bluuebunny/crossref_metadata_2025 huggingface dataset:
β-arrestin1 protects intestinal tight junction through promoting mitofusin 2 transcription to drive parkin-dependent mitophagy in colitis
Authors: Wu Shuyun , Liu Huiling , Yi Jiazhi , Xu Minyi , Jiang Jie , Tao Jin , Wu Bin
Published: September 2024

Background

Intestinal barrier defect is an essential inflammatory bowel disease (IBD) pathogenesis. Mitochondrial dysfunction results in energy deficiency and oxidative stress, which contribute to the pathogenesis of IBD. β-arrestin1 (ARRB1) is a negative regulator that promotes G protein-coupled receptors desensitization, endocytosis, and degradation. However, its role in maintaining the intestinal barrier remains unclear.

Methods

Dextran sulfate sodium-induced colitis was performed in ARRB1 knockout and wild-type mice. Intestinal permeability and tight junction proteins were measured to evaluate the intestinal barrier. Mitochondria function and mitophagic flux in mice and cell lines were detected. Finally, the interaction between ARRB1 and mitofusin 2 was investigated by co-immunoprecipitation and dual luciferase assay.

Results

We identified that ARRB1 protected the intestinal tight junction barrier against experimental colitis in vivo. ARRB1 deficiency was accompanied by abnormal mitochondrial morphology, lower adenosine triphosphate (ATP) production, and severe oxidative stress. In vitro, the knockdown of ARRB1 reduced ATP levels and mitochondrial membrane potential while increasing reactive oxygen species levels and oxidative stress. Upon ARRB1 ablation, mitophagy was inhibited, accompanied by decreased LC3BII, phosphatase and tension homologue-induced protein kinase1 (PINK1), and parkin, but increased p62 expression. Mitophagy inhibition via PINK1 siRNA or mitochondrial division inhibitor 1 impaired ARRB1-mediated tight junction protection. The interaction of ARRB1 with E2F1 activated mitophagy by enhancing the transcription of mitofusin 2.

Conclusions

Our results suggest that ARRB1 is critical to maintaining the intestinal tight junction barrier by promoting mitophagy. These results reveal a novel link between ARRB1 and the intestinal tight junction barrier, which provides theoretical support for colitis treatment.
A New Model and Dating for the Evolution of Complex Plastids of Red Alga Origin
Authors: Pietluch Filip , Mackiewicz Paweł , Ludwig Kacper , Gagat Przemysław
Published: September 2024

Complex plastids, characterized by more than two bounding membranes, still present an evolutionary puzzle for the traditional endosymbiotic theory. Unlike primary plastids that directly evolved from cyanobacteria, complex plastids originated from green or red algae. The Chromalveolata hypothesis proposes a single red alga endosymbiosis that involved the ancestor of all the Chromalveolata lineages: cryptophytes, haptophytes, stramenopiles, and alveolates. As extensive phylogenetic analyses contradict the monophyly of Chromalveolata, serial plastid endosymbiosis models were proposed, suggesting a single secondary red alga endosymbiosis within Cryptophyta, followed by subsequent plastid transfers to other chromalveolates. Our findings based on 97 plastid-encoded markers, 112 species, and robust phylogenetic methods challenge all the existing models. They reveal two independent secondary endosymbioses, one within Cryptophyta and one within stramenopiles, precisely the phylum Ochrophyta, with two different groups of red algae. Consequently, we propose a new model for the emergence of red alga plastid–containing lineages and, through molecular clock analyses, estimate their ages.
Azooxanthellate Palythoa (Cnidaria: Anthozoa) Genomes Reveal Toxin-related Gene Clusters and Loss of Neuronal Genes in Hexacorals
Authors: Yoshioka Yuki , Yamashita Hiroshi , Uchida Taiga , Shinzato Chuya , Kawamitsu Mayumi , Fourreau Chloé Julie Loïs , Castelló Guillermo Mironenko , Fiedler Britta Katharina , van den Eeckhout Timotheus Maximilian , Borghi Stefano , Reimer James Davis , Shoguchi Eiichi
Published: September 2024

Zoantharia is an order among the Hexacorallia (Anthozoa: Cnidaria), and includes at least 300 species. Previously reported genomes from scleractinian corals and actiniarian sea anemones have illuminated part of the hexacorallian diversification. However, little is known about zoantharian genomes and the early evolution of hexacorals. To explore genome evolution in this group of hexacorals, here, we report de novo genome assemblies of the zoantharians Palythoa mizigama (Pmiz) and Palythoa umbrosa (Pumb), both of which are members of the family Sphenopidae, and uniquely live in comparatively dark coral reef caves without symbiotic Symbiodiniaceae dinoflagellates. Draft genomes generated from ultra-low input PacBio sequencing totaled 373 and 319 Mbp for Pmiz and Pumb, respectively. Protein-coding genes were predicted in each genome, totaling 30,394 in Pmiz and 24,800 in Pumb, with each set having ∼93% BUSCO completeness. Comparative genomic analyses identified 3,036 conserved gene families, which were found in all analyzed hexacoral genomes. Some of the genes related to toxins, chitin degradation, and prostaglandin biosynthesis were expanded in these two Palythoa genomes and many of which aligned tandemly. Extensive gene family loss was not detected in the Palythoa lineage and five of ten putatively lost gene families likely had neuronal function, suggesting biased gene loss in Palythoa. In conclusion, our comparative analyses demonstrate evolutionary conservation of gene families in the Palythoa lineage from the common ancestor of hexacorals. Restricted loss of gene families may imply that lost neuronal functions were effective for environmental adaptation in these two Palythoa species.
An anatomical atlas of Drosophila melanogaster—the wild-type
Authors: Jürgens Kai J , Drechsler Maik , Paululat Achim
Published: September 2024

