bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical microscopic imaging, manipulation, and analysis methods for morphogenesis research
Authors: Katoh Takanobu A , Fukai Yohsuke T , Ishibashi Tomoki
Published: December 2023

Morphogenesis is a developmental process of organisms being shaped through complex and cooperative cellular movements. To understand the interplay between genetic programs and the resulting multicellular morphogenesis, it is essential to characterize the morphologies and dynamics at the single-cell level and to understand how physical forces serve as both signaling components and driving forces of tissue deformations. In recent years, advances in microscopy techniques have led to improvements in imaging speed, resolution and depth. Concurrently, the development of various software packages has supported large-scale, analyses of challenging images at the single-cell resolution. While these tools have enhanced our ability to examine dynamics of cells and mechanical processes during morphogenesis, their effective integration requires specialized expertise. With this background, this review provides a practical overview of those techniques. First, we introduce microscopic techniques for multicellular imaging and image analysis software tools with a focus on cell segmentation and tracking. Second, we provide an overview of cutting-edge techniques for mechanical manipulation of cells and tissues. Finally, we introduce recent findings on morphogenetic mechanisms and mechanosensations that have been achieved by effectively combining microscopy, image analysis tools and mechanical manipulation techniques.
Out of Africa: Increasing reports of artemether-lumefantrine treatment failures of uncomplicated Plasmodium falciparum infection
Authors: Halsey Eric S , Plucinski Mateusz M
Published: December 2023

Studies of travellers returning from Africa with uncomplicated Plasmodium falciparum infection are starting to provide signals of failure of artemether-lumefantrine, a first-line treatment of uncomplicated malaria. Traveller-based reports offer an important adjunct to antimalarial efficacy studies performed in endemic regions.
THE SOLACE OF PILGRIMS: MOVEMENT, REST, AND SLEEP IN THE PILGRIM’S PROGRESS
Authors: Christner Sharon Rose
Published: December 2023

Scholars of John Bunyan have understandably emphasised the progress of The Pilgrim’s Progress. However, the description of the places of rest along Christian’s journey call into question the role of the pause in the pilgrim’s journey, as well as the exclusive ‘futureness’ of the peace and rest of God as depicted by Bunyan. The encounter with Simple, Sloth, and Presumption, the Arbour on the Hill Difficulty, and the temptation of the Enchanted Ground are shown as moments of illusory or disobedient rest, where falling asleep is equated with spiritual drowsiness. The House Beautiful, the Delectable Mountains, and Beulah prove places that challenge the idea of unrelenting progress as ideal for the faithful pilgrim.
LEONTES’ ORIGINAL SIN: GENESIS 3 AND THE WINTER’S TALE
Authors: Kanary Jonathan
Published: December 2023

Scholars have often noted the presence of language about penance and repentance in The Winter’s Tale, but less attention has been paid to the way Shakespeare portrays sinfulness itself. This article argues that, especially in the first three acts, the playwright uses repeated allusions to Genesis 3, along with a theological interpretation of evil as privation, to reveal the nature, development, and consequences of Leontes’ sin. This biblically-inflected portrait of sin and evil, in turn, significantly shapes the themes of penitence and forgiveness in the latter half of the play, as Leontes’ repentant sinfulness is transfigured by grace.
Scientific preparation for CSST: classification of galaxy and nebula/star cluster based on deep learning
Authors: Zhang Yuquan , Cao Zhong , Wang Feng , Lam Man I , Deng Hui , Mei Ying , Tan Lei
Published: December 2023

The Chinese Space Station Telescope (abbreviated as CSST) is a future advanced space telescope. Real-time identification of galaxy and nebula/star cluster (abbreviated as NSC) images is of great value during CSST survey. While recent research on celestial object recognition has progressed, the rapid and efficient identification of high-resolution local celestial images remains challenging. In this study, we conducted galaxy and NSC image classification research using deep learning methods based on data from the Hubble Space Telescope. We built a local celestial image data set and designed a deep learning model named HR-CelestialNet for classifying images of the galaxy and NSC. HR-CelestialNet achieved an accuracy of 89.09 per cent on the testing set, outperforming models such as AlexNet, VGGNet, and ResNet, while demonstrating faster recognition speeds. Furthermore, we investigated the factors influencing CSST image quality and evaluated the generalization ability of HR-CelestialNet on the blurry image data set, demonstrating its robustness to low image quality. The proposed method can enable real-time identification of celestial images during CSST survey mission.
Therapeutic effects and mechanisms of action of ginger and its bioactive components on inflammatory response, oxidative stress, the immune system, and organ failure in sepsis: a comprehensive systematic review
Authors: Velayati Aynaz , Vafa Mohamad Reza , Sani'ee Nadia , Darabi Zahra
Published: December 2023

Context

Sepsis refers to a usually lethal medical condition that results from an extreme, uncontrolled, and multifaceted immune system response to infection. Ginger (Zingiber officinale Roscoe; Zingiberaceae) is 1 of the most popular spice. It is widely used as a traditional herb and as medicine in the treatment of some inflammatory conditions, such as vomiting, pain, cancer, diabetes, and cardiovascular diseases, because of its varied medical characteristics, including anti-inflammatory, antioxidant, antimicrobial, and antitumor effects.

Objective

The aim of this study was to demonstrate the potential roles of ginger and its elements in sepsis.

