bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frontal theta power prospectively associated with response inhibition
Authors: van Rooij Daan , van Bijnen Sam , Schutte Iris , van der Stoep Nathan , Kenemans J. Leon 
Published: May 2024

AbstractA proactive mechanism has been postulated to promote successful inhibition (Kenemans, 2015). Specifically, this mechanism is thought to operate before any action demanding or countermanding event has occurred. In the current study, we investigated whether EEG theta power could reflect this mechanism, in a sample of healthy individuals performing a stop-signal paradigm. By comparing frontal theta power preceding failed versus successful stop trials, we tested whether frontal theta is predictive of inhibition success. We hypothesized that proactive cognitive control manifests in frontal theta power preceding a countermanding go-stop event. Our results demonstrate that frontal theta is indeed higher preceding successful as compared to preceding failed stopping events. We also show that frontal theta power preceding stopping events is associated with Stop-Signal Reaction Times (SSRT), with a higher theta being indicative of shorter SSRTs. This association was not present for go-RT. This study may be the first to reveal a relationship between lower frontal theta power and subsequent stopping failure, suggesting theta’s role in proactive response inhibition.
Adjuvanted subunit intranasal vaccine prevents SARS-CoV-2 onward transmission in hamsters
Authors: Sui Yongjun , Kar Swagata , Chawla Bhavna , Hoang Tanya , Yu YuanKai , Wallace Shannon M. , Andersen Hanne , Berzofsky Jay A. 
Published: May 2024

AbstractMost COVID-19 vaccine trials have focused on recipient protection, not protection of their contacts, a critical need. As a subunit intranasal COVID-19 vaccine reduced nasopharyngeal virus more than did an intramuscular (IM) vaccine, we hypothesized that this vaccine might reduce onward transmission to others. We vaccinated hamsters with either the IM-administrated Moderna mRNA vaccine twice or one dose of mRNA IM followed by adjuvanted subunit intranasal vaccine. 24 hours after SARS-CoV-2 challenge, these animals were housed with naïve recipients in a contactless chamber that allows airborne transmission. Onward airborne transmission was profoundly blocked: the donor and recipients of the intranasal vaccine-boosted group had lower oral and lung viral loads (VL), which correlated with mucosal ACE2 inhibition activity. These data strongly support the use of the intranasal vaccine as a boost to protect not only the vaccinated person, but also people exposed to the vaccinated person, a key public health goal.Author summaryNatural transmission of SARS-CoV-2 is primarily airborne, through the respiratory mucosal route. However, current licensed COVID-19 vaccines are all intramuscular and induce more systemic than mucosal immunity. Here, we did a head-to-head comparison of COVID-19 booster vaccines on SARS-CoV-2 onward transmission. We found that compared to boosting with a Moderna mRNA systemic vaccine, a nanoparticle intranasal COVID-19 vaccine much more effectively prevents onward airborne transmission to naïve recipient hamsters. The protection was correlated with local mucosal antibody. Thus, a mucosal nanoparticle vaccine should be considered for preventing onward airborne transmission, a key public health necessity that has not been adequately studied.
AFFIPred: AlphaFold2 Structure-based Functional Impact Prediction of Missense Variations
Authors: Pir Mustafa Samet , Timucin Emel 
Published: May 2024

