bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 Mediated Inhibition Of Respiratory Syncytial Virus
Authors: Thornhill Elena M , Verhoeven David
Published: September 2024

With circulation of SARS-CoV-2, fears about coinfection with other respiratory viruses such as influenza and RSV were significant, but the opposite was observed. Distancing/barriers played a major role in reducing other viral co-infections, however, some infrequent co-infections still occurred. We investigated the relationship between SARS-CoV-2 and RSV during coinfection to understand how they might compete or synergize. We found only RSV’s replication was significantly reduced when coinfected with SARS-CoV-2. Investigation of the mechanism revealed that the SARS-CoV-2 protein Nsp1 disrupts the RSV M2-2 protein but not the upstream M2-1 protein on the same biscistronic mRNA transcript. The impact of Nsp1 on M2-2 was not dependent on M2-2 being the second ORF in a bicistronic mRNA transcript, but likely from prevention of ribosomal termination-reinitiation necessary for M2-2 production. Additional viral ORFs from influenza A, influenza B, or Sendai virus dependent on the same or other ribosomal initiation mechanisms were tested and we found only influenza B M/M2 which likely uses a similar method as M2-2 was disrupted. Various M2-2 constructs, with/without the proposed site of ribosomal termination-reinitiating, co-transfected with Nsp1 and were in agreement that disruption to M2-2 expression occurs if the site of re-initiation was present upstream. These data not only suggest Sars-CoV-2 can outcompete RSV through suppression of M2, but may also point to potential ways to interfere with RSV by targeted therapies.
Musical training does not enhance neural sound encoding at early stages of the auditory system: A large-scale multisite investigation
Authors: Whiteford Kelly L. , Baltzell Lucas S. , Chiu Matt , Cooper John K. , Faucher Stefanie , Goh Pui Yii , Hagedorn Anna , Irsik Vanessa C. , Irvine Audra , Lim Sung-Joo , Mesik Juraj , Mesquita Bruno , Oakes Breanna , Rajappa Neha , Roverud Elin , Schrlau Amy E. , Van Hedger Stephen C. , Bharadwaj Hari M. , Johnsrude Ingrid S. , Kidd Gerald , Luebke Anne E. , Maddox Ross K. , Marvin Elizabeth W. , Perrachione Tyler K. , Shinn-Cunningham Barbara G. , Oxenham Andrew J.
Published: September 2024

Musical training has been associated with enhanced neural processing of sounds, as measured via the frequency following response (FFR), implying the potential for human subcortical neural plasticity. We conducted a large-scale multi-site preregistered study (n > 260) to replicate and extend the findings underpinning this important relationship. We failed to replicate any of the major findings published previously in smaller studies. Musical training was related neither to enhanced spectral encoding strength of a speech stimulus (/da/) in babble nor to a stronger neural-stimulus correlation. Similarly, the strength of neural tracking of a speech sound with a time-varying pitch was not related to either years of musical training or age of onset of musical training. Our findings provide no evidence for plasticity of early auditory responses based on musical training and exposure.
Contribution of GC content to differentiated region formation along a speciation continuum
Authors: Ke Fushi , Vasseur Liette
Published: September 2024

Genome features can interact with external evolutionary processes and are involved in the formation of highly differentiated regions (i.e., genomic islands) potentially containing adaptation and speciation loci. However, GC content that can elevate both regional recombination and mutation has not been investigated in evolving lineages to test its effects on formation of heterozygous differentiation landscape. Here, we employed the genomes of 499 Asian honey bee (Apis cerana), with a widely-distributed central lineage diverged and admixed with its peripheral lineages at both population genetic and phylogenetic levels, to investigate the effects of GC content on mutation accumulation and lineage divergence along the speciation continuum. We find that genomic islands are generally with low GC content (i.e., lower-than-average), and with lower-than-average divergence (dxy) initially to higher-than-average ones at deeper divergence, corresponding to the suggested evolution models transforming from linked selection to divergent selection. When comparing with high-GC regions however, we find higher mutation load indicating inefficient natural selection in low-GC regions, which thus support the important role of low GC content instead of evolutionary process (e.g., natural selection) in genomic island formation. Finally, low-GC regions possess higher proportion of lineage-specific polymorphisms than high-GC regions due to limited recombination and admixture under the gene-flow scenario, and reconciliate discordance between mitochondrial and nuclear phylogenies inA. cerana. Our results shed light on the contribution of polymorphisms in low-GC regions to divergent region formation along the speciation continuum and their application in reconstruction of intraspecific phylogeny, especially in lineages with gene flow.
Evaluating the Impact of NHS Strikes on Patient Flow through Emergency Departments
Authors: Garner Alex , Ashcroft Quin , Kirkwood Dale , Chandrabalan Vishnu , Emsley Hedley , Mason Suzanne M , Preston Nancy , Knight Jo
Published: September 2024

Background

Since December 2022, the NHS has experienced large-scale strikes over pay by staff. Strikes heavily impact elective care delivery. The NHS cancels approximately 12 million elective care appointments each year. One million appointments have been cancelled due to strikes between 2022 and 2024. During this time emergency care is prioritised, and in a recent opinion piece, the president of the Royal College of Emergency medicine claimed the Emergency Department ran ‘better than usual’. The aim of this paper was to investigate changes in patient flow into hospitals through the ED during the strike periods.