Scanning electron microscopy is the method of choice to visualize the surface structures of animals, fungi, plants, or inorganic objects at the highest resolution and often with impressive appeal. Numerous scanning electron microscope (SEM) images exist of Drosophila melanogaster, one of the most important model organisms in genetics and developmental biology, which have been taken partly for esthetics and often to solve scientific questions. Our work presents a collection of images comprising many prominent anatomical details of D. melanogaster in excellent quality to create a research and teaching resource for all Drosophilists.
Genetic background affects the strength of crossover interference in house mice
Authors: Morgan Andrew P , Payseur Bret A
Published: September 2024

Meiotic recombination is required for faithful chromosome segregation in most sexually reproducing organisms and shapes the distribution of genetic variation in populations. Both the overall rate and the spatial distribution of crossovers vary within and between species. Adjacent crossovers on the same chromosome tend to be spaced more evenly than expected at random, a phenomenon known as crossover interference. Although interference has been observed in many taxa, the factors that influence the strength of interference are not well understood. We used house mice (Mus musculus), a well-established model system for understanding recombination, to study the effects of genetics and age on recombination rate and interference in the male germline. We analyzed crossover positions in 503 progeny from reciprocal F1 hybrids between inbred strains representing the three major subspecies of house mice. Consistent with previous studies, autosomal alleles from M. m. musculus tend to increase recombination rate, while inheriting a M. m. musculus X chromosome decreases recombination rate. Old males transmit an average of 0.6 more crossovers per meiosis (5.0%) than young males, though the effect varies across genetic backgrounds. We show that the strength of crossover interference depends on genotype, providing a rare demonstration that interference evolves over short timescales. Differences between reciprocal F1s suggest that X-linked factors modulate the strength of interference. Our findings motivate additional comparisons of interference among recently diverged species and further examination of the role of paternal age in determining the number and positioning of crossovers.
Incentivizing primary care utilization in China: the impact of health insurance coverage on health-seeking behaviour
Authors: Fu Liping , Han Jiarui , Xu Kaibo , Pei Tong , Zhang Ruiyu
Published: September 2024

China’s healthcare system faces significant challenges, notably the underutilization of primary healthcare resources and the inefficient distribution of healthcare services. In response, this article explores the effectiveness of the New Rural Cooperative Medical System (NRCMS) in improving healthcare accessibility and primary care utilization. Employing a multi-period difference-in-differences model and using data from the China Family Panel Studies spanning 2012-20, it aims to empirically examine how health insurance policy incentivizing primary care influences rural residents’ health-seeking behaviour and enhances the efficiency of resource utilization. Results indicate that NRCMS significantly improves the probability of rural residents seeking healthcare services at primary healthcare centres (PHCs), especially for outpatient services. This effect can be attributed to the substantially higher outpatient reimbursement rates at PHCs compared to higher-level medical institutions. Conversely, the Urban Resident Basic Medical Insurance fails to increase urban residents’ engagement with primary care, reinforcing the role of price sensitivity in healthcare choices among insured lower-income rural population. Furthermore, the study reveals a stronger preference for PHCs among younger, less-educated insured residents and highlights a synergistic effect between the availability of primary healthcare resources and insurance coverage on primary care utilization. These findings offer crucial implications for refining health insurance policies to improve healthcare service accessibility and efficiency.
HIV incidence among non-migrating persons following a household migration event in Uganda
Authors: Young Ruth , Ssekasanvu Joseph , Kagaayi Joseph , Ssekubugu Robert , Kigozi Godfrey , Reynolds Steven J , Wawer Maria J , Nonyane Bareng Aletta Sanny , Nantume Betty , Quinn Thomas C , Tobian Aaron A R , Santelli John , Chang Larry W , Kennedy Caitlin E , Paina Ligia , Anglewicz Philip A , Serwadda David , Nalugoda Fred , Grabowski Mary Kate
Published: September 2024

Background

The impact of migration on HIV risk among non-migrating household members is poorly understood. We measured HIV incidence among non-migrants living in households with and without migrants in Uganda.

Methods

We used four survey rounds of data collected from July 2011 to May 2018 from non-migrant participants aged 15–49 years in the Rakai Community Cohort Study. Non-migrants were individuals with no-migration between surveys or at the prior survey. Household migration was defined as ≥1 household member migrating into or out of the house from another community between surveys (∼18 months). Incident HIV was defined as testing HIV seropositive following a negative result. Incidence rate ratios (IRRs) were estimated using Poisson regression with generalized estimating equations. Analyses were stratified by gender, migration into or out of the household and the relationship between non-migrants and migrants (e.g. spouse, child).

