bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCDC113 promotes colorectal cancer tumorigenesis and metastasis via TGF-β signaling pathway
Authors: Hou Chenying , Yang Yanmei , Wang Peiwen , Xie Huimin , Jin Shuiling , Zhao Liangbo , Wu Guanghua , Xing Hao , Chen Hong , Liu Benyu , Du Chunyan , Sun Xiao , He Luyun 
Published: September 2024

AbstractColorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Although CRC patients’ survival is improved with surgical resection and immunotherapy, metastasis and recurrence remain major problems leading to poor prognosis. Therefore, exploring pathogenesis and identifying specific biomarkers are crucial for CRC early diagnosis and targeted therapy. CCDC113, a member of CCDC families, has been reported to play roles in ciliary assembly, ciliary activity, PSCI, asthma and early lung cancer diagnosis. However, the functions of CCDC113 in CRC still remain unclear. In this study, we find that CCDC113 is significantly highly expressed in CRC. High expression of CCDC113 is significantly correlated with CRC patients’ poor prognosis. CCDC113 is required for CRC tumorigenesis and metastasis. RNA-seq and TCGA database analysis indicate that CCDC113 is positively correlated with TGF-β signaling pathway. TGF-β signaling pathway inhibitor galunisertib could reverse the increased proliferation and migration ability of CRC cells caused by CCDC113 overexpression in vitro and in vivo. These results indicate that CCDC113 promotes CRC tumorigenesis and metastasis via TGF-β signaling pathway. In conclusion, it is the first time to explore the functions and mechanisms of CCDC113 in CRC tumorigenesis and metastasis. And CCDC113 may be a potential biomarker and therapeutic target for CRC intervention.
Usefulness and caveats of real-world data for research on hypertension and its association with cardiovascular or renal disease in Japan
Authors: Satoh Michihiro , Nakayama Shingo , Toyama Maya , Hashimoto Hideaki , Murakami Takahisa , Metoki Hirohito 
Published: September 2024

AbstractThe role of real-world data, collected from clinical practice rather than clinical trials, has become increasingly important for investigating real-life situations, such as treatment effects. In Japan, evidence on hypertension, cardiovascular diseases, and kidney diseases using real-world data is increasing. These studies are mainly based on “the insurer-based real-world data” collected as electronic records, including data from health check-ups and medical claims such as JMDC database, DeSC database, the Japan Health Insurance Association (JHIA) database, or National Databases of Health Insurance Claims and Specific Health Checkups (NDB). Based on the insurer-based real-world data, traditional but finely stratified associations between hypertension and cardiovascular or kidney diseases can be explored. The insurer-based real-world data are also useful for pharmacoepidemiological studies that capture the distribution and trends of drug prescriptions; combined with annual health check-up data, the effectiveness of drugs can also be examined. Despite the usefulness of insurer-based real-world data collected as electronic records from a wide range of populations, we must be cautious about several points, including issues regarding population uncertainty, the validity of cardiovascular outcomes, the accuracy of blood pressure, traceability, and biases, such as indication and immortal biases. While a large sample size is considered a strength of real-world data, we must keep in mind that it does not overcome the problem of systematic error. This review discusses the usefulness and pitfalls of insurer-based real-world data in Japan through recent examples of Japanese research on hypertension and its association with cardiovascular or kidney disease.
The aryl hydrocarbon receptor and FOS mediate cytotoxicity induced by Acinetobacter baumannii
Authors: Kew Chun , Prieto-Garcia Cristian , Bhattacharya Anshu , Tietgen Manuela , MacNair Craig R. , Carfrae Lindsey A. , Mello-Vieira João , Klatt Stephan , Cheng Yi-Lin , Rathore Rajeshwari , Gradhand Elise , Fleming Ingrid , Tan Man-Wah , Göttig Stephan , Kempf Volkhard A. J. , Dikic Ivan 
Published: September 2024