Methodology

Data from two different emergency departments (EDs) in the North West of England is analysed using Cox-regression to model time between patient arrival at the ED, and subsequent admission. Various systematic and patient-level factors are controlled for. The impact of different striking groups (nurses, junior doctors etc.) on patient time to admission is analysed.

Results

For the Type 1 ED, hazard ratios indicate that patients are admitted through the ED more quickly on strike days where any single group of staff were striking compared to non-strike days (HRs: 1.16-1.39, all p ≤ 0.003). This increased flow was only seen for consultant strikes in the smaller ED.

Interpretation

These findings for all strike types indicate that improved patient flow on strike days is likely due to the increased inpatient capacity from elective care postponement. This result may indicate that there is room for change in NHS hospital systems to improve turnaround time and reduce ED crowding.

Key Messages

What is already known on this topic

Exit block is a primary issue for NHS Emergency Departments (EDs), increasing patient time spent in ED. The president of the Royal College of Emergency Medicine claimed that NHS EDs run ‘better than usual’ during strikes. There is little quantitative evidence to support this claim.

What this study adds

This study identifies significant increases in flow of admitted patients into the hospital during the strikes, when accounting for differences in admission patterns.

How this study might affect research, practice or policy

The improvement in flow indicates that, although strike day service is unsustainable, elements of strike preparation can have a positive impact on the running of the emergency departments - demonstrating scope to improve patient flow through NHS EDs.
Sex differences in the trajectories of plasma biomarkers, brain atrophy, and cognitive decline relative to amyloid onset
Authors: Joynes Cassandra M , Bilgel Murat , An Yang , Moghekar Abhay R , Ashton Nicholas J , Kac Przemysław R , Karikari Thomas K , Blennow Kaj , Zetterberg Henrik , Thambisetty Madhav , Ferrucci Luigi , Resnick Susan M , Walker Keenan A
Published: September 2024

Abstract INTRODUCTION: The factors that influence the progression of Alzheimer's disease (AD) after individuals become amyloid-positive are poorly understood. This study examines how sex influences the longitudinal trajectories of plasma AD and neurodegenerative biomarkers in the years following a person's estimated onset of amyloid-β. METHODS: Linear mixed effects modeling investigated overall and sex-specific longitudinal trajectories of plasma biomarkers, brain volumes, and cognition relative to estimated age of amyloid onset in a cohort of 78 amyloid-positive Baltimore Longitudinal Study of Aging participants (n=45 male; follow-up time: 6.8 years [SD 3.31]). Amyloid status was ascertained with 11C-Pittsburgh compound B (PiB) PET imaging. RESULTS: After amyloid onset, men displayed steeper increases in pTau181, pTau231, and NfL compared to women. In this same period, men demonstrated steeper declines in brain volume and cognitive performance. DISCUSSION: These findings suggest that sex influences the trajectory of AD pathology, neuronal injury, and symptom progression after individuals become amyloid-positive.
Using functional near-infrared spectroscopy to explore neurocognitive function in adult survivors of childhood acute lymphoblastic leukemia
Authors: Skau Simon , Jarfelt Marianne , Glavå Gustaf , Jess Laura , Kuhn H. Georg
Published: September 2024

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Due to the drastic increase in survivor rate over the last 50 years, long lasting treatment effect on moods and neurocognitive function has become a present issue. Most studies of late effects of treatment of ALL survivors investigate patients in their adolescents. This pilot study aims to identify measurements for evaluating late effect of childhood ALL survivors regarding neurocognitive and mood problems in adulthood. ALL survivors who received neurotoxic treatment with high-dose methotrexate and cranial radiotherapy (Chemo+CRT) (n=10) and ALL survivors only treated with high-dose methotrexate (Chemo) (n=10), plus age and sex match controls (n=20) where recruited to the study. The study protocol involved questionnaires, neurocognitive tests and optical brain imaging with functional near infrared spectroscopy (fNIRS) over the frontal and parietal cortex. The fNIRS results indicate a reduced involvement of the parietal cortex during conflict processing for the ALL survivors compared to controls. The study protocol shows promising results for identifying subgroups that suffers from neurocognitive and mood problems and we aim to expand upon it in a larger study. As our results indicate increased challenges among female ALL survivors, especially pathological fatigue, anxiety, and information processing, it is important to explore in future investigations the interplay between the risk of hormonal interaction with chemotherapy during development and occupational and social pressure during adulthood.
Antiplatelet Therapy Following Spontaneous Coronary Artery Dissection: Systemic Review
Authors: Park Huijun Edelyn , Cho Leslie S. , Fendrikova-Mahlay Natalia , Chaudhury Pulkit , Cameron Scott J.
Published: September 2024

Background

Spontaneous coronary artery dissection (SCAD) is an understudied cause of acute coronary syndrome (ACS), particularly in women. Heart muscle damage may result from spontaneous dissection of coronary arteries. There is no clear consensus regarding the optimum antiplatelet medication regimen and treatment duration for SCAD despite current American Heart Association (AHA) consensus guidelines recommending 12-month regimen of dual antiplatelet therapy (DAPT) consisting of a P2Y12inhibitor and aspirin for patients following myocardial infarction (MI). The objective of this study was to evaluate the safety and effectiveness of DAPT compared to using a single antiplatelet therapy (SAPT) as part of the medical armamentarium to treat SCAD.