Results

About 11 318 non-migrants (5674 women) were followed for 37 320 person-years. Twenty-eight percent (6059/21 370) of non-migrant person-visits had recent migration into or out of the household, and 240 HIV incident cases were identified. Overall, non-migrants in migrant households were not at greater risk of acquiring HIV than non-migrants in households without any migration. However, men were significantly more likely to acquire HIV if their spouse had recently migrated in [adjusted IRR: 2.12; 95% confidence interval (CI): 1.05–4.27] or out (adjusted IRR: 4.01; 95% CI, 2.16–7.44) compared with men with no spousal migration.

Conclusions

HIV incidence is higher among non-migrant men with migrant spouses. Targeted HIV testing and prevention interventions like pre-exposure prophylaxis could be considered for men with migrant spouses.
Performance of vacuum-insulated central pipes for deep borehole heat exchangers in geothermal systems
Authors: Kubačka Ján , Karayiannis Tassos G
Published: September 2024

Geothermal energy is considered a promising future energy prospect, with the geothermal well outlet temperature being one of the important parameters affecting possible utilization options. For ground source heat pump applications or direct district heating, using lower temperatures can be acceptable. However, efficient electricity production requires a higher enthalpy gradient, which cannot be achieved without high temperature at the wellhead. The selection of the dry co-axial close-loop deep borehole systems (DBHE) may be, in some cases, very beneficial. The operating performance of co-axial DBHE can be optimized if the undesired heat transfer between the central pipe and annular fluid zones is minimized. Therefore, the operational performance of such a system depends strongly on the high thermal resistance of the central pipe. The most common option would be a low thermal conductivity material, such as high-density polyethylene (HDPE). In addition, vacuum-insulated tubing (VIT) used as the central pipe could be considered. The article presents results from the study aimed at the comparison of the homogeneous central pipe made of HDPE material and the gap-insulated central pipe. In the study, various air pressure levels as well as variations of surface emissivity were examined to reveal the effect on the heat transfer between the fluid channels. The simulation has been performed using a new purposely developed WellTH simulation software. A coaxial heat exchanger system using a VIT outperforms significantly the heat exchanger with an HDPE for deep geothermal wells. However, this advantage diminishes for shallow wells and therefore this tendency should be considered in the design stage.
Comparative analysis on heat and moisture transfer of composite insulation walls
Authors: Wang Yang , Wang Qun , Chen Ruifeng , Zhang Cheng , Song Jihong
Published: September 2024

Firstly, the influence of heat and moisture transfer on composite insulation walls was initially considered. Relying on the established theory of heat and moisture coupled transfer in walls and taking into account the specific climate conditions of regions with hot summers and cold winters, a non-steady-state heat and moisture coupled model was developed to simulate the processes of heat and moisture transfer. Subsequently, based on the one-dimensional stable heat transfer theory, the heat transfer situation for winter insulation was calculated. Then, practical methods for on-site temperature and humidity measurements were explored and implemented. Through analysis, comparison, and mutual verification of the calculated values and the measured values, it was observed that both sets of data showed consistent trends, thereby verifying their accuracy and correlation. The findings of this study provide valuable reference data for understanding the heat and moisture migration within building walls and offer solutions for optimizing thermal insulation strategies.
Video-sharing-platforms and Brussels Ia regulation: navigating contractual jurisdictional challenges
Authors: Suquet Josep
Published: September 2024

This article examines international jurisdiction in the resolution of contractual disputes involving Video-Sharing Platforms (VSP). It situates VSPs within the broader context defined by the Audio-visual Media Services Directive and identifies areas of litigation. The article discusses specific cases where national courts have resolved conflicts related to VSPs and sheds light onto the application of contractual and consumer forums under Regulation 1215/2012.
Quantitative performance of humanized serum and epithelial lining fluid exposures of tigecycline and levofloxacin against a challenge set of Klebsiella pneumoniae and Pseudomonas aeruginosa in a standardized neutropenic murine pneumonia model
Authors: Fratoni Andrew J , Padgett Alissa M , Duffy Erin M , Nicolau David P
Published: September 2024

Background

Lack of uniformity in infection models complicates preclinical development. The COMBINE protocol has standardized the murine neutropenic pneumonia model. Herein we provide benchmark efficacy data of humanized exposures of tigecycline and levofloxacin in plasma and epithelial lining fluid (ELF) against a collection of Klebsiella pneumoniae and Pseudomonas aeruginosa.

Methods

Following the COMBINE protocol, plasma and ELF human-simulated regimens (HSRs) of tigecycline 100 mg followed by 50 mg q12h and levofloxacin 750 mg once daily were developed and confirmed in the murine neutropenic pneumonia model. Tigecycline HSRs were tested against seven K. pneumoniae isolates. Levofloxacin HSRs were assessed against 10 K. pneumoniae and 9 P. aeruginosa. The change in cfu/lung over 24 h for each treatment was calculated. Each isolate was tested in duplicate against both the plasma and ELF HSRs on separate experiment days.

Results

Tigecycline 1.8 and 3 mg/kg q12h achieved humanized exposures of serum and ELF, respectively. Levofloxacin 120 and 90 mg/kg q8h led to fAUC exposures in plasma and ELF similar to in humans. Both tigecycline regimens were ineffective across the MIC range. Levofloxacin regimens achieved multilog kill against susceptible isolates, and no appreciable cfu/lung reductions in isolates with an MIC of ≥32 mg/L. Differences in cfu/lung were evident between the levofloxacin plasma and ELF HSRs against isolates with MICs of 4 and 8 mg/L.

