bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence specificity of an essential nuclear localization sequence in Mcm3
Authors: Wang Ziyi , Zhang Yun Jing , Zhang Qian-yi , Bilsborrow Kate , Leslie Matthew , Suhandynata Raymond T. , Zhou Huilin 
Published: November 2024

AbstractProteins with nuclear localization sequences (NLSs) are directed into the cell nucleus through interactions between the NLS and importin proteins. NLSs are generally short motifs rich in basic amino acids; however, identifying NLSs can be challenging due to the lack of a universally conserved sequence. In this study, we characterized the sequence specificity of an essential and conserved NLS in Mcm3, a subunit of the replicative DNA helicase. Through mutagenesis and AlphaFold 3 (AF3) modeling, we demonstrate that the precise positioning of basic residues within the NLS is critical for nuclear transport of Mcm3 through optimal interactions with importin. Disrupting these interactions impairs the nuclear import of Mcm3, resulting in defective chromatin loading of MCM and poor cell growth. Our results provide a structure-guided framework for predicting and analyzing monopartite NLSs, which, despite lacking a single consensus sequence, retain key characteristics shared between the NLSs of Mcm3 and the SV40 large T antigen.Author SummaryTransporting proteins into and out of the cell nucleus is essential for chromosome-associated activities. Nuclear localization sequences (NLSs), short motifs rich in basic amino acids, are commonly found in nuclear proteins. NLSs work by interacting with importin, a key transport receptor responsible for recognizing and guiding NLS-containing proteins through the nuclear pore complex into the nucleus. Other than being rich in basic amino acids, NLSs generally lack a discernible consensus sequence, raising questions about how they specifically control nuclear transport through their interactions with importins. Through a detailed mutagenesis study of a conserved and essential NLS in Mcm3, a subunit of the replicative DNA helicase, we demonstrate that the use of AlphaFold 3 (AF3), alongside genetic, biochemical, and cell biological analyses, define key contacts between Mcm3’s NLS and importin that are required for nuclear import of Mcm3.
Unveiling novel mechanisms of strobilurin resistance in the cacao pathogenMoniliophthora perniciosa
Authors: Prado P.F.V. , Mendes C.V.C. , Pires B.A. , Fiorin G.L. , Mieczkowski P. , Pereira G.A.G. , Teixeira P.J.P.L. , Thomazella D.P.T. 
Published: November 2024

ABSTRACTWitches’ broom disease (WBD) is a major constraint for cacao production in the Americas. The severe socioeconomic impact of WBD encouraged the evaluation of different control strategies, including the use of strobilurin fungicides. These molecules inhibit mitochondrial respiration, thus impairing ATP generation and leading to oxidative stress. These chemicals, however, have proven ineffective against the WBD pathogenMoniliophthora perniciosa. Here, we demonstrate thatM. perniciosatolerates high concentrations of strobilurins underin vitroconditions and highlight a set of molecular alterations that correlate with strobilurin tolerance in this fungus. Short-term exposure ofM. perniciosato the commercial strobilurin azoxystrobin led to the up-regulation of genes encoding enzymes of the glyoxylate cycle, gluconeogenesis, and fatty acid and amino acid catabolism, indicating that the fungal metabolism is remodeled to compensate for reduced ATP production. Furthermore, cell division, ribosome biogenesis, and sterol metabolism were repressed, which agrees with the impaired mycelial growth on azoxystrobin. Genes associated with cellular detoxification and response to oxidative stress (e.g., cytochrome P450s, membrane transporters and glutathione s-transferases) were strongly induced by the drug and represent potential strategies used by the pathogen to mitigate the toxic effects of the fungicide. Remarkably, exposure ofM. perniciosato azoxystrobin resulted in the spontaneous generation of a mutant with increased resistance to strobilurin. Comparative genomics and transcriptomics revealed alterations that may explain the resistance phenotype, including a large deletion in a putative transcriptional regulator and significant changes in the mutant transcriptome. Overall, this work provides important advances towards a comprehensive understanding of the molecular basis of strobilurin resistance in a tropical fungal pathogen. This is a fundamental step to efficiently employ these fungicides in agriculture and to prevent the emergence of strobilurin resistance.
Identification and characterization of substrate- and product-selective nylon hydrolases
Authors: Drufva Erin E. , Cahill John F. , Saint-Vincent Patricia M.B. , Williams Alexis N. , Bocharova Vera , Capra Nikolas , Meilleur Flora , Carper Dana L. , Bourgery Célestin , Miyazaki Kaito , Yonemura Maina , Shiraishi Yuki , Parks Jerry M. , Zhou Muchu , Dishner Isaiah T. , Foster Jeffrey C. , Koehler Stephen J. , Valentino Hannah R. , Sedova Ada , Kertesz Vilmos , Vasileva Delyana P. , Hochanadel Leah H. , Figg C. Adrian , Negoro Seiji , Kato Dai-ichiro , Chen Serena H. , Michener Joshua K. 
Published: November 2024