Methods

A comprehensive search of the literature was conducted to identify studies that examined SCAD outcomes including mortality, recurrence, and major adverse cardiovascular events (MACE) between 2000-2023 after antiplatelet therapy was administered. Based on the documentation in various studies, only 17 relevant studies were identified in which SAPT (primarily aspirin) and DAPT (aspirin combined with a P2Y12inhibitor) were administered. Medications used in cardiovascular medicine that did not provide comprehensive data were excluded from the studies.

Results

DAPT treatment was associated with a poorer prognosis than SAPT 12 months after patients presented with SCAD. A key observation was the prevalence of antiplatelet treatment in SCAD patients, with DAPT prescribed for the majority of cases. At the 12-month time point, DAPT demonstrated had a higher rate of mortality (P = 0.0245), MACE (P = 0.0265), and angina admission rate (P = 0.071), as well as a higher rate of recurrent SCAD (P =0.0579) (Fig. 2). An increased incidence of non-fatal myocardial infarction or emergency percutaneous coronary intervention primarily drove these adverse outcomes.

Conclusion

In patients treated with antiplatelet therapy, adverse events that include unstable angina, mortality, and repeat revascularization were greater in patients with more aggressive antiplatelet therapy consisting of DAPT compared with these treated with SAPT.
Association Between Seasonal Respiratory Virus Activity and Invasive Pneumococcal Disease in Central Ontario, Canada
Authors: Simmons Alison E. , Berry Isha , Buchan Sarah A. , Tuite Ashleigh R. , Fisman David N.
Published: September 2024

Background

In central Ontario, influenza, respiratory syncytial virus (RSV), and invasive pneumococcal disease (IPD) follow similar seasonal patterns, peaking in winter. We aimed to quantify the independent and joint impact of influenza A, influenza B, and RSV on IPD risk at the population level.

Methods

We used a 2:1 self-matched case-crossover study design to evaluate acute effects of respiratory virus activity on IPD risk. This design ensures that effects are not confounded by within-individual characteristics that remain constant over short periods of time. We included 3,892 IPD cases occurring between January 2000 and June 2009. Effects were measured using univariable and multivariable conditional logistic regression. Multivariable models included environmental covariates (e.g., temperature, absolute humidity, and UV index) and interaction terms between viruses.

Results

Influenza A activity and influenza B activity were both independently associated with increased IPD risk; however, co-circulation of influenza A and B reduced the impact of both viruses. RSV activity was positively associated with increased IPD risk only in the presence of increased influenza A or influenza B activity.

Conclusions

To our knowledge this represents the first study to consider the impact of interactions between these viruses on IPD risk in Canada. Our findings suggest that the prevention of IPD should be considered as a potential health benefit of influenza and RSV vaccination programs.
Similar performance of 8 machine learning models on 71 censored medical datasets: a case for simplicity
Authors: Rebaud Louis , Capobianco Nicolò , Captier Nicolas , Escobar Thibault , Spottiswoode Bruce , Buvat Irène
Published: September 2024

In the analysis of medical data with censored outcomes, identifying the optimal machine learning pipeline is a challenging task, often requiring extensive preprocessing, feature selection, model testing, and tuning. To investigate the impact of the choice of pipeline on prediction performance, we evaluated 9 machine learning models on 71 medical datasets with censored targets. Only the decision tree model was consistently underperforming, while the other 8 models performed similarly across datasets, with little to no improvement from preprocessing optimization and hyperparameter tuning. Interestingly, more complex models did not outperform simpler ones, and reciprocally. ICARE, a straightforward model univariately learning only the sign of each feature instead of a weight, demonstrated similar performance to other models across most datasets while exhibiting lower overfitting, particularly in high-dimensional datasets. These findings suggest that using the ICARE model to build signatures between centers could improve reproducibility. Our findings also challenge the traditional approach of extensive model testing and tuning to improve performance.
Neurodegenerative Plasma Biomarkers for Prediction of Hippocampal Atrophy in Older Adults with Suspected Alzheimer’s Disease in Kinshasa, Democratic Republic of Congo
Authors: Ikanga Jean , Jean Kharine , Medina Priscilla , Patel Saranya Sundaram , Schwinne Megan , Epenge Emmanuel , Gikelekele Guy , Tshengele Nathan , Kavugho Immaculee , Mampunza Samuel , Mananga Lelo , Teunissen Charlotte E. , Stringer Anthony , Rojas Julio C. , Chan Brandon , Lario Lago Argentina , Kramer Joel H. , Boxer Adam L. , Jeromin Andreas , Hanseeuw Bernard , Gross Alden L. , Alonso Alvaro
Published: September 2024

Objective

The hippocampus is one of the first brain structures affected by Alzheimer’s disease (AD), and its atrophy is a strong indicator of the disease. This study investigates the ability of plasma biomarkers of AD and AD-related dementias— amyloid-β (Aβ42/40), phosphorylated tau-181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP)—to predict hippocampal atrophy in adult individuals in Kinshasa, Democratic Republic of Congo (DRC).

