bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid assessment of cosmic radiation exposure in aviation based on BP neural network method
Authors: Wang Biao , Fang Meihua , Song Dingyi , Cheng Jianfei , Wu Kang
Published: May 2024

Cosmic radiation exposure is one of the important health concerns for aircrews. In this work, we constructed a back propagation neural network model for the real-time and rapid assessment of cosmic radiation exposure to the public in aviation. The multi-dimensional dataset for this neural network was created from modeling the process of cosmic ray transportation in magnetic field by geomagnetic cutoff rigidity method and air shower simulation by a Monte Carlo based Geant4 code. The dataset was characterized by parameters including cosmic ray energy spectrum, Kp-index, coordinated universal time, altitude, latitude, and longitude. The effective dose and dose rate was finally converted from the particle fluxes at flight position by the neural network. This work shows a good agreement with other models from International Civil Aviation Organization. It is also illustrated that the effective dose rate by galactic cosmic ray is <10 μSv h−1 and the value during ground level enhancement (GLE) 42 is 4 ~ 10 times larger on the routes calculated in this work. In GLE 69, the effective dose rate reaches several mSv h−1 in the polar region. Based on this model, a real-time warning system is achieved.
Differentiating neural sensitivity and bias during face-emotion processing in youth: a computational approach
Authors: Haller Simone P , Stoddard Joel , Cardenas Sofia I , Dombek Kelly , MacGillivray Caroline , Botz-Zapp Christian , Bui Hong N. T , Stavish Caitlin M , Kircanski Katharina , Jones Matt , Brotman Melissa A
Published: May 2024

The ability to interpret face-emotion displays is critical for the development of adaptive social interactions. Using a novel variant of a computational model and fMRI data, we examined behavioral and neural associations between two metrics of face-emotion labeling (sensitivity and bias) and age in youth. Youth and adults (n = 44, M age = 20.02, s.d. = 7.44, range = 8–36) completed an explicit face-emotion labeling fMRI task including happy to angry morphed face emotions. A drift-diffusion model was applied to choice and reaction time distributions to examine sensitivity and bias in interpreting face emotions. Model fit and reliability of parameters were assessed on adult data (n = 42). Linear and quadratic slopes modeled brain activity associated with dimensions of face-emotion valence and ambiguity during interpretation. Behaviorally, age was associated with sensitivity. The bilateral anterior insula exhibited a more pronounced neural response to ambiguity with older age. Associations between sensitivity and bias metrics and activation patterns indicated that systems encoding face-emotion valence and ambiguity both contribute to the ability to discriminate face emotions. The current study provides evidence for age-related improvement in perceptual sensitivity to facial affect across adolescence and young adulthood.
Meeting report: microbes as safeguards of the environment
Authors: Ramos Juan L , de Lorenzo Víctor , López Puri
Published: May 2024

From 12 to 14 March, a gathering of microbiologists and biotechnologists convened at the International University of Andalucía (UNIA) in Baeza (Jaén, Spain) under the auspices of UNIA and the Applied Microbiology International (AMI) Society. The primary objective of this meeting was to analyse the pivotal role microbes play in sustaining our planet in a broader context—both from the descriptive (what is the state of affairs) and the prescriptive perspective (what to do and look for regarding activities of interest). The workshop focused on exploring the ecological aspects of microbes in soil and water, including some extreme environments, the potential of microorganisms as promoters of plant growth and biocontrol agents as well as active large-scale catalysts for environmental health. Various topics were examined in this context, encompassing the application of microbes as platforms for the biosynthesis of value-added chemicals, bioremediation technologies, the concept of the circular economy, the emergence of zoonotic concerns within a dynamically changing global environment, and the role of microbes in precision nutrition and precision medicine. In alignment with the strategic plan of AMI, the discussion was focused on the background of the United Nations Sustainability Development Goals (UN SDGs). These targets were formulated at the beginning of the past decade to guide humanity towards a sustainable future. The UN SDGs aim to prevent the overstepping of planetary boundaries, which are endangering Earth’s biodiversity and even human survival.
Effect of acidosis in the late-finishing phase on rumen fermentation in feedlot steers
Authors: Linder Haley F , Berger Larry L , McCann Joshua C
Published: May 2024