AbstractEnzymes have evolved to rapidly and selectively hydrolyze diverse natural and anthropogenic polymers, but only a limited group of related enzymes have been shown to hydrolyze synthetic polyamides. In this work, we synthesized and characterized a panel of 95 diverse enzymes from the N-terminal nucleophile hydrolase superfamily with 30-50% pairwise amino acid identity. We found that nearly 40% of the enzymes had substantial nylon hydrolase activity, in many cases comparable to that of the best-characterized nylon hydrolase, NylC. There was no relationship between phylogeny and activity, nor any evidence of prior selection for nylon hydrolase activity. Several newly-identified hydrolases showed significant substrate selectivity, generating up to 20-fold higher product titers with Nylon 6,6 versus Nylon 6. Finally, we determined the crystal structure and oligomerization state of a Nylon 6,6-selective hydrolase to elucidate structural factors that could affect activity and selectivity. These new enzymes provide insights into the widespread potential for nylon hydrolase evolution and opportunities for analysis and engineering of improved hydrolases.SignificanceNylons are common industrial polyamides with few recycling options. As an alternative to mechanical or chemical recycling, enzymes may provide a selective and energy-efficient route to deconstruct nylons from mixed waste. Several nylon hydrolases have been identified, most notably NylC, but these enzymes are all closely related and demonstrated similar activity and substrate range. In this work, we investigated a diverse set of enzymes and showed that nylon hydrolase activity is common, providing new insights into the evolution of microbial nylon hydrolysis. Unlike NylC, several enzymes demonstrated unprecedented substrate selectivity, preferentially hydrolyzing Nylon 6,6 compared to Nylon 6. These enzymes can be used to understand substrate selectivity in nylon hydrolysis and to engineer enzymes for nylon recycling from mixed waste.
Spontaneous Brain Dynamics Associated With Acceleration Of Long-term Functional Connectome In Postnatal Development
Authors: Ma Liang , Shultz Sarah , Fu Zening , Seraji Masoud , Iraji Armin , Calhoun Vince 
Published: November 2024

ABSTRACTThe first six postnatal months are a critical period for brain development, marked by rapid changes in functional neural circuits. However, long-term changes in neonatal functional connectome lacks an interpretive imaging indicator for the future development due to the non-linearity characteristics. In this study, we introduce an approach to extract intrinsic brain states from short-term brain dynamics to study the long-term (longitudinal) development. We found a high association (r=0.460) between the co-activated pattern of specific brain state and the acceleration pattern of non-linear development of static functional connectome. The fractional occupancy, self-sustaining probability of this short-term state share the similar age tendency with the long-term change rate within the majority of the function connectome. These findings suggest that short-term brain dynamics could serve as potential biomarkers for predicting the long-term development of functional connectome.
Leaf size determines damage- and herbivore-induced volatile emissions in maize
Authors: Waterman Jamie M. , Cofer Tristan M. , Von Laue Ophélie M. , Mateo Pierre , Wang Lei , Erb Matthias 
Published: November 2024