AbstractAcinetobacter baumannii is a pathogenic and multidrug-resistant Gram-negative bacterium that causes severe nosocomial infections. To better understand the mechanism of pathogenesis, we compare the proteomes of uninfected and infected human cells, revealing that transcription factor FOS is the host protein most strongly induced by A. baumannii infection. Pharmacological inhibition of FOS reduces the cytotoxicity of A. baumannii in cell-based models, and similar results are also observed in a mouse infection model. A. baumannii outer membrane vesicles (OMVs) are shown to activate the aryl hydrocarbon receptor (AHR) of host cells by inducing the host enzyme tryptophan-2,3-dioxygenase (TDO), producing the ligand kynurenine, which binds AHR. Following ligand binding, AHR is a direct transcriptional activator of the FOS gene. We propose that A. baumannii infection impacts the host tryptophan metabolism and promotes AHR- and FOS-mediated cytotoxicity of infected cells.
IL-2 delivery to CD8+ T cells during infection requires MRTF/SRF-dependent gene expression and cytoskeletal dynamics
Authors: Maurice Diane , Costello Patrick , Diring Jessica , Gualdrini Francesco , Frederico Bruno , Treisman Richard 
Published: September 2024

AbstractParacrine IL-2 signalling drives the CD8 + T cell expansion and differentiation that allow protection against viral infections, but the underlying molecular events are incompletely understood. Here we show that the transcription factor SRF, a master regulator of cytoskeletal gene expression, is required for effective IL-2 signalling during L. monocytogenes infection. Acting cell-autonomously with its actin-regulated cofactors MRTF-A and MRTF-B, SRF is dispensible for initial TCR-mediated CD8+ T cell proliferation, but is required for sustained IL-2 dependent CD8+ effector T cell expansion, and persistence of memory cells. Following TCR activation, Mrtfab-null CD8+ T cells produce IL-2 normally, but homotypic clustering is impaired both in vitro and in vivo. Expression of cytoskeletal structural and regulatory genes, most notably actins, is defective in Mrtfab-null CD8+ T cells. Activation-induced cell clustering in vitro requires F-actin assembly, and Mrtfab-null cell clusters are small, contain less F-actin, and defective in IL-2 retention. Clustering of Mrtfab-null cells can be partially restored by exogenous actin expression. IL-2 mediated CD8+ T cell proliferation during infection thus depends on the control of cytoskeletal dynamics and actin gene expression by MRTF-SRF signalling.
Histones and histone variant families in prokaryotes
Authors: Schwab Samuel , Hu Yimin , van Erp Bert , Cajili Marc K. M. , Hartmann Marcus D. , Hernandez Alvarez Birte , Alva Vikram , Boyle Aimee L. , Dame Remus T. 
Published: September 2024

AbstractHistones are important chromatin-organizing proteins in eukaryotes and archaea. They form superhelical structures around which DNA is wrapped. Recent studies have shown that some archaea and bacteria contain alternative histones that exhibit different DNA binding properties, in addition to highly divergent sequences. However, the vast majority of these histones are identified in metagenomes and thus are difficult to study in vivo. The recent revolutionary breakthroughs in computational protein structure prediction by AlphaFold2 and RoseTTAfold allow for unprecedented insights into the potential function and structure of previously uncharacterized proteins. Here, we categorize the prokaryotic histone space into 17 distinct groups based on AlphaFold2 predictions. We identify a superfamily of histones, termed α3 histones, which are common in archaea and present in several bacteria. Importantly, we establish the existence of a large family of histones throughout archaea and in some bacteriophages that, instead of wrapping DNA, bridge DNA, thereby diverging from conventional nucleosomal histones.
Biological activities of derived pigments and polyphenols from the newly recorded alga Phyllymenia gibbesii
Authors: El-Din Nihal G. Shams , Hafez Mohamed S. M. Abd El , El-Wahab Miral G. Abd , Ibrahim Hassan A. H. 
Published: September 2024

AbstractThe newly recorded Phyllymenia gibesii in the Mediterranean Sea at Alexandria coast of Egypt is regarded as a significant source of bioactive substances and is applied as an antioxidant, anti-inflammatory, and antimicrobial agent. According to the HPLC chromatograms, the acetone extract of P. gibesii comprised ten photosynthetic pigments (chlorophyll-a, chlorophyll-d, α-carotene, β-carotene, phycocyanin, allophycocyanin, antheraxanthin, β-cryptoxanthin, lutein, and violaxanthin). Total carotenoids were the dominant class in the pigments’ profile, achieving a concentration of 257 g/g dry weight. The P. gibbesii extract had a total content of phenols (146.67 mg/g) and a total content of flavonoids (104.40 mg/g). The capacity of all the investigated biological activities augmented with the concentration of the algal extract. The maximal DPPH scavenging capacity was 81.44%, with an inhibitory concentration (IC50) of 9.88 μg/mL. Additionally, the highest ABTS scavenging capacity was 89.62%, recording an IC50 of 21.77 μg/mL. The hemolytic activity of P. gibbesii attained a maximum capacity of 49.88% with an IC50 of 100.25 μg/mL. Data also showed the maximum anti-inflammatory effectiveness at 81.25%, with an IC50 of 99.75 μg/mL. Furthermore, the extract exhibited antimicrobial capacity against all reference strains, particularly at high concentrations (0.1 mg/mL), with the greatest effect on C. albicans and E. coli.
Hydrogeochemical and isotopic investigations of groundwater in the reclaimed desert located between EL Nasr canal and Mariut Tableland, NW Coast, Egypt
Authors: Alezabawy Ahmed K. , Eissa Mustafa , Salem Zenhom El-Said 
Published: September 2024