The objective was to determine the effects of induced acidosis in the late-finishing phase on rumen fermentation in feedlot steers. Eleven ruminally cannulated steers (body weight [BW] = 795 kg ± 54) were blocked into two groups based on initial BW. For 195 d prior to the start of the study, cattle were consuming a basal finishing diet (60% dry-rolled corn, 15% modified distillers grains, 15% corn silage, and 10% ground corn-based supplement). Steers were randomly assigned to one of the two treatments: control (CON), or induced acidosis (ACD). Both treatments were fasted for 24 h then fed the basal finishing diet. Steers on the ACD treatment received 0.05% of BW of wheat starch via rumen cannula at 0800 and 2000 hours on day 1 and ad libitum refeeding following the fast. On days 1 and 2, CON steers were provided 25% of allotted feed every 6 h. Rumen fluid was collected every 4 h during the challenge period (hours 0 to 48), and 0, 6, and 12 h after feeding during the recovery period (hours 54 to 96). Rumen fluid was analyzed for pH, ammonia, volatile fatty acids (VFA), and lactate. Fecal grab samples were collected every 8 h to determine fecal pH. A treatment × day interaction (P = 0.03) was observed for dry matter intake during the challenge period with steers on the ACD treatments consuming more on day 1 than CON steers. Intake was not different on day 2 (P = 0.88). A treatment × hour effect (P < 0.01) was observed for ruminal pH during the challenge period with the ACD steers having a lesser pH than CON from hours 12 to 32. Duration of time below a pH of 5.6 during the challenge period was greater (P < 0.01) for ACD steers than CON. During the challenge period, a treatment × time interaction (P = 0.04) was observed for total VFA concentration with ACD steers having greater total VFA concentration from hours 12 to 36. Acetate to propionate ratio (A:P) was affected by treatment × hour (P = 0.04) with CON steers having greater A:P from hours 28 to 48. Rumen ammonia and lactate concentrations did not differ (P ≥ 0.25) between treatments or the interaction with time. Challenge and recovery period fecal pH were not affected (P ≥ 0.13) by treatment, time, or their interaction. Recovery period ruminal pH was not different (P = 0.99) between treatments. For the recovery period, total VFA and ammonia concentration were not affected by treatment, time, or their interaction (P ≥ 0.07). Ruminal pH and VFA were affected in the initial 48 h of induced acidosis in the late-finishing phase.
Scaling and sustaining research tested interventions: Lessons learned from Rhode Island Childhood Obesity Research Demonstration 3.0
Authors: Darling Katherine E , Evans Erin Whitney , Elwy Anashua Rani , Klinepier Kelly , Jelalian Elissa
Published: May 2024

Childhood obesity is a significant health problem associated with negative physical and mental health outcomes. Although evidence-based family healthy weight programs (FHWPs), such as JOIN for ME, have been developed, there is a significant lag before these are disseminated more broadly. This study outlines the process of participating in the Speeding Research-tested Interventions (SPRINT) program, highlighting lessons learned, to increase the reach of a previously tested and efficacious FHWP, JOIN for ME. Qualitative interviews were conducted with policymakers, benefits providers, employers, philanthropists, community stakeholders, and medical providers to iteratively test the developed JOIN for ME business model and identify themes regarding effective scaling and sustainability of an evidence-based FHWP. Rapid qualitative analysis of 45 interviews identified four key themes regarding scaling of an FHWP. These were (i) virtual program delivery, (ii) focus on equity, (iii) return on investment, and (iv) tie-in to local community. The process of engaging stakeholders from multiple backgrounds is critical to refining an efficacious program to ensure scalability and sustainment. The SPRINT process allows researchers to understand the marketplace for evidence-based interventions and develop adaptations for sustaining and scaling research tested programs.
Integrative taxonomic revision of the African thicket rats (Murinae: Grammomys): how genomics decreases the number of currently recognized species
Authors: Bryja Josef , Kerbis Peterhans Julian C , Lavrenchenko Leonid A , Nicolas Violaine , Denys Christiane , Bryjová Anna , Šumbera Radim , Mikula Ondřej
Published: May 2024

Thicket rats of the genus Grammomys are partly arboreal rodents distributed across a large part of sub-Saharan Africa. Previous work showed that their highest diversity is in forests and woodlands of Eastern Africa, that the evolutionary history of the genus roughly mirrors the evolution of African forests, and that the currently delimited species (names) do not correspond to major genetic clades. We used thousands of single nucleotide polymorphisms to perform phylogenomic analysis and to delimit genomic pools (i.e. candidate biological species). The resulting molecular operational taxonomic units were then compared with the most comprehensive sets of other available data (mitochondrial DNA variability, ecological requirements, morphology, karyotypes, sequences from the type material, etc.) and used for an integrative solution to the taxonomy of the genus. Our revision delimited seven species, which is less than the 12 recognized in the most recent literature on African rodents. We conclude that the African thicket rats represent a classic example of challenging problems in current integrative taxonomy. It is now relatively easy to obtain genomic data and to delimit candidate species, but it is much more complicated to give them species names using the valid rules of zoological nomenclature.
Liver‐specific deletion of de novo DNA methyltransferases protects against glucose intolerance in high‐fat diet‐fed male mice
Authors: Yao S. , Prates K. , Freydenzon A. , Assante G. , McRae A. F. , Morris M. J. , Youngson N. A.
Published: May 2024

Alterations to gene transcription and DNA methylation are a feature of many liver diseases including fatty liver disease and liver cancer. However, it is unclear whether the DNA methylation changes are a cause or a consequence of the transcriptional changes. It is even possible that the methylation changes are not required for the transcriptional changes. If DNA methylation is just a minor player in, or a consequence of liver transcriptional change, then future studies in this area should focus on other systems such as histone tail modifications. To interrogate the importance of de novo DNA methylation, we generated mice that are homozygous mutants for both Dnmt3a and Dnmt3b in post‐natal liver. These mice are viable and fertile with normal sized livers. Males, but not females, showed increased adipose depots, yet paradoxically, improved glucose tolerance on both control diet and high‐fat diets (HFD). Comparison of the transcriptome and methylome with RNA sequencing and whole‐genome bisulfite sequencing in adult hepatocytes revealed that widespread loss of methylation in CpG‐rich regions in the mutant did not induce loss of homeostatic transcriptional regulation. Similarly, extensive transcriptional changes induced by HFD did not require de novo DNA methylation. The improved metabolic phenotype of the Dnmt3a/3b mutant mice may be mediated through the dysregulation of a subset of glucose and fat metabolism genes which increase both glucose uptake and lipid export by the liver. However, further work is needed to confirm this.
Chaperone‐mediated autophagy protects the bone formation from excessive inflammation through PI3K/AKT/GSK3β/β‐catenin pathway
Authors: Hang Kai , Wang YiBo , Bai JinWu , Wang ZhongXiang , Wu WeiLiang , Zhu WeiWei , Liu ShuangAi , Pan ZhiJun , Chen JianSong , Chen WenHao
Published: May 2024

Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone‐mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic‐specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active‐β‐catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF‐α, through the PI3K/AKT/GSK3β/β‐catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF‐α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.
Dietary resilience of coral reef fishes to habitat degradation
Authors: Clever Friederike , Preziosi Richard F. , Nguyen Bryan , De Gracia Brígida , Quintero Helio , McMillan W. Owen , Altieri Andrew H. , O’Dea Aaron , Knowlton Nancy , Leray Matthieu
Published: May 2024

The ability of consumers to adjust their diet in response to resource shifts is a key mechanism allowing the persistence of populations and underlying species’ adaptive capacity. Yet on coral reefs, one of the marine habitats most vulnerable to global change, the extent to which species alter their diet remains poorly understood. Here, we integrated DNA-based gut content analyses (metabarcoding), otolith analysis, body condition, and field surveys to test how diet can mediate effects of habitat degradation on two invertivorous fishes:Chaetodon capistratus, a browser, andHypoplectrus puella, an active predator. Metabarcoding revealed significant dietary variation in both species across a habitat gradient. However, the response was more pronounced in the browser, whose diet was anthozoan-dominated on healthy reefs, whereas annelid-dominated on degraded reefs. We found reduced growth and body condition on degraded reefs in the browser but not the active predator. Our results reveal that dietary versatility can serve as a mechanism to cope with degraded environments, but that species differ as to whether these changes are sufficient to buffer from changes in habitat. We detected intraspecific dietary variation across sites that suggests food webs and energy flow differ at relatively small scales between healthy and degraded reefs.
Investigating Subpopulation Dynamics in Clonal CHO-K1 Cells with Single-Cell RNA Sequencing
Authors: Morina Luke B , Cao Haoyu Chris , Chen Alice , Kumar Swetha , McFarland Kevin S , Majewska Natalia I , Betenbaugh Michael J , Timp Winston
Published: May 2024

Chinese Hamster Ovary (CHO) cells are used to produce monoclonal antibodies and other biotherapeutics at industrial scale. Despite their ubiquitous nature in the biopharmaceutical industry, little is known about the behaviors of individual transfected clonal CHO cells. Most CHO cells are assessed on their ability to produce the protein of interest over time, known as their stability. But these CHO cells have primarily been studied in bulk, working under the assumption that these bulk samples are identical because of genetic clonality across the sample; however, this does not address other forms of cellular heterogeneity in these ostensibly clonal cells. It is possible these variable stability phenotypes reflect heterogeneity within the clonal samples. In this study, we performed single-cell RNA sequencing on two clonal CHO-K1 cell populations with different stability phenotypes over a 90 day culture period. Our data showed that the instability of the unstable clone was due in part to the emergence of a low-producing subpopulation in the aged samples. This low-producing subpopulation did not exhibit markers of cellular stress which were expressed in the higher-producing populations. Further multiomic investigation should be performed to better characterize this heterogeneity.
Stomata: Gatekeepers of Uptake and Defense Priming by Green Leaf Volatiles in plants
Authors: Maleki Feizollah A. , Seidl-Adams Irmgard , Felton Gary W. , Kersch-Becker Mônica F. , Tumlinson James H.
Published: May 2024

Plants adapt to balance growth-defense tradeoffs in response to both biotic and abiotic stresses. Green leaf volatiles (GLVs) are released after biotic and abiotic stresses and function as damage-associated signals in plants. Although, GLVs enter plants primarily through stomata, the role of stomatal regulation on the kinetics of GLVs uptake remain largely unknown. Here, we illustrate the effect of stomatal closure on the timing and magnitude of GLVs uptake. We closed stomata by either exposing plants to darkness or applying abscisic acid, a phytohormone that closes the stomata in light. Then, we exposed maize seedlings toZ-3-hexen-1-oland compared the dynamic uptake ofZ-3-hexen-1-olunder different stomatal conditions. Additionally, we usedE-3-hexen-1-ol, an isomer ofZ-3-hexen-1-olnot made by maize, to exclude the role of internal GLVs in our assays. We demonstrate closed stomata effectively prevent GLVs entry into exposed plants, even at high concentrations. Furthermore, our findings indicate that reduced GLV uptake impairs GLVs-driven induction of sesquiterpenes biosynthesis, a group of GLV-inducible secondary metabolites, with or without herbivory. These results elucidate how stomata regulate the perception of GLV signals, thereby dramatically changing the plant responses to herbivory, particularly under water stress or dark conditions.

