bluuebunny/crossref_metadata_2025 huggingface dataset:
Could care giving have altered the evolution of human immune strategies?
Authors: Gilbert Bethany L P , Kessler Sharon E
Published: January 2024

Life history theory indicates that individuals/species with a slow pace of life invest more in acquired than innate immunity. Factors that decrease the pace of life and predict greater investment in acquired immunity include increased nutritional resources, increased pathogen exposure and decreased risk of extrinsic mortality. Common care behaviors given to sick individuals produce exactly these effects: provisioning increases nutritional resources; hygiene assistance increases disease exposure of carers; and protection can reduce the risk of extrinsic mortality to sick individuals. This study, therefore, investigated under what conditions care giving behaviors might impact immune strategy and pace of life. The study employed an agent-based model approach that simulated populations with varying levels of care giving, disease mortality, disease transmissibility, and extrinsic mortality, enabling measurements of how the immune strategy and age structure of the populations changed over evolutionary time. We used multiple regressions to examine the effects of these variables on immune strategy and the age structure of the population. The findings supported our predictions that care was selected for an acquired immunity. However, the pace of life did not slow as expected. Instead, the population shifted to a faster, but also more cost-intensive reproductive strategy in which care improved child survival by subsidizing the development of acquired immune responses.
Description of self-care behaviours in patients with non-valvular atrial fibrillation on oral anticoagulant therapy: a scoping review
Authors: Magon Arianna , Hendriks Jeroen M , Conte Gianluca , Caruso Rosario
Published: January 2024

Aims

The primary aim of this scoping review was to explore and categorize the medication-related self-care behaviours exhibited by patients with non-valvular atrial fibrillation (NVAF) who are on oral anticoagulant (OAC) therapy.

Methods and results

A scoping review was performed, and the systematic search of the literature yielded an initial 887 records. After deduplication and screening, 61 studies were included in the analysis, ranging from 2003 to 2023. The studies represented a wide geographical distribution and diverse methodologies. The results identified 16 self-care behaviours: a higher focus of the included literature on self-care monitoring (60.65% of studies), followed by self-care management and self-care maintenance (each 16.39%). These behaviours ranged from regular blood testing to consulting healthcare providers and lifestyle changes. The results also highlighted the relationship between treatment satisfaction, self-efficacy, and adherence. Several studies emphasized the critical role of healthcare providers in influencing medication adherence. Furthermore, patient knowledge, quality of life, and psychological factors were identified as key elements affecting self-care behaviours.

Conclusion

The review provides a comprehensive landscape of medication-related self-care behaviours among NVAF patients on OAC therapy. It underscores the predominance of self-care monitoring behaviours and the critical roles of healthcare providers, psychological factors, and patient knowledge in influencing these behaviours. The findings also highlight the necessity for an integrated, patient-centred approach to improving self-care and self-management in OAC treatment. Future research should focus on addressing the identified gaps, including the relative lack of studies on lifestyle modification, emotional well-being, and technology-assisted interventions.

Registration

This review is part of a broader project and is documented at ClinicalTrials.gov: NCT05820854.
The evolution of sexual dimorphism in gene expression in response to a manipulation of mate competition
Authors: Mishra Prashastha , Rundle Howard D , Agrawal Aneil F
Published: January 2024

Many genes are differentially expressed between males and females and patterns of sex-biased gene expression (SBGE) vary among species. Some of this variation is thought to have evolved in response to differences in mate competition among species that cause varying patterns of sex-specific selection. We used experimental evolution to test this by quantifying SBGE and sex-specific splicing in 15 Drosophila melanogaster populations that evolved for 104 generations in mating treatments that removed mate competition via enforced monogamy, or allowed mate competition in either small, simple, or larger, structurally more complex mating environments. Consistent with sex-specific selection affecting SBGE, initially sex-biased genes diverged in expression more among treatments than unbiased genes, and there was greater expression divergence for male- than female-biased genes. It has been suggested the transcriptome should be “feminized” under monogamy because of the removal of sexual selection on males; we did not observe this, likely because selection differs in additional ways between monogamy vs. polygamy. Significant divergence in average expression dimorphism between treatments was observed and, in some treatment comparisons, the direction of the divergence differed across different sex-bias categories. There was not a generalized reduction in expression dimorphism under enforced monogamy.
Mutations of ribosomal protein genes induce overexpression of catalase in Saccharomyces cerevisiae
Authors: Hsu Ching-Hsiang , Liu Ching-Yu , Lo Kai-Yin
Published: January 2024

Ribosome assembly defects result in ribosomopathies, primarily caused by inadequate protein synthesis and induced oxidative stress. This study aimed to investigate the link between deleting one ribosomal protein gene (RPG) paralog and oxidative stress response. Our results indicated that RPG mutants exhibited higher oxidant sensitivity than the wild type (WT). The concentrations of H2O2 were increased in the RPG mutants. Catalase and superoxide dismutase (SOD) activities were generally higher at the stationary phase, with catalase showing particularly elevated activity in the RPG mutants. While both catalase genes, CTT1 and CTA1, consistently exhibited higher transcription in RPG mutants, Ctt1 primarily contributed to the increased catalase activity. Stress-response transcription factors Msn2, Msn4, and Hog1 played a role in regulating these processes. Previous studies have demonstrated that H2O2 can cleave 25S rRNA via the Fenton reaction, enhancing ribosomes’ ability to translate mRNAs associated with oxidative stress-related genes. The cleavage of 25S rRNA was consistently more pronounced, and the translation efficiency of CTT1 and CTA1 mRNAs was altered in RPG mutants. Our results provide evidence that the mutations in RPGs increase H2O2 levels in vivo and elevate catalase expression through both transcriptional and translational controls.
Epigenetic and Genetic Differentiation Between Coregonus Species Pairs
Authors: Venney Clare J , Mérot Claire , Normandeau Eric , Rougeux Clément , Laporte Martin , Bernatchez Louis
Published: January 2024