Data Sources

This systematic review article was conducted and reported by following the guideline of the Preferred Reporting for Systematic Reviews (PRISMA). Electronic databases, including Web of Sciences, Google Scholar, PubMed, Scopus, and ProQuest, were searched using related key words up to January 2023.

Data Extraction

Among 141 found articles, 48 eligible articles were included and reviewed for their details. Data were extracted, including the first author's name, year of publication, name of origin country, study design, number and type of subject, dosage and type of intervention, study duration, assay, and main results.

Data Analysis

The data from the included articles showed that ginger and its bioactive elements, such as gingerol (1–300 µg/mL or 1–100 mg/kg for 24 hours to 14 days), shogaol (0.2–100 µg/mL or 10–40 mg/kg body weight for 24 hours to 8 days), gingerdione (1–100 µg/mL for 20–48 hours), and zingerone (2–20 µM for 4 hours to 8 days), can be effective in sepsis via suppressing the gene expression and production of pro-inflammatory cytokines and oxidant agents, downregulating immune response, and protecting against sepsis-induced organ failures in experimental and animal models.

Conclusion

Ginger has potential therapeutic effects in sepsis. Human clinical trials are recommended.

Systematic Review Registration

PROSPERO registration no. CRD42023373613.
Effect of breakfast protein intake on muscle mass and strength in adults: a scoping review
Authors: Khaing Inn-Kynn , Tahara Yu , Chimed-Ochir Odgerel , Shibata Shigenobu , Kubo Tatsuhiko
Published: December 2023

Background

The distribution of protein intake throughout the day is frequently skewed, with breakfast having the lowest protein intake across all age groups. There is no review that addresses the association between breakfast protein intake and muscle mass and strength.

Objective

This scoping review aims to summarize the literature on the relationship between protein intake during breakfast and muscle mass and strength in adults.

Methods

This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Two independent reviewers screened and appraised the articles identified from 3 electronic databases (Medline, Web of Science, and Scopus) that focused on protein intake per meal and its impact on muscle-related outcomes.

Results

A total of 14 763 articles were retrieved from 3 databases, and after the screening process, 15 articles were included for analysis. Approximately 58.8% of findings from 11 studies examining the association between high protein intake during breakfast and muscle mass indicated an increase in muscle mass among participants. Half of 6 studies (50.0%) exploring the relationship between high protein intake at breakfast and muscle strength demonstrated an increase in muscle strength. Consuming high amounts of protein at breakfast or more protein in the morning than in the evening was associated with an increase in the skeletal muscle index and lean body mass.

Conclusion

Protein consumption at breakfast revealed potential benefits in increasing muscle mass across 5 studies involving an elderly population and 2 studies encompassing middle-aged women and young men in our review. However, the relationship between protein intake at breakfast and muscle strength remains unclear. Further high-quality randomized controlled trials are required to examine whether adults can preserve skeletal muscle health outcomes by consuming higher amounts of protein at breakfast.
Effects of intermittent dieting with break periods on body composition and metabolic adaptation: a systematic review and meta-analysis
Authors: Poon Eric Tsz-Chun , Tsang Jaclyn Hei , Sun Fenghua , Zheng Chen , Wong Stephen Heung-Sang
Published: December 2023

Context

Intermittent dieting incorporated with break periods (INT-B) has recently been promoted as an alternative dietary approach for optimal weight management.

Objective

This study assessed the effectiveness of INT-B compared with that of conventional continuous energy restriction (CER) for improving body composition and attenuating metabolic adaptation.

Data Sources

A systematic search was conducted on 6 databases using all available records until July 2023.

Data Extraction

The extracted data included the lead author, year of publication, population characteristics, intervention protocols, duration, and adherence.

Data Analysis

Random-effects meta-analyses were conducted for within-group and between-group comparisons of anthropometric and metabolic outcomes. Subgroup moderator analysis was performed for the types of INT-B, intervention duration, and population characteristics.

Results

Of the 1469 records, 12 randomized trials (with 881 participants) were included. Within-group analyses demonstrated significant improvements in body mass, fat mass, body mass index, body fat percentage, and waist circumference following both INT-B and CER, with no significant group differences. However, resting metabolic rate (RMR) was significantly reduced following CER only. The compensatory reduction in RMR was significantly smaller following INT-B compared with CER, suggesting a lesser degree of metabolic adaptation. INT-B had a more significant effect on RMR retention in individuals with overweight/obesity compared with resistance-trained individuals.

Conclusion

This review provides up-to-date evidence for INT-B as a viable dietary strategy to improve body composition and attenuate metabolic adaptation.

