bluuebunny/crossref_metadata_2025_split huggingface dataset:
The beneficial impact of curcumin on cardiac lipotoxicity
Authors: Abolfazli Sajad , Butler Alexandra E , Kesharwani Prashant , Sahebkar Amirhossein 
Published: August 2024

Abstract
Lipotoxicity is defined as a prolonged metabolic imbalance of lipids that results in ectopic fat distribution in peripheral organs such as the liver, heart, and kidney. The harmful consequences of excessive lipid accumulation in cardiomyocytes cause cardiac lipotoxicity, which alters the structure and function of the heart. Obesity and diabetes are linked to lipotoxic cardiomyopathy. These anomalies might be caused by a harmful metabolic shift that accumulates toxic lipids and shifts glucose oxidation to less fatty acid oxidation. Research has linked fatty acids, fatty acyl coenzyme A, diacylglycerol, and ceramide to lipotoxic stress in cells. This stress can be brought on by apoptosis, impaired insulin signaling, endoplasmic reticulum stress, protein kinase C activation, p38 Ras-mitogen-activated protein kinase (MAPK) activation, or modification of peroxisome proliferator–activated receptors (PPARs) family members. Curcuma longa is used to extract curcumin, a hydrophobic polyphenol derivative with a variety of pharmacological characteristics. Throughout the years, curcumin has been utilized as an anti-inflammatory, antioxidant, anticancer, hepatoprotective, cardioprotective, anti-diabetic, and anti-obesity drug. Curcumin reduces cardiac lipotoxicity by inhibiting apoptosis and decreasing the expression of apoptosis-related proteins, reducing the expression of inflammatory cytokines, activating the autophagy signaling pathway, and inhibiting the expression of endoplasmic reticulum stress marker proteins.
Barriers and backslides: How economic instability impedes refugee self-reliance in Kakuma refugee camp, Kenya
Authors: Sackett Blair 
Published: August 2024

Abstract
Studies reveal that refugees develop a wide range of economic activity in displacement. In recent years, priorities of refugee self-reliance have had a resurgence among humanitarian organizations and policymakers. Within these programs, models of self-reliance have focused on employment and income for individual refugee households. Based on ethnographic observations, interviews, and longitudinal questionnaires in Kakuma refugee camp in Kenya, I demonstrate the need to broaden our models of self-reliance to incorporate the role economic shocks, or exogenous and unpredictable events that affect household resources. Rather than rare events, economic shocks were common across sectors and compounded by cuts to humanitarian support. Nor were shocks isolated events. Households faced multiple intersecting shocks, which rippled across communities as households were affected by shocks to others in their social networks. Across employment type and income, shocks destabilized the economic trajectories of refugee households and impeded progress toward self-reliance.
A Bayesian valuation framework for catastrophe bonds
Authors: Domfeh Dixon , Chatterjee Arpita , Dixon Matthew 
Published: August 2024

Abstract
Catastrophe (CAT) bond markets are incomplete and hence carry uncertainty in instrument pricing. Various pricing approaches have been proposed, but none treats the uncertainty in catastrophes and interest rates in a sufficiently flexible and statistically reliable way within an asset valuation framework. Consequently, little is known empirically about the expected risk premium of CAT bonds. The primary contribution of this article is to present a Bayesian CAT bond valuation framework based on uncertainty quantification of catastrophes and interest rates. We leverage this framework to estimate fair value prices and expected risk premiums for CAT bonds with varying catastrophe risk profiles.
Unravelling the secrets of non-host resistance in plant–insect interactions
Authors: Pinheiro Daniel Gonçalves da Silva , Espirito-Santo Ana Beatriz Moreira Menezes do , Fasoli José Vitor Botter , Sobral-Souza Thadeu , Campos Marcelo Lattarulo 
Published: August 2024