AbstractA complete understanding of groundwater dynamics and its interaction with surface water under the impact of agricultural activities is vital for local agriculture, ecology, and residents of dry regions, which is not commonly recognized in arid areas. This research outlines the geochemical characteristics, recharge sources, and potential factors impacting groundwater quality in a new land reclamation located in the small basin of Abu Mina, which is part of the Western Nile Delta region.1 Thirty-one groundwater samples and two surface water samples were collected in 2021 to represent the Pleistocene aquifer and were subjected to multivariate statistical, hydrochemical, and stable isotope analyses. Data analysis demonstrates that Na+> Ca2+> Mg2+> K+and SO42– > Cl– > HCO3– > NO3–are the predominant cations and anions, respectively. Groundwater salinity ranged from 465.60 to 6455.18 mg/l, with slightly alkaline. Most of the water samples fall into one of three types of facies: Ca–Cl, Na–Cl, and Mixed Ca–Mg–Cl, in decreasing order. The meteoric genesis index (r2) indicates that deep meteoric water percolation dominates the Pleistocene aquifer. The aquiline diagrams, correlation matrix, and different ionic ratios indicate that evaporation, reverse ion exchange reactions, and the dissolution of carbonate and silicate minerals are the main processes governing groundwater chemistry. Factor analysis (FA) indicated that three factors explain groundwater hydrochemistry, accounting for 71.98% of the total variance. According to the rotating components matrix (F1–F3), the chemistry of the Quaternary aquifer is principally affected by evaporation, ion exchange reactions, and anthropogenic influences. Additionally, salinity increases due to the return flow of irrigation activities and mixing between old and recent water. The stable isotopes (δ18Oand δ2H) indicate that the Quaternary aquifer receives groundwater recharge through the return flow of excess irrigation and canal seepage. Under desert reclamation conditions, groundwater salinization processes should be given special consideration. All groundwater samples are appropriate for agricultural irrigation based on the Sodium Adsorption Ratio (SAR), Permeability Index (PI), Percent Sodium (%Na), and Residual Sodium Carbonate (RSC).
Evaluation of gold mineralisation potential using AHP systems and weighted overlay analysis
Authors: Abubakar Fahad , Alao Joseph Omeiza , Ogah Arewa James , Ayuba Rufai , Lekdukun Mercy Omojo , Baba Yahaya , Sadiq Fatihu Kabir , Samson Emmanuel Ejiga , Aliyu Abubakar 
Published: September 2024

AbstractThe demand for sustainable development goals and the absence of systematic development and organised exploration for gold has prompted this study to integrate magnetic and radiometric datasets with lithology to evaluate the gold mineralisation potential in the Ilesha schist belt. This study considers 3168.72 km2 of the Ilesha schist belt in southwestern Nigeria, a frontier belt for gold deposits. The high-resolution airborne magnetic and radiometric datasets were processed using enhancement techniques, including the analytical signal, lineament density, and K/Th ratio. CET grid analysis, Euler deconvolution, and analytical signal depth estimation methods were used to aid the interpretation. The spatial integration and interpolation were performed using the Analytical Hierarchy Process (AHP) and weighted overlay analytical tools within the ArcGIS environment. The dominant structural controls for potential mineralisation are ENE–WSW and ESE–WNW trends. The depth of the magnetic sources revealed by the analytical signal ranged from 63.17 to 629.47 m, while depths ranging from 47.32 to 457.22 m were obtained from Euler deconvolution. The delineated highly magnetic edge sources, dense lineaments, radiometrically highlighted alteration zones, and lithological hosts for gold mineralisation were integrated to establish the gold mineralisation potential map. The AHP deductions reveal that 10.52% of the study site is within the high mineralisation potential class, a remarkable 60.39% falls within the moderate class, a significant portion (28.86%) falls within the poor class, and 0.23% is considered unfavourable. The result was optimised by validation using known mines, with 94% (i.e., 15 out of 16 mining sites) plotting within the high mineralisation potential class. This assessment provides invaluable insight for stakeholders and policymakers to embark on gold exploration and exploitation and promote sustainable mineral development.
SARS-CoV-2 envelope protein alters calcium signaling via SERCA interactions
Authors: Berta Blanka , Tordai Hedvig , Lukács Gergely L. , Papp Béla , Enyedi Ágnes , Padányi Rita , Hegedűs Tamás 
Published: September 2024