Phenotypic diversification is classically associated with genetic differentiation and gene expression variation. However, increasing evidence suggests that DNA methylation is involved in evolutionary processes due to its phenotypic and transcriptional effects. Methylation can increase mutagenesis and could lead to increased genetic divergence between populations experiencing different environmental conditions for many generations, though there has been minimal empirical research on epigenetically induced mutagenesis in diversification and speciation. Whitefish, freshwater members of the salmonid family, are excellent systems to study phenotypic diversification and speciation due to the repeated divergence of benthic–limnetic species pairs serving as natural replicates. Here we investigate whole genome genetic and epigenetic differentiation between sympatric benthic–limnetic species pairs in lake and European whitefish (Coregonus clupeaformis and Coregonus lavaretus) from four lakes (N = 64). We found considerable, albeit variable, genetic and epigenetic differences between species pairs. All SNP types were enriched at CpG sites supporting the mutagenic nature of DNA methylation, though C>T SNPs were most common. We also found an enrichment of overlaps between outlier SNPs with the 5% highest FST between species and differentially methylated loci. This could possibly represent differentially methylated sites that have caused divergent genetic mutations between species, or divergent selection leading to both genetic and epigenetic variation at these sites. Our results support the hypothesis that DNA methylation contributes to phenotypic divergence and mutagenesis during whitefish speciation.
On the retrieval of body waves from ambient noise based on regional seismic arrays
Authors: Xie Jinyun , Luo Yinhe , Bao Xueyang , Dai Andy , Xie Yanan , Yang Yingjie
Published: January 2024

Ambient noise technology can efficiently extract surface wave signals from seismic background noise and has been extensively utilized in imaging lithospheric structures. However, retrieving crustal body wave signals, such as PmP or SmS phases, still poses a challenge. Only a limited number of reports have successfully extracted these regional-scale body wave signals from ambient noise in only a few limited study areas. It remains unclear why these signals are difficult to retrieve from ambient noise data. To investigate the mechanism of recovering body wave signals in noise cross-correlations, we calculate cross-correlation functions at four regions and observe the similarity of the recovered body waves. Through a series of synthetic simulations, we demonstrate that the appearance of body wave signals in noise cross-correlations is closely related to the distribution of noise sources. Among these signals, the post-critical SmS wave proves to be the most readily recoverable from ambient noise data, primarily stemming from distant sources. In contrast, the recovery of P-wave requires the array to be in proximity to the sources. Our experiments also reveal that the main origin of PL waves is the multiple reflections of S-waves propagating in the crust.
SPINT2 mutations in the Kunitz domain 2 found in SCSD patients inactivate HAI-2 as prostasin inhibitor via abnormal protein folding and N-glycosylation
Authors: Huang Nanxi , Wang Qiaochu , Bernard Robert B , Chen Chao-Yang , Hu Je-Ming , Wang Jehng-Kang , Chan Khee-Siang , Johnson Michael D , Lin Chen-Yong
Published: January 2024

Mutations in the Kunitz-type serine protease inhibitor HAI-2, encoded by SPINT2, are responsible for the pathogenesis of syndromic congenital sodium diarrhea (SCSD), an intractable secretory diarrhea of infancy. Some of the mutations cause defects in the functionally required Kunitz domain 1 and/or subcellular targeting signals. Almost all SCSD patients, however, harbor SPINT2 missense mutations that affect the functionally less important Kunitz domain 2. How theses single amino acid substitutions inactivate HAI-2 was, here, investigated by the doxycycline-inducible expression of three of these mutants in HAI-2-knockout Caco-2 human colorectal adenocarcinoma cells. Examining protein expressed from these HAI-2 mutants reveals that roughly 50% of the protein is synthesized as disulfide-linked oligomers that lose protease inhibitory activity due to the distortion of the Kunitz domains by disarrayed disulfide bonding. Although the remaining protein is synthesized as monomers, its glycosylation status suggests that the HAI-2 monomer remains in the immature, lightly glycosylated form, and is not converted to the heavily glycosylated mature form. Heavily glycosylated HAI-2 possesses full anti-protease activity and appropriate subcellular targeting signals, including the one embedded in the complex-type N-glycan. As predicted, these HAI-2 mutants cannot suppress the excessive prostasin proteolysis caused by HAI-2 deletion. The oligomerization and glycosylation defects have also been observed in a colorectal adenocarcinoma line that harbors one of these SPINT2 missense mutations. Our study reveals that the abnormal protein folding and N-glycosylation can cause widespread HAI-2 inactivation in SCSD patents.
CYTOKINE MULTI-OMICS AND MACHINE LEARNING IDENTIFY MIP1ALPHA AS A NOVEL MEDIATOR IN INFLAMMATORY BOWEL DISEASE
Authors: O'Brien Eileen , Potdar Chinmay , Mulder Daniel
Published: January 2024

BACKGROUND

Macrophage inflammatory protein 1 alpha (MIP1a) is a proinflammatory cytokine previously related to murine models of inflammatory bowel disease (IBD), but not definitively in the human disease. MIP1a acts as a chemoattractant of immune cells from the blood to the gut mucosa. We aimed to delineate the alterations to MIP1a and macrophages in relation to a range of IBD severity.

