bluuebunny/crossref_metadata_2025_split huggingface dataset:
PepCleav: a classification method for evaluating the cleavability of peptide fragments presented by MHC class I
Authors: Jiang Dawei , Zhu Wenxin , Xi Binbin , Du Hongli 
Published: July 2024

AbstractNeoantigens, due to their tumor specificity and lack of central tolerance, are promising targets for cancer immunotherapy. Evaluating the cleavability of peptide fragments generated by proteasomes and aminopeptidases is crucial for neoantigen identification, but tools for this purpose are scarce. To address this, we developed PepCleav, a method for evaluating peptide cleavability by classifying the amino acids at the proteasome and aminopeptidase recognition sites of the C- and N-termini. By integrating C- and N-terminal cleavability, PepCleav accurately predicted the overall cleavability of peptide fragments in test datasets, correctly identifying 84-89% of cleavable peptides and 63-92% of non-cleavable peptides. We also found that highly cleavable peptides have a higher likelihood of being effective neoantigens, highlighting PepCleav’s potential to improve neoantigen identification. PepCleav’s source code is publicly available athttps://github.com/Dulab2020/PepCleav.
Metabolomic differentiation of amino acid profiles in adult deltamethrin-resistantAedes albopictus(L.)
Authors: Ong Song-Quan , Ishak Intan H , Nair Gomesh , Paulous Rolinus 
Published: July 2024

AbstractUnderstanding the susceptibility status of mosquitoes to insecticides is critical for effective decision making regarding the use or rotation of insecticides in control programs. In this study, we demonstrated the use of amino acid profiling for the detection of deltamethrin-resistantAedes albopictus(L.). Mosquitoes collected in the field were first tested with WHO adulticide bioassay kits, and the amino acid profiles of the resistant mosquitoes were compared with the susceptible strain ofAe. albopictus. Samples were lyophilized and derived by silylation and then analyzed by gas chromatography-mass spectrometry (GC-MS). Using standardized, known concentrations of amino acids, we quantified the amino acids in both resistant and susceptible strains. An independent t-test was performed to compare the concentrations of each amino acid between strains. Logistic regression was then performed to assess the relationship between amino acid concentrations and susceptibility status of the mosquitoes. Our results showed that the amino acids in resistant mosquitoes differed significantly from those in susceptible mosquitoes, with the exception of serine. Further regression analysis showed that seven amino acids significantly predicted susceptibility, suggesting that they are suitable as biological indicators for rapid assessment of resistance status in field mosquitoes.Graphic abstractIdentification of deltamethrin-resistant mosquitoes based on differences in the amino acid profile: Deltamethrin-susceptible and -resistant mosquito strains were lyophilised and converted into esters by silylation, which were then analysed using a gas chromatography-mass spectrometer (GC-MS). The difference between susceptible and resistant could be classified by developing a classification model with logistic regression.
The guardians of mitochondrial dynamics: a novel role for intermediate filament proteins
Authors: Hemel Irene MGM , Steen Carlijn , Denil Simon LIJ , Ertaylan Gökhan , Kutmon Martina , Adriaens Michiel , Gerards Mike 
Published: July 2024

AbstractMitochondria are dynamic organelles and the main source of cellular energy. Their dynamic nature is crucial to meet cellular requirements. However, the processes and proteins involved in mitochondrial dynamics are not fully understood. Using a computational protein-protein interaction approach, we identified ITPRIPL2, which caused mitochondrial elongation upon knockdown. ITPRIPL2 co-localizes with the intermediate filament protein vimentin and interacts with vimentin according to protein simulations. ITPRIPL2 knockdown alters vimentin processing, disrupts intermediate filaments and transcriptomics analysis revealed changes in vimentin-related pathways. Our data illustrates that ITPRIPL2 is essential for vimentin related intermediate filament structure. Interestingly, like ITPRIPL2 knockdown, vimentin knockdown results in mitochondrial elongation. Our data highlights ITPRIPL2 as a vimentin-associated protein and reveals a role for intermediate filaments in mitochondrial dynamics, improving our understanding of mitochondrial dynamics regulators. Moreover, our study demonstrates that protein- protein interaction analysis is a powerful approach for identifying novel mitochondrial dynamics proteins.
In the AlphaFold era, when is experimental phasing of protein crystals still required?
Authors: Keegan Ronan M. , Simpkin Adam J. , Rigden Daniel J. 
Published: July 2024

