bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactation Support Services in Level III Neonatal Intensive Care Units in Canada
Authors: Pan Lingnong , Cooper Maeve Hay , Fucile Sandra
Published: August 2024

Introduction:

Lactation support services can improve exclusive breastfeeding rates among infants in the neonatal intensive care unit (NICU). There are limited data on how many NICUs offer these services.

Objective:

To assess prevalence and type of lactation services provided in level III Canadian NICUs.

Methods:

A nationwide comprehensive point-prevalence study was undertaken via a telephone survey of level III NICUs in Canada. Availability of lactation consultants, type of services offered, infrastructure such as centralized milk labs, private space for expressing milk, and refrigerators to store breast milk, and follow-up support programs were assessed.

Results:

There are 31 level III NICUs in Canada. Nineteen of the 31 NICUs participated in the survey, representing a 61% response rate. Of these, 79% (n = 15) offered lactation consultant services. Most (n = 13, 68%) noted they had International Board-Certified Lactation Consultants (IBCLCs). The types of lactation services offered were either a reactive care model, a proactive care model, or a combination of both. Seven (37%) units, both with and without LCs, offered alternate lactation assistance, such as helping mothers at the bedside with breastfeeds. Several units had available infrastructure (n = 10, 53%) and offered follow-up lactation support (n = 10, 53%).

Conclusion:

Most of the surveyed level III NICUs in Canada provided lactation support services; however, there was variation in type. More research is needed to identify barriers that NICUs face in offering lactation services for mothers of NICU babies.
Phase II Study Shows the Effect of Adenoviral Vascular Endothelial Growth Factor C and Lymph Node Transfer in Lymphedema
Authors: Rannikko Eeva H. , Pajula Susanna , Suominen Sinikka H. , Kiiski Juha , Mani Maria R. , Halle Martin , Kaartinen Ilkka S. , Lahdenperä Outi , Arnardottir Tinna H. , Kauhanen Susanna M. , Kavola Heli , Majava Marja , Niemi Tarja S. , Brück Nina M. , Mäki Maija T. , Seppänen Marko P. , Saarikko Anne M. , Hartiala Pauliina
Published: August 2024

Background:

Breast cancer–related lymphedema is a common complication lacking medical treatment. Lymfactin is an adenovirus type 5–based gene therapy and prolymphangiogenic growth factor vector that induces vascular endothelial growth factor C expression. The authors’ aim was to evaluate the therapeutic effect of Lymfactin with vascularized lymph node transfer (VLNT).

Methods:

This phase II, double-blind, placebo-controlled, randomized, multicenter study evaluated the efficacy and safety of Lymfactin in combination with VLNT. The primary endpoints were edema volume, quality of life, and lymphoscintigraphy. All adverse events were recorded. A mixed model of repeated measures analysis of covariance was performed. This study was a continuation of a previous phase I Lymfactin study.

Results:

Thirty-nine patients with breast cancer–related lymphedema were recruited between June of 2018 and December of 2019 and randomized to receive either Lymfactin (n = 20) or placebo (n = 19). The primary endpoints showed a positive effect of VLNT in both groups compared with the baseline, but without statistical differences between groups at 12 months. In addition, greater improvements were observed in the tissue dielectric constant ratios measuring skin interstitial fluid levels in the Lymfactin group compared with the placebo group (P = 0.020). No differences in adverse events were detected between the groups.

Conclusions:

This study was one of the few studies to objectively show a positive effect of VLNT in a prospective, clinical, multicenter setting. It was also the first-ever randomized prospective clinical study showing a quantitatively positive effect of a medical therapy on the edema of lymphedema but failed to show differences between groups in primary outcome measures.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Orsay virus infection increases
Caenorhabditis elegans
resistance to heat-shock
Authors: Castiglioni Victoria G. , Elena Santiago F.
Published: August 2024

The heat-shock response plays a key role in the immune defence against viruses across various organisms. Studies on model organisms have shown that inducing this response prior to viral exposure enhances host resistance to infections, while deficient responses make individuals more susceptible. Moreover, viruses rely on components of the heat-shock response for their own stability and viral infections improve thermal tolerance in plants, giving infected individuals an advantage in extreme conditions, which aids the virus in replication and transmission. Here, we examine the interaction between the nematode
Caenorhabditis elegans
and its natural pathogen the Orsay virus (OrV) under heat stress. We found that OrV infection leads to differential expression of heat-stress-related genes, and infected populations show increased resistance to heat-shock. This resistance correlates with increased expression of argonautes
alg-1
and
alg-2
, which are crucial for survival after heat-shock and for OrV replication. Overall, our study suggests an environmental-dependent mutualistic relationship between the nematode and OrV, potentially expanding the animal’s ecological niche and providing the virus with extra opportunities for replication and adaptation to extreme conditions.
A macroevolutionary analysis of European Late Upper Palaeolithic stone tool shape using a Bayesian phylodynamic framework
Authors: Matzig David N. , Marwick Ben , Riede Felix , Warnock Rachel C. M.
Published: August 2024