HYPOTHESIS

To characterize the changes to MIP1a production and localization in response to disease activity in IBD.

APPROACH

Both IBD (n=63) and control patients (n=118) were enrolled in this study (HSREB 6033229). Cytokine profiles were investigated using a 17-plex multi-fluorescent bead-based immunoassay (FirePlex, Abcam, Cambridge, UK) on serum from a subset of patients. Disease activity and macrophage levels were extracted from the clinical record. Activity was quantified using the Physician Global Assessment Score. Machine learning (ML) was performed with custom R scripts utilizing the tidymodels package (version 1.1) to determine the optimal model. Immunohistochemistry (IHC) was used to localize MIP1a in patient biopsies and quantified using QuPath software (v0.4).

RESULTS

An extreme gradient boost ML model was found to have optimal sensitivity and specificity for predicting disease activity based on serum cytokine levels. Within this model lower levels of serum MIP1a were associated with higher severity of IBD activity. However, in GI mucosal biopsies, the percentage of MIP1a positive cells in colon tissue increased with the severity of IBD. Macrophage concentrations in the peripheral blood were higher in patients on prednisone, and relatively similar across all other medications used in our cohort.

CONCLUSIONS

With the data collected, we identify MIP1a as a possible prognostic tool for quantifying IBD activity.
TRENDS OF INFLAMMATORY BOWEL DISEASE BURDEN IN THE UNITED STATES (1990-2019), PROJECTIONS OF DEATHS TO 2040: INSIGHTS FROM THE 2019 GLOBAL BURDEN OF DISEASE STUDY
Authors: Patel Rahul , Roy Vivek , Kunhipurayil Suraj , Patel Krina Manojbhai , Elassar Samar , Sojitra Vani , Desai Hardik Dineshbhai
Published: January 2024

BACKGROUND

Inflammatory Bowel Disease (IBD) ranks as the 9th primary cause of deaths and 7th for disabilities among all digestive diseases, affecting over 3 million Americans with a continuous upsurge.

METHOD

Utilizing the Global Burden of Disease methodology, we evaluated the prevalence, incidence, mortality, and Disability Adjusted Life Years (DALYs) of IBD from 1990 to 2019 in the U.S. based on age, sex, and year via a standardized statistical model. Furthermore, we forecasted deaths and Years of Life Lost (YLLs) up to 2040 through a regression framework.

RESULTS

IBD prevalence showed a decline from 982,981 (95%UI: 846,832-1,129,782) in 1990 to 762,889 (712,356-813,653) in 2019. From 1990-2019, the total annual incidence reduced by 12% (4-18), while deaths surged by 172% (81-199), and DALYs increased by 16% (2-34) (Figure 1). The Age-Standardized Rate (ASR) for mortality rose from 0.62 (0.60-0.82) per 100,000 cases in 1990 to 1.02 (0.8-1.11) in 2019. In raw counts, Nevada saw the most significant rise in incidence (87%), deaths (486%), and DALYs (174%) from 1990-2019. Based on ASR, West Virginia and Kentucky led in mortality increases with 87% and 83% respectively (Figure 2). In 2019, the age group 80-84 reported the highest deaths (848), while ages 25-29 saw the most significant incidence (8429), and ages 60-64 the highest DALYs (20933). Comparing genders, females had a steeper increase in DALYs (17% vs. 13% for males), whereas males saw a higher rise in deaths (181% vs. 167% for females) between 1990-2019. By 2040, IBD-related age-standardized mortality rates are predicted to climb by 0.9 per 100,000.

CONCLUSION

In 2019, IBD was responsible for 4.56% of all digestive disease deaths. Highlighting a comprehensive challenge for the U.S. healthcare, IBD's impact is not just clinical or economic but also profoundly psychosocial. Emphasizing early detection, cutting-edge treatments, and comprehensive patient support is crucial to lessen the severe implications of IBD in the U.S.
THE PATHOGENIC ROLE OF MICROBIAL TRIMETHYLAMINE IN IBD ASSOCIATED INTESTINAL FIBROSIS
Authors: Massey William , Mukherjee Pranab , Nguyen Quang Tam , Mrdjen Marko , Wang Zeneng , Brown J Mark , Rieder Florian
Published: January 2024

INTRODUCTION

Intestinal fibrosis significantly contributes to the burden of inflammatory bowel diseases (IBD). No specific anti-fibrotic therapy is available. Two modifiable risk factors that may be exploited to limit fibrosis in IBD are the diet and gut microbiome. In the metaorganismal metabolism model, microbes metabolize dietary components to primary metabolites that may themselves signal through host receptor systems or be further metabolized to secondary metabolites by other microbes or host enzymes to exert a physiological or pathophysiological effect. We hypothesize that gut microbes profoundly influence intestinal fibrosis through small molecule metabolites and may provide novel targets to address the fibrotic burden in IBD.

METHODS

To understand how the trimethylamine-N-oxide (TMAO) pathway is affected by inflammation in the intestine, LC-MS was used to quantitate a dietary precursor, choline, primary microbial metabolite, trimethylamine (TMA), and secondary metabolite, TMAO, in mice subjected to acute DSS colitis. The cellular effects of choline, TMA, and TMAO on the deposition of fibronectin and collagen I were quantitated in primary human intestinal myofibroblasts (HIMFs). Single cell RNA-sequencing (scRNA-seq) data were interrogated to determine whether expression of the TMA-to-TMAO converting enzyme, FMO3, was downregulated in human intestinal cells of Crohn’s disease patients.