Methods

Eighty-five adult individuals (40 healthy and 45 suspected AD) over 65 years old were evaluated using the Community Screening Instrument for Dementia and Alzheimer’s Questionnaire (AQ). Core AD biomarkers (Aβ42/40 and p-tau181) and non-specific neurodegeneration biomarkers (NfL, GFAP) were measured in blood samples collected at the study visit. Hippocampal volumes were measured using magnetic resonance imaging (MRI). General linear regression was used to evaluate differences in biomarker concentrations by neurological status. Logistic regression models were used to create receiver operating characteristic curves and calculate areas under the curve (AUCs) with and without clinical covariates to determine the ability of biomarker concentrations to predict hippocampal atrophy. Plasma biomarkers were used either individually or in combination in the models.

Results

Elevated p-tau181 was associated with left hippocampal (LH) atrophy p= 0.020). Only higher p-tau181 concentrations were significantly associated with 4.2-fold increased odds [OR=4.2 (1.5-18.4)] of hippocampal atrophy per standard deviation. The AUC of plasma biomarkers without clinical covariates to discriminate LH, RH, and total hippocampal (TH) or both hippocampi atrophy ranged between 90% to 94%, 76% to 82%, and 85% to 87%, respectively. The AUC of models including clinical covariates and AD biomarkers used in combination to discriminate LH, RH, and TH ranged between 94%-96%, 81%-84%, and 88%-90%, respectively.

Conclusion

These results indicate that, consistent with studies in other settings, core AD plasma biomarkers can predict hippocampal atrophy in a population in Sub-Saharan Africa.
Heat stress sensitizes zebrafish embryos to neurological and cardiac toxicity
Authors: Haapanen-Saaristo Anna-Mari , Virtanen Noora , Tcarenkova Elena , Vaparanta Katri , Ampuja Minna , Vehniäinen Eeva-Riikka , Paatero Ilkka
Published: September 2024

Global warming increases the risk of dangerous heat waves, which may have deleterious effects on humans and wildlife. Here, we have utilized zebrafish embryos as a model to analyse heat stress and effect of chemical compounds on responses to heat stress. The temperature adaptation limit of zebrafish embryos was 37°C in behavioural test and 38°C in cardiac test. Polyaromatic hydrocarbon phenanthrene completely blocked the behavioural adaptation to heat stress. Interestingly, the cardiotoxic effects of lapatinib, phenanthrene and paclitaxel were induced by heat stress. Taken together, our data indicates that motility and cardiac function of zebrafish embryos can be utilized as a model to analyze modulatory effects of compounds on heat stress.

Highlights

Zebrafish embryos can be utilized as an in vivo model for acute heat stress

Phenanthrene inhibited motility increase upon heat stress

Cardiotoxicity of lapatinib, paclitaxel and phenanthrene was potentiated by heat stress
Long read sequencing and assembly of wild diploid relatives and cultivars in support of banana breeding programs
Authors: Chen Andrew , Zhou Xuefeng , Decker Keith , Havecker Ericka , Du Zijin , Brown Allan F. , Aitken Elizabeth A. B. , Trushar Shah , Uwimana Brigitte , Hresko Chelly , Swennen Rony , Lowdon Rebecca F.
Published: September 2024

Banana is an important fruit and staple crop, which is vital for food and income security in developing countries. A genomics initiative was undertaken as part of the Global Alliance against TR4 (Tropical Race 4 of Fusarium Wilt of Banana) Alliance, with Bayer Crop Science, International Institute of Tropical Agriculture, and University of Queensland to collectively accelerate the breeding efforts in Eastern Africa. The goal of this project is to develop genomics resources to improve banana breeding, productivity, and quality traits amid a changing climate and shifting disease pressures for breeding. Here, we present the PacBio HiFi sequencing, assembly, and comparative analysis of seven genomes of wild and edible diploid banana accessions belonging to subspecies considered important progenitors to cultivated banana varieties and part of breeding programs. This banana genome resource will help power genome editing, a pangenome effort, and conventional breeding programs for germplasm improvement.
Neuronal autophagosomes are transported to astrocytes for degradation
Authors: Linda K. , Schuurmans I.M.E. , Smeenk H. , Vints K. , Negwer M. , Peredo N. , Lewerissa E.I. , Swerts J. , Hoekstra M. , Mordelt A. , Kuenen S. , Gallego S.F. , de Vrij F.M.S , Nadif Kasri N. , Verstreken P.
Published: September 2024

Autophagy is a vital catabolic process responsible for the degradation of cytosolic components, playing a key role in cellular homeostasis and survival. At synapses, autophagy is crucial for regulating neuronal activity and utilizes a specialized machinery. While considerable progress has been made in understanding the initiation of autophagy and autophagosome formation, the mechanisms governing the clearance of autophagosomes from synaptic sites remain poorly understood. Here, we identify a novel pathway in which astrocytes actively participate in the clearance of pre-synaptic autophagosomes. Using neurons derived from human induced pluripotent stem cell (hiPSC) lines expressing fluorescent autophagy markers and chimeric mouse models, we demonstrate that neuronal autophagosomal vesicles are physically transferred to astrocytes, a process that is enhanced when synaptic activity is suppressed. Autophagosome transfer does not require direct physical cellular contact, but it does require Dynamin and cholesterol-dependent endocytosis for the internalized neuronal autophagosomes to ultimately fuse with astrocytic lysosomes. Our findings reveal a previously unrecognized mechanism of neuronal autophagosome clearance that does not require slow axonal retrograde transport but their transfer to nearby astrocytes.
Malaria parasites undergo a rapid and extensive metamorphosis after invasion of the host erythrocyte
Authors: Fréville Aline , Moreira-Leite Flavia , Roussel Camille , Russell Matthew R.G. , Fricot Aurelie , Carret Valentine , Sissoko Abdoulaye , Hayes Matthew J. , Dialo Aissatou Bailo , Kerkhoven Nicole Cristine , Ressurreição Margarida , Dokmak Safi , Blackman Michael J. , Collinson Lucy M. , Buffet Pierre A. , Vaughan Sue , Ndour Papa Alioune , van Ooij Christiaan
Published: September 2024