Phylogenetic models are commonly used in palaeobiology to study the patterns and processes of organismal evolution. In the human sciences, phylogenetic methods have been deployed for reconstructing ancestor–descendant relationships using linguistic and material culture data. Within evolutionary archaeology specifically, phylogenetic analyses based on maximum parsimony and discrete traits dominate, which sets limitations for the downstream role cultural phylogenies, once derived, can play in more elaborate analytical pipelines. Recent methodological advances in Bayesian phylogenetics, however, now allow us to infer evolutionary dynamics using continuous characters. Capitalizing on these developments, we here present an exploratory analysis of cultural macroevolution of projectile point shape evolution in the European Final Palaeolithic and earliest Mesolithic (approx. 15 000–11 000 BP) using a Bayesian phylodynamic approach and the fossilized birth–death process model. This model-based approach leaps far beyond the application of parsimony, in that it not only produces a tree, but also divergence times, and diversification rates while incorporating uncertainties. This allows us to compare rates to the pronounced climatic changes that occurred during our time frame. While common in cultural evolutionary analyses of language, the extension of Bayesian phylodynamic models to archaeology arguably represents a major methodological breakthrough.
A century of wild bee sampling: historical data and neural network analysis reveal ecological traits associated with species loss
Authors: Graham Kelsey K. , Glaum Paul , Hartert Joseph , Gibbs Jason , Tucker Erika , Isaacs Rufus , Valdovinos Fernanda S.
Published: August 2024

We analysed the wild bee community sampled from 1921 to 2018 at a nature preserve in southern Michigan, USA, to study long-term community shifts in a protected area. During an intensive survey in 1972 and 1973, Francis C. Evans detected 135 bee species. In the most recent intensive surveys conducted in 2017 and 2018, we recorded 90 species. Only 58 species were recorded in both sampling periods, indicating a significant shift in the bee community. We found that the bee community diversity, species richness and evenness were all lower in recent samples. Additionally, 64% of the more common species exhibited a more than 30% decline in relative abundance. Neural network analysis of species traits revealed that extirpation from the reserve was most likely for oligolectic ground-nesting bees and kleptoparasitic bees, whereas polylectic cavity-nesting bees were more likely to persist. Having longer phenological ranges also increased the chance of persistence in polylectic species. Further analysis suggests a climate response as bees in the contemporary sampling period had a more southerly overall distribution compared to the historic community. Results exhibit the utility of both long-term data and machine learning in disentangling complex indicators of bee population trajectories.
Mosaic evolution underlies feliform morphological disparity
Authors: Barrett Paul Z. , Hopkins Samantha S. B.
Published: August 2024

Constraint is a fundamental concept in evolutionary theory. Morphology and ecology both are limited by functional, historical and developmental factors to a subset of the theoretical range species could occupy. Cat-like carnivorans (Feliformia) offer a unique opportunity to investigate phenotypic constraint, as several feliform clades are purported to be limited to generalized ecomorphological roles, while others possess extremely specialized durophagous (bone-crushing) and sabretooth morphology. We investigated the evolutionary history of feliforms by considering their phylogeny, morphological disparity and rates of evolution. We recover results that show a mosaic pattern exists in the degree of morphological disparity per anatomical region per clade and ecology. Non-hypercarnivores, such as viverrids (civets and genets), Malagasy euplerids and lophocyonids (extinct hypocarnivores), have the greatest dental disparity, while hypercarnivores (felids, nimravids, many hyaenids) have the lowest dental disparity but highest cranial and mandibular disparity (excluding dentition). However, high disparity is not necessarily associated with high rates of evolution, but instead with ecological radiations. We reveal that relationships between specialization and disparity are not as simple as past research has concluded. Instead, morphological disparity results from an anatomical mosaic of evolution, where different ecologies correlate with and likely channel unique patterns/combinations of disparity per anatomical partition.
Camouflage patterning modulates neural signatures of attention and decision-making
Authors: Billington Jac , Hassall Christopher , Craddock Matt
Published: August 2024

Many animals rely on visual camouflage to avoid detection and increase their chances of survival. Edge disruption is commonly seen in the natural world, with animals evolving high-contrast markings that are incongruent with their real body outline in order to avoid recognition. While many studies have investigated how camouflage properties influence viewer performance and eye movement in predation search tasks, researchers in the field have yet to consider how camouflage may directly modulate visual attention and object processing. To examine how disruptive coloration modulates attention, we use a visual object recognition model to quantify object saliency. We determine if object saliency is predictive of human behavioural performance and subjective certainty, as well as neural signatures of attention and decision-making. We show that increasing edge disruption not only reduces detection and identification performance but is also associated with a dampening of neurophysiological signatures of attentional filtering. Increased self-reported certainty regarding decisions corresponds with neurophysiological signatures of evidence accumulation and decision-making. In summary, we have demonstrated a potential mechanism by which edge disruption increases the evolutionary fitness of animals by reducing the brain’s ability to distinguish signal from noise, and hence to detect and identify the camouflaged animal.
Paradoxes in the coevolution of contagions and institutions
Authors: St-Onge Jonathan , Burgio Giulio , Rosenblatt Samuel F. , Waring Timothy M. , Hébert-Dufresne Laurent
Published: August 2024