Conclusions

Administering HSRs of tigecycline and levofloxacin based on both serum/plasma and ELF in the COMBINE pneumonia model resulted in cfu/lung values reasonably aligned with MIC. These data serve as translational benchmarks for future investigations with novel compounds.
Multi-omics analysis reveals associations between host gene expression, gut microbiota, and metabolites in chickens
Authors: Shi Kai , Liu Xiangping , Duan Ying , Ding Jiqiang , Jia Yimin , Jiang Ziqin , Feng Chungang
Published: September 2024

Egg-laying is an important trait in chickens, and it is affected by many factors, such as hormones regulated by the hypothalamic-pituitary axis and precursors synthesized by the liver. Recent studies showed that gut microbiota was associated with egg-laying, however, its underlying mechanism remains unclear. We comprehensively analyzed the host transcriptome, gut microbiota, and metabolome in broiler breeder hens during the pre-laying, peak-laying, and late-laying periods. The transcriptome analysis of the tissues related to the hypothalamic-pituitary-liver (HPL) axis revealed dynamic gene expression during egg-laying periods. Differentially expressed genes (DEGs) (i.e., PENK, NPY, AVP, PRL, RLN3, and FST) from the hypothalamus and pituitary gland were involved in female gonadal development, hormone secretion, response to endogenous stimulus, liver development, and amide metabolism. In liver, DEGs (i.e., FABP3, VTG1, LPL, APOA5, APOV1, and RBP5) were enriched in efferocytosis, sphingolipid metabolism, amide, and peptide biosynthesis. Alpha and beta diversity changed significantly in cecum microbiota during different laying periods. The abundance of Firmicutes was decreased and the abundance of Bacteroidota was increased during the peak-laying period. Functional analysis showed that the biosynthesis of secondary metabolites, amino acids, purine, and steroid hormones was altered during laying. The metabolome analysis from cecal contents showed that amino acid metabolism and steroid hormone biosynthesis changed during laying. Integrated analysis of the cecal microbiota and metabolites showed the genus Megasphaera was involved in amino acid metabolism, which included 3-phenyllatic acid, quinic acid, caffeic acid, and folic acid, and the genus Hungatella participated in steroid hormone biosynthesis through its strong correlation with estradiol. These results explored the dynamic changes in tissues related to the HPL axis and cecal microbiota and provided new insights into the interaction between the host and microbiota during egg-laying in chickens.
The only terrestrial lineage in the Branchiopoda redefined: a new species of Bryospilus Frey, 1980 (Cladocera: Anomopoda) from India and adaptations of waterfleas to life on land
Authors: Van Damme Kay , Padhye Sameer M
Published: September 2024

Only a small proportion of the world’s crustacean taxa is adapted to limno-terrestrial microhabitats that are disconnected from conventional surface waterbodies. In rare occasions, water films on terrestrial tropical and subtropical vegetation may also harbour specialised cladocerans. Bryospilus Frey, 1980 (Chydoridae) is the only genus within the class Branchiopoda that is specialised to living almost exclusively in water-saturated terrestrial moss patches, leaf litter, and phytotelms. The remarkable waterflea lineage, which has a suite of highly unusual characters within the family, has been found in terrestrial habitats in rainforests of West Africa, South and Central America, and New Zealand. We discovered a new moss-inhabiting chydorid from western India, Bryospilus (Indobryospilus) bharaticus n. sp., the first representative of the genus from the Oriental Region. Its morphology and behaviour are highly unusual for a species of Bryospilus. In comparison to its congeners, the new species can swim and it has significantly less oligomerisation, with three terminal setae on the antennal endopod instead of two and seven exopod setae on the third limb instead of six, among other features. We define a new subgenus Indobryospilus nov. and we amend the genus Bryospilus. The new species is a living evolutionary connection, characterised by a phenotype which provides us with new clues about evolutionary transitions in the only terrestrial branchiopod genus. Our results are informative beyond Cladocera, as the morphology of this species provides insights about the evolution and parallelisms of aquatic crustaceans that have specialised in limno-terrestrial habitats. We revisit the morphology of the genus, the disjunct biogeographical pattern with a potential ancient signature, and discuss the functional adaptations of these cladocerans to life on land, as well as convergences with subterranean lineages. A new key to the world species of Bryospilus species is included.
Fitness implications of low-temperature storage for Eocanthecona furcellata (Hemiptera: Pentatomidae)
Authors: Pan Chun-Ni , Zhou Wei , Lu Chang-Hao , Pan Ying-Na , Liu Ling-Yi , Chen Wen-Long
Published: September 2024

Exploring the impact of low-temperature storage on the fitness of natural enemy insects is crucial for practical field applications because this parameter directly influences their potential for population growth and effective pest control. Eocanthecona furcellata (Wolff) (Hemiptera: Pentatomidae) is widely used in biological pest control. This study aimed to identify optimal storage stages, temperatures, and durations for E. furcellata to produce high-quality individuals for practical use. The quality of E. furcellata after storage was evaluated by assessing parameters such as predatory capacity and fecundity, along with age-stage, two-sex life table. The findings revealed that the adult stage was the optimal storage form for E. furcellata, and the most favorable temperature for storage was 12 °C. Adult females had the highest predatory ability after 15 days of storage at 12 °C. Although survival rates declined with prolonged storage, they remained above 50% after 30 days, and longevity, fecundity, and predatory capacity of surviving individuals remained comparable to those of individuals in the control group (rearing at a constant temperature of 26 °C without low-temperature storage). The effects of low-temperature storage extended to the F1 generation of E. furcellata, which exhibited maximum mean longevity, fecundity, net reproductive rate, and mean generation time as well as fastest population growth after 30 days of storage at 12 °C. These results can be used to achieve optimal low-temperature storage conditions for E. furcellata production, particularly for extending its shelf life.
Victims’ Perspectives on Participation in the Ongwen Case
Authors: Massidda Paolina , Akwenyu Joseph , Moffett Luke
Published: September 2024

