bluuebunny/crossref_metadata_2025 huggingface dataset:
Associating with kin selects for disease resistance and against tolerance
Authors: Walsman Jason C. , Lambe Madalyn , Stephenson Jessica F.
Published: May 2024

Behavioural and physiological resistance are key to slowing epidemic spread. We explore the evolutionary and epidemic consequences of their different costs for the evolution of tolerance that trades off with resistance. Behavioural resistance affects social cohesion, with associated group-level costs, while the cost of physiological resistance accrues only to the individual. Further, resistance, and the associated reduction in transmission, benefit susceptible hosts directly, whereas infected hosts only benefit indirectly, by reducing transmission to kin. We therefore model the coevolution of transmission-reducing resistance expressed in susceptible hosts with resistance expressed in infected hosts, as a function of kin association, and analyse the effect on population-level outcomes. Using parameter values for guppies,
Poecilia reticulata
, and their gyrodactylid parasites, we find that: (1) either susceptible or infected hosts should invest heavily in resistance, but not both; (2) kin association drives investment in physiological resistance more strongly than in behavioural resistance; and (3) even weak levels of kin association can favour altruistic infected hosts that invest heavily in resistance (versus selfish tolerance), eliminating parasites. Overall, our finding that weak kin association affects the coevolution of infected and susceptible investment in both behavioural and physiological resistance suggests that kin selection may affect disease dynamics across systems.
Trophic interactions in microbiomes influence plant host population size and ecosystem function
Authors: Tan Jiaqi , Wei Na , Turcotte Martin M.
Published: May 2024

Plant microbiomes that comprise diverse microorganisms, including prokaryotes, eukaryotes and viruses, are the key determinants of plant population dynamics and ecosystem function. Despite their importance, little is known about how species interactions (especially trophic interactions) between microbes from different domains modify the importance of microbiomes for plant hosts and ecosystems. Using the common duckweed
Lemna minor
, we experimentally examined the effects of predation (by bacterivorous protists) and parasitism (by bacteriophages) within microbiomes on plant population size and ecosystem phosphorus removal. Our results revealed that the addition of predators increased plant population size and phosphorus removal, whereas the addition of parasites showed the opposite pattern. The structural equation modelling further pointed out that predation and parasitism affected plant population size and ecosystem function via distinct mechanisms that were both mediated by microbiomes. Our results highlight the importance of understanding microbial trophic interactions for predicting the outcomes and ecosystem impacts of plant–microbiome symbiosis.
Physicochemical and organoleptic properties of hot-air dried oriental
melon slices prepared using different physical pretreatments
Authors: Kim Young Min , Kim Minhui , Jung Yujung , Kim Jiyoon , Kim Jung Soo , Kim Dong Hyun , Lee Sae-Byuk , Kim Juhyun , Lee Sang-Han , Moon Kwang-Deog , Ku Seockmo , Choe Deokyeong
Published: May 2024

The oriental melon poses challenges in terms of long-term storage and
distribution. Addressing these issues requires an extension of the storage life
through appropriate processing. In this study, pretreated hot-air dried oriental
melon slices (steamed and freeze-thawed) were prepared, and their
physicochemical and organoleptic properties were examined. The control group
(CON) consisted of hot-air dried oriental melon slices without pretreatment,
while the steamed group (STG) and freeze-thawed group (FTG) consisted of hot-air
dried oriental melon slices pretreated using steaming and freeze-thawing
methods, respectively. The moisture contents detected in the CON, STG, and FTG
groups ranged from 15.96% to 27.30%, with variations of 7.53 to
8.40 °Brix for the soluble solid contents. The CON group showed the
highest Hunter color value for lightness (L*) and the lowest value for
redness (a*). The texture profile analysis revealed the highest hardness
and chewiness in the order of STG > CON > FTG. Considerable
differences were observed in springiness and adhesiveness in the FTG group
compared to the other groups. The organoleptic evaluation showed that the CON
group had the highest sensory scores for overall preference. These findings
indicate that the properties of hot-air dried oriental melon slices were
influenced by physical pretreatments and that manufacturing these slices without
pretreatment is the most effective method in terms of processing simplicity and
cost efficiency.
Effects of chestnut powder content on the quality characteristics and antioxidant activity of rice muffins
Authors: Choi Jin-Hee , Ahn Hyun-Do , Hwang Jun-Min , Kim Ye-ji , Kim Soo-bin , Kim In-beom , Choi Hae-Yeon
Published: May 2024

This study examined the effects of chestnut powder content (2.5%, 5%, 7.5%, and 10%) on the antioxidant activity and quality characteristics of rice muffins. With the increasing chestnut powder content, the total polyphenol content, flavonoid content, antioxidant activity (determined by radical scavenging activity and reducing power), hardness, gumminess, chewiness, and overall acceptability (determined by sensory evaluation) increased, whereas the moisture content, pH, specific volume, and cooking loss decreased. Regarding color, chestnut powder content was negatively correlated with L and b and positively correlated with a. Notably, overall acceptability abruptly decreased to its minimum at 10%. Thus, adding powder at loadings of <7.5% improved the antioxidant activity and acceptability of rice muffins. Our results can be used as preparatory data for developing a rice muffin model.
Changes in physiologically active ingredients and anti-inflammatory
properties of underutilized wild vegetables by complex fermentation using
beneficial microorganisms
Authors: Sim Sang-Hyeob , Choi Ha Kyoung , Lee Da Eun , Na Soo Chang , Hwang Dae Il , Oh Hyo Bin , Lim Yi Teak , Kim Tae-Young , Kim Dae-Woon
Published: May 2024