We elucidate the role of stomata, small pores on plants’ leaf surface, in regulating the entry of green leaf volatiles, damage-associated signals, into plants, and thus influencing their signaling functions.
Thermoregulation and Diurnal Roost Selection of Boreal Bats During Pre-Hibernation Period
Authors: Suominen Kati M. , Fritzén Niclas R. , Fjelldal Mari A. , Blomberg Anna S. , Viljamaa Minna J.K. , Lilley Thomas M.
Published: May 2024

Living in a seasonal environment poses challenges for small mammals, such as bats, reliant on insects as their primary food source. Bats may adeptly navigate these energetic challenges by reducing their metabolism and body temperature, entering a state of torpor. Particularly during the winter, bats remain torpid for extended periods, but are dependent on sufficient energy reserves to survive until spring. With the onset of autumn and declining temperature, bats face the challenge of building their fat deposits during a time of decreasing food availability. Bats may therefore transition to cooler roosts to initiate torpor, thereby reducing energy expenditure. However, little is still known about torpor use or roost selection by bats in autumn. This study explores the factors influencing roost selection and torpor use and –duration in two bat species during this critical transition period between the breeding and overwintering season. We show that date in autumn is a stronger driver of torpor use than prevailing ambient temperature, and that bats employ specific strategies in which they first increase daytime torpor use before also increasing the use of night-time torpor during the pre- hibernation fattening period, most likely to facilitate rapid fat accumulation. Notably, bats commenced night-time torpor use after spending entire days in torpor. These findings underscore the dynamic nature of torpor and the energy-saving strategies employed during the crucial pre- hibernation period, marking the transition from summer to winter.
SETBP1 Haploinsufficiency and Related Disorders Clinical and Neurobehavioral Phenotype Study
Authors: Oyler Haley O. , Hudac Caitlin M. , Chung Wendy K. , Snyder LeeAnne G. , Robertson Stephanie , Srivastava Siddharth , Geye Trina
Published: May 2024

To comprehensively investigate the neurodevelopmental profile and clinical characteristics associated with SETBP1 haploinsufficiency disorder (SETBP1-HD) and SETBP1-related disorders (SETBP1-RD). We reported genetic results on 34 individuals, with behavior and clinical data from 22 with SETBP1-HD and 5 with SETBP1-RD, by assessing results from medical history interviews and standardized adaptive, clinical, and social measures provided from Simons Searchlight. All individuals with SETBP1-HD and SETBP1-RD exhibited neurological impairments including intellectual disability/developmental delay (IDD), attention- deficit/hyperactivity disorder, autism spectrum disorder, and/or seizures, as well as speech and language delays. While restricted interests and repetitive behaviors present challenges, a relative strength was observed in social motivation within both cohorts. Individuals with SETBP1-RD reported a risk for heart issues and compared to SETBP1-HD greater risks for orthopedic and somatic issues with greater difficulty in bowel control. Higher rates for neonatal feeding difficulties and febrile seizures were reported for individuals with SETBP1-HD. Additional prominent characteristics included sleep, vision, and gastrointestinal issues, hypotonia, and high pain tolerance. This characterization of phenotypic overlap (IDD, speech challenges, autistic and attention deficit traits) and differentiation (somatic and heart issue risks for SETBP1-RD) between the distinct neurodevelopmental disorders SETBP1-HD and SETBP1- RD is critical for medical management and diagnosis.
UBR1 Promotes Sex-Dependent ACE2 Ubiquitination in Hypertension
Authors: Elgazzaz Mona , Lakkappa Navya , Berdasco Clara , Mohan Uma Priya , Nuzzo Anna , Restivo Luke , Martinez Alexa , Scarborough Amy , Guidry Jessie J. , Sriramula Srinivas , Xu Jiaxi , Daoud Hisham , Mendiola Plá Michelle A. , Bowles Dawn E. , Beyer Andreas M. , Mauvais-Jarvis Franck , Yue Xinping , Filipeanu Catalin M. , Lazartigues Eric
Published: May 2024

Background

Angiotensin (Ang)-II impairs the function of the antihypertensive enzyme ACE2 by promoting its internalization, ubiquitination and degradation thus contributing to hypertension. However, few ACE2 ubiquitination partners have been identified and their role in hypertension remains unknown.

Methods

Proteomics and bioinformatic analysis were used to identify ACE2 ubiquitination partners in the brain, heart, and kidney from Ang-II-infused C57BL6/J mice from both sexes and validated the interaction between UBR1 and ACE2 in cells. Central and peripheral UBR1 knockdown was then performed in male mice to investigate its role in the maintenance of hypertension.

Results

Proteomics analysis from hypothalamus identified UBR1 as a potential E3 ligase promoting ACE2 ubiquitination. Enhanced UBR1 expression, associated with ACE2 reduction, was confirmed in various tissues from hypertensive male mice and human samples. Treatment of endothelial and smooth muscle cells with testosterone, but not 17β-estradiol, confirmed a sex-specific regulation of UBR1. In vivo silencing of UBR1 using chronic administration of small interference RNA resulted in the restoration of ACE2 levels in hypertensive males. A transient decrease in blood pressure following intracerebroventricular, but not systemic, infusion was also observed. Interestingly, UBR1 knockdown increased the brain activation of Nedd4-2, an E3 ligase promoting ACE2 ubiquitination and reduced expression of SGK1, the kinase inactivating Nedd4-2. Conclusions: These data demonstrate that UBR1 is a novel ubiquitin ligase targeting ACE2 in hypertension. UBR1 and Nedd4-2 E3 ligases appear to work synergistically to ubiquitinate ACE2. Targeting of these ubiquitin ligases may represent a novel strategy to restore ACE2 compensatory activity in hypertension.
LOW-COST PELVIC PHANTOM PROTOTYPE WITH MATERIALS RESEMBLING HUMAN TISSUES
Authors: Coya Javiera García , Meier Catalina Nazar , Herrera TM Marco Jiménez , TM Ricardo Castillo V.
Published: May 2024

Introduction

Phantoms are elements used in radiological services for quality control tests. In the case of equipment with ionizing radiation, quality control tests focus on image quality and dosimetry. These phantoms are made with materials that resemble human tissues internally but are high-cost and difficult to access for radiology services.