The Ongwen case has so far involved one of the largest number of victims represented before the International Criminal Court, both in terms of participation in trial proceedings (4,095) and potential beneficiaries for reparations (49,772). This piece offers some new insights following the trial from victims represented by both victim legal teams that are not captured in victims’ statements or submissions before the Court. It draws on additional interviews with victims after the completion of the trial and sentencing, but before the reparation order issued in the case. It focuses on three elements — victims’ role in proceedings; how victims felt they were represented before the Court; and victims’ satisfaction with the outcome of the proceedings.
Explanatory frameworks in complex change and resilience system modelling
Authors: Addis Mark , Eckert Claudia
Published: September 2024

Heterogenous flows across system boundaries continue to pose significant problems for efficient resource allocation especially with respect to long term strategic planning and immediate problems about allocation to address particular resource shortages. The approach taken here to modelling such flows is an engineering change prediction one. This enables margin modelling by producing system models in dependency matrices with different linkage types. Change prediction approaches from engineering design can analyse where these bottlenecks in integrated systems would be so that resources can be deployed flexibility to avoid them and address them when they occur. Current state of the art of margin research can be furthered by identifying margins on multiple levels of system composition. It can usefully be complemented by a category theory based approach which allows representation of variable and constant properties of models under changing conditions, and the identification of flows within models. Category theory is useful for formalising such explanatory frameworks as it can both structure systems and permit analysis of their applications in a complementary way.
Microservices architecture to enable an open platform for realizing zero defects in cyber-physical manufacturing
Authors: Pedro Lopes Rui , Ibrahim Ahmed , Barbosa José , Leitao Paulo
Published: September 2024

The market’s demand for high-quality products necessitates innovative manufacturing approaches that emphasize flexibility, adaptability, and the reduction of defects. Traditional systems are currently evolving towards embracing I4.0 technologies, including data collection, processing, analytics and digital twin, aiming for zero-defect manufacturing quality. This paper introduces an open platform, compliant with RAMI4.0 standards, designed to improve manufacturing quality. The platform integrates data using Asset Administration Shells with microservices adaptation for data ingestion and advanced analytics. Additionally, it incorporates Non-Destructive Inspection tools, demonstrating a seamless integration of measurement and quality assurance. This study details the architectural specification and validation of the openZDM platform, employing microservices to ensure flexibility, modularity and scalability, aligning with the RAMI4.0 model. The platform was validated through deployment in an automotive assembly line, highlighting its effectiveness in integrating inspection scenarios and early defect detection tools. The architecture employs a choreographed approach to manage loosely coupled microservices, enabling efficient data lifecycle management from collection through analytics to visualization.
Sparganothis sulfureana (Lepidoptera: Tortricidae) egg surface characteristics stimulate parasitism by Ascogaster mimetica (Hymenoptera: Braconidae)
Authors: Ben-Zvi Yahel , Rodriguez-Saona Cesar
Published: September 2024

Ascogaster mimetica Viereck is an egg-larval parasitoid that targets Sparganothis sulfureana Clemens, a major cranberry pest in North America. While previous studies have shown that other Ascogaster species respond to cues from their hosts’ eggs, it remains unknown whether A. mimetica utilizes these cues to recognize S. sulfureana. We hypothesized that female A. mimetica recognizes S. sulfureana from another cranberry pest, Choristoneura parallela Robinson, based on the presence of surface cues on eggs. To test this, we observed female A. mimetica behavior when exposed to eggs from its host, S. sulfureana; a nonhost, C. parallela; and eggs of S. sulfureana that were washed clean with hexane. Additionally, we tracked parasitism rates in each group. Our results revealed that A. mimetica spent 9.5 times longer walking when exposed to C. parallela eggs and 6 times longer when exposed to hexane-washed S. sulfureana eggs compared to unwashed S. sulfureana eggs. Also, A. mimetica spent 3 times longer grooming when exposed to hexane-washed than unwashed S. sulfureana eggs. In contrast, females spent 6 and 18 times longer drumming and probing/ovipositing on unwashed S. sulfureana eggs than on C. parallela eggs and 5 times longer probing/ovipositing on unwashed S. sulfureana eggs than on hexane-washed S. sulfureana eggs. Higher parasitism rates were observed from unwashed S. sulfureana eggs compared to those from C. parallela eggs and hexane-washed S. sulfureana eggs. Our findings suggest that the presence of egg surface cues, like scales, of S. sulfureana likely plays a crucial role in host acceptance and parasitism success for A. mimetica.
Glia maturation factor-γ regulates amyloid-β42 phagocytosis through scavenger receptor class A type I in murine macrophages
Authors: Aerbajinai Wulin , Zhu Jianqiong , Chin Kyung , Rodgers Griffin P
Published: September 2024