It was confirmed that complex fermentation (CF) was more efficient than
single-strain fermentations in inducing changes in the contents of phenolic
compounds of Maclura tricuspidate and Pyrus
Montana Nakai. A mixture of Maclura tricuspidata,
Pyrus montana Nakai, Platycodon
grandiflorum and Codonopsis lanceolata were
fermented in CF using Aspergillus shirousamii
(koji), yeast, and lactic acid bacteria (LAB) for 24 days,
and the pH, °Brix, total acidity, anti-oxidant activity, polyphenol
content, nitric oxide (NO), and Western blotting of inducible nitric oxide
synthase (iNOS), cyclo-oxygenase-2 (COX-2), and tumor necrosis
factor-α (TNF-α) of the
sample were determined. There was no significant change in pH and total acidity.
°Brix significantly decreased from day 6 onwards. HPLC confirmed that the
concentrations of chlorogenic acid, 4-hydrobenzoic acid, vanillic acid, and
caffeic acid significantly increased from day 18 during the fermentation.
Additionally, DPPH, ABTS radical scavenging activity, total phenol, and total
flavonoid were confirmed to be increased until 18 days. NO was significantly
inhibited from day 6, along with significant inhibition of iNOS, COX-2, and
TNF-a. In conclusion, this study confirmed that CF of low-use (or underutilized)
wild vegetables enhances phenolic compounds. It effectively suppresses NO, iNOS,
COX-2, and TNF-α, markers of inflammation-related
pathogenesis. Altogether, our results suggest that CF of the above plants has a
potential anti-inflammatory effect.
Effect of mixed plant-extract powder on the regulation of differentiation and oxidative stress-induced apoptosis in C2C12 cells
Authors: Park Se-Eun , Choi Dabin , Oh Kyo-nyeo , Kim Hanjoong , Park Hyungbum , Kim Ki-Man
Published: May 2024

This study evaluated the differentiation and protective effects of mixed plant-extract powder in C2C12 muscle cells. Cells were differentiated into myotubes in 2% horse serum (HS)-containing medium with mixed plant-extract powder (MPEP) for 6 days. Treatment with MPEP increased the expression of myogenin and myosin heavy chain (MHC) protein in cells compared with non-treated cells. Differentiated cells were pretreated with MPEP, and hydrogen peroxide (H2O2). Our results revealed that treatment with MPEP before H2O2 treatment increased cell viability and decreased H2O2-induced lactate dehydrogenase (LDH) and creatine kinase (CK). In addition, MPEP attenuated H2O2-induced upregulation of Bax, downregulation of Bcl-2, and activation of caspase-9 and -3. These results suggest the MPEP can stimulate C2C12 muscle cell differentiation into myotubes and observe the protective effect of mixed plant-extract powder against muscle oxidative stress. In conclusion, MPEP may be useful as a prevention and treatment material for skeletal muscle disease caused by age-related diseases.
Analyzing RNA-Seq Data fromChlamydiawith Super Broad Transcriptomic Activation: Challenges, Solutions, and Implications for Other Systems
Authors: Wan Danny , Cheng Andrew , Wang Yuxuan , Zhong Guangming , Li Wei Vivian , Fan Huizhou
Published: May 2024

Motivation

RNA sequencing (RNA-Seq) offers profound insights into the complex transcriptomes of diverse biological systems. However, standard differential expression analysis pipelines based on DESeq2 and edgeR encounter challenges when applied to the immediate early transcriptomes ofChlamydiaspp., obligate intracellular bacteria. These challenges arise from their reliance on assumptions that do not hold in scenarios characterized by extensive transcriptomic activation and limited repression. Standard analyses using unique chlamydial RNA-Seq reads alone identify nearly 300 upregulated and about 300 downregulated genes, significantly deviating from actual RNA-Seq read trends.

Results

By incorporating both chlamydial and host reads or adjusting for total sequencing depth, the revised normalization methods each detected over 700 upregulated genes and 30 or fewer downregulated genes, closely aligned with observed RNA-Seq data. Further validation through qRT-PCR analysis confirmed the effectiveness of these adjusted approaches in capturing the true extent of transcriptomic activation during the immediate early phase of chlamydial infection. While the strategies employed are developed in the context ofChlamydia, the principles of flexible and context-aware normalization may inform adjustments in other systems with unbalanced gene expression dynamics, such as bacterial spore germination.

