bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of mulberry leaf powder water extract supplementation on the growth performance, immunity, antioxidant, meat quality and intestinal microbiota of yellow feather broilers
Authors: Xing Dongxu , Fu Bing , Zhou Donglai , Li Erna , Li Qingrong , Ruan Dong , Liao Sentai , Zou Yuxiao
Published: June 2024

A 50‐day feeding trial was conducted to evaluate the effects of mulberry leaf powder water extract (MLE) on the growth performance, immunity, antioxidant, meat quality and intestinal microbiota of yellow feather broilers. A total of 720 birds (initial body weight 40.07 ± 0.05 g) were randomly distributed into four groups with six replicates per group and 30 birds per replicate. Four diets were formulated with 0% (CON), 200 mg/kg MLE (MLE200), 400 mg/kg MLE (MLE400) and 600 mg/kg MLE (MLE600) supplementation. Results showed that the addition of 200–600 mg/kg MLE to the diet significantly increased the body weight (BW) and average daily weight gain (ADG), but feed to gain ratio (F/G) were linearly decreased (p = 0.045) as dietary MLE increased. Birds fed MLE400 had higher (p < 0.05) total antioxidant capacity (T‐AOC), interleukin‐10 (Il‐10), secretory immunoglobulin A (SIgA) and complement 3 (C3) contents than those fed CON, whereas MLE400 had lower malondialdehyde (MDA) content than CON (p < 0.05). Analysis of 16 S rDNA indicated that supplementation with 200 mg/kg MLE increased the Shannon indices in the caecum (p < 0.05). Supplementation with MLE decreased the abundance of the phylum Proteobacteria and genus Helicobacter, and increased the abundance of the phylum Bacteroidetes in the caecum in broiler chickens (p < 0.05). The drip loss rate in the MLE600 was significantly diminished (p < 0.05), whereas the shear force was significantly elevated (p < 0.05). In summary, dietary supplementation with MLE can effectively improve growth performance, intestinal immunity, serum antioxidant capacity, meat quality and intestinal microbiota of yellow feather broilers. The most appropriate MLE supplementation level was 400 mg/kg. This study provides a practical strategy for the dietary application of MLE in yellow feather broilers.
The stability of slow‐wave sleep and EEG oscillations across two consecutive nights of laboratory polysomnography in cognitively normal older adults
Authors: Mullins Anna E. , Pehel Shayna , Parekh Ankit , Kam Korey , Bubu Omonigho M. , Tolbert Thomas M. , Rapoport David M. , Ayappa Indu , Varga Andrew W. , Osorio Ricardo S.
Published: June 2024

Laboratory polysomnography provides gold‐standard measures of sleep physiology, but multi‐night investigations are resource intensive. We assessed the night‐to‐night stability via reproducibility metrics for sleep macrostructure and electroencephalography oscillations in a group of cognitively normal adults attending two consecutive polysomnographies. Electroencephalographies were analysed using an automatic algorithm for detection of slow‐wave activity, spindle and K‐complex densities. Average differences between nights for sleep macrostructure, electroencephalography oscillations and sleep apnea severity were assessed, and test–retest reliability was determined using two‐way intraclass correlations. Agreement was calculated using the smallest real differences between nights for all measures. Night 2 polysomnographies showed significantly greater time in bed, total sleep time (6.3 hr versus 6.8 hr, p < 0.001) and percentage of rapid eye movement sleep (17.5 versus 19.7, p < 0.001). Intraclass correlations were low for total sleep time, percentage of rapid eye movement sleep and sleep efficiency, moderate for percentage of slow‐wave sleep and percentage of non‐rapid eye movement 2 sleep, good for slow‐wave activity and K‐complex densities, and excellent for spindles and apnea–hypopnea index with hypopneas defined according to 4% oxygen desaturation criteria only. The smallest real difference values were proportionally high for most sleep macrostructure measures, indicating moderate agreement, and proportionally lower for most electroencephalography microstructure variables. Slow waves, K‐complexes, spindles and apnea severity indices are highly reproducible across two consecutive nights of polysomnography. In contrast, sleep macrostructure measures all demonstrated poor reproducibility as indicated by low intraclass correlation values and moderate agreement. Although there were average differences in percentage of rapid eye movement sleep and total sleep time, these were numerically small and perhaps functionally or clinically less significant. One night of in‐laboratory polysomnography is enough to provide stable, reproducible estimates of an individual's sleep concerning measures of slow‐wave activity, spindles, K‐complex densities and apnea severity.
Practical recommendations for biochemical and genetic diagnosis of the porphyrias
Authors: Aarsand Aasne K. , To‐Figueras Jordi , Whatley Sharon , Sandberg Sverre , Schmitt Caroline
Published: June 2024