Epidemic models study the spread of undesired agents through populations, be it infectious diseases through a country, misinformation in social media or pests infesting a region. In combating these epidemics, we rely neither on global top-down interventions, nor solely on individual adaptations. Instead, interventions commonly come from local institutions such as public health departments, moderation teams on social media platforms or other forms of group governance. Classic models, which are often individual or agent-based, are ill-suited to capture local adaptations. We leverage developments of institutional dynamics based on cultural group selection to study how groups attempt local control of an epidemic by taking inspiration from the successes and failures of other groups. Incorporating institutional changes into epidemic dynamics reveals paradoxes: a higher transmission rate can result in smaller outbreaks as does decreasing the speed of institutional adaptation. When groups perceive a contagion as more worrisome, they can invest in improved policies and, if they maintain these policies long enough to have impact, lead to a reduction in endemicity. By looking at the interplay between the speed of institutions and the transmission rate of the contagions, we find rich coevolutionary dynamics that reflect the complexity of known biological and social contagions.
Fossils indicate marine dispersal in osteoglossid fishes, a classic example of continental vicariance
Authors: Capobianco Alessio , Friedman Matt
Published: August 2024

The separation of closely related terrestrial or freshwater species by vast marine barriers represents a biogeographical riddle. Such cases can provide evidence for vicariance, a process whereby ancient geological events like continental rifting divided ancestral geographical ranges. With an evolutionary history extending tens of millions of years, freshwater ecology, and distribution encompassing widely separated southern landmasses, osteoglossid bonytongue fishes are a textbook case of vicariance attributed to Mesozoic fragmentation of the Gondwanan supercontinent. Largely overlooked fossils complicate the clean narrative invoked for extant species by recording occurrences on additional continents and in marine settings. Here, we present a new total-evidence phylogenetic hypothesis for bonytongue fishes combined with quantitative models of range evolution and show that the last common ancestor of extant osteoglossids was likely marine, and that the group colonized freshwater settings at least four times when both extant and extinct lineages are considered. The correspondence between extant osteoglossid relationships and patterns of continental fragmentation therefore represents a striking example of biogeographical pseudocongruence. Contrary to arguments against vicariance hypotheses that rely only on temporal or phylogenetic evidence, these results provide direct palaeontological support for enhanced dispersal ability early in the history of a group with widely separated distributions in the modern day.
A Novel Blood-Based Epigenetic Clock for Intrinsic Capacity Predicts Mortality and is Associated with Clinical, Immunological and Lifestyle Factors
Authors: Fuentealba Matías , Rouch Laure , Guyonnet Sophie , Lemaitre Jean-Marc , de Souto Barreto Philipe , Vellas Bruno , Andrieu Sandrine , Furman David
Published: August 2024

Age-related decline in intrinsic capacity (IC), defined as the sum of an individual’s physical and mental capacities, is a cornerstone for promoting healthy aging and longevity, as it emphasizes maximizing function throughout the aging process instead of merely treating diseases. However, accurate assessments of IC are resource-intensive, and the molecular and cellular basis of its decline are poorly understood. Herein, we used the INSPIRE-T cohort, consisting of 1,014 individuals aged 20 to 102, to construct the IC clock, a DNA methylation (DNAm)-based predictor of IC trained on the clinical evaluation of cognition, locomotion, psychological well-being, sensory abilities, and vitality. In the Framingham Heart Study, age-adjusted DNAm IC correlates with first- and second-generation epigenetic clocks, predicts all-cause mortality, and is strongly associated with changes in molecular and cellular immune and inflammatory biomarkers, functional and clinical endpoints, health risk factors, and diet.
Simplified and Rapid Workflow Enhances Throughput ofDe NovoSequencing of COVID-19 Neutralizing Antibodies
Authors: Xiong Yueting , Xiao Jin , Jiang Wenbin , Wang Jingyi , Bu Qingfang , Chen Xiaoqing , Wu Yangtao , Yu Rongshan , Yuan Quan , Xia Ningshao
Published: August 2024

During the current COVID-19 pandemic, precise antibody sequencing is crucial for the rapid development of broad-spectrum or pan-β-coronavirus neutralizing antibodies (NAbs) to prevent new variants of the coronavirus and other highly pathogenic β-coronaviruses. However, mass spectrometry-basedde novosequencing remains challenging due to its high cost, low throughput, and unexpected missing of certain ion information. We developed an innovative approach using solely bottom-up to provide a rapid, robust, and refined solution for the currentde novosequencing challenges. The methodology, referred to as SP-MEGD for Single-Pot and Multi-Enzymatic Gradient Digestion, capitalizes on a five-protease gradient digestion by sampling every two hours for a total of 6 hours in an integrative reactor. The SP-MEGD method could engender numerous missed cleavage events and produce various peptide products of diverse lengths with overlapping stretches of residues, enabling efficient database-freede novosequencing. Antibody assembly for single or mixed COVID-19-NAbs with publicly available sequences and commercial antibodies with unknown sequences was efficiently deciphered using our previously proposed optimization method, Fusion assembler. Our innovative study represents the first successful simultaneous discrimination and achieving over 99% accurate sequence coverage of a mixture containing three humanized COVID-19-NAbs (S2P6LH, BD5514LH, and BD5840LH). Furthermore, we utilized SP-MEGD and Fusion to sequence commonly used anti-CD8 and anti-CD4, and successfully confirmed their impact on immune cell clearance through in vivo experiments. Overall, our developed workflow demonstrates promise in facilitating the discovery and development of vaccines and antibody therapeutics while providing deeper insights into monoclonal antibodies (mAbs).
A novel candidate neuromarker of central motor dysfunction in childhood apraxia of speech
Authors: Anastasopoulou Ioanna , Cheyne Douglas O. , van Lieshout Pascal , Wilson Peter H. , Ballard Kirrie J. , Johnson Blake W.
Published: August 2024