RESULTS

Acute DSS colitis showed increased TMA and reduced levels of TMAO, in colon tissue, which is consistent with reduced TMA-to-TMAO conversion by FMO3. Additionally, TMA was increased in intestinal contents, which suggests that microbial production of TMA from choline may also be upregulated during intestinal inflammation. In HIMFs, TMA, but not its dietary precursor, choline, nor the secondary metabolite, TMAO, increased the deposition of the extracellular matrix proteins fibronectin and collagen I. scRNA-seq analysis of the mesenchymal compartment of human intestine revealed expression of FMO3 specifically in the fibroblast cluster and downregulation of this expression in Crohn’s disease (CD) strictures compared to controls, an observation that could contribute to TMA accumulation in vivo.

CONCLUSION

TMA is increased in experimental colitis and activates fibroblasts towards a pro-fibrogenic phenotype. This may be mediated by reduced levels of FMO3. We next aim to measure TMAO pathway metabolites in human tissues, functionally block the TMAO pathway in vivo, and explore TMA signaling through its putative receptor, trace amine-associated receptor 5 (TAAR5).

Diet-microbe-host interaction pathways represent an untapped opportunity for therapeutic intervention in multiple human disease states, such as inflammatory bowel diseases (IBD).
Calibrating ecosystem models to support ecosystem-based management of marine systems
Authors: Bentley Jacob W , Chagaris David , Coll Marta , Heymans Johanna J , Serpetti Natalia , Walters Carl J , Christensen Villy
Published: January 2024

Ecosystem models, such as Ecopath with Ecosim (EwE), provide a platform to simulate intricate policy scenarios where multiple species, pressures, and ecosystem services interact. Complex questions often return complex answers, necessitating evidence and advice to be communicated in terms of trade-offs, risks, and uncertainty. Calibration procedures for EwE, which can act as a source of uncertainty and bias in model results, have yet to be explored in a comprehensive way that communicates how sensitive model outputs are to different calibration approaches. As the EwE community has grown, multiple divergent approaches have been applied to calibrate models through the estimation of vulnerability multipliers: parameters that augment the consumption rate limits of predators. Here we explore the underlying principles of vulnerability multipliers as well as existing calibration approaches and their justification. Two case studies are presented: the first explores how vulnerability multipliers emerge based on the chosen calibration approach using simulated data, while the second takes two operational EwE models (Irish Sea and Northwest Atlantic Continental Shelf) and compares their outputs when calibrated following alternate calibration approaches. We show how calibration approaches can impact model-derived advice and provide a list of best practice recommendations for EwE calibration.
Social network analysis as a tool to inform anguillid eel conservation and management
Authors: Williamson Michael J , Jacoby David M P , Bašić Tea , Walker Alan , Piper Adam T
Published: January 2024

Eel Management Plans demand European silver eel (Anguilla anguilla) escapement to the sea of at least 40% of that expected historically in the absence of human impacts. Landlocked lentic waterbodies, such as drinking water reservoirs, host substantial numbers of eel, which could represent a significant contribution to catchment-based conservation targets. To optimize netting strategies for eel management policies, information on their aggregation behaviour is currently needed but lacking. We performed a fine-scale acoustic tracking study to monitor the movements of 86 European eel in a UK reservoir. Social network sampling and sensitivity analyses were used to assess whether eel aggregate at scales relevant for current capture techniques. European eel were found to aggregate at spatial and temporal scales of 50 m and 2 days, respectively, which complements current capture methodologies and recommendations. Aggregations were not driven by fixed resources, indicating that other factors, such as sociality, may drive aggregation behaviour. Results also show that current netting practices could be optimized by increasing netting lengths from 50 to 80 m. In addition to aiding conservation and management protocols, these results provide an ecological foundation for exploring the role of social behaviour in this Critically Endangered species.
The Universe Inside Hall Algebras of Coherent Sheaves on Toric Resolutions
Authors: Tsvelikhovskiy Boris
Published: January 2024

Let $\mathfrak {g}\neq \mathfrak {s}\mathfrak {o}_{8}$ be a simple Lie algebra of type $A,D,E$ with $\widehat {\mathfrak {g}}$ the corresponding affine Kac–Moody algebra and $\mathfrak {n}_{+}\subset \widehat {\mathfrak {g}}$ is the standard positive nilpotent subalgebra. Given $\mathfrak {n}_{+}$ as above, we provide an infinite collection of cyclic finite abelian subgroups of $SL_{3}(\mathbb {C})$ with the following properties. Let $G$ be any group in the collection, $Y=G\operatorname {-}\mbox {Hilb}(\mathbb {C}^{3})$, and $\Psi : D^{b}_{G}(Coh(\mathbb {C}^{3}))\rightarrow D^{b}(Coh(Y))$ the derived equivalence of Bridgeland, King, and Reid. We present an (explicitly described) subset of objects in $Coh_{G}(\mathbb {C}^{3})$, s.t. the Hall algebra generated by their images under $\Psi $ is isomorphic to $U(\mathfrak {n}_{+})$. In case the field $\Bbbk $ (in place of $\mathbb {C}$) is finite and $\mbox {char}(\Bbbk )$ is coprime with the order of $G$, we establish isomorphisms of the corresponding “counting” Ringel–Hall algebras and the specializations of quantized universal enveloping algebras $U_{v}(\mathfrak {n}_{+})$ at $v=\sqrt {|\Bbbk |}$.
On the Hessian of Cubic Hypersurfaces
Authors: Bricalli Davide , Francesco Favale Filippo , Pietro Pirola Gian
Published: January 2024