The porphyrias are a group of rare inborn errors of metabolism associated with various clinical presentations and long‐term complications, making them relevant differential diagnoses to consider for many clinical specialities, especially hepatologists, gastroenterologists and dermatologists. To diagnose a patient with porphyria requires appropriate biochemical investigations, as clinical features alone are not specific enough. Furthermore, it is important to be aware that abnormalities of porphyrin accumulation and excretion occur in many other disorders that are collectively far more common than the porphyrias. In this review, we provide an overview of porphyria‐related tests with their strengths and limitations, give recommendations on requesting and diagnostic approaches in non‐expert and expert laboratories for different clinical scenarios and discuss the role of genetic testing in the porphyrias. To diagnose porphyria in a currently symptomatic patient requires analysis of biochemical markers to demonstrate typical patterns of haem precursors in urine, faeces and blood. The use of genomic sequencing in diagnostic pathways for porphyrias requires careful consideration, and the demonstration of increased porphyrin‐related markers is necessary prior to genomic testing in symptomatic patients. In the acute porphyrias, genomic testing is presently a useful adjunct for genetic counselling of asymptomatic family members and the most common cutaneous porphyria, porphyria cutanea tarda, is usually a sporadic, non‐hereditary disease. Getting a correct and timely porphyria diagnosis is essential for delivering appropriate care and ensuring best patient outcome.
Glycaemic index and glycaemic load of selected packaged vegan foods
Authors: Bayindir Gümüş Aylin , Keser Alev , Gökgöz Murat , Güngüneş Aşkın
Published: June 2024

While there are data regarding the glycaemic index (GI) and glycaemic load (GL) of many foods in the literature, the values for packaged vegan analogue foods have not been previously published, although processed vegan foods usually contain more carbohydrates than their animal‐based counterparts. This study was carried out to determine the GI and GL values of a selection of packaged vegan foods popular in Türkiye. To determine the GI and GL of test foods, 12 healthy volunteer females participated in the study. Participants randomly consumed test and reference foods (glucose and white bread) on each trial day, and capillary blood glucose was measured at baseline, 15, 30, 45, 60, 90 and 120 mins in duplicate. The GIs of vegan schnitzel, vegan chickpea burger, vegan mince pita, vegan chocolate, vegan snack bar and vegan cheese were 26.1 ± 19.61 (low), 27.1 ± 17.21 (low), 65.1 ± 28.60 (moderate), 42.7 ± 22.32 (low), 63.6 ± 45.86 (moderate), 36.4 ± 16.85 (low), respectively, according to the glucose reference, and were 28.2 ± 16.17 (low), 34.7 ± 18.26 (low), 81.2 ± 31.96 (high), 48.8 ± 12.87 (low), 82.0 ± 54.05 (high), 46.7 ± 28.66 (low), respectively, according to the white bread reference. GLs were 3.5 ± 2.66 (low), 8.6 ± 5.46 (low), 26.6 ± 11.67 (high), 6.1 ± 3.19 (low), 14.2 ± 10.28 (moderate), 5.7 ± 2.63 (low), respectively, according to the glucose reference, and were 3.8 ± 2.19 (low), 11.0 ± 5.80 (moderate), 33.1 ± 13.04 (high), 7.0 ± 1.84 (low), 18.4 ± 12.12 (moderate), 7.3 ± 4.47 (low), respectively, according to the white bread reference. The data from this study provide preliminary data for the GIs and GLs of packaged and processed vegan foods and show that the GIs and GLs of meat and cheese vegan analogues, while still low or moderate, tend to be higher than their animal‐based counterparts which have lower or no glycaemic responses. Further research on the GIs and GLs of more vegan foods is needed.
Keratinocytes stimulate MAIT cells to produce granzyme B via MR1 and cytokines in oral lichen planus
Authors: Jiang Qin , Wang Fang , Zhou Gang
Published: June 2024

Objective

Oral lichen planus (OLP) is a chronic inflammatory disease characterized by a dense T‐cell infiltration and the degeneration of basal keratinocytes. The potential functions of mucosal associated invariant T (MAIT) cells in OLP have been analyzed in our previous study. Keratinocytes under proinflammatory conditions have been demonstrated to activate T cells. This study was aimed to investigate how keratinocytes stimulate MAIT cells in OLP, and to explore the role of activated MAIT cells on keratinocytes.

Methods and Results

Increased MAIT cells and higher activation marker CD69 were detected in OLP lesions by flow cytometry. The enhanced expression of MHC class I‐like molecule (MR1) required for MAIT cell activation in the epithelial layer of OLP lesions was determined by immunohistochemistry. Keratinocytes treated by 5‐A‐RU prodrug and lipopolysaccharide, respectively, exhibited higher expression of MR1 and secretion of IL‐18. In direct coculture systems consisting of keratinocytes and peripheral blood mononuclear cells, both 5‐A‐RU prodrug‐pretreated keratinocytes and lipopolysaccharide‐pretreated keratinocytes activated MAIT cells to secrete granzyme B, contributing to elevated keratinocyte apoptosis.

Conclusions

Keratinocytes were capable to activate MAIT cells via MR1 and cytokines in OLP, and granzyme B produced by activated MAIT cells intensified keratinocyte apoptosis, engaging in the pathogenesis of OLP.
Assessing the links between pollinators and the genetic and epigenetic features of plant species with contrasting distribution ranges
Authors: Valverde Javier , Medrano Mónica , Herrera Carlos M. , Alonso Conchita
Published: June 2024