Abstract
Despite the existence of over half a million species of plant-eating insects, our planet remains predominantly green. In fact, susceptibility to herbivory is the exception, as plants are resistant to most insect species. This phenomenon is known as non-host resistance (NHR), where every individual of a plant species is resistant to all variants of a pest or pathogen. While NHR represents the most common and durable outcome of the plant immune system, several aspects of this type of plant defence remain elusive, particularly in plant–insect interactions. In this review, we clarify the concept of NHR in plant–insect interactions. We emphasize that NHR is a phenomenon arising as a consequence of effective plant defences providing invulnerability to most insect herbivores. This underscores that NHR is one of the main ecological features delimiting the range of plant–insect interactions on Earth. We further highlight the traits and molecular components of the plant immune system known to participate in NHR against insects. Finally, we discuss how NHR can be leveraged as a tool to develop pest-resilient crops. Given the significant threat insects pose to global food security, research in plant NHR represents a crucial focal point with immense potential for ensuring food security worldwide.
Ray-tracing versus Born approximation in full-sky weak lensing simulations of the MillenniumTNG project
Authors: Ferlito Fulvio , Davies Christopher T , Springel Volker , Reinecke Martin , Greco Alessandro , Delgado Ana Maria , White Simon D M , Hernández-Aguayo César , Bose Sownak , Hernquist Lars 
Published: August 2024

ABSTRACT
Weak gravitational lensing is a powerful tool for precision tests of cosmology. As the expected deflection angles are small, predictions based on non-linear N-body simulations are commonly computed with the Born approximation. Here, we examine this assumption using DORIAN, a newly developed full-sky ray-tracing scheme applied to high-resolution mass-shell outputs of the two largest simulations in the MillenniumTNG suite, each with a 3000 Mpc box containing almost 1.1 trillion cold dark matter particles in addition to 16.7 billion particles representing massive neutrinos. We examine simple two-point statistics like the angular power spectrum of the convergence field, as well as statistics sensitive to higher order correlations such as peak and minimum statistics, void statistics, and Minkowski functionals of the convergence maps. Overall, we find only small differences between the Born approximation and a full ray-tracing treatment. While these are negligibly small at power-spectrum level, some higher order statistics show more sizeable effects; ray-tracing is necessary to achieve per cent level precision. At the resolution reached here, full-sky maps with 0.8 billion pixels and an angular resolution of 0.43 arcmin, we find that interpolation accuracy can introduce appreciable errors in ray-tracing results. We therefore implemented an interpolation method based on non-uniform fast Fourier transforms (NUFFT) along with more traditional methods. Bilinear interpolation introduces significant smoothing, while nearest grid point sampling agrees well with NUFFT, at least for our fiducial source redshift, $z_s=1.0$, and for the 1 arcmin smoothing we use for higher order statistics.
Angular momentum transfer in cosmological simulations of Milky Way-mass discs
Authors: Trapp Cameron W , Kereš Dušan , Hopkins Philip F , Faucher-Giguère Claude-André , Murray Norman 
Published: August 2024

ABSTRACT
Fuelling star formation in large, discy galaxies requires a continuous supply of gas accreting into star-forming regions. Previously, we characterized this accretion in four Milky Way mass galaxies ($M_{\rm halo}\sim 10^{12}{\rm M}_{\odot }$) in the FIRE-2 cosmological zoom-in simulations. At $z\sim 0$, we found that gas within the inner circumgalactic medium (iCGM) approaches the disc with comparable angular momentum (AM) to the disc edge, joining in the outer half of the gaseous disc. Within the disc, gas moves inwards at velocities of $\sim$1–5 km s$^{-1}$ while fully rotationally supported. In this study, we analyse the torques that drive these flows. In all cases studied, we find that the torques in discs enable gas accreted near the disc edge to transport inwards and fuel star formation in the central few kpc. The primary sources of torque come from gravity, hydrodynamical forces, and the sub-grid $P \mathrm{ d}V$ work done by supernova (SN) remnants interacting with gas on $\lesssim$10 pc scales. These SNe remnant interactions induce negative torques within the inner disc and positive torques in the outer disc. The gas–gas gravitational, hydro, and ‘feedback’ torques transfer AM outwards to where accreting gas joins the disc, playing an important role in driving inflows and regulating disc structure. Gravitational torques from stars and dark matter provide an AM sink within the innermost regions of the disc and iCGM, respectively. Feedback torques are dominant within the disc, while gravitational and hydrodynamical torques have similar significance depending on the system/region. Torques from viscous shearing, magnetic forces, stellar winds, and radiative transfer are less significant.
Stellar formation and young clusters in NGC 2366 – main properties
Authors: Feinstein C , Baume G , Vergne M M , Rodríguez M J 
Published: August 2024

