bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nek2A prevents centrosome clustering and induces cell death in cancer cells via KIF2C interaction
Authors: Kalkan Batuhan Mert , Ozcan Selahattin Can , Cicek Enes , Gonen Mehmet , Acilan Ceyda 
Published: March 2024

AbstractUnlike normal cells, cancer cells frequently exhibit supernumerary centrosomes, leading to formation of multipolar spindles that can trigger cell death. Nevertheless, cancer cells with supernumerary centrosomes escape the deadly consequences of unequal segregation of genomic material by coalescing their centrosomes into two poles. This unique trait of cancer cells presents a promising target for cancer therapy, focusing on selectively attacking cells with supernumerary centrosomes. Nek2A is a kinase involved in mitotic regulation, including the centrosome cycle, where it phosphorylates linker proteins to separate centrosomes. In this study, we investigated if Nek2A also prevents clustering of supernumerary centrosomes, akin to its separation function. Reduction of Nek2A activity, achieved through knockout, silencing, or inhibition, promotes centrosome clustering, whereas its overexpression results in inhibition of clustering. Significantly, prevention of centrosome clustering induces cell death, but only in cancer cells with supernumerary centrosomes, both in vitro and in vivo. Notably, none of the known centrosomal (e.g., CNAP1, Rootletin, Gas2L1) or non-centrosomal (e.g., TRF1, HEC1) Nek2A targets were implicated in this machinery. Additionally, Nek2A operated via a pathway distinct from other proteins involved in centrosome clustering mechanisms, like HSET and NuMA. Through TurboID proximity labeling analysis, we identified novel proteins associated with the centrosome or microtubules, expanding the known interaction partners of Nek2A. KIF2C, in particular, emerged as a novel interactor, confirmed through coimmunoprecipitation and localization analysis. The silencing of KIF2C diminished the impact of Nek2A on centrosome clustering and rescued cell viability. Additionally, elevated Nek2A levels were indicative of better patient outcomes, specifically in those predicted to have excess centrosomes. Therefore, while Nek2A is a proposed target, its use must be specifically adapted to the broader cellular context, especially considering centrosome amplification. Discovering partners such as KIF2C offers fresh insights into cancer biology and new possibilities for targeted treatment.
Comparison of the use of internal limiting membrane flaps versus conventional ILM peeling on post-operative anatomical and visual outcomes in large macular holes
Authors: Riding George , Teh Boon Lin , Yorston David , Steel David H. 
Published: March 2024

Abstract
Background
Idiopathic full-thickness macular hole (iFTMH) closure rates following conventional vitrectomy, gas tamponade and internal limiting membrane (ILM) peeling decrease when the minimum linear diameter (MLD) ≥ 500 microns. ILM flap creation has been proposed to improve closure in larger holes. This study evaluated the anatomical and functional impact of ILM flap introduction to routine practice in iFTMH ≥500 microns.

Methods
Retrospective, interventional analysis of prospectively collected data of 191 eyes from consecutive surgeries for primary iFTMH ≥500 microns performed by two surgeons between June 2018 and June 2022, during which both surgeons replaced ILM peeling with ILM flap creation. Post-operative best-corrected visual acuity (BCVA) and anatomical closure were compared between Group 1 (ILM peel) and Group 2 (ILM flap) in an intention-to-treat analysis.

Results
Rates of iFTMH closure were greater in the ILM flap group (77/80; 96.3%) than the ILM peel group (94/110; 85.5%) (OR = 4.37, 95% CI = 1.23–15.55, p = 0.023). A non-significant increase in post-operative BCVA improvement was observed in the ILM flap group (p = 0.084). There was no statistically significant difference in final BCVA (p = 0.83). Multivariate logistic regression found only MLD (OR = 0.993, 95% CI = 0.989–0.997, p = 0.001) and ILM flap group (OR = 5.795, 95% CI = 1.313–25.570, p = 0.020) predicted primary closure.