In flowering plants, pollinators contribute to gene flow while they also respond to variation in plant traits together determined by genetic, epigenetic and environmental sources of variation. Consequently, a correlation between abundance and diversity of pollinators and the genetic and epigenetic characteristics of plant populations such as diversity or distinctiveness is expected. However, no study has explored these long‐term dimensions of plant–pollinator interactions. Mediterranean narrow endemics often exhibit unexpectedly high levels of population genetic and epigenetic diversity. We hypothesize that pollinators may contribute to explain this pattern. Specifically, given the higher sensitivity of small, isolated population to gene flow, we expect a stronger association of pollinators with population genetic and epigenetic variability in narrow endemics than in widely distributed congeners. We studied five pairs of congeneric plant species, consisting of one narrow endemic with a restricted distribution and one widespread congener, found in the Sierra de Cazorla mountains (SE Spain). We characterized the pollinators in up to three populations per species to estimate their diversity and visitation rates. Additionally, we calculated the genetic and epigenetic diversity and distinctiveness of each population using AFLP markers and methylation‐sensitive AFLP markers (MSAP), respectively. We assessed the relationship between pollinator diversity and visitation rates. The diversity of pollinators did not vary according to the plant´s distribution range, but visitation rate was higher in widespread species. As predicted, only narrow endemics showed a significant association between pollinators and their population genetic and epigenetic characteristics. Specifically, higher pollinator diversity and visitation rates entailed higher population genetic diversity and lower epigenetic distinctiveness. This work shows the importance of investigating the relationship between pollinator diversity and population genetics and epigenetics to better understand the evolution of plant rarity.
Experiences of imagery‐based treatment for anxiety in bipolar disorder: A qualitative study embedded within the image based emotion regulation feasibility randomised controlled trial
Authors: Elkington Susan , Brown Michael , Wright Kim , Regan Jemma , Pattarnaraskouwski Kate , Steel Craig , Hales Susie , Holmes Emily , Morant Nicola
Published: June 2024

Objectives

Intrusive mental imagery is associated with anxiety in bipolar disorder (BD) and presents a novel treatment target. Imagery‐based treatments show promise in targeting anxiety and improving mood instability. This qualitative study explored experiences of receiving up to 12 sessions of a brief structured psychological intervention: Image‐Based Emotion Regulation (IBER), which targets maladaptive mental imagery in the context of BD with an aim to modify the emotional impact of these images.

Design

A qualitative study embedded within the Image Based Emotion Regulation (IBER) feasibility randomised controlled trial.

Methods

Semi‐structured interviews were conducted with 12 participants in the treatment arm of the trial who received IBER + treatment as usual. Data were analysed using thematic analysis.

Results

Despite some initial scepticism about imagery‐focused treatment, all participants expressed broadly positive accounts of treatment experiences. High levels of engagement with imagery modification techniques, beneficial use of techniques post treatment and improvements in anxiety management and agency were described by some. Three sub‐groups were identified: those who reported a powerful transformative impact of treatment; those who embedded some new techniques into their daily lives, and those who felt they had techniques to use when needed. No participants reported overall negative experiences of the IBER treatment.

Conclusions

Findings from this study highlight the value for treatment recipients of modifying the underlying meanings associated with maladaptive imagery, and the personalised skills development to manage anxiety within bipolar disorders. Findings can inform treatment refinements and further trial‐based evaluations.
The multidimensionality of plant drought stress: The relative importance of edaphic and atmospheric drought
Authors: Berauer Bernd J. , Steppuhn Anke , Schweiger Andreas H.
Published: June 2024

Drought threatens plant growth and related ecosystem services. The emergence of plant drought stress under edaphic drought is well studied, whilst the importance of atmospheric drought only recently gained momentum. Yet, little is known about the interaction and relative contribution of edaphic and atmospheric drought on the emergence of plant drought stress. We conducted a gradient experiment, fully crossing gravimetric water content (GWC: maximum water holding capacity—permanent wilting point) and vapour pressure deficit (VPD: 1−2.25 kPa) using five wheat varieties from three species (Triticum monococcum, T. durum & T. aestivum). We quantified the occurrence of plant drought stress on molecular (abscisic acid), cellular (stomatal conductance), organ (leaf water potential) and stand level (evapotranspiration). Plant drought stress increased with decreasing GWC across all organizational levels. This effect was magnified nonlinearly by VPD after passing a critical threshold of soil water availability. At around 20%GWC (soil matric potential 0.012 MPa), plants lost their ability to regulate leaf water potential via stomata regulation, followed by the emergence of hydraulic dysfunction. The emergence of plant drought stress is characterized by changing relative contributions of soil versus atmosphere and their non‐linear interaction. This highly non‐linear response is likely to abruptly alter plant‐related ecosystem services in a drying world.
How will i know if he really loves me? Toward an epistemology of love
Authors: Stringer Ryan
Published: June 2024

This paper attempts to fill an epistemological gap in our theorizing about love with a sketch of an epistemology of love that unfolds by addressing Whitney Houston's famous epistemological questions pertaining to how we can know whether another loves us. After arguing for three possible sources of the knowledge of love, it offers initial answers to how the knowledge of the presence or absence of another's love can be acquired from the relevant possible sources previously established. These initial answers, though, are unsatisfying because they invite more difficult questions that are then addressed, such as those pertaining to the kinds of things that constitute love's expressions along with how to detect these expressions given the possibility of false‐positives. Addressing these questions ultimately leads to a sharpened, Aristotle‐inspired account of how to acquire the knowledge of the presence or absence of another's love by inferring it, respectively, from the successful or failed detection of love's expressions.
Addressing the international illegal wildlife trade through a human rights approach
Authors: Osorio Chad Patrick , Bernaz Nadia
Published: June 2024