In this paper, we analyze the Hessian locus associated to a general cubic hypersurface, by describing its singular locus and its desingularization for every dimension. The strategy is based on strong connections between the Hessian and the quadrics defined as partial derivatives of the cubic polynomial. In particular, we focus our attention on the singularities of the Hessian hypersurface associated to the general cubic four-fold. It turns out to be a minimal surface of general type: its analysis is developed by exploiting the nature of this surface as a degeneracy locus of a symmetric vector bundle map and by describing an unramified double cover, which is constructed in a more general setting.
Lung Function Trajectories in Mild COVID-19 With 2-year Follow-up
Authors: Iversen Katrine K , Ronit Andreas , Ahlström Magnus G , Nordestgaard Børge G , Afzal Shoaib , Benfield Thomas
Published: January 2024

Background

The long-term pulmonary sequelae of mild coronavirus disease 2019 (COVID-19) remains unknown. In this study, we aimed to characterize lung function trajectories in individuals with mild COVID-19 from preinfection to 2 years postinfection.

Methods

We reinvited participants 2 years after infection from our matched cohort study of the Copenhagen General Population who had initially been examined 5.4 months after infection. We repeated lung tests and questionnaires. Linear mixed models were used to estimate dynamics in lung volumes in individuals with COVID-19 patients versus uninfected controls over two intervals: from pre-infection to 6 months postinfection and 6 months postinfection to 2 years postinfection.

Results

52 individuals (48.6%) attended the 2-year examination at median 1.9 years (interquartile range, 1.8–2.4) after COVID-19, all with mild infection. Individuals with COVID-19 had an adjusted excess decline in forced expiratory volume in 1 second (FEV1) of 13.0 mL per year (95% confidence interval [CI], −23.5 to −2.5; P = .02) from before infection to 6 months after infection compared to uninfected controls. From 6 to 24 months after infection, they had an excess decline of 7.5 mL per year (95% CI, −25.6–9.6; P = .40). A similar pattern was observed for forced vital capacity (FVC). Participants had a mean increase in diffusing capacity for carbon monoxide (DLco) of 3.33 (SD 7.97) between the 6- and 24-month examination.

Conclusions

Our results indicate that mild COVID-19 infection affects lung function at the time of infection with limited recovery 2 years after infection.
Does Youth Resentment Matter in Understanding the Surge of Extremist Violence in Burkina Faso?
Authors: Tapsoba Alexandra T , Combes Jean-Louis , Combes Motel Pascal
Published: January 2024

The year 2019 marked an unprecedented step in violence in Burkina Faso. Before 2018, attacks targeted central government officials and expatriates. In 2019, the victims of sexual assaults, attacks, abductions or forced disappearances and assassinations were mostly local civilians. The surge in these violent attacks against civilians generates population movements. As of 2023, internally displaced people represent about 10% of the total population in the country. Several observers point to the youth of the attackers. This study investigates the motives that could drive young people to resort to violence in the country. It aims to highlight youth resentment's effect on violence against civilians in the country as of 2019. It takes advantage of one of the latest nationwide United Nations Children’s Fund (UNICEF)-sponsored surveys conducted in Burkina Faso before some parts of the country became inaccessible because of attacks. Among other information, this survey collected data on youth resentment towards the ability of their kinship to fulfil their needs in 2018, namely before the shift in violence against civilians. We merge this survey into an original dataset that gathers data from the Armed Conflict Location and Event Data Project (ACLED), mining data from the MINEX project and distance data computed using Burkina Faso's roads information. The results of an event count model show that youth resentment matters in understanding the occurrence of conflicts. Moreover, the presence of mining companies, the remoteness of infrastructures, ethnic diversity and polarisation also significantly affect violence against civilians.
Urechistachykinin I triggers mitochondrial dysfunction leading to a ferroptosis-like response in Saccharomyces cerevisiae
Authors: Han Giyeol , Lee Dong Gun
Published: January 2024

Aims

The purpose of this paper was to demonstrate the antimicrobial activity of urechistachykinin I (LRQSQFVGSR-NH2) extracted from Urechis unicinctus,and its mode of action dependent on mitochondrial dysfunction.

Methods and results

The antifungal activity of urechistachykinin I generated reactive oxygen species (ROS), as demonstrated with MitoSOX Red and hydroxyphenyl fluorescein (HPF). Overaccumulation of ROS caused oxidative damage to cells by inducing mitochondrial dysfunction. Mitochondrial disruption resulted in cell death, creating several hallmarks that included lipid peroxidation, glutathione oxidation, and depolarization. Moreover, the loss of mitochondria changed the calcium ion imbalance by depolarization of the mitochondrial membrane. In particular, iron accumulation and DNA fragmentation measurement determined the type of cell death. Our results indicate that urechistachykinin I treatment induced ferroptosis-like death in Saccharomyces cerevisiae via mitochondrial dysfunction.

Conclusions

Urechistachykinin I treatment induced mitochondrial dysfunction in S. cerevisiae by generating ROS, and the subsequent oxidative damage caused the ferroptosis-like cell death.
Lactobacillus rhamnosus dampens cytokine and chemokine secretion from primary human nasal epithelial cells infected with rhinovirus
Authors: Yarlagadda Tejasri , Zhu Yanshan , Snape Natale , Carey Alison , Bryan Emily , Maresco-Pennisi Diane , Coleman Andrea , Cervin Anders , Spann Kirsten
Published: January 2024

Aims

To investigate the effect of Lactobacillus rhamnosus on viral replication and cellular response to human rhinovirus (HRV) infection, including the secretion of antiviral and inflammatory mediators from well-differentiated nasal epithelial cells (WD-NECs).