Objectives

To design a methodology for creating an anthropomorphic radiology phantom with materials correlating to human tissues of the pelvis for various uses, using Hounsfield Units (HU) as a comparison.

Methodology

Data from 34 female patients with bone pelvis exams were collected. HU was measured in bone, muscle, and adipose tissue of the hip. Simultaneously, HU of different material mixtures was measured to correlate data between patients and materials for the creation of a right hip phantom.

Results

HU values of the materials match human tissues except for adipose tissue, which is slightly increased. The costs for phantom creation were low.

Discussion and Conclusion

HU estimates of materials and human tissue mostly align with those estimated in the sample and reported in the literature, achieving the creation of a low-cost phantom easily accessible for institutions or educational centers requiring quality, dosimetry, or educational tests.
Quantification of rose rosette emaravirus (RRV) titers in eriophyoid mites: insights into viral dynamics and vector competency
Authors: Druciarek Tobiasz , Rojas Alejandro , Tzanetakis Ioannis
Published: May 2024

Understanding the interaction between rose rosette emaravirus (RRV) and its vectors is pivotal in addressing the epidemic outbreak of rose rosette disease. This study employed quantitative real-time RT-PCR to assess RRV genome copy numbers inPhyllocoptes fructiphilusandP. adalius, providing insights into the viral dynamics and vector competency. Our findings suggest active virus replication withinP. fructiphilus, a confirmed vector species, unlikeP. adalius, highlighting its non-vector status. Furthermore, the study highlights the variability in virus concentration in mites over time, underlining possible developmental stage-specific response and influence of mite lifestyle on RRV retention and replication. This research is the first step in understanding the virus-mite interactome, which is essential for developing effective management strategies against rose rosette disease.
Staphylococcal aconitase expression during iron deficiency is controlled by an sRNA-driven feedforward loop and moonlighting activity
Authors: Barrault Maxime , Chabelskaya Svetlana , Coronel-Tellez Rodrigo H. , Toffano-Nioche Claire , Jacquet Eric , Bouloc Philippe
Published: May 2024

Pathogenic bacteria employ complex systems to cope with metal ion shortage conditions and propagate in the host. IsrR is a regulatory RNA (sRNA) whose activity is decisive for optimumS. aureusfitness upon iron starvation and for full virulence. IsrR down-regulates several genes encoding iron-containing enzymes to spare iron for essential processes. Here we report that IsrR regulates the tricarboxylic acid (TCA) cycle by controlling aconitase (CitB), an iron-sulfur cluster-containing enzyme, and its transcriptional regulator, CcpE. This IsrR-dependent dual-regulatory mechanism provides an RNA-driven feedforward loop, underscoring the tight control required to prevent aconitase expression. Beyond its canonical enzymatic role, aconitase becomes an RNA-binding protein with regulatory activity in iron-deprived conditions, a feature that is conserved inS. aureus. Aconitase not only negatively regulates its own expression, but also impacts the enzymes involved in both its substrate supply and product utilization. This moonlighting activity concurrently upregulates pyruvate carboxylase expression, allowing it to compensate for the TCA cycle deficiency associated with iron scarcity. These results highlight the cascade of complex posttranscriptional regulations controllingS. aureuscentral metabolism in response to iron deficiency.
Subtle alteration in transcriptional memory governs the lineage-level cell cycle duration heterogeneities of mammalian cells
Authors: Charan Kajal , Kar Sandip
Published: May 2024

Cell cycle duration heterogeneities within a malignant tumor significantly reduce the therapeutic efficacy of cancer treatment. However, identifying factors governing such heterogeneities remains challenging. Here, we demonstrate that correlated fluctuations of the inherited transcription rates during cell cycle progression in combination with the random resetting of them during mitosis are sufficient to account for the experimentally observed cell cycle duration correlation patterns for daughter-daughter, mother-daughter, and cousin-cousin cell lineage pairs. The model elucidates that the variations in the transcriptional inheritance pattern dictate the extent of the cousin-mother inequality phenomenon. It further predicts that the longer the cell cycle duration, the lower will be the lineage pair correlations. However, higher S-G2-M phase duration will only increase daughter-daughter and mother-daughter correlations, hence, reducing the extent of cousin-mother inequality. Overall, the model shows how alteration of the inherited transcriptional fluctuations across lineages finetunes the lineage-level heterogeneities.
Molecular phylogenetics of the superfamily Stromboidea (Caenogastropoda): new insights from increased taxon sampling
Authors: Irwin Alison R. , Bouchet Philippe , Crame J. Alistair , Harper Elizabeth M. , Kronenberg Gijs C. , Strong Ellen E. , Williams Suzanne T.
Published: May 2024