Childhood apraxia of speech (CAS) is conceived as an impairment of the central motor system’s ability to program multiple speech movements, resulting in inaccurate transitions between and relative timing across speech sounds. However, the extant neuroimaging evidence base is scant and inconclusive and the neurophysiological origins of these motor planning problems remain highly underspecified. In the first magnetoencephalography study of this disorder, we measured brain activity from typically developing children (N = 19) and children with CAS (N=7) during performance of a speech task designed to interrogate function of the speech areas of primary sensorimotor cortex. Relative to their typically developing peers, our sample of CAS children showed abnormal speech-related responses within the mu-band motor rhythm, and beamformer source reconstruction analyses specify a brain origin of this speech rhythm in the left cerebral hemisphere, within or near pre-Rolandic motor areas crucial for the planning and control of speech and oromotor movements. These results provide a new and specific candidate mechanism for the core praxic features of CAS; point to a novel and robust neurophysiological marker of typical and atypical expressive speech development; and support an emerging neuroscientific consensus which assigns a central role for programming and coordination of speech movements to the motor cortices of the precentral gyrus.
Large Language Models Improve the Identification of Emergency Department Visits for Symptomatic Kidney Stones
Authors: Bejan Cosmin A. , Reed Amy M , Mikula Matthew , Zhang Siwei , Xu Yaomin , Fabbri Daniel , Embí Peter J. , Hsi Ryan S.
Published: August 2024

Background

Recent advancements of large language models (LLMs) like Generative Pre-trained Transformer 4 (GPT-4) have generated significant interest among the scientific community. Yet, the potential of these models to be utilized in clinical settings remains largely unexplored. This study investigated the abilities of multiple LLMs and traditional machine learning models to analyze emergency department (ED) reports and determine if the corresponding visits were caused by symptomatic kidney stones.

Methods

Leveraging a dataset of manually annotated ED reports, we developed strategies to enhance the performance of GPT-4, GPT-3.5, and Llama-2 including prompt optimization, zero- and few-shot prompting, fine-tuning, and prompt augmentation. Further, we implemented fairness assessment and bias mitigation methods to investigate the potential disparities by these LLMs with respect to race and gender. A clinical expert manually assessed the explanations generated by GPT-4 for its predictions to determine if they were sound, factually correct, unrelated to the input prompt, or potentially harmful. The evaluation includes a comparison between LLMs, traditional machine learning models (logistic regression, extreme gradient boosting, and light gradient boosting machine), and a baseline system utilizing International Classification of Diseases (ICD) codes for kidney stones.

Results

The best results were achieved by GPT-4 (macro-F1=0.833, 95% confidence interval [CI]=0.826–0.841) and GPT-3.5 (macro-F1=0.796, 95% CI=0.796–0.796), both being statistically significantly better than the ICD-based baseline result (macro-F1=0.71). Ablation studies revealed that the initial pre-trained GPT-3.5 model benefits from fine-tuning when using the same parameter configuration. Adding demographic information and prior disease history to the prompts allows LLMs to make more accurate decisions. The evaluation of bias found that GPT-4 exhibited no racial or gender disparities, in contrast to GPT-3.5, which failed to effectively model racial diversity. The analysis of explanations provided by GPT-4 demonstrates advanced capabilities of this model in understanding clinical text and reasoning with medical knowledge.
Nationwide Epidemiological Analysis of Surgically Treated Upper Limb Vascular Trauma Over 16 Years in Brazil
Authors: Ceratti Marcella Moura , Sorbello Carolina Carvalho Jansen , da Silva Marcelo Fiorelli Alexandrino , Teivelis Marcelo Passos , Wolosker Nelson
Published: August 2024

Background

Upper limb vascular trauma (ULVT) is a prevalent injury associated with significant morbidity and mortality. Despite its clinical importance, epidemiological studies on ULVT are scarce, particularly in developing countries where the incidence may be heightened by factors such as traffic accidents and violence.

Objective

To analyze the epidemiology of ULVT across Brazil, a developing country, evaluating incidence rates, demographic characteristics, mortality rates, days of hospitalization, and related healthcare costs.

Methods

A cross-sectional, retrospective analysis using data from the Brazilian public health system (SUS) over a sixteen-year period (2008-2023). The automated data extraction utilized Python-based tools to gather information on vascular trauma procedures identified by ICD-10 codes. Statistical analyses were performed to assess variations in incidence, mortality, and treatment costs across Brazilian regions.

Results

A total of 25,573 cases of ULVT were recorded, representing approximately 0.02% of the studied population. The majority of cases occurred in males (79.8%) with a mean age of 34.71 years, with a peak incidence in the 20-24 age group. The region in Brazil with the highest incidence of ULVT was the North (16.6 cases per 100,000 inhabitants) and the region with the lowest was the Southeast (10.7 cases per 100,000 inhabitants). The average hospital stay was 4.39 days and 92,8% of patients did not need to be admitted to an intensive care unit (ICU). Of the patients admitted to the ICU, the average length of stay was 4.52 days. Overall lethality (deaths per cases of ULVT) was 2.37%, with higher lethality observed in bilateral ULVT cases (3.81%).