Methods and results

The WD-NECs from healthy adult donors (N = 6) were cultured in vitro, exposed to different strains of L. rhamnosus (D3189, D3160, or LB21), and infected with HRV (RV-A16) after 24 h. Survival and adherence capacity of L. rhamnosus in a NEC environment were confirmed using CFSE-labelled isolates, immunofluorescent staining, and confocal microscopy. Shed virus and viral replication were quantified using TCID50 assays and RT-qPCR, respectively. Cytotoxicity was measured by lactate dehydrogenase (LDH) activity. Pro-inflammatory mediators were measured by multiplex immunoassay, and interferon (IFN)-λ1/3 was measured using a standard ELISA kit. Lactobacillus rhamnosus was able to adhere to and colonize WD-NECs prior to the RV-A16 infection. Lactobacillus rhamnosus did not affect shed RV-A16, viral replication, RV-A16-induced IFN-λ1/3 production, or LDH release. Pre-exposure to L. rhamnosus, particularly D3189, reduced the secretion of RV-A16-induced pro-inflammatory mediators by WD-NECs.

Conclusions

These findings demonstrate that L. rhamnosus differentially modulates RV-A16-induced innate inflammatory immune responses in primary NECs from healthy adults.
Bridging the digital health divide—patient experiences with mobile integrated health and facilitated telehealth by community-level indicators of health disparity
Authors: Daniels Brock , McGinnis Christina , Topaz Leah Shafran , Greenwald Peter , Turchioe Meghan Reading , Creber Ruth Marie Masterson , Sharma Rahul
Published: January 2024

Objective

Evaluate the impact of community tele-paramedicine (CTP) on patient experience and satisfaction relative to community-level indicators of health disparity.

Materials and Methods

This mixed-methods study evaluates patient-reported satisfaction and experience with CTP, a facilitated telehealth program combining in-home paramedic visits with video visits by emergency physicians. Anonymous post-CTP visit survey responses and themes derived from directed content analysis of in-depth interviews from participants of a randomized clinical trial of mobile integrated health and telehealth were stratified into high, moderate, and low health disparity Community Health Districts (CHD) according to the 2018 New York City (NYC) Community Health Survey.

Results

Among 232 CTP patients, 55% resided in high or moderate disparity CHDs but accounted for 66% of visits between April 2019 and October 2021. CHDs with the highest proportion of CTP visits were more adversely impacted by social determinants of health relative to the NYC average. Satisfaction surveys were completed in 37% of 2078 CTP visits between February 2021 and March 2023 demonstrating high patient satisfaction that did not vary by community-level health disparity. Qualitative interviews conducted with 19 patients identified differing perspectives on the value of CTP: patients in high-disparity CHDs expressed themes aligned with improved health literacy, self-efficacy, and a more engaged health system, whereas those from low-disparity CHDs focused on convenience and uniquely identified redundancies in at-home services.

Conclusions

This mixed-methods analysis suggests CTP bridges the digital health divide by facilitating telehealth in communities negatively impacted by health disparities.
Effects of dietary Nisin on growth performance, immune function, and gut health of broilers challenged by Clostridium perfringens
Authors: Yuan Hua , Bai Guangdong , Lin Yu , Yu Xilong , Yang Qinghui , Dou Renkai , Sun Hao , Zhao Zeyu , Li Zhongyu , Chen Zhihui , Xu Liangmei
Published: January 2024

Nisin (Ni) is a polypeptide bacteriocin produced by lactic streptococci (probiotics) that can inhibit the majority of gram-positive bacteria, and improve the growth performance of broilers, and exert antioxidative and anti-inflammatory properties. The present study investigated the potential preventive effect of Nisin on necrotic enteritis induced by Clostridium perfringens (Cp) challenge. A total of 288 Arbor Acres broiler chickens of 1-d-olds were allocated using 2 × 2 factorial arrangement into four groups with six replicates (12 chickens per replicate), including: (1) control group (Con, basal diet), (2) Cp challenge group (Cp, basal diet + 1.0 × 108 CFU/mL Cp), (3) Ni group (Ni, basal diet + 100 mg/kg Ni), and (4) Ni + Cp group (Ni + Cp, basal diet + 100 mg/kg Ni + 1.0 × 108 CFU/mL Cp). The results showed that Cp challenge decreased the average daily gain (ADG) of days 15 to 21 (P<0.05) and increased interleukin-6 (IL-6) content in the serum (P < 0.05), as well as a significant reduction in villus height (VH) and the ratio of VH to crypt depth (VCR) (P<0.05) and a significant increase in crypt depth (CD) of jejunum (P<0.05). Furthermore, the mRNA expressions of Occludin and Claudin-1 were downregulated (P<0.05), while the mRNA expressions of Caspase3, Caspase9, Bax, and Bax/Bcl-2 were upregulated (P<0.05) in the jejunum. However, the inclusion of dietary Ni supplementation significantly improved body weight (BW) on days 21 and 28, ADG of days 15 to 21 (P<0.05), decreased CD in the jejunum, and reduced tumor necrosis factor-α (TNF-α) content in the serum (P<0.05). Ni addition upregulated the mRNA levels of Claudin-1 expression and downregulated the mRNA expression levels of Caspase9 in the jejunum (P<0.05). Moreover, Cp challenge and Ni altered the cecal microbiota composition, which manifested that Cp challenge decreased the relative abundance of phylum Fusobacteriota and increased Shannon index (P<0.05) and the trend of phylum Proteobacteria (0.05<P<0.10), while Ni addition increased the relative abundance of phylum Cyanobacteria (P<0.05). In conclusion, the results demonstrated that the addition of Ni effectively mitigated the negative impact of Cp challenge-induced the damage of growth performance and intestine in broilers via reducing inflammatory responses and intestinal apoptosis and modulating cecal microbial composition.
Stress indicators in dairy cows adapting to virtual fencing
Authors: Fuchs Patricia , Stachowicz Joanna , Schneider Manuel K , Probo Massimiliano , Bruckmaier Rupert M , Umstätter Christina
Published: January 2024