AbstractStructural information holds immense potential for pathogenicity prediction of missense variations, albeit structure-based pathogenicity classifiers are limited compared to their sequence-based counterparts due to the well-known gap between sequence and structure data. Leveraging the highly accurate protein structure prediction method, AlphaFold2 (AF2), we introduce AFFIPred, an ensemble machine learning classifier that combines established sequence and AF2-based structural characteristics to predict disease-causing missense variant pathogenicity. Based on the assessments on unseen datasets, AFFIPred reached a comparable level of performance with the state-of-the-art predictors such as AlphaMissense and Rhapsody. We also showed that the recruitment of AF2 structures that are full-length and represent the unbound states ensures more precise SASA calculations compared to the recruitment of experimental structures. Second, in line with the the completeness of the AF2 structures, their use provide a more comprehensive view of the structural characteristics of the missense variation datasets by capturing all variants. AFFIPred maintains high-level accuracy without the well-known limitations of structure-based pathogenicity classifiers, paving the way for the development of more sophisticated structure-based methods without PDB dependence. AFFIPred has predicted over 210 million variations of the human proteome, which are accessible athttps://affipred.timucinlab.com/.
Nerve injury converts Schwann cells in a persisting repair state in human neuroma tissue
Authors: Deininger Stefanie , Schumacher Jakob , Blechschmidt Anna , Song Jialei , Klugmann Claudia , Antoniadis Gregor , Pedro Maria , Knöll Bernd , Meyer zu Reckendorf Sofia 
Published: May 2024

AbstractPeripheral nerve injury (PNI) induces neuroma formation at the severed nerve stump resulting in impaired nerve regeneration and functional recovery in patients. So far, molecular mechanisms and cell types present in the neuroma impeding on regeneration have only sparsely been analyzed. Herein we compare resected human neuroma tissue with intact donor nerves from the same patient. Neuroma from several post-injury timepoints (1-13 months) were included, thereby allowing for temporal correlation with molecular and cellular processes. We observed reduced axonal area and percentage of myelin producing Schwann cells (SCs) compared to intact nerves. However, total SOX10 positive SC numbers were comparable. Notably, markers for SCs in a repair mode including c-JUN and SHH (sonic hedgehog) and SC proliferation (pH3) were upregulated in neuroma, suggesting presence of SCs in repair rather than differentiated status. In agreement, in neuroma, pro-regenerative markers such as phosphorylated i.e. activated CREB (pCREB), ATF3, GAP43 and SCG10 were upregulated. Neuroma tissue was infiltrated by several types of macrophages. Finally, when taken in culture, neuroma SCs were indistinguishable from controls SCs with regard to proliferation and morphology. However, cultured neuroma SCs retained a different molecular signature from control SCs including increased inflammation and reduced gene expression for differentiation markers such as myelin genes.In summary, human neuroma tissue consists of SCs with a repair status and is infiltrated strongly by several types of macrophages.
Interdependence between SEB-3 and NLP-49 peptides shifts across predator-induced defensive behavioral modes inCaenorhabditis elegans
Authors: Quach Kathleen T , Hughes Gillian A , Chalasani Sreekanth H 
Published: May 2024

AbstractPrey must balance the need to avoid predators with the need to feed, a dilemma central to prey refuge theory. Additionally, prey must also assess predatory imminence, or how close predator threats are in space and time. Predatory imminence theory classifies defensive behaviors into three defense modes—pre-encounter, post-encounter, and circa-strike—each corresponding to increasing levels of predatory imminence—suspecting a predator, detecting a predator, and contact with a predatory attack. Although prey often simultaneously face variations in predatory imminence and spatial distribution of predation risks, research on how these factors intersect to influence defensive behaviors has been limited. Integrating these factors into a complex, naturalistic environment could enable comprehensive analysis of multiple defense modes in consistent conditions within the same study, unlike laboratory tests designed to examine only one mode at a time. Here, we combine prey refuge and predatory imminence theories to develop a model system of nematode defensive behaviors, withCaenorhabditis elegansas prey andPristionchus pacificusas predator. We show thatC. elegansinnately exhibits circa-strike behaviors in a foraging environment comprised of a food-rich, high-risk patch and a food-poor, predator-free refuge. However, after extended experience in this environment,C. elegansacquires post- and pre-encounter behaviors that proactively anticipate threats rather than merely reacting to attacks. We also demonstrate that these defense modes are potentiated by increasingly harmful predators, with only life-threatening predators capable of eliciting all three defense modes. Finally, our model system reveals that SEB-3 receptors and NLP-49 peptides, key to stress response regulation, vary in their impact and interdependence across defense modes. We find that SEB-3 has a greater impact on the highest-imminence defense mode, while NLP-49 peptides have a stronger effect on the lowest-imminence defense mode. Overall, our model system reveals detailed and comprehensive insights into how stress-related molecular signaling affects behavioral responses to threats.
Replay without sharp wave ripples in a spatial memory task
Authors: Widloski John , Foster David J. 
Published: May 2024