The superfamily Stromboidea is a clade of morphologically distinctive gastropods which include the iconic Strombidae, or ‘true conchs’. In this study, we present the most taxonomically extensive phylogeny of the superfamily to date, using fossil calibrations to produce a chronogram and extant geographical distributions to reconstruct ancestral ranges. From these results, we confirm the monophyly of all stromboidean families; however, six genera are not monophyletic using current generic assignments (Strombidae:Lentigo, Canarium,Dolomena,Doxander; Xenophoridae:Onustus, Xenophora). Within Strombidae, analyses resolve an Indo-West Pacific (IWP) clade sister to an East Pacific/Atlantic clade, together sister to a second, larger IWP clade. Our results also indicate two pulses of strombid diversification within the Miocene, and a Tethyan/IWP origin for Strombidae – both supported by the fossil record. However, conflicts between divergence time estimates and the fossil record warrant further exploration. Species delimitation analyses using the COI barcoding gene support several taxonomic changes. We synonymiseEuprotomus aurorawithEuprotomus bulla,Strombus alatuswithStrombus pugilis,Dolomena abbottiwithDolomena labiosa, andDolomena operosawithDolomena vittata. We identified cryptic species complexes withinTerebellum terebellum,Lambis lambis,“Canarium” wilsonorum, Dolomena turturellaandMaculastrombus mutabilis. We reinstateRimellopsis laurentias a species (previously synonymised withR. laurenti) and recogniseHarpago chiragra rugosusandLambis truncata sowerbyivalid at the rank of species. Finally, we establish several new combinations, renderingLentigo,Dolomena, andCanariummonophyletic:Lentigo thersites,Dolomena robusta,Dolomena epidromis,Dolomena turturella,Dolomena taeniata, Dolomena vanikorensis,D. vittata,“Canarium” wilsonorum,Hawaiistrombus scalariformis,Maculastrombus mutabilis,Maculastrombus microurceus.
A Near Infrared Fluorescent Nanosensor for Spatial and Dynamic Measurements of Auxin, Indole-3-Acetic Acid,in Planta
Authors: Khong Duc Thinh , Vu Kien Van , Sng Benny Jian Rong , Choi Ian Kin Yuen , Porter Thomas K. , Cui Jianqiao , Gong Xun , Wang Song , Nguyen Nguyen Hoai , Ang Mervin , Park Minkyung , Lew Tedrick Thomas Salim , Loh Suh In , Ahsim Riza , Chin Hui Jun , Singh Gajendra Pratap , Chan-Park Mary B. , Chua Nam-Hai , Strano Michael S. , Jang In-Cheol
Published: May 2024

Auxins, particularly indole-3-acetic acid (IAA), is a phytohormone critical for plant growth, development, and response to environmental stimuli. Despite its importance, there is a lack of species-independent sensors that allow direct and reversible detection of IAA. Herein, we introduce a novel near infrared fluorescent nanosensor for spatial and temporal measurement of IAAin plantausing Corona Phase Molecular Recognition. The IAA nanosensor shows high specificity to IAAin vitroand was validated to localize and function in plant cells. The sensor works across different plant species without optimization and allows visualization of dynamic changes to IAA distribution and movement in leaf tissues. The results highlighted the utility of IAA nanosensor for understanding IAA dynamicsin planta.
Downregulations of mRNA expressions in theEPAS1andEGLN1: Unraveling a genetic mechanism for high-altitude hypoxia adaptation in Sherpa highlanders
Authors: Droma Yunden , Yue Fengming , Ota Masao , Kobayashi Nobumitsu , Kitaguchi Yoshiaki , Hanaoka Masayuki
Published: May 2024

Sherpa highlanders exhibit unique hypoxia-tolerant traits, likely evolved through natural selection in response to high-altitude conditions. Previous research has implicatedEPAS1andEGLN1in this adaptation, but their functional mechanisms remain unclear. This study aims to elucidate these mechanisms by exploring mRNA expressions ofEPAS1andEGLN1in Sherpa highlanders. Field investigations enrolled 54 healthy Sherpa highlanders and 25 non-Sherpa lowlanders in Namche Bazaar (3,440 m) and Kathmandu (1,300 m), respectively. Venous blood was collected for erythropoietin (EPO) measurements,EPAS1andEGLN1mRNA expression analyses, and genotyping of single nucleotide polymorphisms (SNPs) rs13419896 and rs4953354 inEPAS1, as well as rs1435166 and rs2153364 SNPs inEGLN1.Comparative analyses were conducted on these elements between highlanders and lowlanders. Despite decreased SpO2in Sherpa highlanders, EPO concentrations did not elevate at high altitudes. TheEPAS1andEGLN1 mRNA expressions were significantly lower in Sherpa highlanders compared to non-Sherpa lowlanders. Moreover, genotype distributions and allele frequencies of rs13419896 and rs4953354 inEPAS1, as well as rs1435166 and rs2153364 inEGLN1, differed significantly between Sherpa highlanders and non-Sherpa lowlanders. Analyses of the relative mRNA expressions ofEPAS1andEGLN1by the SNPs suggested that the rs13419896/G and rs4953354/A alleles inEPAS1, as well as the rs1435166/G and rs2153364/A alleles inEGLN1,have down-regulatory effects on the gene mRNA expressions in Sherpa highlanders, contributing to inhibiting the EPO hypoxia response and exhibiting hypoxia-tolerant EPO levels in Sherpa highlanders. Natural selection, driven by high-altitude hypoxia, has encouraged adaptive evolution in Sherpa highlanders, including modifications inEPAS1andEGLN1genes. This evolutionary process leads to the downregulation of gene mRNA expressions, effectively tempering EPO responses to hypoxia and thereby enabling adaptation to high-altitude environments.
Cell-type specific inference from bulk RNA-sequencing data by integrating single cell reference profiles via EPIC-unmix
Authors: Tang Chenwei , Sun Quan , Zeng Xinyue , Yang Xiaoyu , Liu Fei , Zhao Jinying , Shen Yin , Liu Boxiang , Wen Jia , Li Yun
Published: May 2024