Conclusions

ULVT is more prevalent in Brazil than in developed countries, even when adjusted for population size. However, mortality rates and hospitalization durations do not appear to differ significantly from those in developed countries.
NF-κB Mediated Thyroid Inflammation and Its Implications for the Risk of Follicular Thyroid Carcinoma: a systematic review
Authors: Shafi Ovais , Raveena  , Arshad Fatima , Kanwal Finza , Khan Osama Jawed , Ashar Muhammad , Jabbar Abdul , Kumar Haresh , Rajpar Rahimeen , Sohail Khizer , Madhwani Manwar , Waqas Muhammad
Published: August 2024

Objective

The objective of this study is to determine how NF-κB-mediated inflammation disrupts thyroid specific genes/TFs/signaling pathways and the resultant increase in the risk of Follicular Thyroid Carcinoma.

Background

Thyroid follicular carcinoma (FTC) is linked to chronic inflammation and NF-κB activation, which disrupts key thyroid-specific genes/transcription factors and signaling pathways. This dysregulation leads to impaired differentiation and increased proliferation, fostering oncogenesis. The interplay between NF-κB and thyroid components is critical for developing possible targeted therapies. This study aims to focus on these mechanisms, with the future potential of possibly improving diagnostic, prognostic, and therapeutic strategies for FTC.

Methods

Databases, including PubMed, MEDLINE, Google Scholar, and open access/ subscription-based journals were searched for published articles without any date restrictions, to investigate how NF-κB-mediated inflammation disrupts thyroid specific genes/TFs/signaling pathways and the resultant increase in the risk of Follicular Thyroid Carcinoma. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate the research question. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).

Results

NF-κB activation disrupts key thyroid transcription factors and signaling pathways, leading to increased risk of thyroid follicular carcinoma. Dysregulation of NKX2-1, PAX8, FOXE1, and HHEX impairs thyroid development and differentiation. NF-κB alters TSH signaling and disrupts RET/PTC, leading to aberrant cell proliferation. It further impacts the MAPK/ERK, PI3K/AKT, and Wnt/β- catenin pathways, driving oncogenic transformations. Additionally, NF-κB-induced changes in FGF, Shh, BMP, Notch, and TGF beta pathways exacerbate tumorigenesis by promoting abnormal cell growth and survival, collectively increasing follicular carcinoma risk.

Conclusion

Chronic inflammation and NF-κB activation disrupt key transcription factors (NKX2-1, PAX8, FOXE1, HHEX) and signaling pathways (TSH, RET/PTC, MAPK/ERK, PI3K/AKT, Wnt/β-catenin, FGF, Shh, BMP, Notch, TGF-β) essential for thyroid development and function. This dysregulation leads to impaired differentiation, increased proliferation, and enhanced survival of thyroid follicular cells, fostering genomic instability and oncogenic transformation. These findings highlight the role of NF-κB in promoting follicular thyroid carcinoma (FTC) and points towards the need for targeted therapies to restore normal signaling and prevent malignancy in thyroid diseases.
Stable isotope analysis (δ13C,δ15N,δ34S) reveal divers manuring practices of rye (Secale cereale) in northern Europe since 1500 years
Authors: Schlütz Frank , Bittmann Felix , Jahns Susanne , König Sonja , Shumilovskikh Lyudmila , Baumecker Michael , Kirleis Wiebke
Published: August 2024

First analysis of stable isotopes in rye from northern and eastern Germany provides insights into the early history of rye cultivation from the migration to the late medieval period. A comparison of theδ15N with modern experiments reveals that already the early cultivation involved the practice of intensive manuring. The intensity of manuring does not demonstrate a discernible trend over time but high variability. In some instances, it is likely that rye was cultivated as part of a rotation cultivation system including manuring. Through itsδ34S values some rye turned out to be manured with marine peats. Rye, reputed to be a frugal crop, was cultivated on poor sandy soils to a limited extent only. Statistically significant correlation between the13C content and yields demonstrates that the highest yield success on dwelling mounds was achieved, while the majority of fields on dry sandy soils yielded in relation only 40 to 70 %. Manured rye facilitated the emergence of multi-headed village communities and towns and stabilized the political power systems. The cultivation on mounds flooded by winter storm surges emphasises that summer rye was initially cultivated, before winter-rye became the dominating crop in Germany until the mid-20th century.
DNA methylation associates with sex-specific effects of experimentally increased yolk testosterone in wild nestlings
Authors: Sepers Bernice , Ruuskanen Suvi , van Mastrigt Tjomme , Mateman A. Christa , van Oers Kees
Published: August 2024

Maternal hormones can profoundly impact offspring physiology and behaviour in sex-dependent ways. Yet little is known on the molecular mechanisms linking these maternal effects to offspring phenotypes. DNA methylation, an epigenetic mechanism, is suggested to facilitate maternal androgens’ effects. To assess whether phenotypic changes induced by maternal androgens associate with DNA methylation changes, we experimentally manipulated yolk testosterone levels in wild great tit eggs (Parus major) and quantified phenotypic and DNA methylation changes in the hatched offspring. Increased yolk testosterone levels decreased the begging probability, emphasised sex-differences in fledging mass and affected methylation at 763 CpG sites, but always in a sex-specific way. These sites associated with genes involved in growth, oxidative stress and reproduction, suggesting sex-specific trade-offs to balance the costs and benefits of exposure to high yolk testosterone levels. Future studies should assess if these effects extend beyond the nestling stage and impact fitness.
The microbiome of Total Suspended Particles (TSP) and its influence on the respiratory microbiome of healthy office workers
Authors: Solazzo Giulia , Rovelli Sabrina , Iodice Simona , Chung Matthew , Frimpong Michael , Bollati Valentina , Ferrari Luca , Ghedin Elodie
Published: August 2024