ABSTRACT
The characteristics of the young stellar population in the nearby irregular galaxy NGC 2366 were investigated. In particular, we focused our attention on its hierarchical clustering distributions and the properties of the stellar groups. This galaxy exhibits a prominent blue helium-burning star feature in the colour-magnitude diagram, suggesting that it has undergone an extended period of stellar formation. The galaxy was observed in two bands by the Hubble Space Telescope covering almost its complete central and intermediate parts, including all the major stellar formation regions. Available photometric data allowed us to select the blue and young stars and, therefore, study the recent stellar formation. Through the path linkage criterion (PLC), we found 23 young star groups and estimated their fundamental parameters, such as their stellar densities, sizes, and number of members. We also performed a fractal substructure analysis to determine the clustering properties of this population, and we built a stellar density map corresponding to the galactic young population. We found that most of the young stellar groups have stars that have a distribution of locations that is compatible with a fractal dimension.
Prevalent Fast Evolution of Genes Involved in Heterochromatin Functions
Authors: Lin Leila , Huang Yuheng , McIntyre Jennifer , Chang Ching-Ho , Colmenares Serafin , Lee Yuh Chwen G 
Published: August 2024

Abstract
Heterochromatin is a gene-poor and repeat-rich genomic compartment universally found in eukaryotes. Despite its low transcriptional activity, heterochromatin plays important roles in maintaining genome stability, organizing chromosomes, and suppressing transposable elements. Given the importance of these functions, it is expected that genes involved in heterochromatin regulation would be highly conserved. Yet, a handful of these genes were found to evolve rapidly. To investigate whether these previous findings are anecdotal or general to genes modulating heterochromatin, we compile an exhaustive list of 106 candidate genes involved in heterochromatin functions and investigate their evolution over short and long evolutionary time scales in Drosophila. Our analyses find that these genes exhibit significantly more frequent evolutionary changes, both in the forms of amino acid substitutions and gene copy number change, when compared to genes involved in Polycomb-based repressive chromatin. While positive selection drives amino acid changes within both structured domains with diverse functions and intrinsically disordered regions, purifying selection may have maintained the proportions of intrinsically disordered regions of these proteins. Together with the observed negative associations between the evolutionary rate of these genes and the genomic abundance of transposable elements, we propose an evolutionary model where the fast evolution of genes involved in heterochromatin functions is an inevitable outcome of the unique functional roles of heterochromatin, while the rapid evolution of transposable elements may be an effect rather than cause. Our study provides an important global view of the evolution of genes involved in this critical cellular domain and provides insights into the factors driving the distinctive evolution of heterochromatin.
N-terminal domain of polypyrimidine-tract binding protein is a dynamic folding platform for adaptive RNA recognition
Authors: Damberger Fred F , Krepl Miroslav , Arora Rajika , Beusch Irene , Maris Christophe , Dorn Georg , Šponer Jiří , Ravindranathan Sapna , Allain Frédéric H-T 
Published: August 2024

Abstract
The N-terminal RNA recognition motif domain (RRM1) of polypyrimidine tract binding protein (PTB) forms an additional C-terminal helix α3, which docks to one edge of the β-sheet upon binding to a stem-loop RNA containing a UCUUU pentaloop. Importantly, α3 does not contact the RNA. The α3 helix therefore represents an allosteric means to regulate the conformation of adjacent domains in PTB upon binding structured RNAs. Here we investigate the process of dynamic adaptation by stem-loop RNA and RRM1 using NMR and MD in order to obtain mechanistic insights on how this allostery is achieved. Relaxation data and NMR structure determination of the free protein show that α3 is partially ordered and interacts with the domain transiently. Stem-loop RNA binding quenches fast time scale dynamics and α3 becomes ordered, however microsecond dynamics at the protein-RNA interface is observed. MD shows how RRM1 binding to the stem-loop RNA is coupled to the stabilization of the C-terminal helix and helps to transduce differences in RNA loop sequence into changes in α3 length and order. IRES assays of full length PTB and a mutant with altered dynamics in the α3 region show that this dynamic allostery influences PTB function in cultured HEK293T cells.
Structural insights into RNA cleavage by a novel family of bacterial RNases
Authors: Wu Ruoxi , Ingle Shakti , Barnes Sarah A , Dahlin Heather R , Khamrui Susmita , Xiang Yufei , Shi Yi , Bechhofer David H , Lazarus Michael B 
Published: August 2024

