KCandKCC−/−mice. The pancreata of ACP-inducedKCmice were subjected to single-cell RNA sequencing (scRNAseq). Further studies involved conducting lineage tracing and acinar cell explant cultures.

RESULTS

ACP induction inKCmice had detrimental effects on the pancreatic damage repair mechanism. The persistent existence of acinar cell-derived ductal lesions demonstrated a prolonged state of hyperactivated CREB. Persistent CREB activation leads to acinar cell reprogramming and increased pro-fibrotic inflammation inKCmice. Acinar-specificCrebablation reduced advanced PanINs lesions, hindered tumor progression, and restored acinar cell function in ACP-induced mouse models.

CONCLUSIONS

Our findings demonstrate that CREB cooperates withKras*to perpetuate an irreversible ADM and PanIN formation. Moreover, CREB sustains oncogenic activity to promote the progression of premalignant lesions toward cancer in the presence of ACP.
Fish Blood Response to Ash-Induced Environmental Alkalinization, and their Implications to Wildfire-Scarred Watersheds
Authors: Kwan Garfield T. , Sanders Trystan , Huang Sammuel , Kilaghbian Kristen , Sam Cameron , Wang Junhan , Weihrauch Kelly , Wilson Rod W. , Fangue Nann A.
Published: January 2024

Changes in land use, warming climate and increased drought have amplified wildfire frequency and magnitude globally. Ash mixing into aquatic systems after wildfires rapidly increases water pH, creating an additional threat to wildlife, especially species that are already threatened, endangered and/or migratory. Here, Chinook salmon (Oncorhynchus tshawytscha) yearlings acclimated to 15 or 20°C were exposed to an environmentally relevant concentration of ash (0.25% w/v) which caused water pH to rapidly rise from ∼8.1 to ∼9.2. Mortalities occurred within the first 12 hours, and was higher at the higher temperature (33 versus 20 %). The greatest differences in blood chemistry between the two temperatures were dramatically greater (∼7.5-fold) and very rapid (within 1 hour) spikes in both plasma total ammonia (to ∼1200 µM) and lactate (to ∼6 mM) in warm-acclimated salmon, whereas cold-acclimated salmon experienced a much smaller and gradual rise in plasma total ammonia. Salmon at both temperatures experienced extracellular and intracellular alkalosis within 1 hour that recovered within 24 hours, but the alkalosis was smaller in magnitude in fish at warmer temperature. Impacts on plasma ion concentrations were relatively mild and plasma glucose increased by 2- to 4-fold at both temperatures. Notably, the increase in plasma total ammonia in fish at the warmer temperature was far faster and much greater than those reported in previous studies exposing fish despite higher water pH (9.4-10.5) induced without using ash. This suggests that ash has physiological impacts that cannot be explained by high water pH alone which may relate to the complex mixture of metals and organic compounds also released from ash. This demonstrates post-wildfire ash input can induce lethal yet previously unexplored physiological disturbances in fish and highlights the complex interaction with warmer temperatures typical of wildfire-scarred landscapes.
ClonalTracker: a tool to elucidate dissemination patterns between vancomycin-resistantEnterococcus faeciumisolates
Authors: Andreu Victoria Pascal
Published: January 2024

The global spread of vancomycin-resistantEnterococcus faecium(VRE), which commonly occurs in hospital environments, has become a major public health concern. To facilitate genomic surveillance and tracking the transmission of VRE, ClonalTracker was designed. This tool assesses the clonal relatedness between two VRE isolates given the respective assembled genomes by analyzing thevanoperon, the respective transposon type and the whole genome similarity. ClonalTracker has been validated using two previously analyzed publicly available datasets and I showcase its applicability on a yet unprocessed third dataset. While the method agrees with previously published results, it is able to provide more resolution at the clustering level even in the absence of plasmid information and using as reference the minimal version of the vancomycin resistance transposon. Within this third dataset composed of 323vanBVRE isolates, ClonalTracker found that clonal expansion is the most common dissemination mode. All in all, this tool provides new bioinformatic means to uncover dissemination patterns and elucidate links between vancomycin-resistance isolates and can be broadly accessible via its webserver hosted atwww.clonaltracker.nl(as of January 2024). The local version of this tool is also available at:https://github.com/victoriapascal/clonaltracker
Towards Real-Time Airborne Pathogen Sensing: Electrostatic Capture and On-Chip LAMP Based Detection of Airborne Viral Pathogens
Authors: Jayakumar Nitin , Caffrey Veronique , Caffrey Michael , Paprotny Igor
Published: January 2024