AbstractStress-induced plant volatiles play an important role in mediating ecological interactions between plants and their environment. The timing and location of the inflicted damage is known to influence the quality and quantity of induced volatile emissions. However, how leaf characteristics and herbivore feeding behavior interact to shape volatile emissions is not well understood. Using a high-throughput volatile profiling system with high temporal resolution, we examined how mechanical damage and herbivore feeding on different leaves shapes plant-level volatile emission patterns in maize. We then tested feeding patterns and resulting consequences on volatile emissions with two generalist herbivores (Spodoptera exiguaandSpodoptera littoralis), and assessed whether feeding preferences are associated with enhanced herbivore performance. We found maize seedlings emit more volatiles when larger leaves are damaged. Larger leaves emitted more volatiles locally, which was the determining factor for higher plant-level emissions. Surprisingly, bothS. exiguaandS. littoralispreferentially consumed larger leaves, and thus maximize plant volatile emission without apparent growth benefits. Together, these findings provide an ecophysiological and behavioral mechanism for plant volatile emission patterns, with potentially important implications for volatile-mediated plant-environment interactions.
SingleMAPTknock-in mouse models of frontotemporal dementia for sharing with the neurodegenerative research community
Authors: Morito Takahiro , Qi Mohan , Kamano Naoko , Sasaguri Hiroki , Bez Sumi , Foiani Martha , Duff Keren , Benner Seico , Endo Toshihiro , Hama Hiroshi , Kurokawa Hiroshi , Miyawaki Atushi , Mizuma Hiroshi , Sahara Naruhiko , Shimojo Masafumi , Higuchi Makoto , Saido Takaomi C. , Watamura Naoto 
Published: November 2024

AbstractWe recently reported development of humanMAPTknock-in mice that carry single or double pathogenic mutations of frontotemporal dementia. However, it takes more than 14 months for the line with the most aggressive phenotypes to exhibit tau pathology without forming high-order tau oligomers, along with concomitant abnormal behavior. We thus generatedMAPTknock-in mice carrying triple mutations, among which theMAPTP301S;Int10+3;S320Fline exhibited robust pathology starting earlier than 6 months. Tau accumulation took place mainly in the thalamus, hypothalamus, amygdala and entorhinal cortex, but less so in the hippocampus, leading to synaptic loss, atrophy and behavioral abnormalities. CrossbreedingMAPTP301S;Int10+3;S320FwithAppknock-in miceAppNL-G-Fresulted in the manifestation of tau pathology in the hippocampus and cortex. These mutant mice will be valuable tools for understanding the mechanisms of frontotemporal dementia, Alzheimer’s disease and other tauopathies.
Bone Morphogenetic Protein signaling pathway – ethanol interactions disrupt palate formation independent ofgata3
Authors: Lovely C. Ben 
Published: November 2024

AbstractFetal Alcohol Spectrum Disorders (FASD) describes a wide array of neurological defects and craniofacial malformations, associated with ethanol teratogenicity. While there is growing evidence for a genetic component to FASD, little is known of the genes underlying these ethanol-induced defects. Along with timing and dosage, genetic predispositions may help explain the variability within FASD. From a screen for gene-ethanol interactions, we found that mutants for Bmp signaling components are ethanol-sensitive leading to defects in the zebrafish palate. Loss of Bmp signaling results in reductions ingata3expression in the maxillary domain of the neural crest in the 1st pharyngeal arch, leading to palate defects while upregulation of humanGATA3rescues these defects. Here, we show that ethanol-treated Bmp mutants exhibit misshaped and/or broken trabeculae. Surprisingly, up regulation ofGATA3does not rescue ethanol-induced palate defects andgata3expression was not altered in ethanol-treated Bmp mutants or dorsomorphin-treated larvae. Timing of ethanol sensitivity shows that Bmp mutants are ethanol sensitive from 10-18 hours post-fertilization (hpf), prior to Bmp’s regulation ofgata3in palate formation. This is consistent with our previous work with dorsomorphin-dependent knock down of Bmp signaling from 10-18 hpf disrupting endoderm formation and subsequent jaw development. Overall, this suggests that ethanol disrupts Bmp-dependent palate development independent of and earlier than the role ofgata3in palate formation by disrupting epithelial development. Ultimately, these data demonstrate that zebrafish is a useful model to identify and characterize gene-ethanol interactions and this work will directly inform our understanding of FASD.HighlightsBmp pathway mutants are ethanol sensitive resulting in palate defects.Ethanol disrupts Bmp-dependent palate development independent ofgata3.Timing of ethanol sensitivity suggests ethanol disrupts Bmp-dependent epithelial morphogenesis.
Dark sector tunneling field potentials for a dark big bang
Authors: Casey Richard , Ilie Cosmin 
Published: November 2024