Dysfunctional phagocytic clearance of β-amyloid (Aβ) in microglia and peripheral macrophages/monocytes has been implicated in Alzheimer's disease, but the mechanisms underlying this dysfunction are not yet well understood. In this study, we examined the role of glia maturation factor-γ (GMFG), an actin-disassembly protein, i.e. highly expressed in immune cells, in macrophage Aβ phagocytosis and in regulating type I class A scavenger receptor, a cell-surface receptor that has previously been implicated in Aβ clearance. GMFG knockdown–increased phagocytosis of Aβ42 in bone marrow-derived macrophages and RAW264.7 murine macrophages, while GMFG overexpression reduced Aβ42 uptake in these cells. Blocking with anti-type I class A scavenger receptor antibodies inhibited Aβ42 uptake in GMFG-knockdown cells, establishing a role for type I class A scavenger receptor in Aβ42 phagocytosis. GMFG knockdown–increased type I class A scavenger receptor protein expression under both basal conditions and in response to Aβ42 treatment via both the transcriptional and posttranscriptional levels in RAW264.7 macrophages. GMFG knockdown modulated Aβ42-induced K48-linked and K63-polyubiquitination of type I class A scavenger receptor, the phosphorylation of type I class A scavenger receptor and c-Jun N-Terminal kinase (JNK), suggesting that GMFG plays a role for intracellular signaling in the type I class A scavenger receptor-–mediated uptake of Aβ. Further, GMFG-knockdown cells displayed increased levels of the transcriptional factor MafB, and silencing of MafB in these cells reduced their type I class A scavenger receptor expression. Finally, GMFG was found to interact with the nuclear pore complex component RanBP2, and silencing of RanBP2 in GMFG-knockdown cells reduced their type I class A scavenger receptor expression. Collectively, these data support the role of GMFG as a novel regulator of type I class A scavenger receptor in macrophage Aβ phagocytosis and may provide insight into therapeutic approaches to potentially slow or prevent the progression of Alzheimer’s disease.
Impact of the serrated pathway on the simulated comparative effectiveness of colorectal cancer screening tests
Authors: Meester Reinier G S , Ladabaum Uri
Published: September 2024

Background

Colorectal cancers (CRCs) arise from adenomas, which can produce fecal occult blood and can be detected endoscopically, or sessile serrated lesions (SSLs), which rarely bleed and may be more challenging to detect. Models informing CRC screening policy should reflect both pathways, accounting for uncertainty.

Methods

Novel decision-analytic model of the adenoma and serrated pathways for CRC (ANSER) to compare current and emerging screening strategies, accounting for differential test sensitivities for adenomas and SSLs, and uncertainty. Strategies included colonoscopy every 10 years, stool-DNA/FIT (sDNA-FIT) every 1-3 years, or fecal immunochemical testing (FIT) every year from age 45 to 75 years. Outcomes included CRC cases and deaths, cost-effectiveness (cost/quality-adjusted life-year [QALY] gained), and burden–benefit (colonoscopies/life-year gained), with 95% uncertainty intervals (UIs).

Results

ANSER predicted 62.5 (95% UI = 58.8-66.3) lifetime CRC cases and 24.1 (95% UI = 22.5-25.7) CRC deaths/1000 45-year-olds without screening, and 78%-87% CRC mortality reductions with screening. The tests’ outcome distributions overlapped for QALYs gained but separated for required colonoscopies and costs. All strategies cost less than $100 000/QALY gained vs no screening. Colonoscopy was the most effective and cost-effective, costing $9300/life-year gained (95% UI = $500-$21 900) vs FIT. sDNA-FIT cost more than $500 000/QALY gained vs FIT. As more CRCs arose from SSLs, colonoscopy remained preferred based on clinical benefit and cost-effectiveness, but cost-effectiveness improved for a next-generation sDNA-FIT.

Conclusion

When the serrated pathway is considered, modeling suggests that colonoscopy is cost-effective vs FIT. In contrast, modeling suggests that sDNA-FIT is not cost-effective vs FIT despite its greater sensitivity for SSLs, even if a substantial minority of CRCs arise from SSLs.
Cost-effectiveness analysis with surrogate endpoint: mobile targeted active case detection for early detection of tuberculosis
Authors: Liaw Yau-Chun , Ramdzan Abdul Rahman , Avoi Richard
Published: September 2024

Objective

This study aimed to determine cost-effectiveness analysis with the surrogate endpoint of mobile targeted active case detection (MTACD) programmes in the early detection of tuberculosis (TB) cases.

Methods

A cross-sectional study to determine the cost-effectiveness with the surrogate endpoint of MTACD as compared with passive case detection (PCD) from the provider’s perspective. Data were gathered on the costs and significant dates (TB screening date, first TB symptoms date, TB diagnosis date, and TB treatment starting date) for 904 patients from five Sabah districts in 2022. A combined step-down and activity-based costing method was used to estimate provider costs. The health outcome measures used were the time taken by the day to detect TB cases. Cost-effectiveness analysis with surrogate endpoint was assessed using cost per TB screening by MTACD and PCD, and the mean of the time taken by the day to detect TB cases.