Considerable loss of life, economic slowdown, and public health risk associated with the transmission of airborne respiratory pathogens was underscored by the recent COVID-19 pandemic. Airborne transmission of zoonotic diseases such as the highly pathogenic avian influenza (HPAI) and porcine reproductive and respiratory syndrome virus (PRRSV) has caused major disruptions to domestic and global food security. Current ambient air pathogen monitoring systems involves the collection of air samples from indoor settings suspected of viral contamination, followed by subsequent processing of capture samples to determine the presence and species of airborne viral matter. Nucleic acid amplification techniques are considered the gold standard for pathogen diagnostics. Currently, the necessary extraction and purification of viral RNA from air collector systems prior to sample analysis is both time consuming and performed manually. A monitoring system with separate air sampling and biochemical detection procedures is prone to delay the response to emergent viral threats. In this paper, we present a pathogen monitoring system that overcomes these limitations related to extraction and purification of viral samples and lays the groundwork for a real-time monitor for airborne viral pathogens. We demonstrate a high flow electrostatic precipitator system, that uses small collection wells as counter electrodes for pathogen collection. Integrated reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) is used for detection of captured viral matter within wells. On-chip heating of collection wells is enabled by integrated planar heaters and small volumes of reagent (30 μL) directly to the collection wells. We present the design of such a system and show experimental results that demonstrate the use of this device for detection of aerosolized SARS-CoV-2 virus like particles (VLPs), a model pathogen for SARV-CoV-2.
DNA methylation enables recurrent endogenization of giant viruses in an animal relative
Authors: Sarre Luke A. , Kim Iana V. , Ovchinnikov Vladimir , Olivetta Marine , Suga Hiroshi , Dudin Omaya , Sebé-Pedrós Arnau , de Mendoza Alex
Published: January 2024

5-methylcytosine (5mC) is a widespread silencing mechanism that controls genomic parasites. However, in many eukaryotes 5mC has gained complex roles in gene regulation beyond parasite control. Animals are a quintessential case for 5mC evolution, as they show widespread variability across lineages, ranging from gene regulation and transposable element control to loss of this base modification. Here we show that the protist closely related to animalsAmoebidium appalachensefeatures both transposon and gene body methylation, a pattern reminiscent of invertebrates and plants. Unexpectedly, large hypermethylated regions of theAmoebidiumgenome derive from viral insertions, including hundreds of endogenized giant viruses contributing 14% of the encoded genes, to an extent never reported before in any eukaryotic genome. Using a combination of inhibitors and functional genomic assays, we demonstrate that 5mC silences these giant virus insertions. Moreover, alternativeAmoebidiumisolates show polymorphic giant virus insertions, highlighting a dynamic process of infection, endogenization and purging. Our results indicate that 5mC is critical for the controlled co-existence of newly acquired viral DNA into eukaryotic genomes, makingAmoebidiuma unique model to understand the hybrid origins of eukaryotic genomes.
Imaging the structural connectome with hybrid diffusion MRI-microscopy tractography
Authors: Zhu Silei , Huszar Istvan N. , Cottaar Michiel , Daubney Greg , Eichert Nicole , Hanayik Taylor , Khrapitchev Alexandre A. , Mars Rogier B. , Mollink Jeroen , Sallet Jerome , Scott Connor , Smart Adele , Jbabdi Saad , Miller Karla L. , Howard Amy F.D.
Published: January 2024