AbstractThe availability of highly accurate protein structure predictions from AlphaFold 2 (AF2) and similar tools has hugely expanded the applicability of Molecular Replacement (MR) for crystal structure solution. Many structures solve routinely using raw models, structures processed to remove unreliable parts or models split into distinct structural units. There is therefore an open question around how many and which cases still require experimental phasing methods such as single-wavelength anomalous diffraction (SAD). Here we address the question using a large set of PDB deposits that were solved by SAD. A large majority (87%) solve using unedited or minimally edited AF2 predictions. A further 17 (4%) yield straightforwardly to MR after splitting of the AF2 prediction using Slice’N’Dice, although different splitting methods succeed on slightly different sets of cases. We also find that further unique targets can be solved by alternative modelling approaches such as ESMFold (four cases), alternative MR approaches such as ARCIMBOLDO and AMPLE (two cases each), and multimeric model building with AlphaFold-Multimer or UniFold (three cases). Ultimately, only 12 cases, or 3% of the SAD-phased set did not yield to any form of MR tested here, offering valuable hints as to the number and characteristics of cases where experimental phasing remains essential for macromolecular structure solution.
Design principles of small intestinal crypt maintenance
Authors: Banjac Isidora , Maimets Martti , Tsang Ingrid , Dioli Marius , Hansen Stine Lind , Krizic Kata , Bressan Raul Bardini , Lövkvist Cecilia , Jensen Kim B. 
Published: July 2024

SummaryThe intestinal epithelium has a remarkably high turnover in homeostasis. It remains unresolved how turnover is orchestrated at the cellular level and how the behaviour of stem and progenitor cells ensures tissue maintenance. To address this, we combined quantitative fate mapping in three complementary mouse models with mathematical modelling and single-cell RNA sequencing. Our integrated approach generated a spatially and temporally defined model of crypt maintenance that is based on two cycling populations: crypt-based columnar (CBC) and transit amplifying (TA) cells. Validation experiments substantiated the predictions from the model revealing TA cells as the major contributor to the absorptive lineage, while balanced CBC cell fate choices controlled the numbers of cells in the secretory lineage. By unravelling these mechanisms, we gain insights into the process of tissue turnover and provide direct evidence to support the notion of CBC cells as the major driver of the intestinal epithelium replenishment.HighlightsSpatially and temporally resolved cellular model of small intestinal crypt maintenance.Stem cells exhibit predisposition towards secretory fate.Secretory lineage has a limited contribution to the high turnover of intestinal epithelium.Cellular differentiation within the crypt occurs rapidly within 72 hours.
Test of a conservation intervention highlights temporal variability in hybridization dynamics inCatostomusfishes
Authors: Campbell Jillian N. , Hooley-Underwood Zachary E. , Mandeville Elizabeth G. 
Published: July 2024

AbstractNon-native species are a leading threat to fish biodiversity. They pose risks to native populations through human-mediated introductions resulting in hybridization events, which could result in demographic or genetic swamping.Catostomusfishes in the Upper Colorado River Basin are an example of this. Extensive hybridization occurs between non-native white suckers (C. commersonii) and native flannelmouth and bluehead suckers (C. latipinnisandC. discobolus). This system provides a suitable model for using genomic analyses to test the efficacy of an intervention to reduce the abundance of non-native species and production of hybrid offspring. This study implemented a Resistance Board Weir (RBW) as a fish barrier across Roubideau Creek, a tributary of the Gunnison River in Colorado (USA), to restrict non-native sucker participation in spawning events. Conducted over four years, the study gathered genomic data from larval fish samples, pre- and post-implementation of the RBW. We used genomic data to determine the efficacy of a RBW at limiting non-native and hybridized sucker larval production. We found no significant effect of the weir on the proportion of white sucker ancestry in larval fish across the four years of the study, which included three years of weir usage when access was successfully controlled for variable amounts of time. Overall, this work provides insight into the efficacy of a resistance board weir as a management tool for non-native suckers, and highlights interannual variability. This work contributes valuable information for policy and fisheries management in Colorado.
Cryopreservation Enables Long-Term Studies ofOctopus vulgarisHemocyte Immune Functions
Authors: Costa MM , Paredes E , Peleteiro M , Gambón F , Dios S , Gestal C 
Published: July 2024