Systematic Review Registration

PROSPERO registration no. CRD42023448959.
Growing ecosystem of deep learning methods for modeling protein–protein interactions
Authors: Rogers Julia R , Nikolényi Gergő , AlQuraishi Mohammed
Published: December 2023

Numerous cellular functions rely on protein–protein interactions. Efforts to comprehensively characterize them remain challenged however by the diversity of molecular recognition mechanisms employed within the proteome. Deep learning has emerged as a promising approach for tackling this problem by exploiting both experimental data and basic biophysical knowledge about protein interactions. Here, we review the growing ecosystem of deep learning methods for modeling protein interactions, highlighting the diversity of these biophysically informed models and their respective trade-offs. We discuss recent successes in using representation learning to capture complex features pertinent to predicting protein interactions and interaction sites, geometric deep learning to reason over protein structures and predict complex structures, and generative modeling to design de novo protein assemblies. We also outline some of the outstanding challenges and promising new directions. Opportunities abound to discover novel interactions, elucidate their physical mechanisms, and engineer binders to modulate their functions using deep learning and, ultimately, unravel how protein interactions orchestrate complex cellular behaviors.
Telehealth technologies in care homes: a gap for dentistry?
Authors: Bhamra Ishmyne B , Gallagher Jennifer E , Patel Rakhee
Published: December 2023

Background

Telehealth technologies are playing an increasing role in healthcare. This study aimed to review the literature relating to the use of telehealth technologies in care homes with a focus on teledentistry.

Methods

Khangura et al.’s (Evidence summaries: the evolution of a rapid review approach. Syst Rev 2012;1:10) rapid review method included an electronic database search on Embase, PubMed, Web of Science and OpenGrey. Out of 1525 papers, 1108 titles and abstracts were screened, and 75 full texts assessed for eligibility. Risk of bias was assessed using the Mixed Methods Assessment Tool 2018.

Results

Forty-seven papers (40 studies) from 10 countries, published 1997–2021, were included in the review, four studies related to teledentistry. Whilst some preferred in-person consultations, perceived benefits by stakeholders included reduced hospitalization rates (n = 14), cost-savings (n = 8) and high diagnostic accuracy (n = 7). Studies investigating teledentistry using intra-oral cameras reported that teleconsultations were feasible with potentially high diagnostic accuracy (n = 2), cost-savings (n = 1) and patient acceptability (n = 1).

Conclusion

There is limited published research on teledentistry, but wider telehealth research is applicable to teledentistry, with findings suggesting that telehealth technologies play a role in care homes consultations that are acceptable, cost-saving and with potential diagnostic accuracy. Further research is needed on the mode, utility and acceptability of teledentistry in care homes.
Long-term ambient air pollution exposure and prospective change in sedentary behaviour and physical activity in individuals at risk of type 2 diabetes in the UK
Authors: Goldney Jonathan , Henson Joseph , Edwardson Charlotte L , Khunti Kamlesh , Davies Melanie J , Yates Thomas
Published: December 2023

Background

Air pollution may be a risk factor for physical inactivity and sedentary behaviour (SED) through discouraging active lifestyles, impairing fitness and contributing to chronic diseases with potentially important consequences for population health.

Methods

Using generalized estimating equations, we examined the associations between long-term particulate matter with diameter ≤2.5 μm (PM2.5), ≤10 μm (PM10) and nitrogen dioxide (NO2) and annual change in accelerometer-measured SED, moderate-to-vigorous physical activity (MVPA) and steps in adults at risk of type 2 diabetes within the Walking Away from Type 2 Diabetes trial. We adjusted for important confounders including social deprivation and measures of the built environment.

Results

From 808 participants, 644 had complete data (1605 observations; 64.7% men; mean age 63.86 years). PM2.5, NO2 and PM10 were not associated with change in MVPA/steps but were associated with change in SED, with a 1 ugm−3 increase associated with 6.38 (95% confidence interval: 0.77, 12.00), 1.52 (0.49, 2.54) and 4.48 (0.63, 8.34) adjusted annual change in daily minutes, respectively.

Conclusions

Long-term PM2.5, NO2 and PM10 exposures were associated with an annual increase in SED: ~11–22 min/day per year across the sample range of exposure (three standard deviations). Future research should investigate whether interventions to reduce pollution may influence SED.
Does pain hurt more in Spanish? The neurobiology of pain among Spanish–English bilingual adults
Authors: Gianola Morgan , Llabre Maria M , Losin Elizabeth A Reynolds
Published: December 2023

We previously found Spanish-English bilingual adults reported higher pain intensity when exposed to painful heat in the language of their stronger cultural orientation. Here, we elucidate brain systems involved in language-driven alterations in pain responses. During separate English- and Spanish-speaking fMRI scanning runs, 39 (21 female) bilingual adults rated painful heat intermixed between culturally evocative images and completed sentence reading tasks. Surveys of cultural identity and language use measured relative preference for US-American vs Hispanic culture (cultural orientation). Participants produced higher intensity ratings in Spanish compared to English. Group-level whole-brain differences in pain-evoked activity between languages emerged in somatosensory, cingulate, precuneus and cerebellar cortex. Regions of interest associated with semantic, attention and somatosensory processing showed higher average pain-evoked responses in participants’ culturally preferred language, as did expression of a multivariate pain-predictive pattern. Follow-up moderated mediation analyses showed somatosensory activity mediated language effects on pain intensity, particularly for Hispanic oriented participants. These findings relate to distinct (‘meddler’, ‘spotlight’ and ‘inducer’) hypotheses about the nature of language effects on perception and cognition. Knowledge of language influences on pain could improve efficacy of culturally sensitive treatment approaches across the diversity of Hispanic adults to mitigate documented health disparities in this population.
The vocal side of empathy: neural correlates of pain perception in spoken complaints
Authors: Mauchand Maël , Armony Jorge L , Pell Marc D
Published: December 2023