Neuroanatomical tract tracing methods are fundamental in providing “gold standard” estimates of brain connectivity. However, tracer methods cannot be performed in humans and even in animals, we can only study projections from typically one or two injection sites per animal sacrificed. Orientation-sensitive microscopy techniques such as PLI provide an alternative where they can visualise detailed fibre orientations at the micron-scale across the whole brain. However, these methods are often most informative on orientations within the 2D imaging plane, with less reliable or missing through-plane information, restricting 3D tract reconstruction. Conversely, dMRI can estimate fibre orientations in 3D but at low resolution, which leads to many false positive and negative estimates of fibre trajectories.

To facilitate reconstruction of the microscopy-informed connectome, we develop a data-fusion method that complements 2D microscopy with through-plane information from diffusion MRI to construct 3D hybrid orientations that are both maximally informed by the high-resolution microscopy, have whole-brain coverage and can be input into existing tractography pipelines. Diffusion MRI can be readily acquired prior to microscopy meaning the same method is translatable across species, including in humans. Here we apply our method to an existing open-access macaque dataset and demonstrate (1) whole-brain microscopy-informed tractography (2) the advantages of hybrid tractography in two known tractography challenges, the gyral bias and bottleneck problem (3) how hybrid tractography appears to outperform diffusion-only tractography when compared to tracer data and (4) the generalisability of our hybrid method to different microscopy contrasts, facilitating wider translation.
Long days induce adaptive secondary dormancy in seed of the Mediterranean plantAethionema arabicum
Authors: Mérai Zsuzsanna , Graeber Kai , Xu Fei , Dona Mattia , Lalatović Katarina , Wilhelmsson Per K.I. , Fernandez-Pozo Noe , Rensing Stefan A. , Leubner-Metzger Gerhard , Scheid Ortrun Mittelsten , Dolan Liam
Published: January 2024

Secondary dormancy is an adaptive trait that increases reproductive success by aligning seed germination with permissive conditions for seedling establishment.Aethionema arabicumis an annual plant and member of the Brassicaceae that grows in environments characterized by hot and dry summers.Aethionema arabicumseeds may germinate in early spring when seedling establishment is permissible. We demonstrate that long-day light regimes induce secondary dormancy in seed ofAethionema arabicum(CYP accession) repressing germination in summer when seedling establishment is riskier. Characterization of mutants screened for defective secondary dormancy demonstrated that RGL2 mediates repression of genes involved in GA signalling. Exposure to high temperature alleviates secondary dormancy, restoring germination potential. These data are consistent with the hypothesis that long-day-induced secondary dormancy and its alleviation by high temperatures, may be part of an adaptive response limiting germination to conditions permissive for seedling establishment in spring and autumn.
Pear flower and leaf microbiome dynamics during the naturally occurring spread ofErwinia amylovora
Authors: Oz Aia , Mairesse Orly , Raikin Shira , Hanani Hila , Dafny Yelin Mery , Sharon Itai
Published: January 2024

Erwinia amylovorais the causal pathogen of fire blight, a contagious disease that affects apple and pear trees and other members of the family Rosaceae. In this study, we investigated the population dynamics of the pear flower microbiome in an agricultural setting during the naturally occurring infection ofE. amylovora. Five potential factors were considered: collection date, the flower’s phenological stage, location on the tree, location within the orchard, and pear cultivar. The phenological stage and the collection date were identified as the most important factors associated with pear flower microbiome composition. The location of the tree in the orchard and the flower’s location on the tree had a marginal effect on the microbiome composition. The leaf microbiome reflected that of the abundant phenological stage on each date. The flower microbiome shifted towardsE. amylovora,dominating the community as time and phenological stages progressed, leading to decreased community diversity. The strain population ofE. amylovoraremained similar throughout the entire collection period. In contrast, other taxa, including Pseudomonas, Pantoea, Lactobacillus, and Sphingomonas, were represented by dozens of amplicon sequence variants (ASVs), and different succession patterns in their populations were observed. Some of the taxa identified include known antagonists toE. amylovora. Overall, our results suggest that flower physiology and the interaction with the environment are strongly associated with the pear flower microbiome and should be considered separately. Strain succession patterns for the different taxa underE. amylovoraspread may help in choosing candidates for antagonist-based treatments for fire blight.