Abstract
Processing of RNA is a key regulatory mechanism for all living systems. Escherichia coli protein YicC belongs to the well-conserved YicC family and has been identified as a novel ribonuclease. Here, we report a 2.8-Å-resolution crystal structure of the E. coli YicC apo protein and a 3.2-Å-cryo-EM structure of YicC bound to an RNA substrate. The apo YicC forms a dimer of trimers with a large open channel. In the RNA-bound form, the top trimer of YicC rotates nearly 70° and closes the RNA substrate inside the cavity to form a clamshell-pearl conformation that resembles no other known RNases. The structural information combined with mass spectrometry and biochemical data identified cleavage on the upstream side of an RNA hairpin. Mutagenesis studies demonstrated that the previously uncharacterized domain, DUF1732, is critical in both RNA binding and catalysis. These studies shed light on the mechanism of the previously unexplored YicC RNase family.
Clinically relevant mutations in regulatory regions of metabolic genes facilitate early adaptation to ciprofloxacin in Escherichia coli
Authors: Pal Arijit , Ghosh Dipannita , Thakur Pratyusha , Nagpal Priya , Irulappan Madhumathi , Maruthan Karthik , Mukherjee Sanket , Patil Nikita G , Dutta Tanmay , Veeraraghavan Balaji , Vivekanandan Perumal 
Published: August 2024

Abstract
The genomic landscape associated with early adaptation to ciprofloxacin is poorly understood. Although the interplay between core metabolism and antimicrobial resistance is being increasingly recognized, mutations in metabolic genes and their biological role remain elusive. Here, we exposed Escherichia coli to increasing gradients of ciprofloxacin with intermittent transfer-bottlenecking and identified mutations in three non-canonical targets linked to metabolism including a deletion (tRNA-ArgΔ414-bp) and point mutations in the regulatory regions of argI (ARG box) and narU. Our findings suggest that these mutations modulate arginine and carbohydrate metabolism, facilitate anaerobiosis and increased ATP production during ciprofloxacin stress. Furthermore, mutations in the regulatory regions of argI and narU were detected in over 70% of sequences from clinical E. coli isolates and were overrepresented among ciprofloxacin-resistant isolates. In sum, we have identified clinically relevant mutations in the regulatory regions of metabolic genes as a central theme that drives physiological changes necessary for adaptation to ciprofloxacin stress.
Structural basis of Cas3 activation in type I-C CRISPR-Cas system
Authors: Kim Do Yeon , Lee So Yeon , Ha Hyun Ji , Park Hyun Ho 
Published: August 2024

Abstract
CRISPR-Cas systems function as adaptive immune mechanisms in bacteria and archaea and offer protection against phages and other mobile genetic elements. Among many types of CRISPR-Cas systems, Type I CRISPR-Cas systems are most abundant, with target interference depending on a multi-subunit, RNA-guided complex known as Cascade that recruits a transacting helicase nuclease, Cas3, to degrade the target. While structural studies on several other types of Cas3 have been conducted long ago, it was only recently that the structural study of Type I-C Cas3 in complex with Cascade was revealed, shedding light on how Cas3 achieve its activity in the Cascade complex. In the present study, we elucidated the first structure of standalone Type I-C Cas3 from Neisseria lactamica (NlaCas3). Structural analysis revealed that the histidine–aspartate (HD) nuclease active site of NlaCas3 was bound to two Fe2+ ions that inhibited its activity. Moreover, NlaCas3 could cleave both single-stranded and double-stranded DNA in the presence of Ni2+ or Co2+, showing the highest activity in the presence of both Ni2+ and Mg2+ ions. By comparing the structural studies of various Cas3 proteins, we determined that our NlaCas3 stays in an inactive conformation, allowing us to understand the structural changes associated with its activation and their implication.
DipR, a GntR/FadR-family transcriptional repressor: regulatory mechanism and widespread distribution of the dip cluster for dipicolinic acid catabolism in bacteria
Authors: Jiang Yinhu , Wang Kexin , Xu Lu , Xu Lanyi , Xu Qimiao , Mu Yang , Hong Qing , He Jian , Jiang Jiandong , Qiu Jiguo 
Published: August 2024

