bluuebunny/crossref_metadata_2025 huggingface dataset:
Microfungal Flora of Apis mellifera anatoliaca (Hymenoptera: Apidae)and Varroa destructor (Mesostigmata: Varroidae)from the Eastern Black Sea Region and Fungal Vector Capacity in Honey Bee Colonies
Authors: USTA MEHTAP
Published: November 2023

Honey bees have great economic importance both in Turkey and in the world with their products and their contribution to pollination. For this reason, many microflora and microbiota studies have been carried out on bees. While these studies were only aimed at the isolation of pathogens, today, the ecological roles of non-pathogenic flora members and how they can be utilised are being investigated. Considering the importance of pathogens, it is expected that the number of studies will be high. This study was carried out to determine the microfungal flora of the body surfaces and digestive systems of dead honey bee (Apis mellifera anatoliaca) and Varroa destructor samples taken from different apiaries in the Eastern Black Sea Region (Gümüşhane, Trabzon, Artvin and Ordu) in 2022. As a result of the study, a total of 11 different fungal species belonging to the genera Penicillium, Alternaria, Mucor, Trichoderma, Fusarium, Aspergillus and Verticillium were identified and the relationships of these fungi with bees were discussed based on the literature.
Molecular epidemiology of Streptococcus agalactiae in non-pregnant populations: a systematic review
Authors: Founou Luria Leslie , Khan Uzma Basit , Medugu Nubwa , Pinto Tatiana C. A. , Darboe Saffiatou , Chendi Zhu , Founou Raspail Carrel , To Ka-Ning , Jamrozy Dorota , Karampatsas Konstantinos , Carr Victoria R. , Pepper Kevin , Dangor Ziyaad , Ip Margaret , Le Doare Kirsty , Bentley Stephen D.
Published: November 2023

Streptococcus agalactiae

(group B

Streptococcus

, GBS) has recently emerged as an important pathogen among adults. However, it is overlooked in this population, with all global efforts being directed towards its containment among pregnant women and neonates. This systematic review assessed the molecular epidemiology and compared how the lineages circulating among non-pregnant populations relate to those of pregnant and neonatal populations worldwide. A systematic search was performed across nine databases from 1 January 2000 up to and including 20 September 2021, with no language restrictions. The Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Tool (PCAT) was used to assess the quality of included studies. The global population structure of GBS from the non-pregnant population was analysed using in silico typing and phylogenetic reconstruction tools. Twenty-four articles out of 13 509 retrieved across 9 databases were eligible. Most studies were conducted in the World Health Organization European region (12/24, 50 %), followed by the Western Pacific region (6/24, 25 %) and the Americas region (6/24, 25 %). Serotype V (23%, 2310/10240) and clonal complex (CC) 1 (29 %, 2157/7470) were the most frequent serotype and CC, respectively. The pilus island PI1 : PI2A combination (29 %, 3931/13751) was the most prevalent surface protein gene, while the tetracycline resistance tetM (55 %, 5892/10624) was the leading antibiotic resistance gene. This study highlights that, given the common serotype distribution identified among non-pregnant populations (V, III, Ia, Ib, II and IV), vaccines including these six serotypes will provide broad coverage. The study indicates advanced molecular epidemiology studies, especially in resource-constrained settings for evidence-based decisions. Finally, the study shows that considering all at-risk populations in an inclusive approach is essential to ensure the sustainable containment of GBS.
Bioinformatic investigation of discordant sequence data for SARS-CoV-2: insights for robust genomic analysis during pandemic surveillance
Authors: Zufan Sara E. , Lau Katherine A. , Donald Angela , Hoang Tuyet , Foster Charles S. P. , Sikazwe Chisha , Theis Torsten , Rawlinson William D. , Ballard Susan A. , Stinear Timothy P. , Howden Benjamin P. , Jennison Amy V. , Seemann Torsten
Published: November 2023

The COVID-19 pandemic has necessitated the rapid development and implementation of whole-genome sequencing (WGS) and bioinformatic methods for managing the pandemic. However, variability in methods and capabilities between laboratories has posed challenges in ensuring data accuracy. A national working group comprising 18 laboratory scientists and bioinformaticians from Australia and New Zealand was formed to improve data concordance across public health laboratories (PHLs). One effort, presented in this study, sought to understand the impact of the methodology on consensus genome concordance and interpretation. SARS-CoV-2 WGS proficiency testing programme (PTP) data were retrospectively obtained from the 2021 Royal College of Pathologists of Australasia Quality Assurance Programmes (RCPAQAP), which included 11 participating Australian laboratories. The submitted consensus genomes and reads from eight contrived specimens were investigated, focusing on discordant sequence data and findings were presented to the working group to inform best practices. Despite using a variety of laboratory and bioinformatic methods for SARS-CoV-2 WGS, participants largely produced concordant genomes. Two participants returned five discordant sites in a high-Cτ replicate, which could be resolved with reasonable bioinformatic quality thresholds. We noted ten discrepancies in genome assessment that arose from nucleotide heterogeneity at three different sites in three cell-culture-derived control specimens. While these sites were ultimately accurate after considering the participants’ bioinformatic parameters, it presented an interesting challenge for developing standards to account for intrahost single nucleotide variation (iSNV). Observed differences had little to no impact on key surveillance metrics, lineage assignment and phylogenetic clustering, while genome coverage <90 % affected both. We recommend PHLs bioinformatically generate two consensus genomes with and without ambiguity thresholds for quality control and downstream analysis, respectively, and adhere to a minimum 90 % genome coverage threshold for inclusion in surveillance interpretations. We also suggest additional PTP assessment criteria, including primer efficiency, detection of iSNVs and minimum genome coverage of 90 %. This study underscores the importance of multidisciplinary national working groups in informing guidelines in real time for bioinformatic quality acceptance criteria. It demonstrates the potential for enhancing public health responses through improved data concordance and quality control in SARS-CoV-2 genomic analysis during pandemic surveillance.
Assessing the Impact of Non-Pharmaceutical Interventions on COVID-19: A Combined CCE and Quantile Regression Approach
Authors: Mishra Kaibalyapati
Published: November 2023