In the extensive neuroimaging literature on empathy for pain, few studies have investigated how this phenomenon may relate to everyday social situations such as spoken interactions. The present study used functional Magnetic Resonance Imaging (fMRI) to assess how complaints, as vocal expressions of pain, are empathically processed by listeners and how these empathic responses may vary based on speakers’ vocal expression and cultural identity. Twenty-four French participants listened to short utterances describing a painful event, which were either produced in a neutral-sounding or complaining voice by both in-group (French) and out-group (French Canadian) speakers. Results suggest that the perception of suffering from a complaining voice increased activity in the emotional voice areas, composed of voice-sensitive temporal regions interacting with prefrontal cortices and the amygdala. The Salience and Theory of Mind networks, associated with affective and cognitive aspects of empathy, also showed prosody-related activity and specifically correlated with behavioral evaluations of suffering by listeners. Complaints produced by in- vs out-group speakers elicited sensorimotor and default mode activity, respectively, suggesting accent-based changes in empathic perspective. These results, while reaffirming the role of key networks in tasks involving empathy, highlight the importance of vocal expression information and social categorization processes when perceiving another’s suffering during social interactions.
The unlikely successful advancement of Japan’s e-government under Suga
Authors: Yamamoto Raymond , Iversen Karen Ejersbo
Published: December 2023

Prime Minister Suga Yoshihide passed a set of digital laws in 2021, which enabled the establishment of the Digital Agency as a central element in the e-government and the digital transition in Japan. Despite its great significance, the laws were prepared and passed in a record-breaking time. This article sets out to determine the factors contributing to the swift acceptance and success of the digital law package utilizing the multiple stream framework by John W. Kingdon. It demonstrates how Suga’s ambitions coincided with a unique policy window opened by an unlikely confluence of the global pandemic and a persistent policy community.
Phylogenetic Biodiversity Metrics Should Account for Both Accumulation and Attrition of Evolutionary Heritage
Authors: Rosindell James , Manson Kerry , Gumbs Rikki , Pearse William D , Steel Mike
Published: December 2023

Phylogenetic metrics are essential tools used in the study of ecology, evolution and conservation. Phylogenetic diversity (PD) in particular is one of the most prominent measures of biodiversity and is based on the idea that biological features accumulate along the edges of phylogenetic trees that are summed. We argue that PD and many other phylogenetic biodiversity metrics fail to capture an essential process that we term attrition. Attrition is the gradual loss of features through causes other than extinction. Here we introduce “EvoHeritage”, a generalization of PD that is founded on the joint processes of accumulation and attrition of features. We argue that while PD measures evolutionary history, EvoHeritage is required to capture a more pertinent subset of evolutionary history including only components that have survived attrition. We show that EvoHeritage is not the same as PD on a tree with scaled edges; instead, accumulation and attrition interact in a more complex non-monophyletic way that cannot be captured by edge lengths alone. This leads us to speculate that the one-dimensional edge lengths of classic trees may be insufficiently flexible to capture the nuances of evolutionary processes. We derive a measure of EvoHeritage and show that it elegantly reproduces species richness and PD at opposite ends of a continuum based on the intensity of attrition. We demonstrate the utility of EvoHeritage in ecology as a predictor of community productivity compared with species richness and PD. We also show how EvoHeritage can quantify living fossils and resolve their associated controversy. We suggest how the existing calculus of PD-based metrics and other phylogenetic biodiversity metrics can and should be recast in terms of EvoHeritage accumulation and attrition.
Leaf nitrogen and phosphorus resorption efficiencies are related to drought resistance across woody species in a Chinese savanna
Authors: Zhang Shu-Bin , Song Yu , Wen Han-Dong , Chen Ya-Jun
Published: December 2023

Leaf nutrient resorption and drought resistance are crucial for the growth and survival of plants. However, our understanding of the relationships between leaf nutrient resorption and plant drought resistance is still limited. In this study, we investigated the nitrogen and phosphorus resorption efficiencies (NRE and PRE), leaf structural traits, leaf osmotic potential at full hydration (Ψosm), xylem water potential at 50% loss of xylem-specific hydraulic conductivity (P50) and seasonal minimum water potential (Ψmin) for 18 shrub and tree species in a semiarid savanna ecosystem, in Southwest China. Our results showed that NRE and PRE exhibited trade-off against drought resistance traits (Ψosm and P50) across woody species. Moreover, this relationship was modulated by leaf structural investment. Species with low structural investment (e.g., leaf mass per area, leaf dry mass content and leaf construction cost [LCC]) tend to have high NRE and PRE, while those with high LCCs show high drought resistance, showing more negative Ψosm and P50.These results indicate that species with a lower leaf structural investment may have a greater need to recycle their nutrients, thus exhibiting higher nutrient resorption efficiencies, and vice versa. In conclusion, nutrient resorption efficiency may be a crucial adaptation strategy for coexisting plants in semiarid ecosystems, highlighting the importance of understanding the complex relationships between nutrient cycling and plant survival strategies.
Nitrogen and phosphorus addition promote invasion success of invasive species via increased growth and nutrient accumulation under elevated CO2
Authors: Zhang Lingling , Luo Xianzhen , Zhang Guihua , Zang Xiaowei , Wen Dazhi
Published: December 2023