Cell type specific (CTS) analysis is essential to reveal biological insights obscured in bulk tissue data. However, single-cell (sc) or single-nuclei (sn) resolution data are still cost-prohibitive for large-scale samples. Thus, computational methods to perform deconvolution from bulk tissue data are highly valuable. We here present EPIC-unmix, a novel two-step empirical Bayesian method integrating reference sc/sn RNA-seq data and bulk RNA-seq data from target samples to enhance the accuracy of CTS inference. We demonstrate through comprehensive simulations across three tissues that EPIC-unmix achieved 4.6% - 109.8% higher accuracy compared to alternative methods. By applying EPIC-unmix to human bulk brain RNA-seq data from the ROSMAP and MSBB cohorts, we identified multiple genes differentially expressed between Alzheimer's disease (AD) cases versus controls in a CTS manner, including 57.4% novel genes not identified using similar sample size sc/snRNA-seq data, indicating the power of our in-silico approach. Among the 6-69% overlapping, 83%-100% are in consistent direction with those from sc/snRNA-seq data, supporting the reliability of our findings. EPIC-unmix inferred CTS expression profiles similarly empowers CTS eQTL analysis. Among the novel eQTLs, we highlight a microglia eQTL for AD risk gene AP3B2, obscured in bulk and missed by sc/snRNA-seq based eQTL analysis. The variant resides in a microglia-specific cCRE, forming chromatin loop with AP3B2 promoter region in microglia. Taken together, we believe EPIC-unmix will be a valuable tool to enable more powerful CTS analysis
Improving allele-specific epigenomic signal coverage by10-foldusing Hidden Markov Modeling and Machine Learning
Authors: Dumont Emmanuel LP , Janati Ali , Bhattacharya Moumita , Jeannin Jean-Baptiste , Do Catherine
Published: May 2024

Allele-specific epigenomic signals refer to differences in epigenomic patterns between the two copies, or “alleles,” of a DNA region inherited from each parent. Epigenomic patterns are defined as alterations of the DNA sequence (e.g., chemical) without modifying the underlying DNA sequence (which would be referred to as “mutations”). Mapping allele-specific epigenomic signals across a genome is crucial, as some can influence gene expression, disease susceptibility, and developmental processes. However, identifying allele-specific epigenomic patterns across an entire genome is limited by the average read length (50-150 nucleotides) of short-read sequencing technologies, which are the most widely-used and affordable whole genome sequencing methods, and by the 99.9% similarity in the DNA sequences inherited from each parent. These limitations restrict the assessment of allele-specific signals to approximately 10% of the genome, potentially overlooking critical regulatory regions. In this paper, we present a highly effective machine-learning approach based on variational hidden Markov modeling, which enables the detection of allele-specific epigenomic signals across the entire genome, resulting in a 10-fold improvement in genomic coverage compared to state-of-the-art methods. We demonstrate our method on DNA methylation, a critical epigenomic regulatory signal.
Generation length of the world’s amphibians and reptiles
Authors: Mancini G. , Santini L. , Cazalis V. , Ficetola F. , Meiri S. , Roll U. , Silvestri S. , Pincheira-Donoso D. , Di Marco M.
Published: May 2024

Variation in life histories influences demographic processes from adaptive changes to population declines leading to extinction. Among life history traits, generation length offers a critical feature to forecast species’ demographic trajectories such as population declines (widely used by the IUCN Red List of Threatened Species) and adaptability to environmental change over time. Therefore, estimates of generation length are crucial to monitor demographic stability or future change in highly threatened organisms, particularly ectothermic tetrapods (amphibians and reptiles) – which rank among the most threatened groups – but for which uncertainty in future impacts remains high. Despite its importance, generation length for amphibians and reptiles is largely missing. Here, we aimed to fill-in this gap by modeling generation lengths for amphibians, squamates and testudines as a function of species size, climate, life history, and phylogeny using generalized additive models and phylogenetic generalized least squares. We obtained estimates of generation lengths for 4,543 (52%) amphibians, 8,464 (72%) squamates and 118 (32%) testudines. Our models performed well for most families, for example Bufonidae in amphibians, Lacertidae and Colubridae in squamates and Geoemydidae in testudines, while we found high uncertainty around the prediction of a few families, notably Chamaeleonidae. Species’ body size and mean temperature were the main predictors of generation length in all groups. Although our estimates are not meant to substitute robust and validated measurements from field studies or natural history museums, they can help reduce existing biases in conservation assessments until field data will be comprehensively available.
FAST-STEM: A human pluripotent stem cell engineering toolkit for rapid design-build-test-learn development of human cell-based therapeutic devices
Authors: Rosenstein Aaron , Sambathkumar Rangarajan , Murareanu Brandon , Dhaliwal Navroop , Sun Fumao , Zhao Xinyaun , Dadvar Abolfazl , Al-attar Rasha , Chai Andrew , Gulati Nitya , Yin Ting , Nguyen Maria , Serra Danielle , Devina Tania , Gandhi Aanshi , Saleh Mohammad , Gilbert Penney M , Kunath Tilo , Laflamme Michael , Ogawa Shinichiro , Muffat Julien , Li Yun , Protze Stephanie , Nostro Cristina , Garton Michael J
Published: May 2024