AbstractAs with their nervous system and other physiological traits, the immune system of cephalopods, in general, and of the common octopus, Octopus vulgaris, in particular, could also present highly evolved characteristics compared to other classes of molluscs. However, to date, there is not much information about it, and studying the defense mechanisms is a key step in understanding their response system to external aggressions and, thus, having the tools to anticipate animal health problems and ensure their welfare.The lack of cell cultures in molluscs is a major problem when carrying outin vitroassays that help to deepen the knowledge of the main immune cells of this species. Cryopreservation becomes an alternative to maintain viable and functional cells after freezing/thawing processes, allowing a larger repertoire of studies to be performed with the same sample or to perform time courses.Having access to good quality cells for long periods will allow to cover a larger repertoire of studies with the same sample or to perform time courses, avoiding logistic bottlenecks that could arise due to the loss of viability and/or functionality of the cells on the lab bench, the lack of time to develop all the desired assays in the same day or the possible losses derived from transporting the samples between different laboratories. Additionally, high-quality suspensions of viable and functional cells are required for successful massive sequencing studies, such as single-cell analysis, where these aspects are the key to an optimal identification.We show here the first functional results from cryopreserved octopus hemocytes, where the cells were able to maintain viability above 80% after two months post cryopreservation and storage at −80°C and their functional ability to phagocytose bacteria similar to fresh cells. Our data revealed that the acclimation process after thawing was essential to recovering the functional activity of the cells.The results presented here will facilitate the study of the functions of the most important immune cells of this species and will provide tools for cell preservation in other molluscs species.
Effects ofBacillus thuringiensissubsp.kurstakiapplication on non-target nocturnal macromoth biodiversity in the eastern boreal forest, Canada
Authors: Young Jodi O. , Bowden Joseph J. , Moise Eric R. D. , Scott Robert , Christian Schmidt B. 
Published: July 2024

AbstractInsect biodiversity is crucial for resilient ecosystems, supporting essential services. Moths play significant roles as herbivores, pollinators, decomposers, and as prey for birds, bats, and predatory invertebrates, emphasizing their conservation importance. However, large-scale studies on the non-target effects ofBacillus thuringiensissubs.kurstaki(Btk) on moth communities are limited, particularly in northern forests where diversity is lower. Btk is commonly used to control pest insect populations, with forest managers in eastern Canada applying it to manage eastern spruce budworm.We established a replicated two-year study in the North American Boreal Forest of western Newfoundland, Canada, using paired Btk-treated and control (untreated) sites.No significant differences in total abundance or richness were found between treated and control sites. In 2021, Hill numbers only differed between our northern treatment and control sites, which may reflect those stands having already received multiple years of treatment compared to just one year in the southern sites. In 2022, control sites showed higher diversity (Shannon and Simpson diversity metrics) compared to treated sites, extending to all locations.Multiple years of Btk treatment led to shifts in community composition and the relative abundance of some common species, without affecting total richness or abundance. Species responses varied, likely due to Btk sensitivity, application timing, and differences in phenology and voltinism, making it difficult to generalize the effects of Btk on moth communities.
Investigating the role of RNA-binding protein Ssd1 in aneuploidy tolerance through network analysis
Authors: Dutcher H. Auguste , Gasch Audrey P. 
Published: July 2024