Conclusion
ILM flap creation improves closure rates in larger holes and should be considered routinely in iFTMH ≥500 microns. Whether ILM flaps affect post-operative visual function remains uncertain.
Broadened quantum critical ground state in a disordered superconducting thin film
Authors: Ienaga Koichiro , Tamoto Yutaka , Yoda Masahiro , Yoshimura Yuki , Ishigami Takahiro , Okuma Satoshi 
Published: March 2024

AbstractA superconductor-insulator transition (SIT) in two dimensions is a prototypical quantum phase transition (QPT) with a clear quantum critical point (QCP) at zero temperature (T = 0). The SIT is induced by a field B and observed in disordered thin films. In some of weakly disordered or crystalline thin films, however, an anomalous metallic (AM) ground state emerges over a wide B range between the superconducting and insulating phases. It remains a fundamental open question how the QPT picture of the SIT is modified when the AM state appears. Here we present measurements of the Nernst effect N, which has great sensitivity to the fluctuations of the superconducting order parameter. From a thorough contour map of N in the B-T plane, we found a thermal-to-quantum crossover line of the superconducting fluctuations, a so-called ghost-temperature line associated with the QPT, as well as a ghost-field line associated with a thermal transition. The QCP is identified as a T = 0 intercept of the ghost-temperature line inside the AM state, which verifies that the AM state is a broadened critical state of the SIT.
A robust ultrasensitive transcriptional switch in noisy cellular environments
Authors: Jeong Eui Min , Kim Jae Kyoung 
Published: March 2024

AbstractUltrasensitive transcriptional switches enable sharp transitions between transcriptional on and off states and are essential for cells to respond to environmental cues with high fidelity. However, conventional switches, which rely on direct repressor-DNA binding, are extremely noise-sensitive, leading to unintended changes in gene expression. Here, through model simulations and analysis, we discovered that an alternative design combining three indirect transcriptional repression mechanisms, sequestration, blocking, and displacement, can generate a noise-resilient ultrasensitive switch. Although sequestration alone can generate an ultrasensitive switch, it remains sensitive to noise because the unintended transcriptional state induced by noise persists for long periods. However, by jointly utilizing blocking and displacement, these noise-induced transitions can be rapidly restored to the original transcriptional state. Because this transcriptional switch is effective in noisy cellular contexts, it goes beyond previous synthetic transcriptional switches, making it particularly valuable for robust synthetic system design. Our findings also provide insights into the evolution of robust ultrasensitive switches in cells. Specifically, the concurrent use of seemingly redundant indirect repression mechanisms in diverse biological systems appears to be a strategy to achieve noise-resilience of ultrasensitive switches.
Long non-coding RNA MLLT4 antisense RNA 1 induces autophagy to inhibit tumorigenesis of cervical cancer through modulating the myosin-9/ATG14 axis
Authors: Zhang Tingting , Ji Tiantian , Duan Zhao , Xue Yuanyuan 
Published: March 2024

AbstractThe regulatory mechanism of long non-coding RNAs (lncRNAs) in autophagy is as yet not well established. In this research, we show that the long non-coding RNA MLLT4 antisense RNA 1 (lncRNA MLLT4-AS1) is induced by the MTORC inhibitor PP242 and rapamycin in cervical cells. Overexpression of MLLT4-AS1 promotes autophagy and inhibits tumorigenesis and the migration of cervical cancer cells, whereas knockdown of MLLT4-AS1 attenuates PP242-induced autophagy. Mass spectrometry, RNA fluorescence in situ hybridization (RNA-FISH), and immunoprecipitation assays were performed to identify the direct interactions between MLLT4-AS1 and other associated targets, such as myosin-9 and autophagy-related 14(ATG14). MLLT4-AS1 was upregulated by H3K27ac modification with PP242 treatment, and knockdown of MLLT4-AS1 reversed autophagy by modulating ATG14 expression. Mechanically, MLLT4-AS1 was associated with the myosin-9 protein, which further promoted the transcription activity of the ATG14 gene. In conclusion, we demonstrated that MLLT4-AS1 acts as a potential tumor suppressor in cervical cancer by inducing autophagy, and H3K27ac modification-induced upregulation of MLLT4-AS1 could cause autophagy by associating with myosin-9 and promoting ATG14 transcription.
Effect of silicon nanoparticle-based biochar on wheat growth, antioxidants and nutrients concentration under salinity stress
Authors: Gill Sidra , Ramzan Musarrat , Naz Gul , Ali Liaqat , Danish Subhan , Ansari Mohammad Javed , Salmen Saleh H. 
Published: March 2024