This paper tries to quantify the impact of government policy intervention on the death due to COVID-19 in India. I use the Oxford COVID-19 Government Response Tracker (OxCGRT), a longitudinal database of daily government response from Jan 28th, 2020, when the first COVID case was diagnosed in India till December 31st, 2022. Here government responses are captured in form of,stringencymeasures,containmentmeasures,economic supportmeasures, and theoverall government support, providing a holistic assessment of the government’s efforts in mitigating the virus’s incidence. I quantify both the average relation and causality at the to understand the impacts of NPIs with COVID-19 incidence in terms of deaths and infections due to COVID-19. Short-term analysis reveals a significant relationship between various non-pharmaceutical interventions (NPIs) and the logarithmic change in COVID-19 deaths. Higher infection rates are strongly associated with increased deaths, with positive coefficients. Stringent measures, containment actions, and economic support show negative coefficients, indicating that these interventions effectively reduce deaths in the short term. The overall government support, which aggregates all three NPIs, also demonstrates a significant negative effect on deaths, highlighting the importance of stringent and immediate measures in controlling the death toll early in the pandemic. In the long term, the analysis continues to emphasize the importance of infection rates and NPIs. Long-term coefficients for infection rates and various NPIs are consistently significant and negative, indicating that sustained interventions significantly reduce mortality over time. Specific measures like stringency, containment, and economic support show substantial negative impacts underscoring the long-term benefits of maintaining rigorous public health measures. Further, causality analysis confirms that relationship among government interventions and COVID-19 incidences were mostly bidirectional, meaning more deaths (or infections) leads to stricter interventions that in turn further reduce deaths.

JEL

C23, C54, I18, I38
WITHDRAWN: Flight muscle coordination and body orientation changes of Locusta migratoria during collision avoidance behaviour
Authors: Manchester Cody W. , Gray John R.
Published: November 2023

Withdrawal Statement

The authors have withdrawn this manuscript because of the need for further data analysis. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Long-term B cell memory emerges at uniform relative rates in the human immune response
Authors: Cvijović Ivana , Swift Michael , Quake Stephen R.
Published: November 2023

B cells generate pathogen-specific antibodies and play an essential role in providing adaptive protection against infection. Antibody genes are modified in evolutionary processes acting on the B cell populations within an individual. These populations proliferate, differentiate, and migrate to long-term niches in the body. However, the dynamics of these processes in the human immune system are primarily inferred from mouse studies. We addressed this gap by sequencing the antibody repertoire and transcriptomes from single B cells in four immune-rich tissues from six individuals. We find that B cells descended from the same pre-B cell (“lineages”) often co-localize within the same tissue, with the bone marrow harboring the largest excess of lineages without representation in other tissues. Within lineages, cells with different levels of somatic hypermutation are uniformly distributed among tissues and functional states. This suggests that the relative probabilities of localization and differentiation outcomes change negligibly during affinity maturation, and quantitatively agrees with a simple dynamical model of B cell differentiation. While lineages strongly co-localize, we find individual B cells nevertheless make independent differentiation decisions. Proliferative antibody secreting cells, however, deviate from these global patterns. These cells are often clonally expanded, their clones appear universally distributed among all sampled organs, and form lineages with an excess of cells of the same type. Collectively, our findings show the limits of peripheral blood monitoring of the immune repertoire, and provide a probabilistic model of the dynamics of antibody memory formation in humans.
In-bore MRI-compatible Transrectal Ultrasound and Photoacoustic Imaging
Authors: Murakami Ryo , Wang Yang , Lesniak Wojciech G. , Tsumura Ryosuke , Tang Yichuan , Tsunoi Yasuyuki , Nycz Christopher J. , Pomper Martin G. , Fischer Gregory S. , Zhang Haichong K.
Published: November 2023

