bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia-enhanced YAP1-EIF4A3 interaction drives circ_0007386 circularization by competing with CRIM1 pre-mRNA linear splicing and promotes non-small cell lung cancer progression
Authors: Li Lixia , Liu Dewei , Chen Tingting , Wei Chunhui , Qiao Youping , Liu Weiliang , Liang Yanmei , Liang Zhu , Chen Chunyuan , Li Dongming , Wu Bin , Zhao Xuanna , Huang Dan , Wu Dong 
Published: July 2024

Abstract
Background
The progression of non-small cell lung cancer (NSCLC) is significantly influenced by circular RNAs (circRNAs), especially in tumor hypoxia microenvironment. However, the precise functions and underlying mechanisms of dysregulated circRNAs in NSCLC remain largely unexplored.

Methods
Differentially expressed circRNAs in NSCLC tissues were identified through high-throughput RNA sequencing. The characteristics of circ_0007386 were rigorously confirmed via Sanger sequencing, RNase R treatment and actinomycin D treatment. The effects of circ_0007386 on proliferation and apoptosis were investigated using CCK8, cloning formation assays, TUNEL staining, and flow cytometry assays in vitro. In vivo, xenograft tumor models were used to evaluate its impact on proliferation. Mechanistically, the regulatory relationships of circ_0007386, miR-383-5p and CIRBP were examined through dual luciferase reporter assays and rescue experiments. Additionally, we detected the binding of EIF4A3 to CRIM1 pre-mRNA by RNA immunoprecipitation and the interaction between YAP1 and EIF4A3 under hypoxic conditions by co-immunoprecipitation.

Results
Our investigation revealed a novel circRNA, designated as circ_0007386, that was upregulated in NSCLC tissues and cell lines. Circ_0007386 modulated proliferation and apoptosis in NSCLC both in vitro and in vivo. Functionally, circ_0007386 acted as a sponge for miR-383-5p, targeting CIRBP, which influenced NSCLC cell proliferation and apoptosis via the PI3K/AKT signaling pathway. Furthermore, under hypoxic conditions, the interaction between YAP1 and EIF4A3 was enhanced, leading to the displacement of EIF4A4 from binding to CRIM1 pre-mRNA. This facilitated the back-splicing of CRIM1 pre-mRNA, increasing the formation of circ_0007386. The circ_0007386/miR-383-5p/CIRBP axis was significantly associated with the clinical features and prognosis of NSCLC patients.

Conclusions
Circ_0007386, regulated by YAP1-EIF4A3 interaction under hypoxia conditions, plays an oncogenic role in NSCLC progression via the miR-383-5p/CIRBP axis.
Description and molecular characterisation of Babesia ailuropodae n. sp., a new piroplasmid species infecting giant pandas
Authors: Xiong Lang , Yang Guangyou 
Published: July 2024

Abstract
Background
Babesia spp. are protozoan parasites that infect the red blood cells of domesticated animals, wildlife and humans. A few cases of giant pandas (a flagship species in terms of wildlife conservation) infected with a putative novel Babesia sp. have been reported. However, comprehensive research on the morphological and molecular taxonomic classification of this novel Babesia sp. is still lacking. This study was designed to close this gap and formally describe this new Babesia sp. infecting giant pandas.

Methods
Detailed morphological, molecular and phylogenetic analyses were conducted to characterise this Babesia sp. and to assess its systematic relationships with other Babesia spp. Blood samples from giant pandas infected with Babesia were subjected to microscopic examination. The 18S ribosomal RNA (18S rRNA), cytochrome b (cytb) and mitochondrial genome (mitogenome) of the new Babesia sp. were amplified, sequenced and assembled using DNA purified from blood samples taken from infected giant pandas. Based on the newly generated 18S rRNA, cytb and mitogenome sequences, phylogenetic trees were constructed.

Results
Morphologically, the Babesia sp. from giant pandas exhibited various forms, including round to oval ring-shaped morphologies, resembling those found in other small canine Babesia spp. and displaying typical tetrads. Phylogenetic analyses with the 18S rRNA, cytb and mitogenome sequences revealed that the new Babesia sp. forms a monophyletic group, with a close phylogenetic relationship with the Babesia spp. that infect bears (Ursidae), raccoons (Procyonidae) and canids (Canidae). Notably, the mitogenome structure consisted of six ribosomal large subunit-coding genes (LSU1-6) and three protein-coding genes (cytb, cox3 and cox1) arranged linearly.