Availability and implementation

The code for reproducing the presented bioinformatic analysis is available athttps://zenodo.org/records/11201379.
π-PrimeNovo: An Accurate and Efficient Non-Autoregressive Deep Learning Model for De Novo Peptide Sequencing
Authors: Zhang Xiang , Ling Tianze , Jin Zhi , Xu Sheng , Gao Zhiqiang , Sun Boyan , Qiu Zijie , Dong Nanqing , Wang Guangshuai , Wang Guibin , Li Leyuan , Abdul-Mageed Muhammad , Lakshmanan Laks V.S. , Ouyang Wanli , Chang Cheng , Sun Siqi
Published: May 2024

Peptide sequencing via tandem mass spectrometry (MS/MS) is fundamental in proteomics data analysis, playing a pivotal role in unraveling the complex world of proteins within biological systems. In contrast to conventional database searching methods, deep learning models excel in de novo sequencing peptides absent from existing databases, thereby facilitating the identification and analysis of novel peptide sequences. Current deep learning models for peptide sequencing predominantly use an autoregressive generation approach, where early errors can cascade, largely affecting overall sequence accuracy. And the usage of sequential decoding algorithms such as beam search suffers from the low inference speed. To address this, we introduceπ-PrimeNovo, a non-autoregressive Transformer-based deep learning model designed to perform accurate and efficient de novo peptide sequencing. With the proposed novel architecture,π-PrimeNovo achieves significantly higher accuracy and up to 69x faster sequencing compared to the state-of-the-art methods. This remarkable speed makes it highly suitable for computation-extensive peptide sequencing tasks such as metaproteomic research, whereπ-PrimeNovo efficiently identifies the microbial species-specific peptides. Moreover,π-PrimeNovo has been demonstrated to have a powerful capability in accurately mining phosphopeptides in a non-enriched phosphoproteomic dataset, showing an alternative solution to detect low-abundance post-translational modifications (PTMs). We suggest that this work not only advances the development of peptide sequencing techniques but also introduces a transformative computational model with wide-range implications for biological research.
The Novel Chimeric Multi-Agonist Peptide (GEP44) Reduces Energy Intake and Body Weight in Male and Female Diet-Induced Obese Mice in a Glucagon-Like Peptide-1 Receptor-Dependent Manner
Authors: Blevins James E. , Honeycutt Mackenzie K. , Slattery Jared D. , Goldberg Matvey , Rambousek June R. , Tsui Edison , Dodson Andrew D. , Shelton Kyra A. , Salemeh Therese S. , Elfers Clinton T. , Chichura Kylie S. , Ashlaw Emily F. , Zraika Sakeneh , Doyle Robert P. , Roth Christian L.
Published: May 2024

We recently reported that a novel chimeric peptide (GEP44) targeting both the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- and Y2 receptor (Y1R and Y2R) reduced energy intake and body weight (BW) in diet-induced obese (DIO) rats. We hypothesized that GEP44 reduces energy intake and BW primarily through a GLP-1R dependent mechanism. To test this hypothesis, GLP-1R+/+mice and GLP-1R null (GLP-1R-/-) mice were fed a high fat diet for 4 months to elicit diet-induced obesity prior to undergoing a sequential 3-day vehicle period, 3-day drug treatment (5, 10, 20 or 50 nmol/kg; GEP44 vs the selective GLP-1R agonist, exendin-4) and a 3-day washout. Energy intake, BW, core temperature and activity were measured daily. GEP44 (10, 20 and 50 nmol/kg) reduced BW after 3-day treatment in DIO male GLP-1R+/+mice by - 1.5±0.6, -1.3±0.4 and -1.9±0.4 grams, respectively (P<0.05), with similar effects being observed in female GLP-1R+/+mice. These effects were absent in male and female DIO GLP-1R-/-mice suggesting that GLP-1R signaling contributes to GEP44-elicited reduction of BW. Further, GEP44 decreased energy intake in both male and female DIO GLP-1R+/+mice, but GEP44 appeared to produce more consistent effects across multiple doses in males. In GLP-1R-/-mice, the effects of GEP44 on energy intake were only observed in males and not females, suggesting that GEP44 may reduce energy intake, in part, through a GLP-1R independent mechanism in males. In addition, GEP44 reduced core temperature and activity in both male and female GLP-1R+/+mice suggesting that it may also reduce energy expenditure. Lastly, we show that GEP44 reduced fasting blood glucose in DIO male and female mice through GLP-1R. Together, these findings support the hypothesis that the chimeric peptide, GEP44, reduces energy intake, BW, core temperature, and glucose levels in male and female DIO mice primarily through a GLP-1R dependent mechanism.
Accuracy of dipole source reconstruction in the 3-layer BEM model against the 5-layer BEM-FMM model
Authors: Nuñez Ponasso Guillermo , McSweeney Ryan C. , Wartman William A. , Lai Peiyao , Haueisen Jens , Maess Burkhard , Knösche Thomas R. , Weise Konstantin , Noetscher Gregory M. , Raij Tommi , Makaroff Sergey N.
Published: May 2024

Objective

To compare cortical dipole fitting spatial accuracy between the widely used yet highly simplified 3-layer and modern more realistic 5-layer BEM-FMM models with and withoutadaptive mesh refinement(AMR) methods.

Methods

We generate simulated noiseless 256-channel EEG data from 5-layer (7-compartment) meshes of 15 subjects from the Connectome Young Adult dataset. For each subject, we test four dipole positions, three sets of conductivity values, and two types of head segmentation. We use theboundary element method(BEM) withfast multipole method(FMM) acceleration, with or without (AMR), for forward modeling. Dipole fitting is carried out with the FieldTrip MATLAB toolbox.

Results

The average position error (across all tested dipoles, subjects, and models) is ∼4 mm, with a standard deviation of ∼2 mm. The orientation error is ∼20° on average, with a standard deviation of ∼15°. Without AMR, the numerical inaccuracies produce a larger disagreement between the 3- and 5-layer models, with an average position error of ∼8 mm (6 mm standard deviation), and an orientation error of 28° (28° standard deviation).