Prostate cancer (PCa) is known as one of the most prevalent and fatal cancer types. This report describes an MRI-compatible photoacoustic/ultrasound (PA/US) imaging platform to improve the diagnosis of PCa. In the proposed solution, PA imaging, which offers real-time, non-ionizing imaging with high sensitivity and specificity, is combined with MRI, aiming to overcome PA’s limited field of view (FOV) and make PA scalable for translation to clinical settings. Central to the design of the system is a reflector-based transrectal probing mechanism composed of MRI-compatible materials. The linear transducer with a center hole for optical fiber delivery can be mechanically actuated to form a multi-angled scan, allowing PA/US imaging from varied cross-sectional views. Performance assessment was carried out in phantom and ex-vivo settings. We confirmed the MRI compatibility of the system and demonstrated the feasibility of its tri-modal imaging capability by visualizing a tubing phantom containing contrast agents. The ex-vivo evaluation of targeted tumor imaging capability was performed with a mouse liver sample expressing PSMA-positive tumors, affirming the system’s compatibility in spectroscopic PA (sPA) imaging with biological tissue. These results support the feasibility of the in-bore MRI-compatible transrectal PA and US and the potential clinical adaptability.
Delayed cortical engagement associated with balance dysfunction after stroke
Authors: Palmer Jacqueline A. , Payne Aiden M. , Mirdamadi Jasmine L. , Ting Lena H. , Borich Michael R.
Published: November 2023

Cortical resources are typically engaged for balance and mobility in older adults, but these resources are impaired post-stroke. Although slowed balance and mobility after stroke have been well-characterized, the effects of unilateral cortical lesions due to stroke on neuromechanical control of balance is poorly understood. Our central hypothesis is that stroke impairs the ability to rapidly and effectively engage the cerebral cortex during balance and mobility behaviors, resulting in asymmetrical contributions of each limb to balance control. Using electroencephalography (EEG), we assessed cortical N1 responses evoked over fronto-midline regions (Cz) during balance recovery in response to backward support-surface perturbations loading both legs, as well as posterior-lateral directions that preferentially load the paretic or nonparetic leg. Cortical N1 responses were smaller and delayed in the stroke group. While older adults exhibited weak or absent relationships between cortical responses and clinical function, stroke survivors exhibited strong associations between slower N1 latencies and slower walking, lower clinical mobility, and lower balance function. We further assessed kinetics of balance recovery during perturbations using center of pressure rate of rise. During backward support-surface perturbations that loaded the legs bilaterally, balance recovery kinetics were not different between stroke and control groups and were not associated with cortical response latency. However, lateralized perturbations revealed slower kinetic reactions during paretic loading compared to controls, and to non-paretic loading within stroke participants. Individuals post stroke had similar nonparetic-loaded kinetic reactions to controls implicating that they effectively compensate for impaired paretic leg kinetics when relying on the non-paretic leg. In contrast, paretic-loaded balance recovery revealed time-synchronized associations between slower cortical responses and slower kinetic reactions only in the stroke group, potentially reflecting the limits of cortical engagement for balance recovery revealed within the behavioral context of paretic motor capacity. Overall, our results implicate individuals after stroke may be uniquely limited in their balance ability by the slowed speed of their cortical engagement, particularly under challenging balance conditions that rely on the paretic leg. We expect this neuromechanical insight will enable progress toward an individualized framework for the assessment and treatment of balance impairments based on the interaction between neuropathology and behavioral context.
Unveiling Vulnerabilities in Maternal-Child Health amidst COVID-19: A Cross-Sectional Study on Food Insecurity and Socio-Demographic Disparities in the U.S.
Authors: Henkes Zoe , Romo-Palafox Maria J.
Published: November 2023

Objective

Early infancy is a critical time of development when stresses, nutritional deficiencies, and other challenges have lifelong consequences. Social distancing regulations due to the COVID-19 pandemic in 2020 led to abrupt changes in work status, childcare accessibility, and food availability.

Design

This cross-sectional study assessed responses regarding experiences during the COVID-19 pandemic, including food insecurity (validated two-question screener), WIC use, and changes in childcare accessibility and work status. Data were assessed using logistic regressions while controlling for sociodemographic factors.

Setting

National U.S. online survey in July–August 2020.

Participants

U.S. mothers (n=1861) with infants ≤12 months old.

Results

We detected a 34% increase in perceived food insecurity during July–August 2020 compared to that before the pandemic. Hispanic mothers had 74% higher odds of becoming food insecure than non-Hispanic White mothers. Mothers with infants <9 weeks old had a 7% increase in WIC utilization, although no overall increase in WIC usage was detected. Most mothers (71%) reported moderate or extreme impacts from the pandemic, with higher odds associated with childcare interruptions, working from home, and identifying as Hispanic or non-Hispanic Black.

Conclusions

Our findings reveal specific sociodemographic groups of mothers with infants who were especially vulnerable during the COVID-19 pandemic. These insights hold significant value for tailoring supportive programs, equipping these groups for potential socioeconomic upheavals, and aiding their transition into the post-pandemic world.
Maternal Controlling Parenting and Child-Perceived Mother-Child Attachment Mediate the Association between Maternal Adverse Childhood Experiences and Adolescent Behavioural Difficulties
Authors: Shi Yuze , Xie Shuya , MacBeth Angus
Published: November 2023

Background

Maternal adverse childhood experiences (ACEs) are risk factors for increased mental health difficulties. However, the intergenerational transmission mechanisms between maternal ACEs and adolescent behavioural difficulties are poorly understood. The current study modelled the mediating effects of maternal controlling parenting and child-perceived mother-child attachment on the association between maternal ACEs and behavioural difficulties.