Key findings

The total cost for a patient to be screened by MTACD was Malaysian Ringgit (MYR) 96.6 (MYR 1 = USD 0.22), while the cost by PCD was MYR 43.1. The MTACD generally costs MYR 1727.1 to detect a case of TB, compared with MYR 586.9 for PCD. However, MTACD used a shorter mean time to detect TB cases (52.7 days) than PCD (98.9 days).

Conclusions

Despite the higher costs per screening, MTACD may shorten the days of diagnosis from the onset of TB symptoms when compared with PCD. This study is beneficial when budgeting for TB programmes since MTACD can detect TB cases earlier and lead to early treatment.
Altered expression of a raspberry homologue of VRN1 is associated with disruption of dormancy induction and misregulation of subsets of dormancy-associated genes
Authors: Mateos Brezo , Preedy Katharine , Milne Linda , Morris Jenny , Hedley Pete E , Simpson Craig , Hancock Robert D , Graham Julie
Published: September 2024

Winter dormancy is a key process in the phenology of temperate perennials. Climate change is severely impacting its course leading to economic losses in agriculture. A better understanding of the underlying mechanisms, as well as the genetic basis of the different responses, is necessary for the development of climate-resilient cultivars. This study aims to provide an insight into winter dormancy in red raspberry (Rubus idaeus L). We report the transcriptomic profiles during dormancy in two raspberry cultivars with contrasting responses. The cultivar ‘Glen Ample’ showed a typical perennial phenology, whereas ‘Glen Dee’ registered consistent dormancy dysregulation, exhibiting active growth and flowering out of season. RNA-seq combined with weighted gene co-expression network analysis identified gene clusters in both genotypes that exhibited time-dependent expression profiles. Functional analysis of ‘Glen Ample’ gene clusters highlighted the significance of the cell and structural development prior to dormancy entry as well the role of genetic and epigenetic processes such as RNAi and DNA methylation in regulating gene expression. Dormancy release in ‘Glen Ample’ was associated with up-regulation of transcripts associated with the resumption of metabolism, nucleic acid biogenesis, and processing signal response pathways. Many of the processes occurring in ‘Glen Ample’ were dysregulated in ‘Glen Dee’ and 28 transcripts exhibiting time-dependent expression in ‘Glen Ample’ that also had an Arabidopsis homologue were not found in ‘Glen Dee’. These included a gene with homology to Arabidopsis VRN1 (RiVRN1.1) that exhibited a sharp decline in expression following dormancy induction in ‘Glen Ample’. Characterization of the gene region in the ‘Glen Dee’ genome revealed two large insertions upstream of the ATG start codon. We propose that expression below detection level of a specific VRN1 homologue in ‘Glen Dee’ causes dormancy misregulation as a result of inappropriate expression of a subset of genes that are directly or indirectly regulated by RiVRN1.1.
PagHAM4a–PagSCL21 and PagHAM4b–PagTCP20 modules positively regulate cambial activity and its differentiation into secondary xylem in poplar
Authors: Zhao Pan , Yu Qiulin , He Yumei , Sun Pengfang , Wang Huilin , Zhou Xinyi , Su Yuting , Guo Huihong
Published: September 2024

Stem secondary xylem produced by cambial division and differentiation is the main source of tree biomass. Secondary xylem formation involves a complex transcriptional regulatory network; however, the underlying mechanism is still being explored. Here, we report that PagHAM4a and PagHAM4b are positive regulators of cambial differentiation into secondary xylem in hybrid poplar (Populus alba × Populus glandulosa clone 84K). Overexpression of PagHAM4a and PagHAM4b enhanced cambial activity and increased the number of secondary xylem cells in the stems of poplar. By contrast, single or double mutations of PagHAM4a and PagHAM4b generated by CRISPR/Cas9 decreased cambial activity, leading to a significant reduction of secondary xylem. Neither overexpression nor mutation of the two genes affected the size of vessels and fibers in xylem. Both PagHAM4a- and PagHAM4b-regulated gene networks were mainly centered at the stage when cambium had just initiated secondary growth, but the molecular networks regulated by the two genes were distinct. Further analysis revealed that PagSCL21 and PagTCP20 are direct targets of PagHAM4a and PagHAM4b, respectively, and their overexpression also promoted cambial differentiation into secondary xylem. Taken together, we identified two novel key regulatory modules in poplar, PagHAM4a–PagSCL21 and PagHAM4b–PagTCP20, which provide new insights into the mechanism of secondary xylem formation in trees.
The labour market differences between the asylum population and other migrants
Authors: Wong Lorraine
Published: September 2024

This article examines economic disparities between the asylum population and other migrants accounting for selection on unobservables. With administrative datasets of arrivals since the 1940s, descriptive evidence suggests that the asylum population is 7%–11% less likely to be employed and earn 15%–19% less than other migrants from 2010 to 2014 in Switzerland. Comparing bias-adjusted results considering selection on unobservables to conventional approaches such as decomposition and matching, I find that the bias-adjusted gaps bias towards zero. This suggests that conventional approaches may overestimate the outcome gaps. My results highlight that the outcome gaps persist, although discrimination and other unexplained factors are decreasing over time.
Reoptimizing Combat and Operational Stress Control in the U.S. Air Force
Authors: Dixon Mark A , Bohman T. Daniel , Polk Nicholas F , Farber Brandon C , Smith Charnell E
Published: September 2024