AbstractThe clinical management of severe COVID-19 cases is not yet well resolved. Therefore, it is important to identify and characterize cell signaling pathways involved in virus pathogenesis that can be targeted therapeutically. Envelope (E) protein is a structural protein of the virus, which is known to be highly expressed in the infected host cell and is a key virulence factor; however, its role is poorly characterized. The E protein is a single-pass transmembrane protein that can assemble into a pentamer forming a viroporin, perturbing Ca2+ homeostasis. Because it is structurally similar to regulins such as, for example, phospholamban, that regulate the sarco/endoplasmic reticulum calcium ATPases (SERCA), we investigated whether the SARS-CoV-2 E protein affects the SERCA system as an exoregulin. Using FRET experiments we demonstrate that E protein can form oligomers with regulins, and thus can alter the monomer/multimer regulin ratio and consequently influence their interactions with SERCAs. We also confirm that a direct interaction between E protein and SERCA2b results in a decrease in SERCA-mediated ER Ca2+ reload. Structural modeling of the complexes indicates an overlapping interaction site for E protein and endogenous regulins. Our results reveal novel links in the host-virus interaction network that play an important role in viral pathogenesis and may provide a new therapeutic target for managing severe inflammatory responses induced by SARS-CoV-2.
Alpha-1 antitrypsin inhibits Clostridium botulinum C2 toxin, Corynebacterium diphtheriae diphtheria toxin and B. anthracis fusion toxin
Authors: Lietz Stefanie , Sokolowski Lena-Marie , Barth Holger , Ernst Katharina 
Published: September 2024

AbstractThe bacterium Clostridium botulinum, well-known for producing botulinum neurotoxins, which cause the severe paralytic illness known as botulism, produces C2 toxin, a binary AB-toxin with ADP-ribosyltranferase activity. C2 toxin possesses two separate protein components, an enzymatically active A-component C2I and the binding and translocation B-component C2II. After proteolytic activation of C2II to C2IIa, the heptameric structure binds C2I and is taken up via receptor-mediated endocytosis into the target cells. Due to acidification of endosomes, the C2IIa/C2I complex undergoes conformational changes and consequently C2IIa forms a pore into the endosomal membrane and C2I can translocate into the cytoplasm, where it ADP-ribosylates G-actin, a key component of the cytoskeleton. This modification disrupts the actin cytoskeleton, resulting in the collapse of cytoskeleton and ultimately cell death. Here, we show that the serine-protease inhibitor α1-antitrypsin (α1AT) which we identified previously from a hemofiltrate library screen for PT from Bordetella pertussis is a multitoxin inhibitor. α1AT inhibits intoxication of cells with C2 toxin via inhibition of binding to cells and inhibition of enzyme activity of C2I. Moreover, diphtheria toxin and an anthrax fusion toxin are inhibited by α1AT. Since α1AT is commercially available as a drug for treatment of the α1AT deficiency, it could be repurposed for treatment of toxin-mediated diseases.
Paleo-climatic control on recharge and fresh-salt groundwater distribution in the Red River delta plain, Vietnam
Authors: Larsen Flemming , Van Hoang Hoan , Tran Long Vu , Pham Nhan Quy 
Published: September 2024