Methods

Data were obtained from Growing Up in Scotland, a nationally representative prospective probability cohort study of Scottish adolescents (N= 2223), followed up at 14-15 years of age. Hierarchical multivariate linear regression analyses were used to examine the strength of predictors (maternal ACEs, maternal controlling parenting, child-perceived mother-child attachment) on levels of adolescent behavioural difficulties. Mediation analyses were used to examine the serial mediating effects of maternal controlling parenting and child-perceived mother-child attachment.

Results

Regression analysis results indicated maternal ACEs were associated with adolescent behavioural difficulties. Serial mediation results indicated a significant indirect effect of maternal ACEs on adolescent mental health outcomes, through maternal controlling parenting and child-perceived mother-child attachment.

Conclusion

The study indicates that maternal controlling parenting and child-perceived mother-child attachment are mechanisms mediating the effect of maternal ACEs on adolescent behavioural difficulties. Consequently, attending to the impact of both maternal and children’s factors may improve policy programming to ameliorate the intergenerational impact of maternal ACEs on adolescent young peoples’ mental health.

Key points

Research suggests maternal adverse childhood experiences have intergenerational impacts on children.

Maternal controlling parenting and child-perceived mother-child attachment potentially mediate the intergenerational link between maternal ACEs and behavioural difficulties of young people.

There is a lack of research examining these mechanisms in adolescence.

Maternal controlling parenting and child-perceived mother-child attachment mediate the link between maternal ACEs and adolescent internalizing behaviours, externalizing behaviours, and anxiety; with a small but significant serial mediating path through these two mediators.

Policy programming should incorporate both consideration of maternal and child factors in adolescent mental health.
Insights into Ancestral Diversity in Parkinson’s Disease Risk: A Comparative Assessment of Polygenic Risk Scores
Authors: Saffie-Awad Paula , Makarious Mary B , Elsayed Inas , Sanyaolu Arinola O. , Crea Peter Wild , Schumacher Schuh Artur F , Levine Kristin S , Vitale Dan , Koretsky Mathew J , Kim Jeffrey , Leal Thiago Peixoto , Periñan María Teresa , Dey Sumit , Noyce Alastair J , Reyes-Palomares Armando , Rodriguez-Losada Noela , Foo Jia Nee , Mohamed Wael , Heilbron Karl , Norcliffe-Kaufmann Lucy , Rizig Mie , Okubadejo Njideka , Nalls Mike A , Blauwendraat Cornelis , Singleton Andrew , Leonard Hampton , Mata Ignacio F. , Bandres-Ciga Sara ,   the Global Parkinson’s Genetics Program (GP2)
Published: November 2023

Objectives

To evaluate and compare different polygenic risk score (PRS) models in predicting Parkinson’s disease (PD) across diverse ancestries, focusing on identifying the most suitable approach for each population and potentially contributing to equitable advancements in precision medicine.

Methods

We constructed a total of 105 PRS across individual level data from seven diverse ancestries. First, a cross-ancestry conventional PRS comparison was implemented by utilizing the 90 known European risk loci with weighted effects from four independent summary statistics including European, East Asian, Latino/Admixed American, and African/Admixed. These models were adjusted by sex, age, and principal components (28 PRS) and by sex, age, and percentage of admixture (28 PRS) for comparison. Secondly, a novel and refined multi-ancestry best-fit PRS approach was then applied across the seven ancestries by leveraging multi-ancestry meta-analyzed summary statistics and using a p-value thresholding approach (49 PRS) to enhance prediction applicability in a global setting.

Results

European-based PRS models predicted disease status across all ancestries to differing degrees of accuracy. Ashkenazi Jewish had the highest Odds Ratio (OR): 1.96 (95% CI: 1.69-2.25, p < 0.0001) with an AUC (Area Under the Curve) of 68%. Conversely, the East Asian population, despite having fewer predictive variants (84 out of 90), had an OR of 1.37 (95% CI: 1.32-1.42) and an AUC of 62%, illustrating the cross-ancestry transferability of this model. Lower OR alongside broader confidence intervals were observed in other populations, including Africans (OR =1.38, 95% CI: 1.12-1.63, p=0.001). Adjustment by percentage of admixture did not outperform principal components. Multi-ancestry best-fit PRS models improved risk prediction in European, Ashkenazi Jewish, and African ancestries, yet didn’t surpass conventional PRS in admixed populations such as Latino/American admixed and African admixed populations.