Air particulate matter (PM) is widely recognized for its potential to negatively affect human health, including changes in the upper respiratory microbiome. However, research on PM-associated microbiota remains limited and mostly focused on PM (e.g., PM2.5and PM10). This study aims to characterize for the first time the microbiome of Total Suspended Particles (TSP) and investigate the correlations of indoor TSP with the human upper respiratory microbiome. Biological and environmental samples were collected over three collection periods lasting three weeks each, between May and July 2022 at the University of Milan and the University of Insubria Como. TSP were sampled using a filter-based technique, while respiratory samples from both anterior nares (AN) and the nasopharynx (NP) were collected using swabs. Microbiome analysis of both human (N = 145) and TSP (N = 51) samples was conducted on metagenomic sequencing data. A comparison of indoor and outdoor TSP microbiomes revealed differences in microbial diversity and taxonomic composition. The indoor samples had higher relative abundance of environmental bacteria often associated with opportunistic infections likeParacoccussp., as well as respiratory bacteria such asStaphylococcus aureusandKlebsiella pneumoniae. Additionally, both indoor and outdoor TSP samples contained broad spectrum antibiotic resistance genes. Indoor TSP exposure was negatively associated with commensal bacteria and positively associated withStaphylococcus aureusrelative abundance. Finally, a correlation between the relative abundance of respiratory bacteria identified in the indoor TSP and the upper respiratory microbiome was found, suggesting a potential interaction between TSP and the upper airways.
Dynamics of duplicated gene regulatory networks governing cotton fiber development following polyploidy
Authors: Xiong Xianpeng , Zhu De , Grover Corrinne E. , Wendel Jonathan F. , Ma Xiongfeng , Hu Guanjing
Published: August 2024

Cotton fiber development entails complex genome-wide gene regulatory networks (GRN) that remain mostly unexplored. Here we present integrative analyses of fiber GRNs using public RNA-seq datasets, integrated with multi-omics genomic, transcriptomic, and cistromic data. We detail the fiber co-expression dynamics and regulatory connections, validating findings with external datasets and transcription factor (TF) binding site data. We elucidate previously uncharacterized TFs that regulate genes involved in fiber-related functions and cellulose synthesis, and identify the regulatory role of two homoeologous G2-like transcription factors on fiber length. Analysis of duplicated gene expression and network relationships in allopolyploid cotton, which has two co-resident genomes (A, D), revealed novel aspects of asymmetric subgenomic developmental contributions. Whereas D-based homoeolog pairs drive higher overall gene expression from the D subgenome, TFs from the A subgenome play a preferential regulatory role in the fiber gene regulatory network. Following allopolyploid formation, it appears that the trans-regulatory roles of TFs diversified more rapidly between homoeologs than did the cis-regulatory elements of their target genes. Our approach underscores the utility of network analysis for detection of master regulators and provides fresh perspectives on fiber development and polyploid functional genomics, through the lens of co-expression and GRN dynamics.
Discovery of a single-subunit oligosaccharyltransferase that enables glycosylation of full-length IgG antibodies inEscherichia coli
Authors: Sotomayor Belen , Donahue Thomas C. , Mahajan Sai Pooja , Taw May N. , Hulbert Sophia W. , Bidstrup Erik J. , Owitipana D. Natasha , Pang Alexandra , Yang Xu , Ghosal Souvik , Alabi Christopher A. , Azadi Parastoo , Gray Jeffrey J. , Jewett Michael C. , Wang Lai-Xi , DeLisa Matthew P.
Published: August 2024

Human immunoglobulin G (IgG) antibodies are one of the most important classes of biotherapeutic agents and undergo glycosylation at the conserved N297 site in the CH2 domain, which is critical for IgG Fc effector functions and anti-inflammatory activity. Hence, technologies for producing authentically glycosylated IgGs are in high demand. While attempts to engineerEscherichia colifor this purpose have been described, they have met limited success due in part to the lack of available oligosaccharyltransferase (OST) enzymes that can installN-linked glycans within the QYNST sequon of the IgG CH2 domain. Here, we identified a previously uncharacterized single-subunit OST (ssOST) from the bacteriumDesulfovibrio marinusthat exhibited greatly relaxed substrate specificity and, as a result, was able to catalyze glycosylation of native CH2 domains in the context of both a hinge-Fc fragment and a full-length IgG. Although the attached glycans were bacterial in origin, conversion to a homogeneous, asialo complex-type G2N-glycan at the QYNST sequon of theE. coli-derived hinge-Fc was achieved via chemoenzymatic glycan remodeling. Importantly, the resulting G2-hinge-Fc exhibited strong binding to human FcγRIIIa (CD16a), one of the most potent receptors for eliciting antibody-dependent cellular cytotoxicity (ADCC). Taken together, the discovery of a unique ssOST fromD. marinusprovides previously unavailable biocatalytic capabilities to the bacterial glycoprotein engineering toolbox and opens the door to usingE. colifor the production and glycoengineering of human IgGs and fragments derived thereof.
Development of a highly efficient base editing system forLactobacillito improve probiotics and dissect essential functions
Authors: Mitsunobu Hitoshi , Kita Yudai , Nambu-Nishida Yumiko , Miyazaki Shoko , Nakajima Kensuke , Taoka Ken-ichiro , Kondo Akihiko , Nishida Keiji
Published: August 2024