Conclusions
Based on coupled morphological and genetic analyses, we describe a novel species of the genus Babesia, namely, Babesia ailuropodae n. sp., which infects giant pandas.

Graphical Abstract
Effects of a 12-week intrinsic foot muscle strengthening training (STIFF) on gait in older adults: a parallel randomized controlled trial protocol
Authors: Willemse Lydia , Wouters Eveline J. M. , Pisters Martijn F. , Vanwanseele Benedicte 
Published: July 2024

Abstract
Background
Falling is highly prevalent among older adults and has serious impact. Age-induced mobility impairments, such as gait modifications, are strongly associated with increased fall risk. Among fall prevention interventions, those including exercises are most effective. However, there is an urgent need to further improve these kinds of interventions. Strengthening the plantar intrinsic foot muscles might benefit mobility in older adults, which may contribute to the reduction of fall risk. The aim of this paper is to provide a protocol to investigate the effect of a plantar intrinsic foot muscle strengthening training versus no training on gait and intrinsic foot muscle function in older adults who are involved in a functional exercise program.

Methods
For this assessor-blinded RCT, older adults (> 65 years) are recruited who are involved in a group-based functional exercise program. Eligibility criteria include: being able to ambulate 10 m barefoot without using a walking aid and reporting to have either fear of falling or experienced a fall in the previous 12 months or have difficulties with mobility, gait, or balance in daily life. Participants are randomly assigned to an intervention and a control group. The intervention group follows a 12-week plantar intrinsic foot muscle strengthening training. The training consists of isolated and functional foot exercises to be performed 5 times a week, each session lasting approximately 20 min. The training is supervised once a week and the intensity gradually increases based on the participant’s progression. Both groups keep a diary to report physical activities, fall incidents and movement related discomfort. The control condition is limited to keeping this diary. Data are collected at baseline and post-intervention. The trial outcomes are the between group differences in the mean change from baseline in maximum gait speed (primary outcome measure), capacity and strength of the plantar intrinsic foot muscles, foot and ankle biomechanics during gait, and various other fall risk-related variables. ANCOVA’s are used to analyze the trial outcomes.

Discussion
The results of this RCT will offer recommendations, related to plantar intrinsic foot muscle strengthening, to existing fall preventive exercise programs.

Trial registration
The trial is registered in the United States National Library of Medicine through ClinicalTrials.gov (NCT05531136, 07/26/2022).
Epigenetic and transcriptional control of adipocyte function by centenarian-associated SIRT6 N308K/A313S mutant
Authors: Frohlich Jan , Liorni Niccolò , Mangoni Manuel , Lochmanová Gabriela , Pírek Pavlína , Kaštánková Nikola , Pata Pille , Kucera Jan , Chaldakov George N. , Tonchev Anton B. , Pata Illar , Gorbunova Vera , Leire Eric , Zdráhal Zbyněk , Mazza Tommaso , Vinciguerra Manlio 
Published: July 2024

Abstract
Background
Obesity is a major health burden. Preadipocytes proliferate and differentiate in mature adipocytes in the adipogenic process, which could be a potential therapeutic approach for obesity. Deficiency of SIRT6, a stress-responsive protein deacetylase and mono-ADP ribosyltransferase enzyme, blocks adipogenesis. Mutants of SIRT6 (N308K/A313S) were recently linked to the in the long lifespan Ashkenazi Jews. In this study, we aimed to clarify how these new centenarian-associated SIRT6 genetic variants affect adipogenesis at the transcriptional and epigenetic level.

Methods
We analyzed the role of SIRT6 wild-type (WT) or SIRT6 centenarian-associated mutant (N308K/A313S) overexpression in adipogenesis, by creating stably transduced preadipocyte cell lines using lentivirus on the 3T3-L1 model. Histone post-translational modifications (PTM: acetylation, methylation) and transcriptomic changes were analyzed by mass spectrometry (LC–MS/MS) and RNA-Seq, respectively, in 3T3-L1 adipocytes. In addition, the adipogenic process and related signaling pathways were investigated by bioinformatics and biochemical approaches.