Abstract
Dipicolinic acid is an essential component of bacterial spores for stress resistance, which is released into the environment after spore germination. In a previous study, a dip gene cluster was found to be responsible for the catabolism of dipicolinic acid in Alcaligenes faecalis JQ135. However, the transcriptional regulatory mechanism remains unclear. The present study characterized the new GntR/FadR family transcriptional factor DipR, showing that the dip cluster is transcribed as the six transcriptional units, dipR, dipA, dipBC, dipDEFG, dipH and dipJKLM. The purified DipR protein has six binding sites sharing the 6-bp conserved motif sequence 5′-GWATAC-3′. Site-directed mutations indicated that these motif sequences are essential for DipR binding. Moreover, the four key amino acid residues R63, R67, H196 and H218 of DipR, examined by site-directed mutagenesis, played crucial roles in DipR regulation. Bioinformatics analysis showed that dip clusters including dipR genes are widely distributed in bacteria, are taxon-related, and co-evolved with their hosts. This paper provides new insights into the transcriptional regulatory mechanism of dipicolinic acid degradation by DipR in bacteria.
A plant-specific clade of serine/arginine-rich proteins regulates RNA splicing homeostasis and thermotolerance in tomato
Authors: Rosenkranz Remus R E , Vraggalas Stavros , Keller Mario , Sankaranarayanan Srimeenakshi , McNicoll François , Löchli Karin , Bublak Daniela , Benhamed Moussa , Crespi Martin , Berberich Thomas , Bazakos Christos , Feldbrügge Michael , Schleiff Enrico , Müller-McNicoll Michaela , Zarnack Kathi , Fragkostefanakis Sotirios 
Published: August 2024

Abstract
Global warming poses a threat for crops, therefore, the identification of thermotolerance mechanisms is a priority. In plants, the core factors that regulate transcription under heat stress (HS) are well described and include several HS transcription factors (HSFs). Despite the relevance of alternative splicing in HS response and thermotolerance, the core regulators of HS-sensitive alternative splicing have not been identified. In tomato, alternative splicing of HSFA2 is important for acclimation to HS. Here, we show that several members of the serine/arginine-rich family of splicing factors (SRSFs) suppress HSFA2 intron splicing. Individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP) combined with RNA-Seq revealed that RS2Z35 and RS2Z36, which make up a plant-specific clade of SR proteins, not only regulate HSFA2 but approximately 50% of RNAs that undergo HS-sensitive alternative splicing, with preferential binding to purine-rich RNA motifs. Single and double CRISPR rs2z mutant lines show a dysregulation of splicing and exhibit lower basal and acquired thermotolerance compared to wild type plants. Our results suggest that RS2Z35 and RS2Z36 have a central role in mitigation of the negative effects of HS on RNA splicing homeostasis, and their emergence might have contributed to the increased capacity of plants to acclimate to high temperatures.
Insights into the Anticancer Mechanisms Modulated by Gamma and Delta Tocotrienols in Colorectal Cancers
Authors: Khalid Ali Qusay , Zaidan Tabarek Najeeb , Bhuvanendran Saatheeyavaane , Magalingam Kasthuri B , Mohamedahmed Shaza M , Ramdas Premdass , Radhakrishnan Ammu K 
Published: August 2024

Abstract
Colorectal cancer (CRC) is a growing concern all over the world. There has been a concerted effort to identify natural bioactive compounds that can be used to prevent or overcome this condition. Tocotrienols (T3s) are a naturally occurring form of vitamin E known for various therapeutic effects, such as anticancer, antioxidant, neuroprotective, and anti-inflammatory activities. The literature evidence suggests that two T3 analogues, ie, gamma (γ)- and delta (δ)-T3, can modulate cancers via several cancer-related signaling pathways. The aim of this review was to compile and analyze the existing literature on the diverse anticancer mechanisms of γT3 and δT3 exhibited in CRC cells, to showcase the anticancer potential of T3s. Medline was searched for research articles on anticancer effects of γT3 and δT3 in CRC published in the past 2 decades. A total of 38 articles (26 cell-based, 9 animal studies, 2 randomized clinical trials, and 1 scoping review) that report anticancer effects of γT3 and δT3 in CRC were identified. The findings reported in those articles indicate that γT3 and δT3 inhibit the proliferation of CRC cells, induce cell cycle arrest and apoptosis, suppress metastasis, and produce synergistic anticancer effects when combined with well-established anticancer agents. There is preliminary evidence that shows that T3s affect telomerase functions and support anticancer immune responses. γT3 and δT3 have the potential for development as anticancer agents.