In the context of the resource allocation hypothesis regarding the trade-off between growth and defence, compared with native species, invasive species generally allocate more energy to growth and less energy to defence. However, it remains unclear how global change and nutrient enrichment will influence the competition between invasive species and co-occurring native species. Here, we tested whether nitrogen (N) and phosphorus (P) addition under elevated CO2 causes invasive species (Mikania micrantha and Chromolaena odorata) to produce greater biomass, higher growth-related compounds and lower defence-related compounds than native plants (Paederia scandens and Eupatorium chinense). We grew these native and invasive species with similar morphology with the addition of N and P under elevated CO2 in open-top chambers. The addition of N alone increased the relative growth rate (RGR) by 5.4% in invasive species, and its combination with P addition or elevated CO2 significantly increased the RGR of invasive species by 7.5 or 8.1%, respectively, and to a level higher than that of native species (by 14.4%, P < 0.01). Combined N + P addition under elevated CO2 decreased the amount of defence-related compounds in the leaf, including lipids (by 17.7%) and total structural carbohydrates (by 29.0%), whereas it increased the growth-related compounds in the leaf, including proteins (by 75.7%), minerals (by 9.6%) and total non-structural carbohydrates (by 8.5%). The increased concentrations of growth-related compounds were possibly associated with the increase in ribulose 1,5-bisphosphate carboxylase oxygenase content and mineral nutrition (magnesium, iron and calcium), all of which were higher in the invasive species than in the native species. These results suggest that rising atmospheric CO2 concentration and N deposition combined with nutrient enrichment will increase the growth of invasive species more than that of native species. Our result also suggests that invasive species respond more readily to produce growth-related compounds under an increased soil nutrient availability and elevated CO2.
A neutral theory of plant carbon allocation
Authors: Thompson R Alex
Published: December 2023

How plants use the carbon they gain from photosynthesis remains a key area of study among plant ecologists. Although numerous theories have been presented throughout the years, the field lacks a clear null model. To fill this gap, I have developed the first null model, or neutral theory, of plant carbon allocation using probability theory, plant biochemistry and graph theory at the level of a leaf. Neutral theories have been used to establish a null hypothesis in molecular evolution and community assembly to describe how much of an ecological phenomenon can be described by chance alone. Here, the aim of a neutral theory of plant carbon allocation is to ask: how is carbon partitioned between sinks if one assumes plants do not prioritize certain sinks over others? Using the biochemical network of plant carbon metabolism, I show that, if allocation was strictly random, carbon is more likely to be allocated to storage, defense, respiration and finally growth. This ‘neutral hierarchy’ suggests that a sink’s biochemical distance from photosynthesis plays an important role in carbon allocation patterns, highlighting the potentially adaptive role of this biochemical network for plant survival in variable environments. A brief simulation underscores that our ability to measure the carbon allocation from photosynthesis to a given sink is unreliable due to simple probabilistic rules. While neutral theory may not explain all patterns of carbon allocation, its utility is in the minimal assumptions and role as a null model against which future data should be tested.
A new genus of alphasatellites associated with banana bunchy top virus in Southeast Asia
Authors: Guyot Valentin , Trieu Tien-Dung , Insisiengmay Oudomphone , Zhang Ting , Iskra-Caruana Marie-Line , Pooggin Mikhail M
Published: December 2023

Autonomously replicating alphasatellites (family Alphasatellitidae) are frequently associated with plant single-stranded (ss)DNA viruses of the families Geminiviridae, Metaxyviridae, and Nanoviridae. Alphasatellites encode a single replication-initiator protein (Rep) similar to Rep proteins of helper viruses and depend on helper viruses for encapsidation, movement, and transmission. Costs versus benefits of alphasatellite-helper virus association are poorly understood. Our surveys in Southeast Asia (SEA) for wild and cultivated banana plants infected with banana bunchy top virus (BBTV, Nanoviridae) and Illumina sequencing reconstruction of their viromes revealed, in addition to a six-component BBTV genome, one to three distinct alphasatellites present in sixteen of twenty-four BBTV-infected plants. Comparative nucleotide and Rep protein sequence analyses classified these alphasatellites into four distinct species: two known species falling into the genus Muscarsatellite (subfamily Petromoalphasatellitinae) previously identified in SEA and two novel species falling into the tentative genus Banaphisatellite (subfamily Nanoalphasatellitinae) so far containing a single species recently identified in Africa. The banaphisatellites were found to be most related to members of the genus Fabenesatellite of subfamily Nanoalphasatellitinae and the genus Gosmusatellite of subfamily Geminialphasatellitinae, both infecting dicots. This suggests a dicot origin of banaphisatellites that got independently associated with distinct strains of monocot-infecting BBTV in Africa and SEA. Analysis of conserved sequence motifs in the common regions driving replication and gene expression of alphasatellites and BBTV strains revealed both differences and similarities, pointing at their ongoing co-evolution. An impact of alphasatellites on BBTV infection and evasion of RNA interference–based antiviral defences was evaluated by measuring relative abundance of BBTV genome components and alphasatellites and by profiling BBTV- and alphasatellite-derived small interfering RNAs. Taken together, our findings shed new light on the provenance of alphasatellites, their co-evolution with helper viruses, and potential mutual benefits of their association.
Blockade of OSMRβ signaling ameliorates skin lesions in a mouse model of human atopic dermatitis
Authors: Komori Tadasuke , Hisaoka Tomoko , Kotaki Ayumi , Iwamoto Miki , Miyajima Atsushi , Esashi Eiji , Morikawa Yoshihiro
Published: December 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by severe pruritus and eczematous skin lesions. Although IL‐31, a type 2 helper T (Th2)‐derived cytokine, is important to the development of pruritus and skin lesions in AD, the blockade of IL‐31 signaling does not improve the skin lesions in AD. Oncostatin M (OSM), a member of IL‐6 family of cytokines, plays important roles in the regulation of various inflammatory responses through OSM receptor β subunit (OSMRβ), a common receptor subunit for OSM and IL‐31. However, the effects of OSM on the pathogenesis of AD remain to be elucidated. When AD model mice were treated with OSM, skin lesions were exacerbated and IL‐4 production was increased in the lymph nodes. Next, we investigated the effects of the monoclonal antibody (mAb) against OSMRβ on the pathogenesis of AD. Treatment with the anti‐OSMRβ mAb (7D2) reduced skin severity score in AD model mice. In addition to skin lesions, scratching behavior was decreased by 7D2 mAb with the reduction in the number of OSMRβ‐positive neurons in the dorsal root ganglia of AD model mice. 7D2 mAb also reduced the serum concentration of IL‐4, IL‐13, and IgE as well as the gene expressions of IL‐4 and IL‐13 in the lymph nodes of AD model mice. Blockade of both IL‐31 and OSM signaling is suggested to suppress both pruritus and Th2 responses, resulting in the improvement of skin lesions in AD. The anti‐OSMRβ mAb may be a new therapeutic candidate for the treatment of AD.
The adverse effects of vitrification on mouse embryo development and metabolic phenotype in offspring
Authors: Chen Qiaoyu , Zhou Dan , Wang Changxin , Ye Mingming , Jia Yanping , Liu Binya , Bukulmez Orhan , Norman Robert J. , Hu Hanxin , Yeung Shu‐Biu , Teng Xiaoming , Liu Wenqiang , Chen Miaoxin
Published: December 2023