Virtual fencing (VF) enables livestock grazing without physical fences by conditioning animals to a virtual boundary delimited with an audio tone (AT) and an electric pulse (EP). The present study followed the adaptation process of lactating dairy cows to a VF system with changing virtual boundaries and investigated its impact on animal welfare. Twenty cows were divided into stratified groups (2× VF; 2× electric fencing, EF) of five individuals. Each group grazed half-days in a separate EF paddock of comparable size during 3 d of acclimation (P0), followed by 21, 14, 14, and 7 d of experimental treatment (P1 to P4). At the start of the trial, all cows were equipped with an IceQube pedometer (Peacock Technology Ltd, Stirling, UK) and a VF collar (Nofence AS, Batnfjordsøra, Norway). During P0, cows were accustomed to their first paddock with a deactivated virtual boundary and wearing the sensors. In P1 to P4, an active virtual boundary for the VF groups, and a second EF for the EF groups was set up parallel to an outer EF within their paddock. Throughout the trial, the sensors continuously tracked cow positions and activity behavior at 15-min intervals. From P1 onwards, the VF collars additionally recorded each AT and EP per cow with a georeferenced time stamp. During P0 to P4, daily feed intake, body weight, and milk yield were recorded in the barn. A total of 26 milk samples were collected per cow to determine milk cortisol levels. Behavioral observations were conducted for 2 h on day 23 to record agonistic behaviors, vocalizations, and excretions. The total number of stimuli per cow ranged from 37 to 225 ATs (mean ± SD: 1.9 ± 3.3 per day) and 3 to 11 EPs (mean ± SD: 0.1 ± 0.7 per day) throughout the trial. The maximum number of EPs per day was 8 for an individual cow and occurred once on D1. Mean EP/AT decreased by 55% during the first three half-days of grazing and with each paddock change from 0.2 EP/AT in week 1 to 0.03, 0.02, and 0 EP/AT in weeks 4, 6, and 8, respectively. Linear and generalized mixed effects models revealed that milk yield and cortisol, feed intake, body weight, and activity and lying behavior did not significantly differ between VF and EF groups. A higher number of agonistic behaviors were observed in the VF groups when the VF system was activated. However, due to the short observation periods only few contacts were observed in total. Overall, all cows adapted to the VF system without evidence of lasting adverse effects on animal welfare.
Deletion of the auxiliary α2δ1 voltage sensitive calcium channel subunit in osteocytes and late-stage osteoblasts impairs femur strength and load-induced bone formation in male mice
Authors: Wright Christian S , Lewis Karl J , Semon Katelyn , Yi Xin , Reyes Fernandez Perla C , Rust Katie , Prideaux Matthew , Schneider Artur , Pederson Molly , Deosthale Padmini , Plotkin Lilian I , Hum Julia M , Sankar Uma , Farach-Carson Mary C , Robling Alexander G , Thompson William R
Published: January 2024

Osteocytes sense and respond to mechanical force by controlling the activity of other bone cells. However, the mechanisms by which osteocytes sense mechanical input and transmit biological signals remain unclear. Voltage-sensitive calcium channels (VSCCs) regulate calcium (Ca2+) influx in response to external stimuli. Inhibition or deletion of VSCCs impairs osteogenesis and skeletal responses to mechanical loading. VSCC activity is influenced by its auxiliary subunits, which bind the channel’s α1 pore-forming subunit to alter intracellular Ca2+ concentrations. The α2δ1 auxiliary subunit associates with the pore-forming subunit via a glycosylphosphatidylinositol anchor and regulates the channel’s calcium-gating kinetics. Knockdown of α2δ1 in osteocytes impairs responses to membrane stretch, and global deletion of α2δ1 in mice results in osteopenia and impaired skeletal responses to loading in vivo. Therefore, we hypothesized that the α2δ1 subunit functions as a mechanotransducer, and its deletion in osteocytes would impair skeletal development and load-induced bone formation. Mice (C57BL/6) with LoxP sequences flanking Cacna2d1, the gene encoding α2δ1, were crossed with mice expressing Cre under the control of the Dmp1 promoter (10 kb). Deletion of α2δ1 in osteocytes and late-stage osteoblasts decreased femoral bone quantity (P < .05) by DXA, reduced relative osteoid surface (P < .05), and altered osteoblast and osteocyte regulatory gene expression (P < .01). Cacna2d1f/f, Cre + male mice displayed decreased femoral strength and lower 10-wk cancellous bone in vivo micro-computed tomography measurements at the proximal tibia (P < .01) compared to controls, whereas Cacna2d1f/f, Cre + female mice showed impaired 20-wk cancellous and cortical bone ex vivo micro-computed tomography measurements (P < .05) vs controls. Deletion of α2δ1 in osteocytes and late-stage osteoblasts suppressed load-induced calcium signaling in vivo and decreased anabolic responses to mechanical loading in male mice, demonstrating decreased mechanosensitivity. Collectively, the α2δ1 auxiliary subunit is essential for the regulation of osteoid-formation, femur strength, and load-induced bone formation in male mice.
Nonsteaming method improves the nutritional value and utilization efficiency of silkworm artificial diets
Authors: Wang Guang , Xu Xiang-Xing , Ma Lu , Yang Jia-Meng , Yang Bao-Cheng , Peng Ru-Ji , Pan Zhong-Hua , Sima Yang-Hu , Xu Shi-Qing
Published: January 2024