Interpretation

The present study represents a novel and comprehensive assessment of PRS performance across seven ancestries in PD, highlighting the inadequacy of a ‘one size fits all’ approach in genetic risk prediction. We demonstrated that European based PD PRS models are partially transferable to other ancestries and could be improved by a novel best-fit multi-ancestry PRS, especially in non-admixed populations.
Interactions between the gut microbiome, dietary restriction, and aging in genetically diverse mice
Authors: Litichevskiy Lev , Considine Maya , Gill Jasleen , Shandar Vasuprada , Cox Timothy O. , Descamps Hélène C. , Wright Kevin M. , Amses Kevin R. , Dohnalová Lenka , Liou Megan J. , Tetlak Monika , Galindo-Fiallos Mario R. , Wong Andrea C. , Lundgren Patrick , Kim Junwon , Uhr Giulia T. , Rahman Ryan J. , Mason Sydney , Merenstein Carter , Bushman Frederic D. , Raj Anil , Harding Fiona , Chen Zhenghao , Prateek G.V. , Mullis Martin , Deighan Andrew G. , Robinson Laura , Tanes Ceylan , Bittinger Kyle , Chakraborty Meenakshi , Bhatt Ami S. , Li Hongzhe , Barnett Ian , Davenport Emily R. , Broman Karl W. , Cohen Robert L. , Botstein David , Freund Adam , Francesco Andrea Di , Churchill Gary A. , Li Mingyao , Thaiss Christoph A.
Published: November 2023

The intestinal microbiome changes with age, but the causes and consequences of microbiome aging remain unclear. Furthermore, the gut microbiome has been proposed to mediate the benefit of lifespan- extending interventions such as dietary restriction, but this hypothesis warrants further exploration. Here, by analyzing 2997 metagenomes collected longitudinally from 913 deeply phenotyped, genetically diverse mice, we provide new insights into the interplay between the microbiome, aging, dietary restriction, host genetics, and a wide range of health parameters. First, we find that microbiome uniqueness increases with age across datasets and species. Moreover, age-associated changes are better explained by cumulative exposure to stochastic events (neutral theory) than by the influence of an aging host (selection theory). Second, we unexpectedly find that the majority of microbiome features are significantly heritable and that the amount of variation explained by host genetics is as large as that of aging and dietary restriction. Third, we find that the intensity of dietary restriction parallels the extent of microbiome changes and that dietary restriction does not rejuvenate the microbiome. Lastly, we find that the microbiome is significantly associated with multiple health parameters — including body composition, immune parameters, and frailty — but not with lifespan. In summary, this large and multifaceted study sheds light on the factors influencing the microbiome and aspects of host physiology modulated by the microbiome.
Stress Knowledge Map: A knowledge graph resource for systems biology analysis of plant stress responses
Authors: Bleker Carissa , Ramšak Živa , Bittner Andras , Podpečan Vid , Zagorščak Maja , Wurzinger Bernhard , Baebler Špela , Petek Marko , Križnik Maja , Dieren Annelotte van , Gruber Juliane , Afjehi-Sadat Leila , Županič Anže , Teige Markus , Vothknecht Ute C. , Gruden Kristina
Published: November 2023

Stress Knowledge Map (SKM,https://skm.nib.si) is a publicly available resource containing two complementary knowledge graphs describing current knowledge of biochemical, signalling, and regulatory molecular interactions in plants: a highly curated model of plant stress signalling (PSS, 543 reactions) and a large comprehensive knowledge network (CKN, 488,390 interactions). Both were constructed by domain experts through systematic curation of diverse literature and database resources. SKM provides a single entrypoint for plant stress response investigations and the related growth tradeoffs. SKM provides interactive exploration of current knowledge. PSS is also formulated as qualitative and quantitative models for systems biology, and thus represents a starting point of a plant digital twin. Here, we describe the features of SKM and show, through two case studies, how it can be used for complex analyses, including systematic hypothesis generation, design of validation experiments, or to gain new insights into experimental observations in plant biology.
Regulators of health and lifespan extension in genetically diverse mice on dietary restriction
Authors: Di Francesco Andrea , Deighan Andrew G. , Litichevskiy Lev , Chen Zhenghao , Luciano Alison , Robinson Laura , Garland Gaven , Donato Hannah , Schott Will , Wright Kevin M. , Raj Anil , Prateek G.V. , Mullis Martin , Hill Warren , Zeidel Mark , Peters Luanne , Harding Fiona , Botstein David , Korstanje Ron , Thaiss Christoph A. , Freund Adam , Churchill Gary A.
Published: November 2023

Caloric restriction (CR) delays aging and extends healthy lifespan in multiple species. Alternative forms of dietary restriction (DR) such as intermittent fasting (IF) have drawn significant interest as a more sustainable regimen, but the landscape of longevity-promoting dietary interventions remains largely unexplored. Identifying the most robust, efficacious, and experimentally tractable modes of DR is key to better understanding and implementing effective longevity interventions for human healthspan. To that end, we have performed an extensive assessment of DR interventions, investigating the effects of graded levels of CR (20% and 40%) and IF (1 day and 2 days of fasting per week) on the health and survival of 960 genetically diverse female mice. All interventions extended lifespan, although only CR significantly reduced the mortality doubling time. Notably, IF did not extend lifespan in mice with high pre-intervention bodyweight. We carried out extensive phenotyping to determine the health effects of long-term DR and to better understand the mechanisms driving within-diet heterogeneity in lifespan. The top within-diet predictor of lifespan was the ability of mice to maintain bodyweight through periods of handling, an indicator of stress resilience. Additional predictors of long lifespan include specific changes in immune cells, red blood cell distribution width (RDW), and retention of adiposity in late life. We found that lifespan is heritable (h2= 0.24), and that genetic background has a larger influence on lifespan than dietary interventions. We identified a significant association for lifespan and RDW on chromosome 18 that explained 4.3% of the diet-adjusted variation in lifespan. Diet-induced changes on metabolic traits, although beneficial, were relatively poor predictors of lifespan, arguing against the long-standing notion that DR works by counteracting the negative effects of obesity. These findings indicate that improving health and extending lifespan are not synonymous and that metabolic parameters may be inappropriate endpoints for evaluating aging interventions in preclinical models and clinical trials.
Pollen production, pollen viability and autofertility in faba bean (Vicia fabaL.) and their relationship with realized paternal success
Authors: Brünjes Lisa , Link Wolfgang
Published: November 2023