Lactobacilliplay essential roles in the food industry and are increasingly explored for their potential as probiotics and therapeutic agents. Beneficial strains are primarily isolated from various natural sources including healthy human bodies, and undergo rigorous characterization and safety evaluations. Genomic and genetic information has increasingly accumulated and been linked to their various functions, to which transgenic approaches are being performed to verify crucial genes. In order to reasonably develop more useful strains, beneficial traits need to be introduced into any given strains and enhanced or combined. However, for practical use as probiotics or foods, organisms with transgene are hardly acceptable. Here, we have introduced the base editing Target-AID system specifically forLactobacilli, enabling precise installation of point mutations without donor DNA and at multiple genomic loci simultaneously.Lactiplantibacillus plantarumhas been successfully engineered to reduce production of imidazole propionate, which has been reported to be associated with type 2 diabetes. Additionally, this system enabled transient knock-out of an essential gene, such as one involved in cell division showing severe filamentous cell phenotype, providing a unique approach for dissecting essential gene function.

Importance

This work provides highly efficient and multiplexable base editing system that installs precise point mutations in the genomes of the two majorLactobacillistrains. As the advanced CRISPR technology so-called non-cleaving genome editing, base editing is less toxic and does not integrate any foreign DNA into the genomes. Our approaches pave the way for dissecting and improving probiotics and food-grade microbes, ultimately creating better human health.
The Epithelial-to-Mesenchymal Transition Supports HCMV Infection and Biosynthesis in Mammary Epithelial Cells Through Two Distinct Mechanisms
Authors: Golconda Preethi , Andrade-Medina Mariana , Matrenec Rachel , McLachlan Alan , Oberstein Adam
Published: August 2024

Human cytomegalovirus (HCMV) infects a wide range of cell types in the body, including a variety of epithelial cell types. Despite the significance of epithelial cells during infection, HCMV has been difficult to study in epithelial cells. In this study, we examined HCMV infection in mammary and prostate epithelial cell lines, finding that the virus establishes a semi-permissive, biosynthetically abortive state. Building on previous work, we hypothesized that shifting epithelial cells to a mesenchymal cell state would restore HCMV biosynthesis and progeny production. To test this hypothesis, we induced epithelial-to-mesenchymal transition (EMT) using TGF-β and the EMT-transcription factor (EMT-TF) SNAIL. We found that shifting strongly epithelial cell lines to a mesenchymal cell state shifted HCMV infection from a semi-permissive to fully permissive state. This effect appeared to involve two distinct mechanisms: EMT-sensitive enhancement of viral entry and EMT-sensitive enhancement of viral mRNA translation. Although the precise mechanisms remain elusive, our findings identify the epithelial-mesenchymal cell state axis as an important regulator of HCMV infection and provide new insights into how cellular differentiation states influence viral replication. They also raise the possibility that the EMT pathway, a fundamental pathway involved in development and cancer metastasis, could regulate HCMV infectionin-vivo, potentially contributing to viral persistence or pathogenesis in epithelial tissues.
Interplay between the cyclophilin homology domain of RANBP2 and MX2 regulates HIV-1 capsid dependencies on nucleoporins
Authors: Flick Haley , Venbakkam Ananya , Singh Parmit K. , Layish Bailey , Huang Szu-Wei , Radhakrishnan Rajalingam , Kvaratskhelia Mamuka , Engelman Alan N. , Kane Melissa
Published: August 2024

Interlinked interactions between the viral capsid (CA), nucleoporins (Nups), the antiviral protein myxovirus resistance 2 (MX2/MXB) influence HIV-1 nuclear entry and the outcome of infection. Although RANBP2/NUP358 has been repeatedly identified as a critical player in HIV-1 nuclear import and MX2 activity, the mechanism by which RANBP2 facilitates HIV-1 infection is not well understood. To explore the interactions between MX2, the viral CA, and RANBP2, we utilized CRISPR-Cas9 to generate cell lines expressing RANBP2 from its endogenous locus but lacking the C-terminal cyclophilin (Cyp) homology domain, and found that both HIV-1 and HIV-2 infection were reduced significantly in RANBP2ΔCypcells. Importantly, although MX2 still localized to the nuclear pore complex in RANBP2ΔCypcells, antiviral activity against HIV-1 was decreased. By generating cells expressing specific point mutations in the RANBP2-Cyp domain we determined that the effect of the RANBP2-Cyp domain on MX2 anti-HIV-1 activity is due to direct interactions between RANBP2 and CA. We further determined that CypA and RANBP2-Cyp have similar effects on HIV-1 integration targeting. Finally, we found that the Nup requirements for HIV infection and MX2 activity were altered in cells lacking the RANBP2-Cyp domain. These findings demonstrate that the RANBP2-Cyp domain affects viral infection and MX2 sensitivity by altering CA-specific interactions with cellular factors that affect nuclear import and integration targeting.