Very recent clinical advances in stem cell derived tissue replacement and gene therapy, in addition to the rise of artificial intelligence aided scientific discovery, have placed the possibility of sophisticated human cell based therapies firmly within reach. However, development of such cells and testing of their engineered gene circuit components, has proven highly challenging, due to the need for generating stable cell lines for each design, build, test, learn engineering cycle. Current approaches to generating stable human induced pluripotent stem cell (hiPSC) lines are highly time consuming and suffer from lack of control, poor integration efficiency, and limited functionality. Validation in clinically relevant stem cell derived tissues is also broadly lacking. Such drawbacks are prohibitive to repeatably conducting cutting edge stem cell engineering with broad application within a realistic timeframe, and will not scale with the future of regenerative medicine. We have developed FASTSTEM (Facile Accelerated Stem cell Transgene integration with SynBio Tunable Engineering Modes), a hiPSC engineering platform that drastically reduces the time to generate differentiation ready stem cell lines from several weeks to 5 days, exhibiting a ~612-fold improvement in transgene integration rate over previous methodologies. Additional FAST-STEM innovations include: (i) rapid and highly efficient transgene integration; (ii) copy number control; (iii) simultaneous or consecutive integration of multiple gene cassettes; (iv) library screen capability. In addition to this unique functional versatility, platform transportability and broad use case for stem cell engineering was confirmed by differentiation into eight different cell types across nine different laboratories. This platform dramatically lowers the bar for integration of synthetic biology with regenerative medicine, enabling experiments which were previously deemed logistically impossible, thus paving the way for sophisticated human cell device development.
Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes
Authors: Galatidou S , Petelski A , Pujol A , Lattes K , Latorraca L B , Fair T , Popovic M , Vassena R , Slavov N , Barragan M
Published: May 2024

Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age. Our findings primarily revealed distinct proteomic profiles between immature fully grown germinal vesicle and mature metaphase II oocytes. Importantly, we further show that a woman’s age is associated with changes in her oocyte proteome. Specifically, when compared to oocytes obtained from young women, advanced maternal age oocytes exhibited lower levels of the proteasome and TRiC complex, as well as other key regulators of proteostasis and meiosis. This suggests that aging adversely affects the proteostasis and meiosis networks in human oocytes. The proteins identified in this study hold potential as targets for improving oocyte quality and may guide future studies into the molecular processes underlying oocyte aging.
Applying nutritional ecology to optimize diets of crickets raised for food and feed
Authors: Muzzatti Matthew J , Harrison Sarah J. , McColville Emily R. , Brittain Caelyn T. , Brzezinski Hunter , Manivannan Sujitha , Stabile Cassandra C. , MacMillan Heath A. , Bertram Susan M.
Published: May 2024

Increasing yield is a primary goal of mass insect rearing for food and feed, and diet shapes insect life history traits important to yield, such as survival, development time, and body size at adulthood. Little is known about how developmental macronutrient intake impacts survival, growth, and adult body size of mass reared insects. Here, we applied the nutritional geometry framework and reared individual tropical house crickets (Gryllodes sigillatus) from hatch to adulthood on a wide range of protein:carbohydrate diets. We measured weekly food consumption, survival, development time to adulthood, and adult body size and mass, and calculated a yield metric to extrapolate our individual-level results and predict how diet influences yield at the mass rearing level. Yield was maximized on a 3P:1Cdiet, as crickets fed this diet were most likely to develop into adults and grew maximum mass and body size. When provided with a choice between diets, crickets selected a relatively balanced 1.05P:1Cdiet throughout development, but males consumed 17% more protein than females. Our results represent a crucial first step towards determining the optimal standard feed formulation required to maximize cricket farming yield.
Virulence evolution: thinking outside of the host
Authors: Silva Luís M. , Koella Jacob C.
Published: May 2024

The main theory of the evolution of virulence relies on a trade-off between virulence and transmission rate. However, it has been difficult to measure the required trade-off. A recent transmission decomposition framework explains this might be due to a lack of information about the parasite’s survival in the environment outside the hosts, where the parasite finds itself during transmission between hosts. In this study, we used parasite lines ofVavraia culiciswith varying levels of virulence upon infecting their host, the mosquitoAnopheles gambiae, to explore the interaction between parasite-driven virulence within its host and its survival outside of the host. Our findings showed that parasite lines with greater virulence and growth within their hosts had a cost in their intrinsic ability to withstand the environment, irrespective of temperature. These results underscore the importance of considering the full context of transmission and other parasite fitness traits in studying and predicting the evolution and spread of infectious diseases.