Embryo vitrification is a standard procedure in assisted reproductive technology. Previous studies have shown that frozen embryo transfer is associated with an elevated risk of adverse maternal and neonatal outcomes. This study aimed to explore the effects of mouse blastocyst vitrification on the phenotype of vitrified‐warmed blastocysts, their intrauterine and postnatal development, and the long‐term metabolic health of the derived offspring. The vitrified‐warmed blastocysts (IVF + VT group) exhibited reduced mitochondrial activity, increased apoptotic levels, and decreased cell numbers when compared to the fresh blastocysts (IVF group). Implantation rates, live pup rates, and crown‐rump length at E18.5 were not different between the two groups. However, there was a significant decrease in fetal weight and fetal/placental weight ratio in the IVF + VT group. Furthermore, the offspring of the IVF + VT group at an age of 36 weeks had reduced whole energy consumption, impaired glucose and lipid metabolism when compared with the IVF group. Notably, RNA‐seq results unveiled disturbed hepatic gene expression in the offspring from vitrified‐warmed blastocysts. This study revealed the short‐term negative impacts of vitrification on embryo and fetal development and the long‐term influence on glucose and lipid metabolism that persist from the prenatal stage into adulthood in mice.
SUMOylation and coupling of eNOS mediated by PIAS1 contribute to maintenance of vascular homeostasis
Authors: Wang Li , Zeng Wenjing , Wang Chaowen , Lu Yanli , Xiong Xiaowei , Chen Sheng , Huang Qianqian , Yan Feixing , Huang Qiren
Published: December 2023

Endothelial dysfunction (ED) is commonly considered a crucial initiating step in the pathogenesis of numerous cardiovascular diseases. The coupling of endothelial nitric oxide synthase (eNOS) is important in maintaining normal endothelial functions. However, it still remains elusive whether and how eNOS SUMOylation affects the eNOS coupling. In the study, we investigate the roles and possible action mechanisms of protein inhibitor of activated STAT 1 (PIAS1) in ED. Human umbilical vein endothelial cells (HUVECs) treated with palmitate acid (PA) in vitro and ApoE−/− mice fed with high‐fat diet (HFD) in vivo were constructed as the ED models. Our in vivo data show that PIAS1 alleviates the dysfunction of vascular endothelium by increasing nitric oxide (NO) level, reducing malondialdehyde (MDA) level, and activating the phosphatidylinositol 3‐kinase‐protein kinase B‐endothelial nitric oxide synthase (PI3K‐AKT‐eNOS) signaling in ApoE−/− mice. Our in vitro data also show that PIAS1 can SUMOylate eNOS under endogenous conditions; moreover, it antagonizes the eNOS uncoupling induced by PA. The findings demonstrate that PIAS1 alleviates the dysfunction of vascular endothelium by promoting the SUMOylation and inhibiting the uncoupling of eNOS, suggesting that PIAS1 would become an early predictor of atherosclerosis and a new potential target of the hyperlipidemia‐related cardiovascular diseases.
Selective block of human Kv1.1 channels and an epilepsy‐associated gain‐of‐function mutation by AETX‐K peptide
Authors: Zhao Ruiming , Qasim Arwa , Sophanpanichkul Punyanuch , Dai Hui , Nayak Maha , Sher Inbal , Chill Jordan , Goldstein Steve A. N.
Published: December 2023