AbstractGlobally, salinity is an important abiotic stress in agriculture. It induced oxidative stress and nutritional imbalance in plants, resulting in poor crop productivity. Applying silicon (Si) can improve the uptake of macronutrients. On the other hand, using biochar as a soil amendment can also decrease salinity stress due to its high porosity, cation exchange capacity, and water-holding capacity. That’s why the current experiment was conducted with novelty to explore the impact of silicon nanoparticle-based biochar (Si-BC) on wheat cultivated on salt-affected soil. There were 3 levels of Si-BC, i.e., control (0), 1% Si-BC1, and 2.5% Si-BC2 applied in 3 replicates under 0 and 200 mM NaCl following a completely randomized design. Results showed that treatment 2.5% Si-BC2 performed significantly better for the enhancement in shoot and root length, shoot and root fresh weight, shoot and root dry weight, number of leaves, number of tillers, number of spikelets, spike length, spike fresh and dry weight compared to control under no stress and salinity stress (200 mM NaCl). A significant enhancement in chlorophyll a (~ 18%), chlorophyll b (~ 22%), total chlorophyll (~ 20%), carotenoid (~ 60%), relative water contents (~ 58%) also signified the effectiveness of treatment 2.5% Si-BC2 than control under 200 mM NaCl. In conclusion, treatment 2.5% Si-BC2 can potentially mitigate the salinity stress in wheat by regulating antioxidants and improving N, K concentration, and gas exchange attributes while decreasing Na and Cl concentration and electrolyte leakage. More investigations at the field level are recommended for the declaration of treatment 2.5% Si-BC2 as the best amendment for alleviating salinity stress in different crops under variable climatic conditions.
State-of-the-art mobile head CT scanner delivers nearly the same image quality as a conventional stationary CT scanner
Authors: Goertz Lukas , Al-Sewaidi Yosef , Habib Mahmoud , Zopfs David , Reichardt Benjamin , Ranft Alexander , Kabbasch Christoph 
Published: March 2024

AbstractThe use of mobile head CT scanners in the neurointensive care unit (NICU) saves time for patients and NICU staff and can reduce transport-related mishaps, but the reduced image quality of previous mobile scanners has prevented their widespread clinical use. This study compares the image quality of SOMATOM On.Site (Siemens Healthineers, Erlangen, Germany), a state-of-the-art mobile head CT scanner, and a conventional 64-slice stationary CT scanner. The study included 40 patients who underwent head scans with both mobile and stationary scanners. Gray and white matter signal and noise were measured at predefined locations on axial slices, and signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were calculated. Artifacts below the cranial calvaria and in the posterior fossa were also measured. In addition, image quality was subjectively assessed by two radiologists in terms of corticomedullary differentiation, subcalvarial space, skull artifacts, and image noise. Quantitative measurements showed significantly higher image quality of the stationary CT scanner in terms of noise, SNR and CNR of gray and white matter. Artifacts measured in the posterior fossa were higher with the mobile CT scanner, but subcalvarial artifacts were comparable. Subjective image quality was rated similarly by two radiologists for both scanners in all domains except image noise, which was better for stationary CT scans. The image quality of the SOMATOM On.Site for brain scans is inferior to that of the conventional stationary scanner, but appears to be adequate for daily use in a clinical setting based on subjective ratings.
Neural inhibition as implemented by an actor-critic model involves the human dorsal striatum and ventral tegmental area
Authors: Araújo Ana , Duarte Isabel Catarina , Sousa Teresa , Oliveira Joana , Pereira Ana Telma , Macedo António , Castelo-Branco Miguel 
Published: March 2024

AbstractInhibition is implicated across virtually all human experiences. As a trade-off of being very efficient, this executive function is also prone to many errors. Rodent and computational studies show that midbrain regions play crucial roles during errors by sending dopaminergic learning signals to the basal ganglia for behavioural adjustment. However, the parallels between animal and human neural anatomy and function are not determined. We scanned human adults while they performed an fMRI inhibitory task requiring trial-and-error learning. Guided by an actor-critic model, our results implicate the dorsal striatum and the ventral tegmental area as the actor and the critic, respectively. Using a multilevel and dimensional approach, we also demonstrate a link between midbrain and striatum circuit activity, inhibitory performance, and self-reported autistic and obsessive–compulsive subclinical traits.
Unveiling microbial guilds and symbiotic relationships in Antarctic sponge microbiomes
Authors: Moreno-Pino Mario , Manrique-de-la-Cuba Maria F. , López-Rodríguez Marileyxis , Parada-Pozo Génesis , Rodríguez-Marconi Susana , Ribeiro Catherine Gérikas , Flores-Herrera Patricio , Guajardo Mariela , Trefault Nicole 
Published: March 2024