Within the human host, the symptoms of malaria are caused by the replication of malaria parasites within erythrocytes. Growth inside the erythrocyte exposes the parasites to the normal surveillance of erythrocytes by the host organism, in particular the clearance of erythrocytes in the spleen. Here we show that the malaria parasitePlasmodium falciparumundergoes a rapid, multi-step metamorphosis that transforms the invasive merozoite into an amoeboid-shaped cell within minutes after invading erythrocytes. This transformation involves an increase in the parasite surface area and is mediated by factors already present in the merozoite, including the parasite phospholipid transfer protein PV6. Parasites lacking PV6 do not assume an amoeboid form and instead are spherical and have a smaller surface area than amoeboid forms. Furthermore, erythrocytes infected with parasites lacking PV6 undergo a higher loss of surface area upon infection byP. falciparum, which affects the traversal of infected erythrocytes through the spleen. This is the first evidence that after invasion, the parasite undergoes a rapid, complex metamorphosis within the host erythrocyte that promotes survival in the host.
Distinct neural manifolds and critical roles of primate caudate nucleus in multimodal decision-making
Authors: ZENG ZHAO , Zhang Ce , Xu Yue , He Hua , Gu Yong
Published: September 2024

Representational redundancy is ubiquitous in the brain with distributed networks encode task variables in a similar way, which may mask the unique roles of each region. Using a multisensory decision paradigm, here we showed that primate caudate nucleus (CN) dramatically differed from decision-related cortices in the reduced low-dimensional neural subspace, although possessing similar choice representations. Specifically, bimodal neural trajectories evolved towards nonvisual (vestibular) in CN, rather than towards visual as in frontal/parietal cortices. This challenges previous hypothesis that striatum mainly reflects cortical decision signals. Following recurrent neural networks simulations suggested that the cortico-subcortical distinction might be due to different intensities of single-modality inputs. We furtherly demonstrated that CN population responses represented the multisensory behavior strategy animal employed within the generalized drift-diffusion framework. Importantly, neural manipulations by unilateral drug injection and microstimulation confirmed CN's causal contributions to multisensory decisions. Overall, our results indicate beyond relay-station in cortico-striatal circuitry, CN plays distinct and critical roles in perceptual decision-making.
Sex-specific differences in brain activity dynamics of youth with a family history of substance use disorder
Authors: Schilling Louisa , Singleton S Parker , Tozlu Ceren , Hédo Marie , Zhao Qingyu , Pohl Kilian M , Jamison Keith , Kuceyeski Amy
Published: September 2024

An individual’s risk of substance use disorder (SUD) is shaped by a complex interplay of potent biosocial factors. Current neurodevelopmental models posit vulnerability to SUD in youth is due to an overreactive reward system and reduced inhibitory control. Having a family history of SUD is a particularly strong risk factor, yet few studies have explored its impact on brain function and structure prior to substance exposure. Herein, we utilized a network control theory approach to quantify sex-specific differences in brain activity dynamics in youth with and without a family history of SUD, drawn from a large cohort of substance-naïve youth from the Adolescent Brain Cognitive Development Study. We summarize brain dynamics by calculating transition energy, which probes the ease with which a whole brain, region or network drives the brain towards a specific spatial pattern of activation (i.e., brain state). Our findings reveal that a family history of SUD is associated with alterations in the brain’s dynamics wherein: i) independent of sex, certain regions’ transition energies are higher in those with a family history of SUD and ii) there exist sex-specific differences in SUD family history groups at multiple levels of transition energy (global, network, and regional). Family history-by-sex effects reveal that energetic demand is increased in females with a family history of SUD and decreased in males with a family history of SUD, compared to their same-sex counterparts with no SUD family history. Specifically, we localize these effects to higher energetic demands of the default mode network in females with a family history of SUD and lower energetic demands of attention networks in males with a family history of SUD. These results suggest a family history of SUD may increase reward saliency in males and decrease efficiency of top-down inhibitory control in females. This work could be used to inform personalized intervention strategies that may target differing cognitive mechanisms that predispose individuals to the development of SUD.
Cholinergic signaling differentially regulates song premotor circuits to stabilize songs in songbirds
Authors: Xu Ning , Zhang Yutao , Sun Yalun , Song Xueqing , Cao YangYang , Yang Xinqi , Wang Songhua , Meng Wei
Published: September 2024

Cholinergic modulation plays an important role in motor skill learning, including vocal learning. In songbirds, song premotor nucleus RA simultaneously receives inputs from song nuclei HVC and LMAN, and then its projection neurons (RAPNs) generate song motor control output. Using electrophysiological and pharmacological methods, we found that cholinergic signaling can enhance song stability by reducing HVC-RAPN excitatory synaptic transmission in adult male zebra finches, mediated by mAChRs. Although nAChRs are not effective overall, cholinergic signaling can also decrease LMAN-RAPN excitatory synaptic transmission induced by electrical stimulation via nAChRs, suggesting the potential role of cholinergic regulation in song behavior through LMAN-RA pathway. On the contrary, in adult female zebra finches, only LMAN-RAPN synaptic transmission was reduced by cholinergic signaling via mAChRs. The role of differential cholinergic regulation of song premotor circuits in songbirds’ singing provides insights into the neural processes of motor skill learning.