Significance Statement

HIV-1 entry into the nucleus is an essential step in viral replication that involves complex interactions between the viral capsid and multiple cellular proteins, including nucleoporins such as RANBP2. Nups also mediate the function of the antiviral protein MX2, however determining the precise role of Nups in HIV infection has proved challenging due to the complex nature of the nuclear pore and significant pleiotropic effects elicited by Nup depletion. We have used precise gene editing to assess the role of the Cyp domain of RANBP2 in HIV-1 infection and MX2 activity. We find that this domain affects viral infection, nucleoporin requirements, MX2 sensitivity, and integration targeting in a CA-specific manner, providing detailed insights into how RANBP2 contributes to HIV-1 infection.
Vesiculation pathways in clathrin-mediated endocytosis
Authors: Wang Xinran , Berro Julien , Ma Rui
Published: August 2024

During clathrin-mediated endocytosis, a patch of flat plasma membrane is internalized to form a vesicle. In mammalian cells, how the clathrin coat deforms the membrane into a vesicle remains unclear and two main hypotheses have been debated. The “constant area” hypothesis assumes that clathrin molecules initially form a flat lattice on the membrane and deform the membrane by changing its intrinsic curvature while keeping the coating area constant. The alternative “constant curvature” hypothesis assumes that the intrinsic curvature of the clathrin lattice remains constant during the formation of a vesicle while the surface area it covers increases. Previous experimental studies were unable to unambiguously determine which hypothesis is correct. In this paper, we show that these two hypotheses are only two extreme cases of a continuum of vesiculation pathways if we account for the free energies associated with clathrin assembly and curvature generation. By tracing the negative gradient of the free energy, we define vesiculation pathways in the phase space of the coating area and the intrinsic curvature of clathrin coat. Our results show that, overall, the differences in measurable membrane morphology between the different models are not as big as expected, and the main differences are most salient at the early stage of endocytosis. Furthermore, the best fitting pathway to experimental data is not compatible with the constant-curvature model and resembles a constant-area-like pathway where the coating area initially expands with minor changes in the intrinsic curvature, later followed by a dramatic increase in the intrinsic curvature and minor change in the coating area. Our results also suggest that experimental measurement of the tip radius and the projected area of the clathrin coat will be the key to distinguish between models.
Exploring the Efimov effect in the
D*D*D*
system
Authors: Ortega P. G.
Published: August 2024

The emergence of the Efimov effect in the D*D*D* system is explored under the assumption that the heavy partner of the Tcc+ exists as a D*D* molecule with (I)JP=(0)1+. The three-to-three relativistic scattering amplitude is obtained from the ladder amplitude formalism, built from an energy-dependent contact two-body potential where the molecular component of the Tcc* state can be varied. We find that (I)JP=(12)0− three-body bound states can be formed, with properties that suggest that the Efimov effect can be realized for reasonable values of the molecular probability and binding energy of the Tcc*.

Published by the American Physical Society
2024
Quadratic coupling of the axion to photons
Authors: Beadle Carl , Ellis Sebastian A. R. , Quevillon Jérémie , Vuong Pham Ngoc Hoa
Published: August 2024

We show that the QCD axion couples to the electromagnetic kinetic term at one loop. The result is that if axions make up dark matter, they induce temporal variation of the fine structure constant α, which is severely constrained. We recast these constraints on the QCD axion parameter space. We also discuss how to generalize our finding to axionlike particles, and the resulting constraints.

Published by the American Physical Society
2024
Impact of reflection Comptonization on x-ray reflection spectroscopy: The case of EXO 1846-031
Authors: Li Songcheng , Liu Honghui , Bambi Cosimo , Steiner James F. , Zhang Zuobin
Published: August 2024

Within the disk-corona model, it is natural to expect that a fraction of reflection photons from the disk are Compton scattered by the hot corona (reflection Comptonization), even if this effect is usually ignored in x-ray reflection spectroscopy studies. We study this effect by using NICER and NuSTAR data of the Galactic black hole EXO 1846-031 in the hard-intermediate state with the model . Our analysis suggests that a scattered fraction of order 10% is required to fit the data, but the inclusion of reflection Comptonization does not change appreciably the measurements of key parameters like the black hole spin and the inclination angle of the disk.

Published by the American Physical Society
2024
Three-dimensional theory of superradiant free-electron lasers
Authors: Robles River R. , Giannessi Luca , Marinelli Agostino
Published: August 2024

The solitonlike superradiant regime of free-electron lasers (FEL) offers a promising path towards ultrashort pulses, beyond the natural limit dictated by the bandwidth of the high-gain FEL instability. In this work we present a three-dimensional theory of the superradiant regime, including the effects of beam emittance and energy spread. Our work takes advantage of recent developments in nonlinear FEL theory to provide a fully analytical description of solitonlike superradiance. Our theory proves the existence of a diffraction-dominated steady-state regime in which the superradiant peak power grows indefinitely while leaving the pulse duration and on-axis intensity almost unchanged. These results are in excellent agreement with three-dimensional simulations and are supported by recent experimental results at the Linac Coherent Light Source. This work advances nonlinear FEL theory and provides a theoretical framework for the next generation of attosecond x-ray FELs.

Published by the American Physical Society
2024