Importance

The spread of pathogens in plants is an important ecological phenomenon and has a significant economic impact on agriculture. Flowers serve as the entry point forE. amylovora,but members of the flower microbiome can inhibit or slow down the proliferation and penetration of the pathogen. Knowledge about leaf and flower microbiome response to the naturally occurring spread ofE. amylovorais still lacking. The current study is the first to describe the flower microbiome dynamics during the naturally occurring infectionof E. amylovora. Unlike previous studies, our experiment design enabled us to evaluate the contribution of five important environmental parameters to the community composition. We identified different strain succession patterns across different taxa in the flower consortia throughout the season. These results contribute to our understanding of plant microbial ecology during pathogen spread and can help to improve biological treatments for these diseases.
Sustained EEG responses to rapidly unfolding stochastic sounds reflect precision tracking
Authors: Zhao Sijia , Skerritt-Davis Benjamin , Elhilali Mounya , Dick Frederic , Chait Maria
Published: January 2024

The brain is increasingly viewed as a statistical learning machine, where our sensations and decisions arise from the intricate interplay between bottom-up sensory signals and constantly changing expectations regarding the surrounding world. Which statistics does the brain track while monitoring the rapid progression of sensory information?

Here, by combining EEG (three experiments N≥22 each) and computational modelling, we examined how the brain processes rapid and stochastic sound sequences that simulate key aspects of dynamic sensory environments. Passively listening participants were exposed to structured tone-pip arrangements that contained transitions between a range of stochastic patterns. Predictions were guided by a Bayesian predictive inference model. We demonstrate that listeners automatically track the statistics of unfolding sounds, even when these are irrelevant to behaviour. Transitions between sequence patterns drove an increase of the sustained EEG response. This was observed to a range of distributional statistics, and even in situations where behavioural detection of these transitions was at floor. These observations suggest that the modulation of the EEG sustained response reflects a universal process of belief updating within the brain. By establishing a connection between the outputs of the computational model and the observed brain responses, we demonstrate that the dynamics of these transition-related responses align with the tracking of ‘precision’ – the confidence or reliability assigned to a predicted sensory signal - shedding light on the intricate interplay between the brain’s statistical tracking mechanisms and its response dynamics.
Inflammatory Cytokines Can Induce Synthesis Of Type-I Interferon
Authors: Sharma Nikhil , Qi Xu , Kessler Patricia , Sen Ganes C.
Published: January 2024

Type I interferon (IFN) is induced in virus infected cells, secreted and it inhibits viral replication in neighboring cells. IFN is also an important player in many non-viral diseases and in the development of normal immune cells. Although the signaling pathways for IFN induction by viral RNA or DNA have been extensively studied, its mode of induction in uninfected cells remains obscure. Here, we report that inflammatory cytokines, such as TNF-α and IL-1β, can induce IFN-β through activation of the cytoplasmic RIG-I signaling pathway. However, RIG-I is activated not by RNA, but by PACT, the protein activator of PKR. In cell lines or primary cells expressing RIG-I and PACT, activation of the MAPK, p38, by cytokine signaling, leads to phosphorylation of PACT, which binds to primed RIG-I and activates its signaling pathway. Thus, a new mode of type I IFN induction by ubiquitous inflammatory cytokines has been revealed.

Key points

Cytochalasin D followed by TNF-α / IL-1β treatment activates IFN-β expression.

IFN-β expression happens due to activation of RIG-I signaling.