Conclusions

The low-resolution 3-layer models provide excellent accuracy in dipole localization. On the other hand, dipole orientation is retrieved less accurately. Therefore, certain applications may require more realistic models for practical source reconstruction. AMR is a critical component for improving the accuracy of forward EEG computations using a high-resolution 5-layer volume conduction model.

Significance

Improving EEG source reconstruction accuracy is important for several clinical applications, including epilepsy and other seizure-inducing conditions.
Millennial-scale societal shifts drive the widespread loss of a marine ecosystem
Authors: Lau Sally C. Y. , Thomas Marine , Williams Jessica M. , Thurstan Ruth H. , Hancock Boze , Russell Bayden D.
Published: May 2024

Degradation of marine ecosystems by human activities is a global problem, with only recent recognition that exploitation of ecosystems over millennia can result in their functional extinction and loss from human memory. To reconstruct the historical distribution of oyster reefs in China, and the context behind loss, we extracted information from archaeological records and historical documents (pre-modern Chinese literature, administration reports, art, maps, newspapers) spanning ∼7600 years, then constrained records with past coastlines and habitable environmental conditions. Oyster reefs were extensively distributed along >750 km of coastline in the Pearl River Delta, and their exploitation underpinned the region’s development into China’s first economic hub in the 6thcentury. Millennial-scale overexploitation alongside societal shifts were central in their regional extirpation by the 19thcentury, but the enduring cultural importance of oysters is maintained by aquaculture expansion. Informed conservation practices can be developed from reconstructing the temporal interplay between human societies and the natural environment.
ZBTB11 Depletion Targets Metabolic Vulnerabilities in K-Ras Inhibitor Resistant PDAC
Authors: Tran Nathan L. , Jiang Jiewei , Ma Min , Gadbois Gillian E. , Gulay Kevin C. M. , Verano Alyssa , Zhou Haowen , Huang Chun-Teng , Scott David A. , Bang Anne G. , Tiriac Herve , Lowy Andrew M. , Wang Eric S. , Ferguson Fleur M.
Published: May 2024

Over 95% of pancreatic ductal adenocarcinomas (PDAC) harbor oncogenic mutations in K-Ras. Upon treatment with K-Ras inhibitors, PDAC cancer cells undergo metabolic reprogramming towards an oxidative phosphorylation-dependent, drug-resistant state. However, direct inhibition of complex I is poorly tolerated in patients due to on-target induction of peripheral neuropathy. In this work, we develop molecular glue degraders against ZBTB11, a C2H2zinc finger transcription factor that regulates the nuclear transcription of components of the mitoribosome and electron transport chain. Our ZBTB11 degraders leverage the differences in demand for biogenesis of mitochondrial components between human neurons and rapidly-dividing pancreatic cancer cells, to selectively target the K-Ras inhibitor resistant state in PDAC. Combination treatment of both K-Ras inhibitor-resistant cell lines and multidrug resistant patient-derived organoids resulted in superior anti-cancer activity compared to single agent treatment, while sparing hiPSC-derived neurons. Proteomic and stable isotope tracing studies revealed mitoribosome depletion and impairment of the TCA cycle as key events that mediate this response. Together, this work validates ZBTB11 as a vulnerability in K-Ras inhibitor-resistant PDAC and provides a suite of molecular glue degrader tool compounds to investigate its function.
Cell surface RNA expression modulates alveolar epithelial function
Authors: Abledu Jubilant Kwame , Herbst Christopher J. , Brandt Raphael , Kocak Alen , Ghosh Pritam , Gorenflos López Jacob L. , Diestelhorst Kevin , Block Stephan , Hackenberger Christian , Seitz Oliver , Lopez-Rodriguez Elena , Ochs Matthias , Kuebler Wolfgang M.
Published: May 2024

Glycosylated RNA (glycoRNA) has recently emerged as a novel constituent of the glycocalyx on cell surfaces, yet its biological functions remain largely unexplored. In this report, we present the first analysis of glycoRNA expression and functionality in alveolar epithelial cells.

To this end, we optimized new techniques for the detection of glycoRNA on living cell surfaces and in cell membrane-associated RNA samples through in-gel imaging after labeling with fluorescent dye conjugates. Specifically, we used conjugation of Cy5-hydrazide following mild oxidation with sodium periodate for detection of the entire cell surface sialoglycoRNA pool. Conjugation of dibenzocyclooctyne-sulfo-Cy5 (DBCO-Sulfo-Cy5) in cells fed with tetraacetylatedN-azidoacetyl-mannosamine (Ac4ManNAz) or 6-azido-L-fucose (FucAz) detectedde novoformed sialoglycoRNA or fucoglycoRNA. Finally, biotinylated lectins in combination with infrared dye-conjugated streptavidin was used to differentiate between specific glycosidic linkages.

Comparisons across primary alveolar epithelial cells and different alveolar-epithelial like cell lines revealed a cell-type specific variation in glycoRNA abundance. Treatment of primary alveolar epithelial cells with an RNAse cocktail reduced epithelial surface glycoRNA and was associated with a reduction in trans-epithelial electrical resistance and influenza A viral particle abundance.