Cross‐border illegal wildlife trade (IWT) poses significant social, political and economic threats. Despite a 2013 recommendation from the Secretariat of the Convention on the International Trade of Endangered Species to incorporate a human rights perspective in counter‐IWT initiatives, our analysis of official documents spanning 2013–2022 reveals a lack of explicit implementation by international bodies. During the same period, global human rights organisations have given limited attention to the connections between IWT and human rights violations. In this article, we explore how integrating a human rights perspective can enhance the international legal framework and domestic measures against IWT. We conclude that to successfully implement counter‐IWT legislation, a shift in mindset is needed. A human rights approach is not just desirable, but rather necessary, in the interpretation, application and revision of policy interventions, for laws against IWT to be truly effective and equitable.
Initiating transformation within a Dutch grassroots agri‐food initiative: An analysis of social processes
Authors: van Oers Laura , Smessaert Jacob , Feola Giuseppe
Published: June 2024

This article brings new empirical evidence and nuanced reflections on the social processes of transformation within grassroots agri‐food initiatives that propose relocalised, decentralised and autonomous ways of organising around food systems. We facilitated and analysed a fieldlab on the initial phase of designing a participatory guarantee system with a Dutch consumer‐buying group (CBG) who explored ways to define, measure and assess sustainable production and consumption in collaboration with its producers. Our analysis focuses on three social processes that emerged from this fieldlab: (a) deepening of community relations around and through agri‐food; (b) learning in agri‐food initiatives and (c) politicisation of agri‐food systems. We analyse the manifestations of and limitations of these three processes concerning the CBG's attempt to become a local food community. We conclude that our findings bring about practical, theoretical and strategic implications to understanding the social dynamics of grassroots agri‐food initiatives within and beyond capitalist agri‐food systems.
Characteristics of gut microbiota and serum metabolism in patients with atopic dermatitis
Authors: Zeng Yibin , Fan Ni , Gu Xiaoli , Zhang Yiwen , Min Wei , Mao Qiuyu , Qian Qihong
Published: June 2024

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15%‐30% of children and 10% of adults globally, with its incidence being influenced by genetic, environmental, and various other factors. While the immune plays a crucial role in the development, the composition of gut microbiota and serum metabolites also contribute to its pathogenesis.

Subject

Study the characteristics of gut microbiota and serum metabolites in patients with atopic dermatitis

Method

In this study, we collected stool and serum samples from 28 AD patients and 23 healthy individuals (NC) for metagenomic sequencing of gut microbiota and non‐targeted metabolomic sequencing of serum.

Result

Our results revealed a lower diversity of gut microbiota in the AD group compared to the NC group. The predominant Phylum in AD patients were Bacteroidetes, Pseudomonas, and Verrucomicrobia, with the most dominant bacterial genus being Faecalibacterium. At the species level, Prevotella copri and Faecalibacterium prausnitzii were found to be the most abundant bacteria. Significant differences in serum metabolite profiles were observed between NC and AD patients, with noticeable variations in metabolite expression levels. The majority of metabolites in the serum of AD patients exhibited low expression, while a few showed high expression levels. Notably, metabolites such as Cholesterol glucuronide, Styrene, Lutein, Betaine, Phosphorylcholine, Taurine, and Creatinine displayed the most pronounced alterations.

Conclusion

These findings contribute to a further understanding of the complexities underlying this disease.
Miliary osteoma cutis in a climbing mantella frog (Mantella laevigata)
Authors: Chiu Elliott S. , Gjeltema Jenessa , Woolard Kevin D. , Affolter Verena K.
Published: June 2024

A climbing mantella frog (Mantella laevigata) was presented with nodular thickened skin. Histological examination revealed dermal nodules composed of differentiated bone consistent with miliary osteoma cutis, a non‐neoplastic condition where bone is abnormally deposited within the skin. This is the first report of idiopathic osteoma cutis in an amphibian.
Acuerdos probatorios: un tema pendiente en Colombia
Authors: Sanabria Villamizar Ronald Jesús
Published: June 2024

Se trata de un trabajo producto de investigación que tiene por objetivo analizar el funcionamiento y las implicaciones procesales de los acuerdos probatorios en el ordenamiento jurídico colombiano, tanto en los procesos judiciales regidos por el Código General del Proceso como por el Código Procesal Penal. El objetivo se desarrolla bajo un estudio sistemático de las fuentes del derecho relevantes al tema, bajo el marco teórico que ofrece la concepción racionalista de la prueba. Como conclusión, se tiene que las diferentes modalidades de acuerdos probatorios permitidos en Colombia fungen como una causal de hechos exentos de prueba —en el sentido epistemológico—, pero que, bajo el objetivo institucional de alcanzar la verdad con base en la racionalidad inductiva, no limitan al juez en caso de que las pruebas acrediten un hecho incompatible con lo acordado, por lo que deben funcionar como presunción relativa o iuris tamtun (admiten prueba en contrario).
Hacia una tutela estatal de niños, niñas y adolescentes privados de cuidado parental en Chile
Authors: Lathrop Fabiola
Published: June 2024