In brief

Xu et al. reveal a mechanism of cholinergic modulation on songbird singing. They find that cholinergic signaling differentially regulates HVC-RAPN and LMAN-RAPN synaptic transmission via mAChRs and nAChRs respectively to stabilize songs in male zebra finches, while in females, only LMAN-RAPN synaptic transmission is regulated by cholinergic signaling via mAChRs.

Highlights

Cholinergic signaling regulates HVC-RA pathway of male songbirds by mAChRs

Cholinergic signaling regulates LMAN-RA pathway of male songbirds by nAChRs

Cholinergic signaling stabilizes birdsongs in males by mAChRs rather than nAChRs

Cholinergic signaling merely regulates LMAN-RA pathway in females by mAChRs
A qPCR assay for the detection ofPhytophthora abietivora, an emerging pathogen on fir species cultivated as Christmas trees
Authors: Charron Guillaume , Gauthier Marie-Krystel , van der Heyden Hervé , Bilodeau Guillaume J. , Tanguay Philippe
Published: September 2024

Emerging species of thePhytophthoragenus are among the most important threats to global plant biodiversity. For instance,Phytophthoraroot rot (PRR) of Christmas trees is responsible for 10% of the observed mortality rate in nurseries. Diagnosis of PRR involves isolation followed by morphological and molecular identification of the causal agents. However, these methods are rarely adapted to larger scale experiments such asin situdetection. For these applications, molecular detection of environmental DNA (eDNA) provides the high-throughput and the fast result generation needed.Phytophthora abietivorawas associated to PRR in firs cultivated as Christmas trees in the province of Québec (Canada). This study focused on developing a sensitive and specific qPCR assay targetingP. abietivoraand validating its efficiency on eDNA samples. A set of primers and probe was designed for this assay, and parameters such as the limit of detection (LoD95%) and limit of quantification (LoQ) were measured. The assay was tested on eDNA obtained from healthy-looking and PRR symptomatic firs. The assay was shown to be semi-specific because it cross-reacted with P. abietivora, and four phylogenetically close species unrelated to fir diseases. The limit of detection (LOD95%) was estimated at 10 copies per reaction (Cqof 35.7). The assay showed reliable detection down to 33P. abietivoraoospores per gram of soil. Out of 488 eDNA samples from soil, 68 tested positive forP. abietivora.While factors such as the tree species, the sampled region or the year of sampling did not affect the proportion of positive results, samples from trees showing PRR-like symptoms had significantly higher odds of testing positive compared to healthy-looking trees. This assay will be useful for rapid diagnostics ofP. abietivorainfected trees and as a prospecting tool to better characterize the natural distribution and dissemination of the disease.
Engineered Transcription Factor Binding Arrays for DNA-based Gene Expression Control in Mammalian Cells
Authors: Zouein Annalise , Lende-Dorn Brittany , Galloway Kate E , Ellis Tom , Ceroni Francesca
Published: September 2024

Manipulating gene expression in mammalian cells is critical for cell engineering applications. Here we explore the potential of transcription factor (TF) recognition element arrays as DNA tools for modifying free TF levels in cells and thereby controlling gene expression. We first demonstrate proof-of-concept, showing that Tet TF-binding recognition element (RE) arrays of different lengths can tune gene expression and alter gene circuit performance in a predictable manner. We then open-up the approach to interface with any TF with a known binding site by developing a new method called Cloning Troublesome Repeats in Loops (CTRL) that can assemble plasmids with up to 256 repeats of any RE sequence. Transfection of RE array plasmids assembled by CTRL into mammalian cells show potential to modify host cell gene regulation at longer array sizes by sequestration of the TF of interest. RE array plasmids built using CTRL were demonstrated to target both synthetic and native mammalian TFs, illustrating the ability to use these tools to modulate genetic circuits and instruct cell fate. Together this work advances our ability to assemble repetitive DNA arrays and showcases the use of TF-binding RE arrays as a method for manipulating mammalian gene expression, thus expanding the possibilities for mammalian cell engineering.
Predictive Coding of Reward in the Hippocampus
Authors: Yaghoubi Mohammad , Nieto-Posadas Andres , Mosser Coralie-Anne , Gisiger Thomas , Wilson Émmanuel , Williams Sylvain , Brandon Mark P.
Published: September 2024