Results
Overexpression of centenarian-associated SIRT6 mutant increased adipogenic differentiation to a similar extent compared to the WT form. However, it triggered distinct histone PTM profiles in mature adipocytes, with significantly higher acetylation levels, and activated divergent transcriptional programs, including those dependent on signaling related to the sympathetic innervation and to PI3K pathway. 3T3-L1 mature adipocytes overexpressing SIRT6 N308K/A313S displayed increased insulin sensitivity in a neuropeptide Y (NPY)-dependent manner.

Conclusions
SIRT6 N308K/A313S overexpression in mature adipocytes ameliorated glucose sensitivity and impacted sympathetic innervation signaling. These findings highlight the importance of targeting SIRT6 enzymatic activities to regulate the co-morbidities associated with obesity.
The Bifidobacterium adolescentis BAD_1527 gene encodes GH43_22 α-L-arabinofuranosidase of AXH-m type
Authors: Fathallah Walid , Puchart Vladimír 
Published: July 2024

AbstractBifidobacterium adolescentis gene BAD_1527 has previously been suggested to code for a β-xylosidase (Kobayashi et al., Mar Drugs 18:174, 2020). Our detailed investigation of the substrate specificity of the GH43_22 protein using a wide spectrum of natural and artificial substrates showed that the enzyme hydrolyzed neither linear xylooligosaccharides nor glucuronoxylan. Xylose was released only from the artificial 4-nitrophenyl β-D-xylopyranoside (1.58 mU/mg). The corresponding α-L-arabinofuranoside was by three orders of magnitude better substrate (2.17 U/mg). Arabinose was the only monosaccharide liberated from arabinoxylan and α-1,3- or α-1,2-singly arabinosylated xylooligosaccharides. Moreover, the enzyme efficiently debranched sugar beet arabinan and singly arabinosylated α-1,5-L-arabinooligosaccharides, although short linear α-1,5-L-arabinooligosaccharides were also slowly degraded. On the other hand, debranched arabinan, arabinogalactan as well as 2,3-doubly arabinosylated main chain residues of arabinan and arabinoxylan did not serve as substrates. Thus, the enzyme encoded by the BAD_1527 gene is a typical α-L-arabinofuranosidase of AXH-m specificity.
An epidemiological investigation into the reasons for high bovine tuberculosis incidence in cattle herds of the Burren, Ireland, prior to 2020
Authors: Tratalos Jamie Alexander , Madden Jamie Michael , Casey Miriam , McSweeney Catherine , Farrell Fidelma Mary , More Simon John 
Published: July 2024

AbstractHerd-level bovine tuberculosis (bTB) incidence was examined in the Burren, an area in the west of Ireland where herd owners practice distinctive transhumance practices, with upland winter grazing. Prior to the initiation of our study in 2020, bTB incidence had for many years been unusually high in the Burren in comparison with the rest of the country, although the most recent figures have come down to being closer to the national average. Using data from the period prior to 2020, we mapped bTB infection in Burren herds alongside a range of indicators thought to have an association with it - herd size, herd density, herd type, cattle movement, and badger (Meles meles) population and control data, as well as rainfall and altitude. We also looked at how summary statistics for these variables differed when Burren herds with a history of bTB were compared to other Burren herds, as well as bTB positive and negative herds from outside the Burren. We found that for many indicators Burren herds would be expected to be low risk when compared to other herds in Ireland. An exception to this was for rainfall: hot spot areas for bTB in the Burren were found in areas of higher rainfall, on average herds in the Burren experienced more rainfall than those outside it, and bTB herds in the Burren experienced higher rainfall than non-bTB herds. Separately, for Burren herds only, a logistic regression model was developed to explain bTB breakdown occurrence using a matched case-control approach. Cases were herds which had experienced a new bTB breakdown between 2015 and 2019 (n = 260) and these were matched on herd type and herd size with the same number of herds not experiencing a breakdown during this period. This showed that, of a range of exogenous variables, rainfall was the most strongly associated with herd-level bTB incidence. These results suggest that high levels of exposure to inclement weather, and/or better environmental survival of Mycobacterium bovis in the environment, may contribute to high bTB rates in the Burren. However, as rainfall showed a highly aggregated distribution, this relationship may be due to an unmeasured factor correlated with it. Mapping and graphical output suggested that, although herd sizes in the Burren were on average lower than nationally, within the Burren they were higher in areas of higher prevalence, suggesting that mechanisms associated with herd size, such as increased contacts between and within herd, and with wildlife, may also play a role.
Evaluation and comparison of infiltration models for estimating infiltration capacity of different textures of irrigated soils
Authors: Mesele Halefom , Grum Berhane , Aregay Gebremeskel , Berhe Gebremeskel Teklay 
Published: July 2024