In animal-pollinated plants, pollen dispersal depends on several plant and animal characteristics which may influence a plant’s paternal success. Different paternal success influences the genetic contribution of a genotype to the next generation. In breeding of partially allogamous faba bean (Vicia fabaL.), synthetic populations are developed where equal contributions of genotypes to the next generation are desired to reduce inbreeding. Since direct assessments of paternity are elaborate and costly, we studied whether components of plant fitness such as pollen production and pollen viability can be used as estimates for paternity. In a field experiment and a caged outdoor pot experiment, a total of 18 genotypes (14 inbred lines, 4 F1 hybrids) of faba bean were evaluated for pollen production, pollen viability and autofertility. Pollen production was higher at the lower than at the upper inflorescences and we found mid-parent heterosis for this trait. The relative pollen viability was high (93 % – 97 % in pots, 88 % – 95 % in field) indicating that fertilization success is rather not limited by a low pollen quality. Only in the field, pollen of F1 hybrids was more viable than pollen of inbred lines. Autofertility ranged from 0 % – 98 %, with very marked average mid-parent heterosis for this trait. Autofertility did not seem to be related to either pollen production, pollen viability or paternal success. However, pollen production and pollen viability were highly correlated with paternal success. Hence, data on pollen production and viability might be useful in breeding of synthetic populations to choose parents with small differences in paternal successes, to reduce inbreeding and better exploit heterosis.
HCN channels enhance robustness of patterned activity propagation in heterogeneous conductance-based ring networks
Authors: Mittal Divyansh , Narayanan Rishikesh
Published: November 2023

Continuous attractor network (CAN) models lend a powerful framework that has provided deep insights about several aspects of brain physiology. However, most CAN models employ homogeneous, rate-based or artificially spiking neurons with precisely structured synaptic connectivity, precluding detailed analyses of the impact of specific neural-circuit components and associated heterogeneities on CAN dynamics. To address this caveat, we built populations of tunable and scalable conductance-based, physiologically constrained, ring network models consisting of distinct rings of excitatory and inhibitory neurons. We assessed the network for its ability to sustain robust propagation of patterned activity across the rings. First, in homogeneous ring networks, we found that robust activity propagation could be sustained through several different combinations of synaptic weights, demonstrating synaptic degeneracy in the emergence of robust activity propagation. We incorporated intrinsic heterogeneity through randomized perturbations to ion channel parameters of all neurons and synaptic heterogeneity by adding jitter to the Mexican-hat connectivity between inhibitory neurons. We found the number of networks exhibiting robust propagation of patterned activity to reduce with increase in the degree of synaptic or intrinsic heterogeneities. Motivated by the ability of intrinsic neuronal resonance to stabilize heterogeneous rate-based CAN models, we hypothesized that increasing HCN-channel (a resonating conductance) density would stabilize activity propagation in heterogeneous ring networks. Strikingly, we observed that increases in HCN-channel density resulted in a pronounced increase in the proportion of heterogeneous networks that exhibited robust activity propagation, across multiple trials and across three degrees of either form of heterogeneity. Together, heterogeneous networks made of neurons with disparate intrinsic properties and variable HCN channel densities yielded robust activity propagation, demonstrating intrinsic degeneracy in the emergence of robust activity propagation. Finally, as HCN channels also contribute to changes in excitability, we performed excitability-matched controls with fast HCN channels that do not introduce resonance. We found that fast HCN channels did not stabilize heterogeneous network dynamics over a wide range of conductance values, suggesting that the slow negative feedback loop introduced by HCN channels is a critical requirement for network stabilization. Together, our results unveil a cascade of degeneracy in ring-network physiology, spanning the molecular-cellular-network scales. These results also demonstrate a critical role for the widely expressed HCN channels in enhancing the robustness of heterogeneous neural circuits by implementing a slow negative feedback loop at the cellular scale.
permGWAS2: Enhanced and Accelerated Permutation-based Genome-Wide Association Studies
Authors: John Maura , Korte Arthur , Grimm Dominik G.
Published: November 2023

Motivation

Permutation-based significance thresholds have been shown to be a robust alternative to Bonferroni-based significance thresholds in genome-wide association studies (GWAS). However, the implementation of permutation-based thresholds is computationally demanding. The recently published methodpermGWASintroduced a batch-wise approach using 4D tensors to efficiently compute permutation-based GWAS. However, running multiple univariate tests in parallel leads to many repetitive computations and increased computational resources. More importantly, the previous version ofpermGWASdoes not take into account the population structure when permuting the phenotype.