As such, the present work identifies glycoRNA as a novel component of the alveolar epithelial glycocalyx, suggesting its potential relevance in epithelial barrier regulation and viral infection.
Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain
Authors: Zhang Chi , Huang Qian , Ford Neil C. , Limjunyawong Nathachit , Lin Qing , Yang Fei , Cui Xiang , Uniyal Ankit , Liu Jing , Mahabole Megha , He Hua , Wang Xue-Wei , Duff Irina , Wang Yiru , Wan Jieru , Zhu Guangwu , Raja Srinivasa N , Jia Hongpeng , Yang Dazhi , Dong Xinzhong , Cao Xu , Tseng Scheffer C. , He Shao-Qiu , Guan Yun
Published: May 2024

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain. Moreover, we unravel the underlying mechanisms of pain inhibition induced by FLO and HC-HA/PTX3.
Analyzing Performance of Twist Bioscience Exome Enrichment with Spike-in CNV Backbone Panels at Various Probe Densities Leveraging Golden Helix VS-CNV Analysis Software
Authors: Fortier Nathan , Rudy Gabe , Han Tina , Davassi Alessandro , Scherer Andreas
Published: May 2024

Clinical Whole Exome Sequencing (WES) offers a high diagnostic yield test by detecting pathogenic variants in all coding genes of the human genome. WES is poised to consolidate multiple genetic tests by accurately identifying Copy Number Variation (CNV) events, typically necessitating microarray analysis. However, standard commercial exome kits are typically limited to targeting exon coding regions, leaving significant gaps in coverage between genes, which could hinder comprehensive CNV detection. To convert microarray CNV calling with NGS, advances in both assay design and computational methods are needed.

Addressing the need for comprehensive coverage, Twist Bioscience has developed an enhanced Exome 2.0 Plus Comprehensive Exome Spike-in panel with added CNV “backbone” probes. These probes target common SNPs polymorphic in multiple populations and are evenly distributed in the intergenic and intronic regions, with three varying densities at 25 kb, 50 kb, and 100 kb intervals from highest to lowest resolution respectively. Concurrently, Golden Helix has developed a multi-modal CNV caller designed specifically for target-capture NGS data to detect single-exon to whole-chromosome aneuploidy CNV events. This study evaluates the combined efficacy of the backbone-probe enhanced exome capture kit and VS-CNV 2.6 in identifying known CNVs using the Coriell CNVPANEL01 reference set.

The integration of the enhanced capture kit with VS-CNV 2.6 achieved a 100% sensitivity rate for the detection of known CNV events at all three probe densities. The application of best-practice quality metrics, annotations, and filters was shown to have a minimal impact on this high sensitivity. These findings underscore the potential of the augmented Twist Exome in tandem with the VS-CNV caller and VarSeq’s annotation and filtering capabilities. This combination presents a promising alternative to conventional microarray assays, potentially consolidating WES and CNV into a single assay obviating the need for additional testing in clinical CNV detection. The study’s results advocate for the implementation of this integrated approach as a more efficient and equally sensitive method for CNV analysis in a clinical setting.
GluN2B-mediated regulation of silent synapses for receptor specification and addiction memory
Authors: Kim Hyun Jin , Lee Sangjun , Kim Gyu Hyun , Sung Kibong , Yoo Taesik , Pyo Jung Hyun , Jo Hee-Jung , Lee Sanghyeon , Lee Hyun-Young , Jung Jung Hoon , Lee Kea Joo , Kim Joung-Hun
Published: May 2024

Psycho-stimulants including cocaine elicit stereotyped, addictive behaviors. Re-emergence of silent synapses containing only NMDA-type glutamate receptors (NMDARs) is a critical mediator of addiction memory and seeking behaviors. Despite the predominant abundance of GluN2B-containing NMDARs in silent synapses, their operational mechanisms are not fully understood. Using conditional depletion/deletion of GluN2B at D1-expressing accumbal medium spiny neurons, we examine the synaptic and behavioral actions that silent synapses incur after repeated exposure to cocaine. GluN2B ablation reduces the proportion of silent synapses, but some of them can persist by substitution to GluN2C, which drives the aberrantly-facilitated synaptic incorporation of calcium-impermeable AMPA-type glutamate receptors (AMPARs). The resultant precocious maturation of silent synapses impairs addiction memory but elevates locomotor activity, which can be normalized by blockade of calcium-impermeable AMPAR trafficking. Collectively, GluN2B supports the competence of cocaine-induced silent synapses for specifying subunit composition of AMPARs, and thereby expression of addition memory and the related behaviors.
SARS-CoV-2 transmission dynamics in Mozambique and Zimbabwe during the First Three Years of the Pandemic
Authors: Kaondera-Shava Roselyn F , Galanti Marta , Perini Matteo , Suh Jiyeon , Farley Shannon M , Chicumbe Sergio , Jani Ilesh , Cassy Annette , Macicame Ivalda , Manafe Naisa , El-Sadr Wafaa , Shaman Jeffrey
Published: May 2024