SUMMARYSharp-wave ripples in the hippocampus are believed to be a fundamental mechanism for the consolidation of episodic memories. During ripples, hippocampal neurons are re-activated in sequences called replay, which have been hypothesized to reflect episodic memory content. Ripples and replay are usually reported to co-occur, and are commonly thought to reflect the same process. Here we report that, in rats performing an open field spatial memory task, replays readily occur in the complete absence of ripples. Moreover, the occurrence of ripple-less and ripple-containing replays is not random, but precisely organized in terms of virtual space: Ripples are confined to “ripple fields”, which are spatially-restricted areas defined over the virtual locations depicted during replay and independent of the actual location of the animal. Similar to allocentric coding by place fields, ripple fields are independent of the direction of travel, and stable throughout the recording session. Ripple fields track changes to environmental structure caused by the addition or subtraction of barriers to movement, consistent with ripples conveying information about the incorporation of novel experiences. Moreover, ripple fields were matched across different rats experiencing the same barrier configuration, highlighting the robustness of the ripple field spatial code. We hypothesize a new relationship between ripples and replay, in which a subset of replays that is particularly relevant to learning or novelty is paired with ripples, in order to promote its selective broadcast to the rest of the brain for consolidation.
Cortical Dynamics during Contour Integration
Authors: He Dongcheng , Yang Angeline , Coates Daniel R. , Ogmen Haluk , Chung Susana TL 
Published: May 2024

AbstractIntegrating visual elements into contours is important for object recognition. Previous studies emphasized the role that the primary visual cortex (V1) plays in this process. However, recent evidence suggests that contour integration relies on the coordination of hierarchical substrates of cortical regions through recurrent connections. Many previous studies presented the contour at the same onset-time as the trial, which caused the subsequent neural imaging data to incorporate both visual evocation and contour integration activities, and thus confounding the two. In this study, we varied both the contour onset-time and contour fidelity and used EEG to examine the cortical activities under these conditions. Our results suggest that the temporal N300 represents the grouping and integration of visual elements into contours. Before this signature, we observed interhemispheric connections between lateral frontal and posterior parietal regions that were contingent on the contour location and peaked at around 150ms after contour appearance. Also, the magnitudes of connections between medial frontal and superior parietal regions were dependent on the timing of contour onset and peaked at around 250ms after contour onset. These activities appear to be related to the bottom-up and top-down attentional processing during contour integration, respectively, and shed light on how these processes cooperate dynamically during contour integration.
Phylogenetic study of local patterns influenza A(H3N2) virus transmission in a semi-isolated population in a remote island in Japan between 2011-2013
Authors: Han Su Myat , Shiino Teiichiro , Masuda Shingo , Furuse Yuki , Yasaka Takahiro , Kanda Satoshi , Komori Kazuhiri , Saito Nobuo , Kubo Yoshiano , Smith Chris , Endo Akira , Robert Alexis , Baguelin Marc , Ariyoshi Koya 
Published: May 2024