El presente trabajo de investigación afirma que el ordenamiento chileno no contempla reglas sobre la responsabilidad legal de niños, niñas y adolescentes (NNA) privados de cuidado parental. Con el objeto de sentar las bases de una reforma que colme este vacío, se analizan estándares internacionales específicos en la materia y las legislaciones mexicana, española, catalana, inglesa y argentina. Se propone: a) establecer una tutela que atribuya al Estado la responsabilidad legal de NNA privados de cuidado parental; b) en defecto de lo anterior y como solución más inmediata, que el juez de familia atribuya a la persona que recibe al NNA en acogimiento, el derecho y el deber de adoptar decisiones en lugar de sus progenitores; y c) revisar la regulación civil de las instituciones de protección de derechos de las personas incapaces para hacer más pertinentes e idóneas las relativas al cuidado alternativo de NNA.
Poroelastic and Viscoelastic Hallmarks in the Response of Porous and Transversely Isotropic Beams to Harmonic Excitation
Authors: Su Xing , Mehrabian Amin
Published: June 2024

A general solution to harmonic excitation of beam-shaped specimens made from porous, fluid-saturated, transversely isotropic, and viscoelastic materials is developed and presented. The solution draws from Biot's theory of dynamic poroviscoelasticity and adopts a modification of Timoshenko beam model to account for the moment due to pore fluid pressure. Closed-form expressions for transverse displacement and rotation angle of the beam are obtained for the case of three-point bending experiments. Solutions for Rayleigh and Euler–Bernoulli beam models are recovered as special cases. Implications for possible characterization through relevant dynamic mechanical analysis testing are discussed for materials which exhibit certain anisotropy in both the mechanical and flow properties. Three timescale groups shape the dynamic response of the vibrating beam. These timescales pertain to energy dissipation rate within the solid phase, viscous flow of the pore fluid, as well as the natural frequencies of the test specimen. The interplay of a varying excitation frequency with the described timescales is shown to enable simultaneous characterization of the viscoelastic and poroelastic parameters of the specimen constitutive behavior through the obtained dynamic moduli and loss angles of beam vibrations.
Ultrasound in bone fracture diagnosis – a comparative meta-analysis and systematic review
Authors: Matschiner Eric , Serban Oana , Fodor Daniela , Blaivas Michael , Horn Rudolf , Koch Jonas , Jakobi Marie-Lise , Grevelding Lara , Osterwalder Joseph , Srivastava David , Dietrich Christoph Frank
Published: June 2024

Aim: This meta-analysis evaluates the diagnostic accuracy of ultrasound (US) for bone fractures over the past 47 years, comparing it to established imaging standards.Material and methods: We adhered to PRISMA 2020 guidelines to search Medline, EMBASE, and the Cochrane Library using tailored search strategies. The primary outcome, US diagnostic performance, was analyzed across various subgroups including clinical relevance, patient age, and anatomical considerations. The QUADAS-2 tool was employed to assess study quality and minimize bias.Results: From 5,107 initially identified studies, 75 met the inclusion criteria, encompassing 7,769 participants and 3,575 diagnosed fractures. The majority of studies were prospective (79%) and compared US primarily with plain radiography (76%) and CT scans (19%). Of these, 61 studies were amenable to systematic analysis, revealing US to have a sensitivity and specificity of 91% (95% CI: 90%-92%) and 91.3% (95% CI: 90.5%-92.1%), respectively. Likelihood ratios were favorable, with a positive value of 9.955 and a negative value of 0.087, and an odds ratio of 132.67. The area under the curve stood at 0.9715, indicating high diagnostic accuracy despite significant heterogeneity (I²=81.3% for sensitivity, 89.3% for specificity).Conclusion: The evidence supports US as a highly accurate diagnostic tool for bone fractures, rivalling standard imaging methods like CT and radiography. Its notable diagnostic efficacy, combined with advantages in reducing pain, wait times, and radiation exposure, advocates for its broader application. Further validation in large-scale, randomized trials is essential to integrate US more fully into clinical guidelines for fracture management.
What’s Your Poison? Is Sitting Always Health Hindering and Moving Always Health Promoting?
Authors: Straker Leon , Lund Rasmussen Charlotte , Gupta Nidhi , Holtermann Andreas
Published: June 2024

The clear public messaging from international health authorities is that individuals should “sit less and move more.” While it is acknowledged that this guidance needs to be tailored to the age of people and also to their health, and abilities, the guidance is not tailored to their current level of physical behaviors. This opinion piece aims to highlight that although people with excessive sitting and insufficient moderate-to-vigorous physical activity should sit more and move less, for other people their health would be promoted by sitting more and moving less. Thus, physical behaviors are not always “poison” or “medicine,” but rather the health impact of changes in physical behaviors depends on people’s initial levels. Policy, research, and practice implications of this realization are presented. Only tailoring messaging to age and health status could be far from optimal for people with very different current levels of physical behaviors. Policy, research, and practice will be enhanced when the potential for physical behaviors to be either health hindering or health promoting is adequately considered.
Neural circuits expressing the serotonin 2C receptor regulate memory in mice and humans
Authors: Liu Hesong , He Yang , Liu Hailan , Brouwers Bas , Yin Na , Lawler Katherine , Keogh Julia M. , Henning Elana , Lee Dong-Kee , Yu Meng , Tu Longlong , Zhang Nan , Conde Kristine M. , Han Junying , Yan Zili , Scarcelli Nikolas A. , Liao Lan , Xu Jianming , Tong Qingchun , Zheng Hui , Sun Zheng , Yang Yongjie , Wang Chunmei , He Yanlin , Farooqi I. Sadaf , Xu Yong
Published: June 2024