Dysfunction of the human voltage‐gated K+ channel Kv1.1 has been associated with epilepsy, multiple sclerosis, episodic ataxia, myokymia, and cardiorespiratory dysregulation. We report here that AETX‐K, a sea anemone type I (SAK1) peptide toxin we isolated from a phage display library, blocks Kv1.1 with high affinity (Ki ~ 1.6 pM) and notable specificity, inhibiting other Kv channels we tested a million‐fold less well. Nuclear magnetic resonance (NMR) was employed both to determine the three‐dimensional structure of AETX‐K, showing it to employ a classic SAK1 scaffold while exhibiting a unique electrostatic potential surface, and to visualize AETX‐K bound to the Kv1.1 pore domain embedded in lipoprotein nanodiscs. Study of Kv1.1 in Xenopus oocytes with AETX‐K and point variants using electrophysiology demonstrated the blocking mechanism to employ a toxin‐channel configuration we have described before whereby AETX‐K Lys23, two positions away on the toxin interaction surface from the classical blocking residue, enters the pore deeply enough to interact with K+ ions traversing the pathway from the opposite side of the membrane. The mutant channel Kv1.1‐L296F is associated with pharmaco‐resistant multifocal epilepsy in infants because it significantly increases K+ currents by facilitating opening and slowing closure of the channels. Consistent with the therapeutic potential of AETX‐K for Kv1.1 gain‐of‐function‐associated diseases, AETX‐K at 4 pM decreased Kv1.1‐L296F currents to wild‐type levels; further, populations of heteromeric channels formed by co‐expression Kv1.1 and Kv1.2, as found in many neurons, showed a Ki of ~10 nM even though homomeric Kv1.2 channels were insensitive to the toxin (Ki > 2000 nM).
Impact of Educational Background on Preoperative Disease Severity and Postoperative Outcomes Among Patients With Cervical Spondylotic Myelopathy
Authors: Agarwal Nitin , DiGiorgio Anthony , Michalopoulos Giorgos D. , Letchuman Vijay , Chan Andrew K. , Shabani Saman , Lavadi Raj Swaroop , Lu Daniel C. , Wang Michael Y. , Haid Regis W. , Knightly John J. , Sherrod Brandon A. , Gottfried Oren N. , Shaffrey Christopher I. , Goldberg Jacob L. , Virk Michael S. , Hussain Ibrahim , Glassman Steven D. , Shaffrey Mark E. , Park Paul , Foley Kevin T. , Pennicooke Brenton , Coric Domagoj , Upadhyaya Cheerag , Potts Eric A. , Tumialán Luis M. , Fu Kai-Ming G. , Asher Anthony L. , Bisson Erica F. , Chou Dean , Bydon Mohamad , Mummaneni Praveen V.
Published: December 2023

Study Design:

Retrospective review of a prospectively maintained database.

Objective:

Assess differences in preoperative status and postoperative outcomes among patients of different educational backgrounds undergoing surgical management of cervical spondylotic myelopathy (CSM).

Summary of Background Data:

Patient education level (EL) has been suggested to correlate with health literacy, disease perception, socioeconomic status (SES), and access to health care.

Methods:

The CSM data set of the Quality Outcomes Database (QOD) was queried for patients undergoing surgical management of CSM. EL was grouped as high school or below, graduate-level, and postgraduate level. The association of EL with baseline disease severity (per patient-reported outcome measures), symptoms >3 or ≤3 months, and 24-month patient-reported outcome measures were evaluated.

Results:

Among 1141 patients with CSM, 509 (44.6%) had an EL of high school or below, 471 (41.3%) had a graduate degree, and 161 (14.1%) had obtained postgraduate education. Lower EL was statistically significantly associated with symptom duration of >3 months (odds ratio=1.68), higher arm pain numeric rating scale (NRS) (coefficient=0.5), and higher neck pain NRS (coefficient=0.79). Patients with postgraduate education had statistically significantly lower Neck Disability Index (NDI) scores (coefficient=-7.17), lower arm pain scores (coefficient=−1), and higher quality-adjusted life-years (QALY) scores (coefficient=0.06). Twenty-four months after surgery, patients of lower EL had higher NDI scores, higher pain NRS scores, and lower QALY scores (P<0.05 in all analyses).

Conclusions:

Among patients undergoing surgical management for CSM, those reporting a lower educational level tended to present with longer symptom duration, more disease-inflicted disability and pain, and lower QALY scores. As such, patients of a lower EL are a potentially vulnerable subpopulation, and their health literacy and access to care should be prioritized.
Molecular epidemiology ofCandida africanaisolates collected from vagina swabs in French Guiana
Authors: Bigot J. , Kalboussi Y. , Nkoy Y. Bonkoto , Benmostefa A. , Vellaissamy S. , Benzerara L. , Sainte-Rose V. , Blanchet D. , Demar M. , Guitard J. , Hennequin C.
Published: December 2023