A fundamental objective of the brain is to anticipate future outcomes1–7. This process requires learning the states of the world as well as the transitional relationships between those states. The hippocampal cognitive map is believed to be one such internal model8. However, evidence for predictive coding9–12and reward sensitivity13–19in the hippocampal neuronal representation suggests that its role extends beyond purely spatial representation. In fact, it raises the question of what kind of spatial representation is most useful for learning and maximizing future rewards? Here, we track the evolution of reward representation over weeks as mice learn to solve a cognitively demanding reward-based task. Our findings reveal a highly organized restructuring of hippocampal reward representations during the learning process. Specifically, we found multiple lines of evidence, both at the population and single-cell levels, that hippocampal representation becomes predictive of reward over weeks. Namely, both population-level information about reward and the percentage of reward-tuned neurons decrease over time. At the same time, the representation of the animals’ choice and reward approach period (the period between choice and reward) increased over time. By tracking individual reward cells across sessions, we found that neurons initially tuned for reward shifted their tuning towards choice and reward approach periods, indicating that reward cells backpropagate their tuning to anticipate reward with experience. These findings underscore the dynamic nature of hippocampal representations, highlighting their critical role in learning through the prediction of future outcomes.
LPA3receptors have orthosteric and allosteric binding sites evidenced under docking studies
Authors: Solís K. Helivier , Romero-Ávila M. Teresa , Rincón-Heredia Ruth , Correa-Basurto José , García-Sáinz J. Adolfo
Published: September 2024

Comparative studies using LPA and the synthetic ligand, oleoyl-methoxy glycerophosphothionate, OMPT, in cells expressing the LPA3receptor revealed differences in these agonists’ action. We observed that the latter agonist exhibits two very different potency values, one in the order of 1-10 nm and the other with 30-100-fold less potency and biased pharmacodynamic behavior. The possibility that more than one site might exist for this ligand in the LPA3receptor was considered. We performed comparative LPA and OMPT docking studies to obtain structural tridimensional details to achieve binding analysis exploring the whole protein. Our study includes blind docking using the unrefined and refined proteins subjected to hot spot predictions, which allowed us to detect that the LPA binding site is preferentially located in the cytoplasmic (orthosteric site) region. In contrast, OMPT displayed an affinity for an additional binding site (allosteric) located in transmembrane and extracellular regions.

Docking studies also focused on the alpha carbons from Trp102 and Tyr293, founded as the centers for the hot spot predictions. Docking targeted to Trp102 favored binding both ligands in the transmembrane and extracellular regions. In contrast, docking targeted to Tyr293 also shared interaction sites for both ligands but in the cytoplasmic region. These data suggest that OMPT might exhibit a biotypic behavior, promoting different structural rearrangements, which could explain the observed biased behavior.

One-sentence summary:Orthosteric and allosteric agonist binding sites in LPA3receptors
Attention defines the context for implicit sensorimotor adaptation
Authors: Wang Tianhe , Li Jialin , Ivry Richard B.
Published: September 2024

Movement errors are used to continuously recalibrate the sensorimotor map, a process known as sensorimotor adaptation. Here we examined how attention influences this automatic and obligatory learning process. Focusing first on spatial attention, we compared conditions in which the visual feedback that provided information about the movement outcome was either attended or unattended. Surprisingly, this manipulation had no effect on the rate of adaptation. We next used a dual-task methodology to examine the influence of attentional resources on adaptation. Here, again, we found no effect of attention, with the rate of adaptation similar under focused or divided attention conditions. Interestingly, we found that attention modulates adaptation in an indirect manner: Attended stimuli serve as cues that define the context for learning. The rate of adaptation was significantly attenuated when the attended stimulus changed from the end of one trial to the start of the next trial. In contrast, similar changes to unattended stimuli had no impact on adaptation. Together, these results suggest that visual attention defines the cues that establish the context for sensorimotor learning.
A best-match approach for gene set analyses in embedding spaces
Authors: Li Lechuan , Dannenfelser Ruth , Cruz Charlie , Yao Vicky
Published: September 2024

Embedding methods have emerged as a valuable class of approaches for distilling essential information from complex high-dimensional data into more accessible lower-dimensional spaces. Applications of embedding methods to biological data have demonstrated that gene embeddings can effectively capture physical, structural, and functional relationships between genes. However, this utility has been primarily realized by using gene embeddings for downstream machine-learning tasks. Much less has been done to examine the embeddings directly, especially analyses of gene sets in embedding spaces. Here, we propose an Algorithm for Network Data Embedding and Similarity (ANDES), a novel best-match approach that can be used with existing gene embeddings to compare gene sets while reconciling gene set diversity. This intuitive method has important downstream implications for improving the utility of embedding spaces for various tasks. Specifically, we show how ANDES, when applied to different gene embeddings encoding protein–protein interactions, can be used as a novel overrepresentation- and rank-based gene set enrichment analysis method that achieves state-of-the-art performance. Additionally, ANDES can use multiorganism joint gene embeddings to facilitate functional knowledge transfer across organisms, allowing for phenotype mapping across model systems. Our flexible, straightforward best-match methodology can be extended to other embedding spaces with diverse community structures between set elements.
Light scalar meson and decay constant in SU(3) gauge theory with eight dynamical flavors
Authors: Brower R. C. , Owen E. , Rebbi C. , Culver C. , Schaich D. , Cushman K. K. , Fleming G. T. , Gasbarro A. , Hasenfratz A. , Neil E. T. , Ingoldby J. , Jin X. Y. , Osborn J. C. , Rinaldi E. , Vranas P. , Weinberg E. , Witzel O. ,   [Lattice Strong Dynamics (LSD) Collaboration]
Published: September 2024

The SU(3) gauge theory with Nf=8 nearly massless Dirac fermions has long been of theoretical and phenomenological interest due to the near-conformality arising from its proximity to the conformal window. One particularly interesting feature is the emergence of a relatively light, stable flavor-singlet scalar meson σ(JPC=0++) in contrast to the Nf=2 theory QCD. In this work, we study the finite-volume dependence of the σ meson correlation function computed in lattice gauge theory and determine the σ meson mass and decay constant extrapolated to the infinite-volume limit. We also determine the infinite-volume mass and decay constant of the flavor-nonsinglet scalar meson a0.