The future of warfare is changing with anticipation of moving toward Agile Combat Employment in contested, degraded, and operationally limited environments. This will require some changes for behavioral health provision within the Air Force during deployments. With over a century of development and refinement, Combat and Operational Stress Control (COSC) has proven to be a sustainable model for behavioral health asset utilization to maximize unit combat effectiveness and individual personnel performance. It allows flexibility of implementation across the force generation cycle through outreach efforts, unit integration, prevention services, and command consultation. COSC teams are versatile: Both enlisted and officer providers have a dynamic opportunity to influence and shape the wellness of an entire population of service members. To maximize this potential, the Air Force needs to formally train for the COSC mission and consider realigning the active duty mental health personnel from working almost exclusively in the Mental Health clinic to primarily working in the units. Employing the key principles of COSC in garrison is possible; however, it will take significant effort and purpose to change from the current policy.
“Holy Cow, Where do I Sign up?” Attitudes of Military Veterans Toward Epigenomic Biomarker Toxic Exposure Testing
Authors: Pereira Stacey , Apodaca Calvin , Slominski Kyle , Lipsky Rachele K , Coarfa Cristian , Walker Cheryl L , McGuire Amy L , Steele Lea , Helmer Drew A
Published: September 2024

Introduction

After the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics Promise to Address Comprehensive Toxics (PACT) Act in 2022, there has been a great interest in studying toxic exposures encountered during military service. Development of epigenomic biomarkers for exposures could facilitate understanding of exposure-related health effects, but such testing could also provide unwanted information.

Materials and Methods

We explored attitudes toward epigenomic biomarker research and the potential to test for past exposures using semistructured interviews with Veterans (n = 22) who experienced potentially harmful exposures.

Results

Twenty Veterans said they would hypothetically want to receive epigenomic information related to their toxic exposures and potential health impacts as part of a research study. Veterans identified 9 potential benefits, including promoting insights concerning intergenerational health, identification of early health interventions, and additional knowledge or explanation for their experiences. Sixteen participants noted potential risks, including psychological distress, receiving nonactionable, uncertain, or inaccurate results, and privacy and discrimination risks. Ten participants identified at least 1 condition in their children that they thought could be related to their exposure and most said they would be interested in receiving research results related to their children’s and grandchildren’s risk.

Conclusion

Results suggest that Veterans might welcome benefits of epigenomic research related to military exposures, yet have some concerns about potential negative impacts.
The active role of co-evolving haloes in stellar bar formation
Authors: Frosst Matthew , Obreschkow Danail , Ludlow Aaron
Published: September 2024

We use idealized N-body simulations of equilibrium discs in live and static haloes to study how dark matter co-evolution impacts the assembly of stellar particles into a bar and the halo response. Initial conditions correspond to a marginally unstable disc according to commonly used disc stability criteria, and are evolved for the equivalent of about 150 disc dynamical times (10 Gyr). An extensive convergence study ensures accurate modelling of the bar formation process. Live haloes lead to the formation of a strong bar, but the same disc remains unbarred when evolved in a static halo. Neither seeded disc instabilities nor longer (60 Gyr) simulations result in the formation of a bar when the halo is static. When the live halo is replaced with a static analogue at later times, the previously robust bar slowly dissipates, suggesting that (1) the co-evolution of the disc and halo is critical for the assembly and long-term survival of bars in marginally unstable discs and (2) global disc stability criteria must be modified for discs in the presence of live haloes. In our live halo runs, a ‘dark bar’ grows synchronously with the stellar bar. Processes that inhibit the transfer of angular momentum between the halo and disc may stabilize a galaxy against bar formation, and can lead to the dissolution of the bar itself. This raises further questions about the puzzling stability of observed discs that are marginally unstable, but unbarred.
The Human Accelerated Region HAR202 Controls NPAS3 Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences
Authors: Caporale Alfredo Leandro , Cinalli Alejandro R , Rubinstein Marcelo , Franchini Lucía F
Published: September 2024

It has been proposed that the phenotypic differences in cognitive abilities between humans and our closest living relatives, chimpanzees, are largely due to changes in the regulation of neurodevelopmental genes. We have previously found that the neurodevelopmental transcription factor gene NPAS3 accumulates the largest number of human accelerated regions (HARs), suggesting it may play some role in the phenotypic evolution of the human nervous system. In this work, we performed a comparative functional analysis of NPAS3-HAR202 using enhancer reporter assays in transgenic zebrafish and mice. We found that the Homo sapiens HAR202 ortholog failed to drive reporter expression to the zebrafish nervous system, in high contrast to the strong expression displayed by the rest of the vertebrate ortholog sequences tested. Remarkably, the HAR202 ortholog from archaic humans (Neanderthals/Denisovans) also displayed a pan-vertebrate expression pattern, despite the fact that archaic and modern humans have only one nucleotide substitution. Moreover, similar results were found when comparing enhancer activity in transgenic mice, where we observed a loss of activity of the modern human version in the mouse developing brain. To investigate the functional importance of HAR202, we generated mice lacking HAR202 and found a remarkable decrease of Npas3 expression in the forebrain during development. Our results place HAR202 as one of the very few examples of a neurodevelopmental transcriptional enhancer displaying functional evolution in the brain as a result of a fast molecular evolutionary process that specifically occurred in the human lineage.