Candida africanacorresponds to the clade 13 ofCandia albicans. It has been mostly involved in vulvovaginal candidiasis worldwide but few data exist in South America. The aim of our study was to investigate the prevalence ofC. africanain women living in French Guiana. For this, we first set up a fluorescent-intercalating-dye-real time PCR targeting the hyphal wall protein 1 gene. The test was applied to 212C. albicansisolates collected from May to August 2019 from vaginal swabs, allowing the identification of 6 women harboringC. africana(8 isolates). No demographics or clinical-specific features could be demonstrated. Genetic diversity of those isolates was analyzed through multilocus sequence typing and showed that diploid sequence type 182 was predominant (n=6) and allowed the report of a new diploid sequence type.
Membrane lipid poly-unsaturation selectively affects ligand induced dopamine D2 receptor internalization
Authors: Sposini Silvia , Baccouch Rim , Lescuyer Mathias , De Smedt-Peyrusse Véronique , Heuninck Joyce , Durroux Thierry , Trifilieff Pierre , Perrais David , Alves Isabel
Published: December 2023

The poly-unsaturation of membrane phospholipids is an important feature for the biophysical properties of membranes and membrane proteins. In particular, it regulates the function of some G protein-coupled receptors (GPCR), such as their binding to ligand and G proteins or their membrane diffusion. However, its effects on GPCR internalization and trafficking remain unknown. The brain is highly enriched in poly-unsaturated fatty acids (PUFAs) and their deficiency has been associated with several neuropsychiatric disorders. Importantly, the Dopamine D2 receptor (D2R), a class A GPCR, is consistently impacted in these disorders and represents the main target of most antipsychotics. Here we show that enrichment in two different PUFAs strongly impairs agonist-induced endocytosis of D2R in HEK293 cells, without affecting clathrin-mediated endocytosis. Strikingly, this effect seems to be specific to the D2R as it does not affect various other GPCRs. Using live cell TIRF imaging, we show that D2R clustering is not affected, but that recruitment of β-arrestin2, that occurs prior to receptor internalization, is strongly impaired and endocytic vesicle formation is slowed down. Finally, we show that mutation of key residues in intracellular loop 2 abolishes the sensitivity of D2R endocytosis to PUFA enrichment. We conclude that D2R trafficking is uniquely dependent on membrane PUFAs, which could influence its role in the control of brain activity and behavior.
Efficient Multiplexing of Pollinator Metabarcodes Using Oxford Nanopore MinION Sequencing: Insights for Meadow Management from Floral Environmental DNA
Authors: Harris Stephen E. , Whitehurst Amelia , Buehrer Madeline , Lonker Sydney , Veverka Budd , Nagy Chris
Published: December 2023

Many pollinating species are experiencing declines globally, making effective, fast, and portable pollinator monitoring methods more important than ever before. Pollinators can leave DNA on the flowers they visit, and metabarcoding of these environmental DNA (eDNA) traces provides an opportunity to detect the presence of flower visitors. This study introduces an efficient, cost-effective workflow for utilizing DNA barcoding to monitor biodiversity through environmental DNA (eDNA) left on flowers from pollinators, employing the portable MinION and Nanopore sequencing. The developed method employs multiplexing with dual molecular tags on universal cytochrome oxidase 1 (COI) barcode primers. We used this approach to compare the arthropod diversity present in three meadows with different vegetation at three time points during the flowering season. The utility of eDNA metabarcoding in investigating pollinator biodiversity and interactions is highlighted through our results, revealing the presence and interactions of 65 species from 30 families. We multiplexed individual eDNA samples from hundreds of flowers and found plant-pollinator dynamics that showed differences in species richness between sampling times and meadow diversity. Comparative analyses with conventional methods showed eDNA metabarcoding’s ability to identify diverse species and ecological interactions compared to field sampling. While some DNA likely came from eggs or microscopic insects difficult to remove from flowers, traces of eDNA from various arthropods on multiple plant species confirmed the method’s applicability, promising robust ecological monitoring and research potential in the wake of global pollinator declines. This is the first reported use of MinION based nanopore sequencing to detect arthropod species from eDNA samples collected from flowers using the described affordable multiplexing method.
Aging-Dependent Loss of Connectivity in Alzheimer’s Model Mice with Rescue by mGluR5 Modulator
Authors: Mandino Francesca , Shen Xilin , Desrosiers-Gregoire Gabriel , O’Connor David , Mukherjee Bandhan , Owens Ashley , Qu An , Onofrey John , Papademetris Xenophon , Chakravarty M. Mallar , Strittmatter Stephen M , Lake Evelyn MR
Published: December 2023

Amyloid accumulation in Alzheimer’s disease (AD) is associated with synaptic damage and altered connectivity in brain networks. While measures of amyloid accumulation and biochemical changes in mouse models have utility for translational studies of certain therapeutics, preclinical analysis of altered brain connectivity using clinically relevant fMRI measures has not been well developed for agents intended to improve neural networks. Here, we conduct a longitudinal study in a double knock-in mouse model for AD (AppNL-G-F/hMapt), monitoring brain connectivity by means of resting-state fMRI. While the 4-month-old AD mice are indistinguishable from wild-type controls (WT), decreased connectivity in the default-mode network is significant for the AD mice relative to WT mice by 6 months of age and is pronounced by 9 months of age. In a second cohort of 20-month-old mice with persistent functional connectivity deficits for AD relative to WT, we assess the impact of two-months of oral treatment with a silent allosteric modulator of mGluR5 (BMS-984923) known to rescue synaptic density. Functional connectivity deficits in the aged AD mice are reversed by the mGluR5-directed treatment. The longitudinal application of fMRI has enabled us to define the preclinical time trajectory of AD-related changes in functional connectivity, and to demonstrate a translatable metric for monitoring disease emergence, progression, and response to synapse-rescuing treatment.