Declined memory is a hallmark of Alzheimer’s disease (AD). Experiments in rodents and human postmortem studies suggest that serotonin (5-hydroxytryptamine, 5-HT) plays a role in memory, but the underlying mechanisms are unknown. Here, we investigate the role of 5-HT 2C receptor (5-HT
2C
R) in regulating memory. Transgenic mice expressing a humanized
HTR2C
mutation exhibit impaired plasticity of hippocampal ventral CA1 (vCA1) neurons and reduced memory. Further, 5-HT neurons project to and synapse onto vCA1 neurons. Disruption of 5-HT synthesis in vCA1-projecting neurons or deletion of 5-HT
2C
Rs in the vCA1 impairs neural plasticity and memory. We show that a selective 5-HT
2C
R agonist, lorcaserin, improves synaptic plasticity and memory in an AD mouse model. Cumulatively, we demonstrate that hippocampal 5-HT
2C
R signaling regulates memory, which may inform the use of 5-HT
2C
R agonists in the treatment of dementia.
Cytokines drive the formation of memory-like NK cell subsets via epigenetic rewiring and transcriptional regulation
Authors: Foltz Jennifer A. , Tran Jennifer , Wong Pamela , Fan Changxu , Schmidt Evelyn , Fisk Bryan , Becker-Hapak Michelle , Russler-Germain David A. , Johnson Jeanette , Marin Nancy D. , Cubitt Celia C. , Pence Patrick , Rueve Joseph , Pureti Sushanth , Hwang Kimberly , Gao Feng , Zhou Alice Y. , Foster Mark , Schappe Timothy , Marsala Lynne , Berrien-Elliott Melissa M. , Cashen Amanda F. , Bednarski Jeffrey J. , Fertig Elana , Griffith Obi L. , Griffith Malachi , Wang Ting , Petti Allegra A. , Fehniger Todd A.
Published: June 2024

Activation of natural killer (NK) cells with the cytokines interleukin-12 (IL-12), IL-15, and IL-18 induces their differentiation into memory-like (ML) NK cells; however, the underlying epigenetic and transcriptional mechanisms are unclear. By combining ATAC-seq, CITE-seq, and functional analyses, we discovered that IL-12/15/18 activation results in two main human NK fates: reprogramming into enriched memory-like (eML) NK cells or priming into effector conventional NK (effcNK) cells. eML NK cells had distinct transcriptional and epigenetic profiles and enhanced function, whereas effcNK cells resembled cytokine-primed cNK cells. Two transcriptionally discrete subsets of eML NK cells were also identified, eML-1 and eML-2, primarily arising from CD56
bright
or CD56
dim
mature NK cell subsets, respectively. Furthermore, these eML subsets were evident weeks after transfer of IL-12/15/18–activated NK cells into patients with cancer. Our findings demonstrate that NK cell activation with IL-12/15/18 results in previously unappreciated diverse cellular fates and identifies new strategies to enhance NK therapies.
Development of a logic regression-based approach for the discovery of host- and niche-informative biomarkers in
Escherichia coli
and their application for microbial source tracking
Authors: Yu Daniel , Andersson-Li Martin , Maes Sharon , Andersson-Li Lili , Neumann Norman F. , Odlare Monica , Jonsson Anders
Published: June 2024

Microbial source tracking leverages a wide range of approaches designed to trace the origins of fecal contamination in aquatic environments. Although source tracking methods are typically employed within the laboratory setting, computational techniques can be leveraged to advance microbial source tracking methodology. Herein, we present a logic regression-based supervised learning approach for the discovery of source-informative genetic markers within intergenic regions across the
Escherichia coli
genome that can be used for source tracking. With just single intergenic loci, logic regression was able to identify highly source-specific (i.e., exceeding 97.00%) biomarkers for a wide range of host and niche sources, with sensitivities reaching as high as 30.00%–50.00% for certain source categories, including pig, sheep, mouse, and wastewater, depending on the specific intergenic locus analyzed. Restricting the source range to reflect the most prominent zoonotic sources of
E. coli
transmission (i.e., bovine, chicken, human, and pig) allowed for the generation of informative biomarkers for all host categories, with specificities of at least 90.00% and sensitivities between 12.50% and 70.00%, using the sequence data from key intergenic regions, including
emrKY–evgAS
,
ibsB–(mdtABCD-baeSR), ompC–rcsDB,
and
yedS–yedR
, that appear to be involved in antibiotic resistance. Remarkably, we were able to use this approach to classify 48 out of 113 river water
E. coli
isolates collected in Northwestern Sweden as either beaver, human, or reindeer in origin with a high degree of consensus—thus highlighting the potential of logic regression modeling as a novel approach for augmenting current source tracking efforts.