AbstractPaleo-climatic induced sedimentation controls present-day recharge and the fresh-salt groundwater distribution in Quaternary delta systems. During sea-level highstands, marine clays with saline pore water were deposited and are interbedded with aquifers of coarse-grained sandy fluvial and shallow marine deposits, laid down during lowstands. The low-permeable marine layers may inhibit recent recharge to deeper aquifers, and thereby limit sustainable use of these freshwater resources. This phenomenon has been investigated in the Red River delta plain, using geophysical borehole logging, transient electromagnetic soundings, groundwater chemistry, stable isotope analysis and 3H and 14C dating of groundwater. Results reveal that marine saline pore water is still present in the Holocene marine clays, implying that fresh water has not entered the clays since their deposition. Therefore, recharge within the delta plain is not occurring and the deeper aquifers are hydraulically disconnected from the upper sandy layers. Today, recharge only occurs from the hinterland. Recharge during the last glacial period has flushed saline pore water from Pleistocene marine clays, but these clays were again affected by saline water during the Holocene transgression. The use of the groundwater resources in the delta plain must be adjusted to the present recharge to be sustainable.
OceanNet: a principled neural operator-based digital twin for regional oceans
Authors: Chattopadhyay Ashesh , Gray Michael , Wu Tianning , Lowe Anna B. , He Ruoying 
Published: September 2024

AbstractWhile data-driven approaches demonstrate great potential in atmospheric modeling and weather forecasting, ocean modeling poses distinct challenges due to complex bathymetry, land, vertical structure, and flow non-linearity. This study introduces OceanNet, a principled neural operator-based digital twin for regional sea-suface height emulation. OceanNet uses a Fourier neural operator and predictor-evaluate-corrector integration scheme to mitigate autoregressive error growth and enhance stability over extended time scales. A spectral regularizer counteracts spectral bias at smaller scales. OceanNet is applied to the northwest Atlantic Ocean western boundary current (the Gulf Stream), focusing on the task of seasonal prediction for Loop Current eddies and the Gulf Stream meander. Trained using historical sea surface height (SSH) data, OceanNet demonstrates competitive forecast skill compared to a state-of-the-art dynamical ocean model forecast, reducing computation by 500,000 times. These accomplishments demonstrate initial steps for physics-inspired deep neural operators as cost-effective alternatives to high-resolution numerical ocean models.
Auditory objects in working memory include task-irrelevant features
Authors: Fischer Cora , Nolting Carina , Schneider Flavia , Bledowski Christoph , Kaiser Jochen 
Published: September 2024

AbstractObject-based attention operates both in perception and visual working memory. While the efficient perception of auditory stimuli also requires the formation of auditory objects, little is known about their role in auditory working memory (AWM). To investigate whether attention to one object feature in AWM leads to the involuntary maintenance of another, task-irrelevant feature, we conducted four experiments. Stimuli were abstract sounds that differed on the dimensions frequency and location, only one of which was task-relevant in each experiment. The first two experiments required a match–nonmatch decision about a probe sound whose irrelevant feature value could either be identical to or differ from the memorized stimulus. Matches on the relevant dimension were detected more accurately when the irrelevant feature matched as well, whereas for nonmatches on the relevant dimension, performance was better for irrelevant feature nonmatches. Signal-detection analysis showed that changes of irrelevant frequency reduced the sensitivity for sound location. Two further experiments used continuous report tasks. When location was the target feature, changes of irrelevant sound frequency had an impact on both recall error and adjustment time. Irrelevant location changes affected adjustment time only. In summary, object-based attention led to a concurrent maintenance of task-irrelevant sound features in AWM.
Impact of heat stress during close-up dry period on performance, fertility and immunometabolic blood indices of dairy cows: prospective cohort study
Authors: Stefanska Barbara , Pruszynska-Oszmalek Ewa , Fievez Veerle , Purwin Cezary , Nowak Włodzimierz 
Published: September 2024

AbstractThis study aimed to investigate whether heat stress, as defined by the temperature-humidity index (THI) during the close-up dry period, had any impact on the productive performance, fertility, and immunometabolic blood indices of dairy cows in the subsequent lactation. Lactation performance was associated with increasing THI values on − 21, − 14, and − 7 d before calving resulting in decreased milk yield by about 2.30, 2.60, and 2.90 kg, respectively. The THI on the − 7 d before the calving was negatively associated with fertility parameters such as delayed first estrus postpartum, an elongated calving interval by approximately 32 d, a higher number of services per conception by 1.00, and an elongated artificial insemination service period, days open, and inter-calving period by about 20, 52, and 52 d, respectively. The study found that the immunometabolic blood indices were associated with increasing THI values during the close-up dry period. The study showed that exposing dairy cows to close-up dry period heat stress had negative consequences on performance, fertility, and immunometabolic blood indices in the subsequent lactation. Therefore, it is recommended that herd management and barn microclimate changes be implemented earlier, starting from the late dry period, to mitigate the negative impact of heat stress.