The 2019 emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid spread created a public health emergency of international concern. However, the impact of the pandemic in Sub-Saharan Africa, as documented in cases, hospitalizations and deaths, appears far lower than in the Americas, Europe, and Asia. Characterization of the transmission dynamics is critical for understanding how SARS-CoV-2 spread and the true scale of the pandemic. Here, to better understand SARS-CoV-2 transmission dynamics in two southern African countries, Mozambique and Zimbabwe, we developed a dynamic model-Bayesian inference system to estimate key epidemiologic parameters, namely the transmission and ascertainment rates. Total infection burdens (reported and unreported) during the first three years of the pandemic were reconstructed using a model-inference approach. Transmission rates rose with each successive wave, which aligns with observations in other continents. Ascertainment rates were found to be low matching prior assumption and consistent with other African countries. Overall, the estimated disease burden was higher than the documented cases, indicating need for improved reporting and surveillance. These findings aid understanding of COVID-19 disease and respiratory virus transmission dynamics in two African countries little investigated to date, and can help guide future public health planning and control strategies.
Rapid screening and identification of genes involved in bacterial extracellular membrane vesicle production using a curvature-sensing peptide
Authors: Inoue Hiromu , Kawano Kenichi , Kawamoto Jun , Ogawa Takuya , Kurihara Tatsuo
Published: May 2024

Bacteria secrete extracellular membrane vesicles (EMVs). Physiology and biotechnological applications of these lipid nanoparticles have been attracting significant attention. However, the molecular basis of EMV biogenesis has not yet been fully elucidated. In the previous research, an N-terminus-substituted FAAV peptide labeled with NBD (nFAAV5-NBD) was developed, which can sense a curvature of a lipid bilayer and selectively bind to EMVs in the presence of the cells. Herein, we applied nFAAV5-NBD to a screening of hyper- and hypo-vesiculation transposon mutants of a Gram-negative bacterium,Shewanella vesiculosaHM13, to identify the genes involved in EMV production. As a result, for 16 and six genes, we found that transposon insertion within or near the gene caused hyper- and hypo-vesiculation, respectively. Targeted gene-disrupted mutants of the identified genes demonstrated that the lack of putative dipeptidyl carboxypeptidase, glutamate synthase β-subunit, LapG protease, metallohydrolase, RNA polymerase sigma-54 factor, inactive transglutaminase, PepSY domain-containing protein, and Rhs-family protein caused EMV overproduction. On the other hand, disruption of the genes encoding putative phosphoenolpyruvate synthase, D-hexose-6-phosphate epimerase, NAD-specific glutamate dehydrogenase, and sensory box histidine kinase/response regulator decreased EMV production. This study shows the utility of a novel screening method using a curvature-sensing peptide and fundamental information on the genes related to EMV production.

IMPORTANCE

Conventional methods for isolation and quantification of EMVs are generally time-consuming. nFAAV5-NBD can detect EMVs in the culture without separating EMVs from cells.In situdetection of EMVs using this peptide facilitated screening of the genes related to EMV production. We succeeded in identifying a number of genes involved in the EMV production ofS. vesiculosaHM13, and the strains obtained in this study would contribute to the elucidation of bacterial EMV formation mechanisms. Additionally, the hyper-vesiculating mutants obtained in this study would be useful in the application of this bacterium, such as in the production of useful substances as cargoes of EMVs and in the production of surface-engineered vesicles.
MECOM promotes leukemia progression and inhibits mast cell differentiation through functional competition with GATA2
Authors: Iida Kohei , Nakanishi Mayuko , Nakahara Jakushin , Asada Shuhei , Isobe Tomoya , Yabushita Tomohiro , Ozawa Manabu , Yamada Yasuhiro , Kitamura Toshio , Yamamoto Keita , Goyama Susumu
Published: May 2024

MECOM is a nuclear transcription factor essential for the proliferation of hematopoietic stem cells (HSCs) and myeloid leukemia cells. MECOM contains N- and C-terminal zinc finger domains (ZFDs) and binding motifs for the corepressor CtBP to regulate gene expression. Recent studies have shown that germlineMECOMvariants are associated with thrombocytopenia, radioulnar synostosis, and bone marrow failure, collectively termed MECOM-associated syndromes. Although the mutations are clustered in the C-terminal ZFD, how these mutations affect MECOM function has remained unclear. In addition, the individual genes and pathways regulated by MECOM are less well understood. In this study, we showed that the C-terminal ZFD is a major DNA-binding domain of MECOM and that the disease-associated mutations abolish the DNA-binding ability. We also found that MECOM functionally antagonizes GATA2 through the C-terminal ZFD-mediated DNA binding and CtBP interaction, thereby promoting myeloid leukemogenesis while inhibiting mast cell differentiation. Furthermore, we generated mutant MECOM knockin mice harboring a C-terminal ZFD mutation that recapitulate several features of MECOM-associated syndromes, including HSC and B-cell reduction. Our study demonstrates that C-terminal ZFD mutations are loss-of-function mutations with reduced DNA-binding ability, reveals the critical role of MECOM in inhibiting GATA2, and provides a novel mouse model for MECOM-associated syndromes.
Targeted anticancer pre-vinylsulfone covalent inhibitors of carbonic anhydrase IX
Authors: Vaškevičius Aivaras , Baronas Denis , Leitans Janis , Kvietkauskaitė Agnė , Rukšėnaitė Audronė , Manakova Elena , Toleikis Zigmantas , Kaupinis Algirdas , Kazaks Andris , Gedgaudas Marius , Mickevičiūtė Aurelija , Juozapaitienė Vaida , Schiöth Helgi B , Jaudzems Kristaps , Valius Mindaugas , Tars Kaspars , Gražulis Saulius , Meyer-Almes Franz-Josef , Matulienė Jurgita , Zubrienė Asta , Dudutienė Virginija , Matulis Daumantas
Published: May 2024

We designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: 1) primary sulfonamide group recognizing carbonic anhydrases (CA), 2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and 3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein followed by complete irreversible inactivation of the protein via covalent modification. Our designed prodrug candidates bearing moderately active pre-vinyl sulfone esters or weakly active carbamates optimized for mild covalent modification activity to avoid toxic non-specific modifications and selectively target CAIX. The lead inhibitors reached 2 pM affinity, highest among known CAIX inhibitors. The strategy could be used for any disease drug target protein bearing a His residue in the vicinity of the active site.
The buoyancy of cryptococcal cells and its implications for transport and persistence ofCryptococcusin aqueous environments
Authors: Jimenez Isabel A. , Stempinski Piotr R. , Dragotakes Quigly , Greengo Seth D. , Sanchez Ramirez Lia , Casadevall Arturo
Published: May 2024

Cryptococcusis a genus of saprophytic fungi with global distribution. Two species complexes,C. neoformansandC. gattii, pose health risks to humans and animals. Cryptococcal infections result from inhalation of aerosolized spores and/or desiccated yeasts from terrestrial reservoirs such as soil, trees, and avian guano. More recently,C. gattiihas been implicated in infections in marine mammals, suggesting that inhalation of liquid droplets or aerosols from the air-water interface is also an important, yet understudied, mode of respiratory exposure. Water transport has also been suggested to play a role in the spread ofC. gattiifrom tropical to temperate environments. However, the dynamics of fungal survival, persistence, and transport via water have not been fully studied. The size of the cryptococcal capsule was previously shown to reduce cell density and increase buoyancy. Here, we demonstrate that cell buoyancy is also impacted by the salinity of the media in which cells are suspended, with formation of a halocline interface significantly slowing the rate of settling of cryptococcal cells through water, resulting in persistence ofC. neoformanswithin 1 cm of the air-water interface for over 60 min andC. gattiifor 4-6 h. Our data also showed that during culture in yeast peptone dextrose media (YPD), polysaccharide accumulating in the supernatant formed a raft that augmented buoyancy and further slowed settling of cryptococcal cells. These findings illustrate new mechanisms by which cryptococcal cells may persist in aquatic environments, with important implications for aqueous transport and pathogen exposure.

Importance

Cryptococcosis is a major fungal disease leading to morbidity and mortality worldwide.C. neoformansis a major fungal species of public health concern, causing opportunistic systemic infections in immunocompromised patients.C. gattiiwas traditionally a tropical pathogen, but in the 1990s emerged in the temperate climates of British Columbia and the Pacific Northwest United States. Outbreaks in these areas also led to the first host record of cryptococcosis in free-ranging cetaceans.C. gattiiis particularly concerning as an emerging fungal pathogen due to its capacity to cause clinical disease in immunocompetent patients, its recent spread to a new ecological niche, and its higher resistance to antifungal therapies. Our research defines characteristics that influence transport of cryptococci through water and its persistence at the air-water interface, which improve our understanding of mechanisms for cryptococcal aqueous transport and persistence.
Landscape of Evolutionary Arms Races between Transposable Elements and KRAB-ZFP Family
Authors: Kosuge Masato , Ito Jumpei , Hamada Michiaki
Published: May 2024

Transposable elements (TEs) are mobile parasitic sequences that have expanded within the host genome. It has been hypothesized that host organisms have expanded the Krüppel-associated box-containing zinc finger proteins (KRAB-ZFPs), which epigenetically suppress TEs, to counteract disorderly TE transpositions. This process is referred to as the evolutionary arms race. However, the extent to which this evolutionary arms race occurred across various TE families remains unclear. In the present study, we systematically explored the evolutionary arms race between TE families and KRAB-ZFPs using public ChIP-seq data. We discovered and characterized new instances of evolutionary arms races with KRAB-ZFPs in endogenous retroviruses. Furthermore, we found that the regulatory landscape shaped by this arms race contributed to the gene regulatory network. In summary, our results provide insight into the impact of the evolutionary arms race on TE families, the KRAB-ZFP family, and host gene regulatory networks.
Genomic analyses inDrosophilado not support the classic allopatric model of speciation
Authors: Yusuf Leeban H. , Laetsch Dominik R. , Lohse Konrad , Ritchie Michael G.
Published: May 2024

The allopatric model of speciation has dominated our understanding of speciation biology and biogeography since the Modern Synthesis. It is uncontroversial because the cessation of gene flow during allopatry will allow reproductive isolation to readily emerge as a by-product of evolutionary divergence. However, whether allopatric speciation is common has rarely been systematically tested across a continuum of closely-related species. Here, we fit a range of demographic models of evolutionary divergence to whole-genome sequence data from 93 pairs ofDrosophilaspecies to infer speciation histories and levels of post-divergence gene flow. We find that speciation with gene flow is common, even between currently allopatric pairs of species. Estimates of historical gene flow are not predicted by current range overlap, nor is there convincing support that secondary contact commonly leads to the cessation of gene flow as predicted by models of reinforcement. Instead, our analyses suggest that most speciation processes involve some long-term gene flow perhaps due to repeated cycles of allopatry and contact, without requiring an extensive allopatric phase.
Single cell RNA-sequencing of feline peripheral immune cells with V(D)J repertoire and cross species analysis of T lymphocytes
Authors: Ramarapu Raneesh , Wulcan Judit M. , Chang Haiyang , Moore Peter F. , Vernau William , Keller Stefan M.
Published: May 2024

Introduction

The domestic cat (Felis catus) is a valued companion animal and a model for virally induced cancers and immunodeficiencies. However, species-specific limitations such as a scarcity of immune cell markers constrain our ability to resolve immune cell subsets at sufficient detail. The goal of this study was to characterize circulating feline T cells and other leukocytes based on their transcriptomic landscape and T-cell receptor repertoire using single cell RNA-sequencing.