IMPORTANCE

The presence of microbial contaminants, particularly from fecal sources, within water poses a serious risk to public health. The health and economic burden of waterborne pathogens can be substantial—as such, the ability to detect and identify the sources of fecal contamination in environmental waters is crucial for the control of waterborne diseases. This can be accomplished through microbial source tracking, which involves the use of various laboratory techniques to trace the origins of microbial pollution in the environment. Building on current source tracking methodology, we describe a novel workflow that uses logic regression, a supervised machine learning method, to discover genetic markers in
Escherichia coli
, a common fecal indicator bacterium, that can be used for source tracking efforts. Importantly, our research provides an example of how the rise in prominence of machine learning algorithms can be applied to improve upon current microbial source tracking methodology.
Role of the intestinal microbiota in contributing to weight disorders and associated comorbidities
Authors: Van Hul Matthias , Neyrinck Audrey M. , Everard Amandine , Abot Anne , Bindels Laure B. , Delzenne Nathalie M. , Knauf Claude , Cani Patrice D.
Published: June 2024

The gut microbiota is a major factor contributing to the regulation of energy homeostasis and has been linked to both excessive body weight and accumulation of fat mass (i.e., overweight, obesity) or body weight loss, weakness, muscle atrophy, and fat depletion (i.e., cachexia). These syndromes are characterized by multiple metabolic dysfunctions including abnormal regulation of food reward and intake, energy storage, and low-grade inflammation. Given the increasing worldwide prevalence of obesity, cachexia, and associated metabolic disorders, novel therapeutic strategies are needed. Among the different mechanisms explaining how the gut microbiota is capable of influencing host metabolism and energy balance, numerous studies have investigated the complex interactions existing between nutrition, gut microbes, and their metabolites. In this review, we discuss how gut microbes and different microbiota-derived metabolites regulate host metabolism. We describe the role of the gut barrier function in the onset of inflammation in this context. We explore the importance of the gut-to-brain axis in the regulation of energy homeostasis and glucose metabolism but also the key role played by the liver. Finally, we present specific key examples of how using targeted approaches such as prebiotics and probiotics might affect specific metabolites, their signaling pathways, and their interactions with the host and reflect on the challenges to move from bench to bedside.
Adherence and metal-ion acquisition gene expression increases during infection with
Treponema phagedenis
strains from bovine digital dermatitis
Authors: Scott Colton , Dias Angelica P. , De Buck Jeroen
Published: June 2024

Digital dermatitis (DD) is an ulcerative foot lesion on the heel bulbs of dairy cattle. DD is a polymicrobial disease with no precise etiology, although
Treponema
spirochetes are found disproportionally abundant in diseased tissue. Within
Treponema,
several different species are found in DD; however, the species
Treponema phagedenis
is uniformly found in copious quantities and deep within the skin layers of the active, ulcerative stages of disease. The pathogenic mechanisms these bacteria use to persist in the skin and the precise role they play in the pathology of DD are widely unknown. To explore the pathogenesis and virulence of
Treponema phagedenis
, newly isolated strains of this species were investigated in a subcutaneous murine abscess model. In the first trial, a dosage study was conducted to compare the pathogenicity of different strains across three different treponemes per inoculum (TPI) doses based on abscess volumes. In the second trial, the expression levels of 11 putative virulence genes were obtained to gain insight into their involvement in pathogenesis. During the RT-qPCR analysis, it was determined that genes encoding for two metal-ion import lipoproteins and two adherence genes were found highly upregulated during infection. Conversely, two genes involved in motility and chemotaxis were found to not be significantly upregulated or utilized during infection. These results were supported by gene expression data from natural M2 lesions of dairy cattle. This gene expression analysis could highlight the preference in strategy for
T. phagedenis
to persist and adhere in the host rather than engage in motility and disseminate.
Proteolytic control of FixT by the Lon protease impacts FixLJ signaling in
Caulobacter crescentus
Authors: Yigit Kubra , Chien Peter
Published: June 2024

Responding to changes in oxygen levels is critical for aerobic microbes. In
Caulobacter crescentus
, low oxygen is sensed by the FixL-FixJ two-component system which induces multiple genes, including those involved in heme biosynthesis, to accommodate microaerobic conditions. The FixLJ inhibitor FixT is also induced under low oxygen conditions and is degraded by the Lon protease when the oxygen levels are sufficient, which together provides negative feedback proposed to adjust FixLJ signaling thresholds during changing conditions. Here, we address whether degradation of FixT by the Lon protease contributes to phenotypic defects associated with loss of Lon. We find that ∆
lon
strains are deficient in FixLJ-dependent heme biosynthesis, consistent with elevated FixT levels as deletion of
fixT
suppresses this defect. Transcriptomics validate this result as, along with heme biosynthesis, there is diminished expression of many FixL-activated genes in ∆
lon
. However, stabilization of FixT in ∆
lo
n strains does not contribute to restoring any known Lon-related fitness defect, such as cell morphology defects or stress sensitivity. In fact, cells lacking both FixT and Lon are compromised in viability during growth in standard aerobic conditions. Our work highlights the complexity of protease-dependent regulation of transcription factors and explains the molecular basis of defective heme accumulation in Lon-deficient
Caulobacter
.