AbstractMarine sponges host diverse microbial communities. Although we know many of its ecological patterns, a deeper understanding of the polar sponge holobiont is still needed. We combine high-throughput sequencing of ribosomal genes, including the largest taxonomic repertoire of Antarctic sponge species analyzed to date, functional metagenomics, and metagenome-assembled genomes (MAGs). Our findings show that sponges harbor more exclusive bacterial and archaeal communities than seawater, while microbial eukaryotes are mostly shared. Furthermore, bacteria in Antarctic sponge holobionts establish more cooperative interactions than in sponge holobionts from other environments. The bacterial classes that established more positive relations were Bacteroidia, Gamma- and Alphaproteobacteria. Antarctic sponge microbiomes contain microbial guilds that encompass ammonia-oxidizing archaea, ammonia-oxidizing bacteria, nitrite-oxidizing bacteria, and sulfur-oxidizing bacteria. The retrieved MAGs showed a high level of novelty and streamlining signals and belong to the most abundant members of the main microbial guilds in the Antarctic sponge holobiont. Moreover, the genomes of these symbiotic bacteria contain highly abundant functions related to their adaptation to the cold environment, vitamin production, and symbiotic lifestyle, helping the holobiont survive in this extreme environment.
Weak coupling between energetic status and the timing of reproduction in an Arctic ungulate
Authors: Tyler N. J. C. , Post E. , Hazlerigg D. G. 
Published: March 2024

AbstractBioenergetic constraints are the ultimate determinant of the timing of reproduction, and seasonal breeding is consequently a widely observed trait. Consistent with this, attention has focused on plasticity in reproductive phenology conceptualized as a response to concomitant advances in the phenology of the environmental energy supply caused by climate change. Few studies, however, have directly compared timing of reproduction with energetic status in free-living wild animals. Here we demonstrate that neither body mass nor adiposity are strong proximate predictors of date of conception in wild reindeer (Rangifer tarandus). Weak coupling between energetic status and the phenology of reproduction accounts for the increasing discrepancy between the phenology of forage (energy supply) and the phenology of reproduction (energy demand) observed across the last 2–4 decades in two populations of this species. The results emphasise that phenological plasticity is not a passive response to changes in energy supply but derives from the way in which environmental factors interact with the core control mechanisms that govern timing. Central in this respect is integration, within the rheostatic centres of the hypothalamus, of information on nutritional status with the circannual life-history calendar.
Multi-trait selection for nutritional and physiological quality of cacao genotypes in irrigated and non-irrigated environments
Authors: Araújo Maurício S. , Chaves Saulo F. S. , Pereira Guilherme R. , Guimarães Matheus H. D. , Alves Andressa K. S. , Dias Luiz Antônio S. , Souza Carlos A. S. , Aguilar Marco A. G. 
Published: March 2024