Methods

Peripheral blood from 4 healthy cats was enriched for T cells by flow cytometry cell sorting using a mouse anti-feline CD5 monoclonal antibody. Libraries for whole transcriptome, alpha/beta T cell receptor transcripts and gamma/delta T cell receptor transcripts were constructed using the 10x Genomics Chromium Next GEM Single Cell 5’ reagent kit and the Chromium Single Cell V(D)J Enrichment Kit with custom reverse primers for the feline orthologs.

Results

Unsupervised clustering of whole transcriptome data revealed 7 major cell populations - T cells, neutrophils, monocytic cells, B cells, plasmacytoid dendritic cells, mast cells and platelets. Sub cluster analysis of T cells resolved naive (CD4+ and CD8+), CD4+ effector T cells, CD8+ cytotoxic T cells and gamma/delta T cells. Cross species analysis revealed a high conservation of T cell subsets along an effector gradient with equitable representation of veterinary species (horse, dog, pig) and humans with the cat. Our V(D)J repertoire analysis demonstrated a skewed T-cell receptor alpha gene usage and a restricted T-cell receptor gamma junctional length in CD8+ cytotoxic T cells compared to other alpha/beta T cell subsets. Among myeloid cells, we resolved three clusters of classical monocytes with polarization into pro- and anti-inflammatory phenotypes in addition to a cluster of conventional dendritic cells. Lastly, our neutrophil sub clustering revealed a larger mature neutrophil cluster and a smaller exhausted/activated cluster.

Discussion

Our study is the first to characterize subsets of circulating T cells utilizing an integrative approach of single cell RNA-sequencing, V(D)J repertoire analysis and cross species analysis. In addition, we characterize the transcriptome of several myeloid cell subsets and demonstrate immune cell relatedness across different species.
SCIITensor: A tensor decomposition based algorithm to construct actionable TME modules with spatially resolved intercellular communications
Authors: Huang Huaqiang , Liu Chuandong , Liu Xin , Tian Jingyi , Xi Feng , Li Mei , Li Guibo , Chen Ao , Xu Xun , Liao Sha , Zhang Jiajun , Liu Xing
Published: May 2024

Advanced spatial transcriptomics (ST) technology has paved the way for elucidating the spatial architecture of the tumor microenvironment (TME) from multiple perspectives. However, available tools only focus on the static molecular and cellular composition of the TME when analyzing the high-throughput ST data, neglecting to uncover the in-depth spatial co-variation of intercellular communications arising from heterogeneous spatial TMEs. Here, we introduce SCIITensor, which decomposes TME modules from the perspective of spatially resolved intercellular communication by spatially quantifying the cellular and molecular interaction intensities between proximal cells within each domain. It then constructs a three-dimensional matrix, formulating the task as a matrix decomposition problem, and identifies biologically relevant spatial interactions and TME patterns using Non-Negative Tucker Decomposition (NTD). We evaluated the performance of SCIITensor on liver cancer datasets obtained from multiple ST platforms. At the research setting of a single-sample investigation, SCIITensor precisely identified a functional TME module indicating a tumor boundary structure specific domain with co-variant interaction contexts, which were involved in construction of immunosuppressive TME. Moreover, we also proved that SCIITensor was able to construct TME meta-modules across multiple samples and to further identify an immune-infiltration associated and sample-common meta-module. We demonstrate that SCIITensor is applicable for dissecting TME modules from a new perspective by constructing spatial interaction contexts using ST datasets of individual and multiple samples, providing new insights into tumor research and potential therapeutic targets.
Effect of the charge asymmetry and orbital angular momentum in the entrance channel on the hindrance to complete fusion
Authors: Khusanov Elzod , Nasirov Avazbek , Nishonov Mukhtorali
Published: May 2024

The hindrance to complete fusion is studied as a function of the charge asymmetry of colliding nuclei and orbital angular momentum of the collision. The formation and evolution of a dinuclear system (DNS) in the heavy-ion collisions at energies near the Coulomb barrier is calculated in the framework of the DNS model. The DNS evolution is considered as nucleon transfer between its fragments. The results prove that a hindrance at formation of a compound nucleus (CN) is related with the quasifission process, which is breakup of the DNS into products instead to reach the equilibrated state of the CN. The role of the angular momentum in the charge (mass) distribution of the reaction products for the given mass asymmetry of the colliding nuclei has been demonstrated. The results of this work have been compared with the measured data for the quasifission yields in the C12+Pb204 and Ca48+Er168 reactions to show the role of the mass asymmetry of the entrance channel.

Published by the American Physical Society
2024