AbstractAccurate estimation of infiltration rates is crucial for effective irrigation system design and evaluation by optimizing irrigation scheduling, preventing soil erosion, and enhancing water use efficiency. This study evaluates and compares selected infiltration models for estimating water infiltration rates in the Shillanat-iv irrigation scheme in northern Ethiopia. Soil samples were collected to determine textural classes using hydrometer soil texture analysis and the United States Department of Agriculture (USDA) textural triangle. The soil textural map of the study was created using the inverse distance weight interpolation technique in ArcGIS version 10.4. Infiltration rates were measured using the double-ring infiltrometer for five soil textures: clay loam, loam, sandy clay loam, clay, and sandy loam. Six infiltration models (Kostiakov, Modified Kostiakov, Revised Modified Kostiakov, Philip, Horton, and Novel) were employed and evaluated using statistical parameters. Model calibration and validation were conducted using data from 38 points within the study area. The parameter values of the infiltration models were optimized using SPSS statistical software using least-squares errors. The results showed that, Revised Modified Kostiakov, Modified Kostiakov, and Novel infiltration models demonstrated superior capability in estimating infiltration rates for clay loam, loam, and sandy loam soil textures, respectively. Horton's model outperformed other models in estimating infiltration rates for both sandy clay loam and clay soil textures. The appropriately fitted infiltration models can be utilized in designing the irrigation system to estimate the infiltration rate of soil textures within the selected irrigation scheme and at similar sites with comparable soil textures.
Persistent enrichment of multidrug-resistant Klebsiella in oral and nasal communities during long-term starvation
Authors: Liu Jett , Spencer Nell , Utter Daniel R. , Grossman Alex S. , Lei Lei , dos Santos Nídia Castro , Shi Wenyuan , Baker Jonathon L. , Hasturk Hatice , He Xuesong , Bor Batbileg 
Published: July 2024

Abstract
Background
The human oral and nasal cavities can act as reservoirs for opportunistic pathogens capable of causing acute infection. These microbes asymptomatically colonize the human oral and nasal cavities which facilitates transmission within human populations via the environment, and they routinely possess clinically significant antibiotic resistance genes. Among these opportunistic pathogens, the Klebsiella genus stands out as a notable example, with its members frequently linked to nosocomial infections and multidrug resistance. As with many colonizing opportunistic pathogens, the essential transmission factors influencing the spread of Klebsiella species among both healthy and diseased individuals remain unclear.

Results
Here, we explored a possible explanation by investigating the ability of oral and nasal Klebsiella species to outcompete their native microbial community members under in vitro starvation conditions, which could be analogous to external hospital environments or the microenvironment of mechanical ventilators. When K. pneumoniae and K. aerogenes were present within a healthy human oral or nasal sample, the bacterial community composition shifted dramatically under starvation conditions and typically became enriched in Klebsiella species. Furthermore, introducing K. pneumoniae exogenously into a native microbial community lacking K. pneumoniae, even at low inoculum, led to repeated enrichment under starvation. Precise monitoring of K. pneumoniae within these communities undergoing starvation indicated rapid initial growth and prolonged viability compared to other members of the microbiome. K. pneumoniae strains isolated from healthy individuals’ oral and nasal cavities also exhibited resistance to multiple classes of antibiotics and were genetically similar to clinical and gut isolates. In addition, we found that in the absence of Klebsiella species, other understudied opportunistic pathogens, such as Peptostreptococcus, increased in relative abundance under starvation conditions.

Conclusions
Our findings establish an environmental and microbiome community circumstance that allows for the enrichment of Klebsiella species and other opportunistic pathogens. Klebsiella’s enrichment may hinge on its ability to quickly outgrow other members of the microbiome. The ability to outcompete other commensal bacteria and to persist under harsh environmental conditions could be an important factor that contributes to enhanced transmission in both commensal and pathogenic contexts.
Gone with the wind: environmental variation influences detection efficiency in a coastal acoustic telemetry array
Authors: Edwards Jena E. , Buijse Anthonie D. , Winter Hendrik V. , Bijleveld Allert I. 
Published: July 2024