Artificial diets for silkworms overcome the seasonal limitations of traditional rearing methods with fresh mulberry leaves. However, the current wet artificial diets, steamed at high temperatures, are not favored by silkworms, and they are cumbersome and challenging to preserve. These conditions adversely affected the development of artificial diet-based sericulture production. In this study, we disinfected dry powder diets with radiation and added distilled water without steaming before use. Then, the nutritional value of finished diets and their impact on silkworm development was assessed. Compared with steamed diets, nonsteamed diets were more attractive to silkworms. Chemical assays showed significantly more essential nutrients for silkworms, including l-ascorbic acid, vitamin B1, vitamin B2, and urease in nonsteamed diets than in steamed diets. Feeding fifth-instar silkworm larvae with nonsteamed diets significantly improved the ammonia utilization efficiency of the diet and increased the cocoon shell rate and diet/silk protein conversion efficiency by 5.9% and 13.3%, respectively. When fed with nonsteamed diets, the abundance of aerobic microorganisms in silkworm intestines increased and the abundance of pathogenic bacteria decreased. Furthermore, the vitality of the silkworm, measured by the dead worm cocoon rate, significantly improved by 16.90%. In summary, preparing sterile wet diets without high-temperature steaming effectively improved the nutritional value of the diet and enhanced silkworm growth.
Development of platensimycin, platencin, and platensilin overproducers by biosynthetic pathway engineering and fermentation medium optimization
Authors: Fluegel Lucas L , Deng Ming-Rong , Su Ping , Kalkreuter Edward , Yang Dong , Rudolf Jeffrey D , Dong Liao-Bin , Shen Ben
Published: January 2024

The platensimycin (PTM), platencin (PTN), and platensilin (PTL) family of natural products continues to inspire the discovery of new chemistry, enzymology, and medicine. Engineered production of this emerging family of natural products, however, remains laborious due to the lack of practical systems to manipulate their biosynthesis in the native-producing Streptomyces platensis species. Here we report solving this technology gap by implementing a CRISPR-Cas9 system in S. platensis CB00739 to develop an expedient method to manipulate the PTM, PTN, and PTL biosynthetic machinery in vivo. We showcase the utility of this technology by constructing designer recombinant strains S. platensis SB12051, SB12052, and SB12053, which, upon fermentation in the optimized PTM-MS medium, produced PTM, PTN, and PTL with the highest titers at 836 mg L−1, 791 mg L−1, and 40 mg L−1, respectively. Comparative analysis of these resultant recombinant strains also revealed distinct chemistries, catalyzed by PtmT1 and PtmT3, two diterpene synthases that nature has evolved for PTM, PTN, and PTL biosynthesis. The ΔptmR1/ΔptmT1/ΔptmT3 triple mutant strain S. platensis SB12054 could be envisaged as a platform strain to engineer diterpenoid biosynthesis by introducing varying ent-copalyl diphosphate-acting diterpene synthases, taking advantage of its clean metabolite background, ability to support diterpene biosynthesis in high titers, and the promiscuous tailoring biosynthetic machinery.

One-Sentence Summary

Implementation of a CRISPR-Cas9 system in Streptomyces platensis CB00739 enabled the construction of a suite of designer recombinant strains for the overproduction of platensimycin, platencin, and platensilin, discovery of new diterpene synthase chemistries, and development of platform strains for future diterpenoid biosynthesis engineering.
A phase II Japanese trial of 90-minute rituximab infusion for untreated B-cell lymphoma
Authors: Saito Toko , Nagai Hirokazu , Izutsu Koji , Ando Kiyoshi , Igarashi Tadahiko , Izumi Tohru , Ohashi Yasuo , Kamiyama Shuhei , Ishizawa Kenichi , Tobinai Kensei
Published: January 2024

Objective

This phase II clinical trial evaluated feasibility and tolerability of 90-minute rituximab infusion and a concentration of 4 mg/mL rituximab infusion in Japanese patients with previously untreated follicular lymphoma or diffuse large B-cell lymphoma.

Methods

Treatment was rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone. In cycle 1, rituximab at a dose of 375 mg/m2 (4 mg/mL) was administered at the standard infusion rate stipulated in the package insert. On confirmed tolerance of rituximab, patients received 90-minute infusion in second and subsequent cycles. The primary endpoint was incidence of grade 3 or higher infusion-related reactions during 90-minute rituximab infusion in cycle 2 of rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone.

Results

All 32 patients (median age 61.5 years, 16 males, 24 with diffuse large B-cell lymphoma) completed the prescribed six or eight cycles of treatment. One patient withdrew consent after cycle 1, and another developed grade 2 erythema and continued receiving 4 mg/mL at the standard infusion rate for cycle 2. The remaining 30 patients received 90-minute rituximab infusion; 28 (93.3%) completed cycle 2 at the scheduled infusion rate and dosage. No grade 3 or higher infusion-related reactions were associated with a concentration of 4 mg/mL rituximab dose or 90-min rituximab infusion in cycle 2. The most common infusion-related reaction symptoms were pruritus, hypertension and oropharyngeal discomfort. During the study, toxicities and adverse events were as expected, with no new safety signals.

Conclusion

High-concentration dosing (4 mg/mL) and 90-minute infusion of rituximab are feasible and tolerable in Japanese patients with previously untreated follicular lymphoma or diffuse large B-cell lymphoma.

Clinical trial number

JapicCTI-173 663.