All of the significant evidence for dark matter observed thus far has been through its gravitational interactions. After 40 years of direct detection experiments, the parameter space for weakly interacting massive particles (WIMPs) as dark matter candidates is rapidly approaching the neutrino floor. Moreover, there have been no signs of WIMPs in any particle production experiments so far. In this light, we consider a dark sector that is strongly decoupled from the visible sector, interacting exclusively through gravity. In this model, proposed by Freese and Winkler [Dark matter and gravitational waves from a dark big bang, ], dark matter can be produced through a first-order phase transition in the dark sector dubbed “the dark big bang.” We fully determine the allowed region of parameter space for the tunneling potential that leads to the realization of a dark big bang and is consistent with all experimental bounds available.

Published by the American Physical Society
2024
Machine learning potential for the Cu-W system
Authors: Liyanage Manura , Turlo Vladyslav , Curtin W. A. 
Published: November 2024

Combining the excellent thermal and electrical properties of Cu with the high abrasion resistance and thermal stability of W, Cu-W nanoparticle-reinforced metal matrix composites and nano-multilayers are finding applications as brazing fillers and shielding material for plasma and radiation. Due to the large lattice mismatch between fcc Cu and bcc W, these systems have complex interfaces that are beyond the scales suitable for methods, thus motivating the development of chemically accurate interatomic potentials. Here, a neural network potential (NNP) for Cu-W is developed within the Behler-Parrinello framework using a curated training dataset that captures metallurgically relevant local atomic environments. The Cu-W NNP accurately predicts (i) the metallurgical properties (elasticity, stacking faults, dislocations, thermodynamic behavior) in elemental Cu and W, (ii) energies and structures of Cu-W intermetallics and solid solutions, and (iii) a range of fcc Cu/bcc W interfaces, and exhibits physically reasonable behavior for solid W/liquid Cu systems. As will be demonstrated in forthcoming work, this near accurate NNP can be applied to understand complex phenomena involving interface-driven processes and properties in Cu-W composites.

Published by the American Physical Society
2024
Exploring the views and experiences of professionals using PBS and emotional development assessment for individuals with an intellectual disability: a case study
Authors: McCarthy Freya Elizabeth Rose , Simpson Stephanie Jane 
Published: November 2024

Purpose
The purpose of this paper was to investigate the utility of including emotional development (ED) assessment into a Positive Behaviour Support (PBS) approach in clinical practice with a patient with an intellectual disability (ID) and challenging behaviour.

Design/methodology/approach
Interviews were conducted with four staff involved in the care of the patient. The interviews were transcribed and analysed using thematic analysis and three reflective sessions were completed with the lead psychologist of the service.

Findings
Using thematic analysis, four themes were identified: getting everyone around the table: a collaborative approach, complementary approaches: a feedback loop, helping to make sense of the individual and ensuring a voice for service users.

Research limitations/implications
This was a case study selected from routine clinical practice and as such generalisability may be limited. This case study was designed as an exploration of the potential benefits of incorporating ED alongside PBS for ID and provides a basis for future research.

Practical implications
This study highlights the value of integration of ED assessment for people with ID and challenging behaviour within a healthcare team.