AbstractWater is a scarce, strategic resource and the most important input for economic development, especially in agricultural countries such as Brazil. Cocoa production is directly related to water availability, and, as climate changes, selecting drought-tolerant genotypes is vital to keep cacao crops sustainable. Here, we evaluated cacao genotypes under irrigated and water-stressed conditions and selected drought-tolerant ones based on nutritional and physiological traits. Thirty-nine genotypes were monitored for three years for agronomic traits and higher fruit yield. After this evaluation, the 18 most promising genotypes were evaluated in a randomized block design, under a 2 (with and without irrigation) $$\times$$
×
18 (genotypes) factorial arrangement, with three replicates and five plants per plot. We evaluated seven physiological and 11 nutritional traits, selecting genotypes based on the Genotype-by-Trait Biplot approach. Significant effects (p < 0.05) were observed for the nutritional traits N, P, Mg, S, Zn, Cu, Mn and for the physiological traits CO2 assimilation rate (A), stomatal conductance (gs), transpiration (E), intercellular and atmospheric CO2 concentrations (Ci/Ca), intrinsic water use efficiency (A/gs), instantaneous water use efficiency (A/E), and instantaneous carboxylation efficiency (A/Ci), as determined by analysis of variance. The genotype $$\times$$
×
irrigation treatment interaction was significant (p < 0.05) for the traits A, gs, and E. Genotypes CP 41, CP 43, and CCN 51 exhibited superior performance for both nutritional and physiological traits (A, gs, and E). In the irrigated environment, CP 41 showed superiority in traits such as P, A/E, A/gs, Mn, S, and Zn. Conversely, under non-irrigated conditions, CP 43 exhibited better performance in nutritional properties, specifically Mn, Mg, and Zn. Notably, in both irrigated and non-irrigated environments, CCN 51 excelled in key physiological traits, including A/Ci, A/E, and A/gs. This robust performance across diverse conditions suggests that these three genotypes possess physiological mechanisms to endure water-stressed conditions. Our research can generate valuable insights into these genotypes informing suitable choices for cocoa cultivation, especially in the context of global climate change.
Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample
Authors: Cinciripini Paul M. , Wetter David W. , Wang Jian , Yu Robert , Kypriotakis George , Kumar Tapsi , Robinson Jason D. , Cui Yong , Green Charles E. , Bergen Andrew W. , Kosten Thomas R. , Scherer Steven E. , Shete Sanjay 
Published: March 2024

AbstractDespite the large public health toll of smoking, genetic studies of smoking cessation have been limited with few discoveries of risk or protective loci. We investigated common and rare variant associations with success in quitting smoking using a cohort from 8 randomized controlled trials involving 2231 participants and a total of 10,020 common and 24,147 rare variants. We identified 14 novel markers including 6 mapping to genes previously related to psychiatric and substance use disorders, 4 of which were protective (CYP2B6 (rs1175607105), HTR3B (rs1413172952; rs1204720503), rs80210037 on chr15), and 2 of which were associated with reduced cessation (PARP15 (rs2173763), SCL18A2 (rs363222)). The others mapped to areas associated with cancer including FOXP1 (rs1288980) and ZEB1 (rs7349). Network analysis identified significant canonical pathways for the serotonin receptor signaling pathway, nicotine and bupropion metabolism, and several related to tumor suppression. Two novel markers (rs6749438; rs6718083) on chr2 are flanked by genes associated with regulation of bodyweight. The identification of novel loci in this study can provide new targets of pharmacotherapy and inform efforts to develop personalized treatments based on genetic profiles.
The association between variability of risk factors and complications in type 2 diabetes mellitus: a retrospective study
Authors: Chen Mengjie , Pu Lihui , Gan Yuqin , Wang Xiaoxia , Kong Laixi , Guo Maoting , Yang Huiqi , Li Zhe , Xiong Zhenzhen 
Published: March 2024

AbstractThe variability in diabetes risk factors, such as uric acid and lipids, may influence the development of complications. This study aimed to investigate the influence of such variability on the occurrence of diabetic complications. A retrospective analysis of electronic medical records was conducted with type 2 diabetic patients who received treatment at a tertiary care hospital in Chengdu, Sichuan Province, between 2013 and 2022. The risk factor variability is presented as the standard deviation (SD). The associations between the variability and complications were examined using a binary logistic regression model. The study included 369 patients with type 2 diabetes. The findings revealed that outpatient special disease management served as a protective factor against the development of complications [OR = 0.53, 95% confidence interval (CI) (0.29–0.10)], particularly for the prevention of diabetic peripheral neuropathy [OR = 0.51, 95% CI (0.30–0.86)]. Variability in total cholesterol (TC-SD) was found to be a risk factor for the development of complications [OR = 2.42, 95% CI (1.18–4.97)] and acted as a risk factor for diabetic peripheral vasculopathy [OR = 2.50, 95% CI (1.25–5.02)]. TC-SD is a risk factor for the occurrence of diabetic peripheral neuropathy and diabetic peripheral vasculopathy, whereas outpatient special disease management functions as a protective factor against complications and diabetic peripheral neuropathy. Thus, in addition to glycaemic control, the regulation of lipid levels should be emphasized, particularly among patients without outpatient special disease management, to delay the onset of complications.