Results

We proposepermGWAS2, an improved and accelerated version that uses a block matrix decomposition to optimize computations, thereby reducing redundant computations. It also introduces an alternative permutation strategy that takes into account the population structure during permutation. We show that this improved framework provides a more streamlined approach to performing permutation-based GWAS with a lower false discovery rate compared to the previous version and the traditional Bonferroni correction.

Availability

permGWAS2is open-source and publicly available on GitHub for download:https://github.com/grimmlab/permGWAS.
Size-dependent harvest mortality indirectly affects boldness, feeding rate, and behaviour-linked gene expression in a decade-long selection experiment on guppies
Authors: Diaz Pauli Beatriz , Tronci Valentina , Gomes Ana S. , Heino Mikko
Published: November 2023

Fisheries-induced mortality is size-selective, commonly targeting large individuals, which leads to evolution towards smaller size and early maturation. However, little is known on whether behaviour is affected. Here we aimed at testing whether size-dependent harvest indirectly affects behavioural traits that might have ecological consequences. Specifically, we assessed feeding rate – which affects prey abundance –, boldness – which determines a fish vulnerability to predators –, and sociability – which determines how a fish interacts with conspecifics and ultimately affects foraging and predation avoidance. In addition, we tested whether the differences in behaviour were associated to differences in selected key genes expression, to understand its molecular regulation. With a decade-long selection experiment on guppiesPoecilia reticulata, we created populations with life histories adapted to positively size-dependent harvest, i.e., like that induced by fishing (fast life history). For comparison, we also created populations adapted to the opposite size-selection, and populations experiencing no size-selection. Fish exposed to positively size-dependent harvest were bolder, more likely to feed, were more social/aggressive, and expressed less brainavt (arginine vasotocin) relative to those exposed to negatively size-dependent harvest. In addition, higher expression ofthandth2(tyrosine hydroxylase 1 and 2), andneuroD2(neuronal differentiation factor 2) were linked with bolder behaviour and higher feeding in normal (no-threat) conditions, while higheravt,th, andneuroD2were associated with higher sociability/aggression after a threat. Fish exposed to positively size-dependent harvest presented behaviours linked to faster life histories as theoretically expected. Therefore, harvest selection does not only affect fish size and life history, but indirectly leads to boldness and higher feeding rates, which potentially results in higher vulnerability to predators and higher pressure on prey abundance, respectively. Our results suggest that size-dependent mortality have further consequences to the ecosystem, beyond the target species.
A rolling circle-replicating plasmid as an Inovirus phage satellite
Authors: Schmid Nicole E , Brandt David , Walasek Claudia , Rolland Clara , Wittmann Johannes , Müsken Mathias , Kalinowski Jörn , Thormann Kai M
Published: November 2023

Bacterial viruses (phages) are potent agents of lateral gene transfer and thus are important drivers of evolution. A group of mobile genetic elements (MGEs), referred to as phage satellites, exploit phages to disseminate their own genetic material. Here we isolated a novel member of the genusInovirus,Shewanellaphage Dolos, along with an autonomous rolling circle-replicating plasmid, pDolos. Dolos causes a chronic infection in its hostShewanella oneidensisby phage production with only minor effects on the host cell proliferation. When present, plasmid pDolos hijacks Dolos functions to be predominantly packaged into phage virions and released into the environment. pDolos can disseminate further genetic material encoding, e.g., resistances, fluorophores, and metabolically active proteins, to host cells sensitive to Dolos infection. Given the rather simple requirements of a plasmid for takeover of an inovirus, the wide distribution of phages of this group and the broad spectrum of rolling circle-replicating plasmids, we speculate that similar phage-satellite systems are common among bacteria.
Humans rationally balance detailed and temporally abstract world models
Authors: Kahn Ari E. , Daw Nathaniel D.
Published: November 2023

How do people model the world’s dynamics to guide mental simulation and evaluate choices? One prominent approach, the Successor Representation (SR), takes advantage of temporal abstraction of future states: by aggregating trajectory predictions over multiple timesteps, the brain can avoid the costs of iterative, multi-step mental simulation. Human behavior broadly shows signatures of such temporal abstraction, but finer-grained characterization of individuals’ strategies and their dynamic adjustment remains an open question. We developed a novel task to measure SR usage during dynamic, trial-by-trial learning. Using this approach, we find that participants exhibit a mix of SR and model-based learning strategies that varies across individuals. Further, by dynamically manipulating the task contingencies within-subject to favor or disfavor temporal abstraction, we observe evidence of resource-rational reliance on the SR, which decreases when future states are less predictable. Our work adds to a growing body of research showing that the brain arbitrates between approximate decision strategies. The current study extends these ideas from simple habits into usage of more sophisticated approximate predictive models, and demonstrates that individuals dynamically adapt these in response to the predictability of their environment.
Oral Fentanyl Consumption and Withdrawal Impairs Fear Extinction Learning and Enhances Basolateral Amygdala Principal Neuron Excitatory-Inhibitory Balance in Male and Female Mice
Authors: Downs Anthony M. , Kmiec Gracianne , McElligott Zoé A.
Published: November 2023