ABSTRACTRNA-binding proteins (RBPs) play critical cellular roles by mediating various stages of RNA life cycles. Ssd1, an RBP with pleiotropic effects, has been implicated in aneuploidy tolerance inSaccharomyces cerevisiaebut its mechanistic role remains unclear. Here we used a network-based approach to inform on Ssd1’s role in aneuploidy tolerance, by identifying and experimentally perturbing a network of RBPs that share mRNA targets with Ssd1. We identified RBPs whose bound mRNA targets significantly overlap with Ssd1 targets. For 14 identified RBPs, we then used a genetic approach to generate all combinations of genotypes for euploid and aneuploid yeast with an extra copy of chromosome XII, with and withoutSSD1and/or the RBP of interest. Deletion of 10 RBPs either exacerbated or alleviated the sensitivity of wild-type and/orssd1Δ cells to chromosome XII duplication, in several cases indicating genetic interactions withSSD1in the context of aneuploidy. We integrated these findings with results from a global over-expression screen that identified genes whose duplication complementsssd1Δ aneuploid sensitivity. The resulting network points to a sub-group of proteins with shared roles in translational repression and p-body formation, implicating these functions in aneuploidy tolerance. Our results reveal a role for new RBPs in aneuploidy tolerance and support a model in which Ssd1 mitigates translation-related stresses in aneuploid cells.
How genotype-by-environment interactions can maintain variation in mutualisms
Authors: Carlson Christopher I. , Frederickson Megan E. , Osmond Matthew M. 
Published: July 2024

AbstractCoevolution requires reciprocal genotype-by-genotype (GXG) interactions for fitness, which occur when the fitnesses of interacting species depend on the match between their genotypes. However, in mutualisms, when GXG interactions are mutually beneficial, simple models predict that positive feedbacks will erode genetic variation, weakening or eliminating the GXG interactions that fuel ongoing coevolution. This is inconsistent with the ample trait and fitness variation observed within real-world mutualisms. Here, we explore how genotype-by-environment (GXE) interactions, which occur when different genotypes respond differently to different environments, maintain variation in mutualisms. We employ a game theoretic model in which the fitnesses of two partners depend on mutually beneficial GXG and GXE interactions. Variation is maintained via migration-selection balance when GXE interactions are slightly stronger than GXG interactions or when they are much stronger than GXG interactions for just one partner. However, unexpectedly, when GXE interactions are much stronger than GXG interactions for both partners and dispersal is high, genotypically mismatched partners can fix, eroding variation and leading to apparent maladaptation between partners. We parameterize our model using data from three published reciprocal transplant experiments and find that the observed strengths of GXE interactions can maintain or erode variation in mutualisms via these mechanisms.
3D printed bioelectronic scaffolds with soft tissue-like stiffness
Authors: Okafor Somtochukwu S. , Park Jae , Liu Tianran , Goestenkors Anna P. , Alvarez Riley M. , Semar Barbara A. , Yu Justin S. , O’Hare Cayleigh P. , Montgomery Sandra K. , Friedman Lianna C. , Rutz Alexandra L. 
Published: July 2024

Abstract3D printing is a leading technique for fabricating tissue engineering scaffolds that facilitate native cellular behavior. Engineering scaffolds to possess functional properties like electronic conductivity is the first step towards integrating new technological capabilities like stimulating or monitoring cellular activity beyond the traditionally presented biophysical and biochemical cues. However, these bioelectronic scaffolds have been largely underdeveloped since the majority of electrically conducting materials possess high stiffness values outside the physiological range and that may negatively impact desired cell behavior. Here, we present methods of 3D printing poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogel scaffolds and provide techniques to achieve stiffness relevant to many soft tissues (<100 kPa). Structures were confirmed as ideal tissue scaffolds by maintaining biostability and promoting high cell viability, appropriate cell morphology, and proliferation. With these findings, we contribute a customizable 3D platform that provides favorable soft cellular microenvironments and envision it to be adaptable to several bioelectronic applications.
Role of Kir4.1/Kir5.1 in mediating Angiotensin-II (Ang-II)-induced stimulation of thiazide-sensitive Na-Cl cotransporter
Authors: Duan Xin-Peng , Meng Xin-Xin , Xiao Yu , Zhang Cheng-Biao , Gu Ruimin , Lin Dao-Hong , Wang Wen-Hui 
Published: July 2024