AbstractBackgroundThe spatial spread and importation risk of influenza A viruses in rural settings remains unclear due to the sparsity of representative spatiotemporal sequence data.MethodsNasopharyngeal (NPS) samples of Rapid Influenza Diagnostic Test (RIDT) positive individuals in Kamigoto Island, Japan, were confirmed using quantitative polymerase chain reaction (RT-PCR). The confirmed influenza A positive samples were processed for whole- genome sequencing. Time-resolved phylogenetic trees were built from HA sequences to classify the circulating clades, with events of introductions and local clustering. Spatio-temporal transmission patterns were then analyzed for the largest local clusters.ResultsWe obtained 178 whole-genome sequences of influenza A/H3N2 collected during 2011/12 and 2012/13 influenza seasons. The time-resolved phylogenetic tree identified at least six independent introduction events in 2011/12 and 2012/13. Majority of Kamigoto strains are closely related to strains from mainland Japan. All 2011/12 strains were identified as clade 3 C.2 (n=29), while 2012/13 strains fell into two clades: clade 3C.2 (n=129), and 3C.3a (n=20). No local persistence over one year was observed for Kamigoto strains. The spatio-temporal analysis of the largest cluster revealed that the first case and a large number of cases came from the busiest district of the island and spread towards the other parts of the island.ConclusionInfluenza A(H3N2) virus outbreaks in Kamigoto island were marked by multiple introductions and fueled by local transmission. All the identified clusters in 2012/13 season circulate simultaneously. These cases may be misinterpreted as part of the same cluster without sequencing data, highlighting the importance of genomic surveillance. The results of this study are based on a two-year analysis of influenza sequences from the island; repeated analyzes for different influenza seasons and geographic locations will help us better understand detailed transmission patterns.
Variability in mineral composition of Canadian lentil cultivars
Authors: Vargas Ana , Podder Rajib , Subedi Maya , Bett Kirstin E. , Vandenberg Albert 
Published: May 2024

ABSTRACTLentils are a good source of essential minerals for the proper functioning of the human body. We evaluated 34 cultivars and elite lentil lines representing the breadth of the Canadian breeding program. Trials were established in 10 site-years across Saskatchewan Province. Concentrations of 27 minerals were quantified with an inductive coupled argon plasma emission spectrometer in whole and dehulled lentil seeds. Li, V, Cr, Co, As, Ag, Cd, Sn, La, Hg, and Pb had concentrations below the quantification limit and were excluded from further analysis. The effects of site year, tissue type (whole and dehulled), and lentil genotypes were analyzed using a mixed model. Mineral concentrations of Na, K, Ca, Mg, Cu, B, and Ba were stable across site years. Na, Zn, P, Cu, Se, and Mo had similar concentrations in whole and dehulled seeds. Ca, Fe, Mg, Mn, B, Al, and Ba were more concentrated in whole seeds, while K, S, and Ni were higher in dehulled seeds. Several lentil genotypes had outstanding concentrations of several minerals. Lentil genotypes with a higher composition of several minerals could be a starting point for enhancing mineral composition in lentils.
Dietary preservatives alter the gut microbiotain vitroandin vivowith sex-specific consequences for host metabolic development
Authors: Schell Laura D. , Chadaideh Katia S. , Allen-Blevins Cary R. , Venable Emily M. , Carmody Rachel N. 
Published: May 2024