The number of opioid overdose deaths has increased over the past several years, mainly driven by an increase in the availability of highly potent synthetic opioids, like fentanyl, in the un-regulated drug supply. Over the last few years, changes in the drug supply, and in particular the availability of counterfeit pills containing fentanyl, have made oral use of opioids a more common route of administration. Here, we used a drinking in the dark (DiD) paradigm to model oral fentanyl self-administration using increasing fentanyl concentrations in male and female mice over 5 weeks. Fentanyl consumption peaked in both female and male mice at the 30 µg/mL dose, with female mice consuming significantly more fentanyl than male mice. Mice consumed sufficient fentanyl such that withdrawal was precipitated with naloxone, with males having more withdrawal symptoms, despite lower pharmacological exposure. We also performed behavioral assays to measure avoidance behavior and reward-seeking during fentanyl abstinence. Female mice displayed reduced avoidance behaviors in the open field assay, whereas male mice showed increased avoidance in the light/dark box assay. Female mice also exhibited increased reward-seeking in the sucrose preference test. Fentanyl-consuming mice of both sexes showed impaired cued fear extinction learning following fear conditioning and increased excitatory synaptic drive and increased excitability of BLA principal neurons. Our experiments demonstrate that long-term oral fentanyl consumption results in wide-ranging physiological and behavioral disruptions. This model could be useful to further study fentanyl withdrawal syndrome and behaviors and neuroplasticity associated with protracted fentanyl withdrawal.
Temperature-dependence and genetic variation in resource acquisition strategies in a model freshwater plant
Authors: Gillies Graydon J. , Angert Amy L. , Usui Takuji
Published: November 2023

Understanding how competition varies with environmental stress is critical to anticipating species and community responses to rapid environmental change. While the stress-gradient hypothesis predicts the strength of competition to decrease with increasing stress, our understanding of how competition varies with stress is limited by a lack of mechanistic understanding of how resource-use traits underlying competitive dynamics respond to stress.

Here, we use duckweeds in theLemnaspecies complex to measure how phenotypic and genetic variation inR*(a resource acquisition trait representing the minimum resource requirement for positive population growth) varies with high-temperature stress to better understand how stress alters competitive ability for essential resources.

We found that heat stress increased theR*ofLemnaplants for nitrogen acquisition. Because lowerR*values predict dominance in competitive dynamics where resources are limiting, this indicates that under stressful, high temperatures, plants could experience increased sensitivity to competition due to the higher resources required to sustain positive population growth rates.

We found minimal genetic variation inR*across 11 local genotypes within theLemnaspecies complex, indicating that selection on resource acquisition strategies for essential resources such as nitrogen may be constrained in nature. The expression of genetic variation inR*for nitrogen was further reduced under heat stress, suggesting that the response to selection forR*could be particularly constrained under high-temperature stress.

Contrary to predictions drawn from the gleaner-opportunist trade-off, we did not find evidence for a trade-off in resource acquisition strategies under benign conditions or high-temperature stress. Plants with lowerR*(i.e., higher growth rates under lower nitrogen levels) were not constrained to have lower growth rates under higher nitrogen levels, possibly because the chosen genotypes have not diverged across resource acquisition strategies or becauseLemnaspp. has escaped this constraint.

Importantly, our work outlines that high-temperature stress could increase sensitivity to competition through increased requirement for resources while reducing the evolutionary potential forLemnaspecies to respond to selection for resource traits. This study acts as a key step to understanding the mechanistic traits behind competitive dynamics in resource-limited and stressful environments.
6-Phosphogluconolactonase is critical for the efficient functioning of the pentose phosphate pathway
Authors: Phégnon Léa , Pérochon Julien , Uttenweiler-Joseph Sandrine , Cahoreau Edern , Millard Pierre , Létisse Fabien
Published: November 2023

The metabolic networks of microorganisms are remarkably robust to genetic and environmental perturbations. This robustness stems from redundancies such as gene duplications, isoenzymes, alternative metabolic pathways, and also from non-enzymatic reactions. In the oxidative branch of the pentose-phosphate pathway (oxPPP), 6-phosphogluconolactone hydrolysis into 6-phosphogluconate is catalysed by 6-phosphogluconolactonase (Pgl) but in the absence of the latter, the oxPPP flux is thought to be maintained by spontaneous hydrolysis. However, in Δpgl Escherichia coli, an extracellular pathway can also contribute to pentose-phosphate synthesis. This raises question as to whether the intracellular non-enzymatic reaction can compensate for the absence of 6-phosphogluconolactonase and, ultimately, on the role of 6-phosphogluconolactonase in central metabolism. Our results validate that the bypass pathway is active in the absence of Pgl, specifically involving the extracellular spontaneous hydrolysis of gluconolactones to gluconate. Under these conditions, metabolic flux analysis reveals that this bypass pathway accounts for the entire flux into the oxPPP. This alternative metabolic route - partially extracellular - sustains the flux through the oxPPP necessary for cell growth, albeit at a reduced rate in the absence of Pgl. Importantly, these findings imply that intracellular non-enzymatic hydrolysis of 6-phosphogluconolactone does not compensate for the absence of Pgl. This underscores the crucial role of Pgl in ensuring the efficient functioning of the oxPPP.