Interaction between RIG-I and PACT activates IFN-β expression.
Majorana-fermion mean field theories of Kitaev quantum spin liquids
Authors: Saheli Shahnam Ghanbari , Lin Jennifer , Hu Huanzhi , Krüger Frank
Published: January 2024

We determine the phase diagrams of anisotropic Kitaev-Heisenberg models on the honeycomb lattice using parton mean-field theories based on different Majorana fermion representations of the S=1/2 spin operators. First, we use a two-dimensional Jordan-Wigner transformation (JWT) involving a semi-infinite snake string operator. To ensure that the fermionized Hamiltonian remains local, we consider the limit of extreme Ising exchange anisotropy in the Heisenberg sector. Second, we use the conventional Kitaev representation in terms of four Majorana fermions subject to local constraints, which we enforce through Lagrange multipliers. For both representations, we self-consistently decouple the interaction terms in the bond and magnetization channels and determine the phase diagrams as a function of the anisotropy of the Kitaev couplings and the relative strength of the Ising exchange. While both mean-field theories produce identical phase boundaries for the topological phase transition between the gapless and gapped Kitaev quantum spin liquids, the JWT fails to correctly describe the magnetic instability and finite-temperature behavior. Our results show that the magnetic phase transition is first order at low temperatures but becomes continuous above a certain temperature. At this energy scale, we also observe a finite-temperature crossover on the quantum-spin-liquid side, from a fractionalized paramagnet at low temperatures, in which gapped flux excitations are frozen out, to a conventional paramagnet at high temperatures.

Published by the American Physical Society
2024
Structure of the outer membrane porin OmpW from the pervasive pathogen Klebsiella pneumoniae
Authors: Seddon Chloe , Frankel Gad , Beis Konstantinos
Published: January 2024

Conjugation is the process by which plasmids, including those that carry antibiotic-resistance genes, are mobilized from one bacterium (the donor) to another (the recipient). The conjugation efficiency of IncF-like plasmids relies on the formation of mating-pair stabilization via intimate interactions between outer membrane proteins on the donor (a plasmid-encoded TraN isoform) and recipient bacteria. Conjugation of the R100-1 plasmid into Escherichia coli and Klebsiella pneumoniae (KP) recipients relies on pairing between the plasmid-encoded TraNα in the donor and OmpW in the recipient. Here, the crystal structure of K. pneumoniae OmpW (OmpWKP) is reported at 3.2 Å resolution. OmpWKP forms an eight-stranded β-barrel flanked by extracellular loops. The structures of E. coli OmpW (OmpWEC) and OmpWKP show high conservation despite sequence variability in the extracellular loops.
Effect of zinc oxide on the electrochemical properties of micro-arc oxidation coatings in seawater
Authors: Sun Qiang , Jiang Quantong , Wu Siwei , Liu Chang , Tang Heng , Song L. , Shi Hao , Duan Jizhou , Hou BaoRong
Published: January 2024

Purpose

The purpose of this paper is to explore the effect of ZnO on the structure and properties of micro-arc oxidation (MAO) coating on rare earth magnesium alloy under large concentration gradient.

Design/methodology/approach

The macroscopic and microscopic morphology, thickness, surface roughness, chemical composition and structure of the coating were characterized by different characterization methods. The corrosion resistance of the film was studied by electrochemical and scanning Kelvin probe force microscopy. The results show that the addition of ZnO can significantly improve the compactness and corrosion resistance of the MAO coating, but the high concentration of ZnO will cause microcracks, which will reduce the corrosion resistance to a certain extent.

Findings

When the concentration of zinc oxide is 8 g/L, the compactness and corrosion resistance of the coating are the best, and the thickness of the coating is positively correlated with the concentration of ZnO.

Research limitations/implications

Too high concentration of ZnO reduces the performance of MAO coating.

Practical implications

The MAO coating prepared by adding ZnO has good corrosion resistance. Combined with organic coatings, it can be applied in corrosive marine environments, such as ship parts and hulls. To a certain extent, it can reduce the economic loss caused by corrosion.

Originality/value

The effect of ZnO on the corrosion resistance of MAO coating in electrolyte solution was studied systematically, and the conclusion was new to the common knowledge.