IMPORTANCE

The Lon protease shapes protein quality control, signaling pathways, and stress responses in many bacteria species. Loss of Lon often results in multiple phenotypic consequences. In this work, we found a connection between the Lon protease and deficiencies in heme accumulation that then led to our finding of a global change in gene expression due in part to degradation of a regulator of the hypoxic response. However, loss of degradation of this regulator did not explain other phenotypes associated with Lon deficiencies demonstrating the complex and multiple pathways that this highly conserved protease can impact.
In situ
fate of Chikungunya virus replication organelles
Authors: Girard Justine , Le Bihan Olivier , Lai-Kee-Him Joséphine , Girleanu Maria , Bernard Eric , Castellarin Cedric , Chee Matthew , Neyret Aymeric , Spehner Danièle , Holy Xavier , Favier Anne-Laure , Briant Laurence , Bron Patrick
Published: June 2024

Chikungunya virus (CHIKV) is a mosquito-borne pathogen responsible for an acute musculoskeletal disease in humans. Replication of the viral RNA genome occurs in specialized membranous replication organelles (ROs) or spherules, which contain the viral replication complex. Initially generated by RNA synthesis-associated plasma membrane deformation, alphavirus ROs are generally rapidly endocytosed to produce type I cytopathic vacuoles (CPV-I), from which nascent RNAs are extruded for cytoplasmic translation. By contrast, CHIKV ROs are poorly internalized, raising the question of their fate and functionality at the late stage of infection. Here, using
in situ
cryogenic-electron microscopy approaches, we investigate the outcome of CHIKV ROs and associated replication machinery in infected human cells. We evidence the late persistence of CHIKV ROs at the plasma membrane with a crowned protein complex at the spherule neck similar to the recently resolved replication complex. The unexpectedly heterogeneous and large diameter of these compartments suggests a continuous, dynamic growth of these organelles beyond the replication of a single RNA genome. Ultrastructural analysis of surrounding cytoplasmic regions supports that outgrown CHIKV ROs remain dynamically active in viral RNA synthesis and export to the cell cytosol for protein translation. Interestingly, rare ROs with a homogeneous diameter are also marginally internalized in CPV-I near honeycomb-like arrangements of unknown function, which are absent in uninfected controls, thereby suggesting a temporal regulation of this internalization. Altogether, this study sheds new light on the dynamic pattern of CHIKV ROs and associated viral replication at the interface with cell membranes in infected cells.

IMPORTANCE

The Chikungunya virus (CHIKV) is a positive-stranded RNA virus that requires specialized membranous replication organelles (ROs) for its genome replication. Our knowledge of this viral cycle stage is still incomplete, notably regarding the fate and functional dynamics of CHIKV ROs in infected cells. Here, we show that CHIKV ROs are maintained at the plasma membrane beyond the first viral cycle, continuing to grow and be dynamically active both in viral RNA replication and in its export to the cell cytosol, where translation occurs in proximity to ROs. This contrasts with the homogeneous diameter of ROs during internalization in cytoplasmic vacuoles, which are often associated with honeycomb-like arrangements of unknown function, suggesting a regulated mechanism. This study sheds new light on the dynamics and fate of CHIKV ROs in human cells and, consequently, on our understanding of the Chikungunya viral cycle.
The pseudogene GBP1P1 suppresses influenza A virus replication by acting as a protein decoy for DHX9
Authors: Yu Xiaohang , Tian Jiaxin , Wang Yihe , Su Ning , Luo Jinna , Duan Ming , Shi Ning
Published: June 2024

Recently, substantial evidence has demonstrated that pseudogene-derived long noncoding RNAs (lncRNAs) as regulatory RNAs have been implicated in basic physiological processes and disease development through multiple modes of functional interaction with DNA, RNA, and proteins. Here, we report an important role for GBP1P1, the pseudogene of guanylate-binding protein 1, in regulating influenza A virus (IAV) replication in A549 cells. GBP1P1 was dramatically upregulated after IAV infection, which is controlled by JAK/STAT signaling. Functionally, ectopic expression of GBP1P1 in A549 cells resulted in significant suppression of IAV replication. Conversely, silencing GBP1P1 facilitated IAV replication and virus production, suggesting that GBP1P1 is one of the interferon-inducible antiviral effectors. Mechanistically, GBP1P1 is localized in the cytoplasm and functions as a sponge to trap DHX9 (DExH-box helicase 9), which subsequently restricts IAV replication. Together, these studies demonstrate that GBP1P1 plays an important role in antagonizing IAV replication.

IMPORTANCE

Long noncoding RNAs (lncRNAs) are extensively expressed in mammalian cells and play a crucial role as regulators in various biological processes. A growing body of evidence suggests that host-encoded lncRNAs are important regulators involved in host–virus interactions. Here, we define a novel function of GBP1P1 as a decoy to compete with viral mRNAs for DHX9 binding. We demonstrate that GBP1P1 induction by IAV is mediated by JAK/STAT activation. In addition, GBP1P1 has the ability to inhibit IAV replication. Importantly, we reveal that GBP1P1 acts as a decoy to bind and titrate DHX9 away from viral mRNAs, thereby attenuating virus production. This study provides new insight into the role of a previously uncharacterized GBP1P1, a pseudogene-derived lncRNA, in the host antiviral process and a further understanding of the complex GBP network.
Draft genome of carotenoid-producing endophytic
Pseudomonas
sp. 102515 from
Taxus chinensis
Authors: Fidan Ozkan
Published: June 2024

Here, we report the draft genome sequence of endophytic
Pseudomonas
sp. 102515 isolated from
Taxus chinensis
collected from Logan, UT, USA. The genome is composed of 36 contigs and around 4.9 Mbp in size. The GC content is 66% with an
N
50
length of 918.9 kbp and
L
50
count of 2.