ABSTRACTAntibiotics in early life can promote adiposity via interactions with the gut microbiota. However, antibiotics represent only one possible route of antimicrobial exposure. Dietary preservatives exhibit antimicrobial activity, contain chemical structures accessible to microbial enzymes, and alter environmental conditions favoring specific microbial taxa. Therefore, preservatives that retain bioactivity in the gut might likewise alter the gut microbiota and host metabolism. Here we conductin vitro, ex vivo, and in vivoexperiments in mice to test the effects of preservatives on the gut microbiota and host physiology. We screened common dietary preservatives against a panel of human gut isolates and whole fecal communities, finding that preservatives strongly altered microbial growth and community structure. We exposed mice to diet-relevant doses of 4 preservatives [acetic acid, BHA (butylated hydroxyanisole), EDTA (ethylenediaminetetraacetic acid) and sodium sulfite], which each induced compound-specific changes in gut microbiota composition. Finally, we compared the long-term effects of early-life EDTA and low-dose antibiotic (ampicillin) exposure. EDTA exposure modestly reduced nutrient absorption and cecal acetate in both sexes, resulting in lower adiposity in females despite greater food intake. Females exposed to ampicillin also exhibited lower adiposity, along with larger brains and smaller livers. By contrast, in males, ampicillin exposure generally increased energy harvest and decreased energy expenditure, resulting in higher adiposity. Our results highlight the potential for everyday doses of common dietary preservatives to affect the gut microbiota and impact metabolism differently in males and females. Thus, despite their generally-regarded-as-safe designation, preservatives could have unintended consequences for consumer health.SIGNIFICANCEEarly-life exposure to antibiotics can alter the gut microbiota and shape adult metabolic health. Here we show that dietary preservatives can have analogous effects. Common dietary preservatives altered gut microbiota compositionin vitro,ex vivoandin vivo. Early-life EDTA exposure had long-term, sex-specific consequences for energy metabolism. Simultaneously, we deliver new mechanistic understanding of early-life antimicrobial-induced effects on adiposity via evidence that low-dose ampicillin treatment increases energy harvest while conserving energy expenditure in males, promoting adiposity, while EDTA treatment dampens energy harvest, promoting leanness in females. Overall, our results emphasize that early-life gut microbiome disruptions can be triggered by diverse antimicrobial exposures, with previously unappreciated metabolic consequences that differ for males and females.
TheNeosartorya (Aspergillus) fischeriantifungal protein NFAP2 has low potential to trigger resistance development inCandida albicans in vitro
Authors: Bende Gábor , Zsindely Nóra , Laczi Krisztián , Kristóffy Zsolt , Papp Csaba , Farkas Attila , Tóth Liliána , Sáringer Szabolcs , Bodai László , Rákhely Gábor , Marx Florentine , Galgóczy László 
Published: May 2024

AbstractDue to the increase in the number of drug-resistantCandida albicansstrains, new antifungal compounds with limited potential for development of resistance are urgently needed. NFAP2, an antifungal protein (AFP) secreted byNeosartorya(Aspergillus)fischeri, is a promising candidate. We investigated the ability ofC. albicansto develop resistance to NFAP2 in a microevolution experiment compared with generic fluconazole (FLC).C. albicansadapted to only 1 × minimum inhibitory concentration (MIC) of NFAP2 compared with 32 × MIC of FLC. Genome analysis revealed non-silent mutations in only two genes in NFAP2-resistant strains and in several genes in FLC-resistant strains. Resistance development to NFAP2 did not influence cell morphology. The susceptibility of NFAP2-resistant strains did not change to FLC, amphotericin B, micafungin, terbinafine. These strains did not show altered susceptibility to AFPs fromPenicillium chrysogenum, except one which had less susceptibility toP. chrysogenumantifungal protein B. FLC-resistant strains had decreased susceptibility to terbinafine and NFAP2, but not to other drugs and AFPs fromP. chrysogenum. NFAP2- and FLC-resistant strains showed decreased and increased NFAP2 binding and uptake, respectively. The development of resistance to NFAP2 decreased tolerance to cell wall, heat, and UV stresses. The development of FLC resistance increased tolerance to cell wall stress and decreased tolerance to heat and UV stresses. Resistance to NFAP2 did not have significant metabolic fitness cost and could not increase virulence, compared with resistance to FLC.ImportanceDue to the increasing number of (multi)drug-resistant strains, only a few effective antifungal drugs are available to treat infections caused by opportunisticCandidaspecies. Therefore, the incidence of hard-to-treat candidiasis has increased dramatically in the past decade, and the demand to identify antifungal compounds with minimal potential to trigger resistance is substantial. The features of NFAP2 make it a promising candidate for the topical treatment ofCandidainfection. Data on the development of resistance to AFPs inC. albicansare lacking. In this study, we provide evidence that NFAP2 has low potential to trigger resistance inC. albicans in vitroand the developed resistance mechanisms to NFAP2 are not associated with severe phenotypic changes compared with development of resistance to generic FLC. These results suggest the slow emergence of NFAP2-resistantCandidastrains and that NFAP2 can reliably be used long-term in the clinic.