Originality/value
There is a lack of literature relating to ED and challenging behaviour within an ID population, particularly exploring ED within a PBS framework. This study provides a starting point for exploring how practice can be improved through incorporating ED assessment for individuals with ID and challenging behaviour.
Bending analysis of viscoelastic plates according to the Reissner’s theory using meshless local Petrov–Galerkin method and hereditary integral formulation
Authors: Monnerat Daniel Dias , Santiago José Antonio Fontes , Telles José Claudio de Faria , Cezario Flavio , Riobom Neto Carlos Gouveia , Costa Edmundo Guimarães de Araújo 
Published: November 2024

Purpose The purpose of this study is to apply the Meshless Local Petrov–Galerkin (MLPG) method to solve the bending problems of linear viscoelastic plates, considering Reissner’s theory.Design/methodology/approachThe weak formulation for the set of equations that govern Reissner’s plate theory is implemented in conjunction with the integral formulation applied to viscoelastic constitutive expressions. A meshless method based on the Moving Least Squares (MLS) approximation is considered in the numerical implementation. The final equation system is assembled by adopting simple and efficient schemes for numerical integration, considering a simplified formulation through centralization of the local interpolation domains and Gaussian quadrature at the same field point. The results obtained are compared with available solutions to demonstrate the efficiency of the proposed formulation.FindingsThe hereditary integral approach proved to be the most general way to analyze the viscoelastic problem, especially when applied together with the modified scheme for numerical integration. In addition, the variable changing technique is demonstrated to be an efficient formulation for solving shear-locking effects in thin plate problems.Originality/valueThe differential of the present study is related to the manner in which the properties of linear viscoelastic materials are considered in the formulation. Although most authors consider this point through the application of the correspondence principle, the present study works with a hereditary integral formulation. In addition, the variable changing technique is applied to solve the shear-locking effects, and an alternative approximation technique is considered to speed up the numerical integration process.
Optimising Malaysia’s power mix for a sustainable future: a multi-scenario modelling approach
Authors: Woo Wing Thye , Leong Yuen Yoong , Low Wai Sern , Liew Jin Soong , Lee Chean Chung 
Published: November 2024

PurposeThis study employs advanced modelling to assess the effectiveness of Malaysia’s current energy policies in achieving a low-carbon future. By optimising a 100% renewable energy mix, including energy storage, the research identifies pathways to decarbonise the power sector while minimising costs. These findings will inform the development of future policies.Design/methodology/approachThis study employs the Stockholm Environment Institute-developed Low Emissions Analysis Platform (LEAP) and Next Energy Modeling system for Optimization (NEMO) to construct and optimise a comprehensive Malaysian power sector model. The model encompasses both electricity supply, including diverse electricity generation sources and demand across key sectors. Three scenarios – existing policy, optimised existing policy and more ambitious policy (near-zero emissions) – are analysed.FindingsSolar photovoltaic (PV) is the dominant technology, but realising its full potential requires significant grid upgrades. While natural gas expansion underpins Malaysia’s decarbonisation strategy, solar and storage offer a cleaner and potentially cost-effective alternative. Rapid technological advancements in clean energy increase stranded asset risk for new gas power plants. Malaysia’s abundant bioenergy resources need more tapping. This can contribute to decarbonisation and rural development. Transitioning to a fully renewable grid necessitates substantial investments in energy storage and grid infrastructure. While falling battery costs and regional interconnection can mitigate costs, careful consideration of potential disruptions and cost fluctuations is essential for resilience.Research limitations/implicationsEnergy sector modelling results are inherently dependent on input assumptions, such as future technology costs, resource availability and fossil fuel prices. These factors can be highly uncertain. While this study did not conduct sensitivity analyses to explore how variations in these assumptions might affect the results (e.g. cost variations across scenarios, technology mix fluctuations), the core findings provide valuable insights into potential decarbonisation pathways for Malaysia’s power sector. Future studies could build upon this work by incorporating sensitivity analyses to provide a more comprehensive understanding of how key results might change under a wider range of future possibilities.Originality/valueThis study co-optimises a 100% renewable energy mix for Malaysia, incorporating a comprehensive range of renewable resources, battery and pumped hydro storage. The research also provides a unique perspective on the interplay of philosophical underpinnings, psychological maturity and energy policy.