Published by the American Physical Society
2024
Restricted baby Skyrme-Maxwell theory in a magnetic medium: BPS configurations and some properties
Authors: Andrade J. , Casana Rodolfo , da Hora E. , Santos A. C.
Published: September 2024

We study the existence of Bogomol’nyi-Prasad-Sommerfield (BPS) configurations in a restricted baby Skyrme-Maxwell enlarged via the inclusion of a nontrivial magnetic permeability. In order to attain such a goal, we use the BPS prescription, which allows us to obtain the lower bound for the energy and the BPS equations whose (electrically neutral) solutions saturate that bound. During the energy minimization procedure, we find a differential constraint which involves the self-dual potential, the superpotential itself, and also the magnetic permeability. In order to solve the BPS system, we focus our attention on those solutions with rotational symmetry. For that, we fix the magnetic permeability and select two BPS potentials which exhibit a similar behavior near to the vacuum. We depict the resulting profiles and proceed to an analytical description of the properties of the BPS magnetic field. Furthermore, we consider some essential aspects of our model, such as the conditions for the overall existence of the BPS solutions, and how the permeability affects the magnetic flux. Finally, we present a family of exact BPS solutions.

Published by the American Physical Society
2024
Gibbons-Hawking-York boundary terms and the generalized geometrical trinity of gravity
Authors: Erdmenger Johanna , Heß Bastian , Meyer René , Matthaiakakis Ioannis
Published: September 2024

General relativity (GR) as described in terms of curvature by the Einstein-Hilbert action is dynamically equivalent to theories of gravity formulated in terms of spacetime torsion or nonmetricity. This forms what is called the geometrical trinity of gravity. The theories corresponding to this trinity are, apart from GR, the teleparallel (TEGR) and symmetric teleparallel (STEGR) equivalent theories of general relativity, respectively, and their actions are equivalent to GR up to boundary terms B. We investigate how the Gibbons-Hawking-York (GHY) boundary term of GR changes under the transition to TEGR and STEGR within the framework of metric-affine gravity. We show that B is the difference between the GHY term of GR and that of metric-affine gravity. Moreover, we show that the GHY term for both TEGR and STEGR must vanish for consistency of the variational problem. Furthermore, our approach allows to extend the equivalence between GR, TEGR and STEGR beyond the Einstein-Hilbert action to any action built out of the curvature two-form, thus establishing the generalized geometrical trinity of gravity. We argue that these results will be particularly useful in view of studying gauge/gravity duality for theories with torsion and nonmetricity.

Published by the American Physical Society
2024
Probing exotic
JPC
resonances from deeply bound charmoniumlike molecules: Insights for identifying exotic hadrons
Authors: Wang Zhi-Peng , Wang Fu-Lai , Wang Guang-Juan , Liu Xiang
Published: September 2024

We investigate the resonance phenomenon in deeply bound charmoniumlike states. By interpreting the Y(4220), Y(4360), and ψ(4415) states as deeply S-wave bound DD¯1, D*D¯1, and D*D¯2* molecules, respectively, we robustly predict the existence of 4 S-wave deeply bound C-parity partner states and 13 P-wave charmoniumlike molecular resonances. These states, formed by exchanging the light mesons and pinpointed through the complex scaling method, include 3 S-wave bound states with exotic quantum numbers I(JPC)=0(1−+) and 5 P-wave resonances with exotic 0(0−+) and 0(2+−). We expect future experiments to search for such exotic molecular resonances, which will not only enrich the ongoing construction of “Particle Zoo 2.0” but also help to scrutinize the hadronic molecular assignments of the Y- family particles including the Y(4220), Y(4360), and ψ(4415) states.

Published by the American Physical Society
2024
Hamiltonian simulation for hyperbolic partial differential equations by scalable quantum circuits
Authors: Sato Yuki , Kondo Ruho , Hamamura Ikko , Onodera Tamiya , Yamamoto Naoki
Published: September 2024

Solving partial differential equations for extremely large-scale systems within a feasible computation time serves in accelerating engineering developments. Quantum computing algorithms, particularly the Hamiltonian simulations, present a potential and promising approach to achieve this purpose. Actually, there are several oracle-based Hamiltonian simulations with potential quantum speedup, but their detailed implementations and accordingly the detailed computational complexities are all unclear. This paper presents a method that enables us to explicitly implement the quantum circuit for Hamiltonian simulation; the key technique is the explicit gate construction of differential operators contained in the target partial differential equation discretized by the finite difference method. Moreover, we show that the space and time complexities of the constructed circuit are exponentially smaller than those of conventional classical algorithms. We also provide numerical experiments and an experiment on a real device for the wave equation to demonstrate the validity of our proposed method.

Published by the American Physical Society
2024