AbstractRange tests play a critical role in designing acoustic telemetry studies, guiding equipment configuration, deployment techniques, and the analysis of animal movement data. These studies often strive to capture the effects of environmental variation on detection efficiency over time but are frequently limited in spatial and temporal scale. This could lead to disparities between test results and the circumstances encountered during animal tracking studies. In this study, we evaluated detection range and efficiency at two distinct spatial and temporal scales in a dynamic intertidal ecosystem. Two range tests were conducted, the first being a small-scale study using 6 receivers deployed over 1 month. Using modern acoustic receivers with built-in transmitters and environmental sensors, we then conducted a large-scale range test with 22 receiver stations over a full year to approximate the area and duration of a typical animal movement study. Differences in detection range between the two studies occurred as a result of environmental variation and tag power output, with midpoint ranges estimated as 123 m (small scale, low power), 149 m (small scale, high power) and 311 m (large scale, very high power). At both scales, wind speed emerged as the most influential factor explaining temporal variation in predicted detection efficiency. However, this effect was modulated by wind direction which varied as a result of land sheltering and fetch between the two study scales. At the small scale, detection efficiency decreased with winds from the south and east, while at the large scale, northern and westerly winds were most detrimental. Water temperature had a positive effect on predicted detection efficiency at both scales, while relative water level was positive at the small scale and negative at the large scale. Additional factors, including precipitation and Topographic Position Index, were found to influence detection efficiency at a large scale. Moreover, sensors associated with receivers in the larger array revealed the significant influences of receiver tilt and ambient noise. These discrepancies in the outcomes of the two studies underscore the critical role of scale in range test design and emphasize the need for long-term, in situ range testing at relevant spatial scales.
Detection of neoplastic-immune hybrid cells with metastatic properties in uveal melanoma
Authors: Anderson Ashley N. , Conley Patrick , Klocke Christopher D. , Sengupta Sidharth K. , Pang Amara , Farley Hannah C. , Gillingham Abigail R. , Dawson Aubrey D. , Fan Yichen , Jones Jocelyn A. , Gibbs Summer L. , Skalet Alison H. , Wu Guanming , Wong Melissa H. 
Published: July 2024

Abstract
Background
Uveal melanoma is the most common non-cutaneous melanoma and is an intraocular malignancy affecting nearly 7,000 individuals per year worldwide. Of these, approximately 50% will progress to metastatic disease for which there are currently no effective curative therapies. Despite advances in molecular profiling and metastatic stratification of uveal melanoma tumors, little is known regarding their underlying biology of metastasis. Our group has identified a disseminated neoplastic cell population characterized by co-expression of immune and melanoma proteins, circulating hybrid cells (hybrids), in patients with uveal melanoma. Compared to circulating tumor cells, which lack expression of immune proteins, hybrids are detected at an increased prevalence in peripheral blood and can be used as a non-invasive biomarker to predict metastatic progression.

Methods
To ascertain mechanisms underlying enhanced hybrid cell dissemination we identified hybrid cells within primary uveal melanoma tumors using single cell RNA sequencing (n = 8) and evaluated their gene expression and predicted ligand-receptor interactions in relation to other melanoma and immune cells within the primary tumor. We then verified expression of upregulated hybrid pathways within patient-matched tumor and peripheral blood hybrids (n = 4) using cyclic immunofluorescence and quantified their protein expression relative to other non-hybrid tumor and disseminated tumor cells.

Results
Among the top upregulated genes and pathways in hybrid cells were those involved in enhanced cell motility and cytoskeletal rearrangement, immune evasion, and altered cellular metabolism. In patient-matched tumor and peripheral blood, we verified gene expression by examining concordant protein expression for each pathway category: TMSB10 (cell motility), CD74 (immune evasion) and GPX1 (metabolism). Both TMSB10 and GPX1 were expressed on significantly higher numbers of disseminated hybrid cells compared to circulating tumor cells, and CD74 and GPX1 were expressed on more disseminated hybrids than tumor-resident hybrids. Lastly, we identified that hybrid cells express ligand-receptor signaling pathways implicated in promoting metastasis including GAS6-AXL, CXCL12-CXCR4, LGALS9-P4HB and IGF1-IGFR1.

Conclusion
These findings highlight the importance of TMSB10, GPX1 and CD74 for successful hybrid cell dissemination and survival in circulation. Our results contribute to the understanding of uveal melanoma tumor progression and interactions between tumor cells and immune cells in the tumor microenvironment that may promote metastasis.