AbstractBackgroundAngiotensin-II (Ang-II) perfusion stimulates Kir4.1/Kir5.1 in the distal-convoluted-tubule (DCT) and thiazide-sensitive Na-Cl-cotransporter (NCC). However, the role of Kir4.1/Kir5.1 in mediating the effect of Ang-II on NCC is not understood.MethodsWe used immunoblotting and patch-clamp-experiments to examine whether Ang-II-induced stimulation of NCC is achieved by activation of Kir4.1/Kir5.1 of the DCT using kidney-renal-tubule-specific AT1aR-knockout (Ks-AT1aR-KO), Ks-Kir4.1-knockout and the corresponding wild-type mice.ResultsAng-II perfusion for 1, 3 and 7 days progressively increased phosphor-NCC (pNCC) and total-NCC (tNCC) expression and the effect of Ang-II-perfusion on pNCC and tNCC was abolished in Ks-AT1aR-KO. Ang-II perfusion for 1-day robustly stimulates Kir4.1/Kir5.1 in the late DCT (DCT2) and to a lesser degree in the early DCT (DCT1), an effect was absent in Ks-AT1aR-KO mice. However, Ang-II perfusion for 7-days did not further stimulate Kir4.1/Kir5.1 in the DCT2 and only modestly increased Kir4.1/Kir5.1-mediated K+currents in DCT1. Deletion of Kir4.1 not only significantly decreased the expression of pNCC and tNCC but also abolished the effect of 1-day Ang-II perfusion on the expression of phospho-with-no-lysine-kinase-4 (pWNK4), phosphor-ste-20-proline-alanine-rich-kinase (pSPAK), pNCC and tNCC. However, 7-days Ang-II perfusion was still able to significantly stimulate the expression of pSPAK, pWNK4, pNCC and tNCC, and increased thiazide-induced natriuresis in kidney-tubule-specific Kir4.1 knockout (Ks-Kir4.1 KO) mice without obvious changes in K+channel activity in the DCT.ConclusionsShort-term Ang-II induced stimulation of pWNK4, pSPAK and pNCC depends on Kir4.1/Kir5.1 activity. However, long-term Ang-II is able to directly stimulate pWNK4, pSPAK and pNCC by a Kir4.1/Kir5.1 independent mechanism.
Axis reset is rate limiting for onset of whole-body regenerative abilities during planarian development
Authors: Booth Clare L.T. , Stevens Brian C. , Stubbert Clover A. , Kallgren Neil T. , Davies Erin L. 
Published: July 2024

SUMMARYFew studies have investigated whether or how regenerative abilities vary across developmental stages of animal life cycles. Determining mechanisms that promote or limit regeneration in certain life cycle stages may pinpoint the most critical factors for successful regeneration and suggest strategies for reverse-engineering regenerative responses in therapeutic settings. In contrast to many mammalian systems, which typically show a loss of regenerative abilities with age, planarian flatworms remain highly regenerative throughout adulthood. The robust reproductive and regenerative capabilities of the planarianSchmidtea polychroa(Spol) make them an ideal model to determine when and how regeneration competence is established during development. We report thatSpolgradually acquires whole body regenerative abilities during late embryonic and early juvenile stages. Posterior (tail) regenerative abilities are constitutive, whereas anterior (head) regenerative abilities are dependent on developmental stage, tissue composition of the amputated fragment, and axial position of the cut plane. Stem-like cells are required, but not sufficient, for onset of head regeneration ability. We propose that regulation of main body axis reset, specifically the ability to remake an anterior organizing center, is a rate-limiting factor for establishment of whole-body regeneration competence. Supporting this hypothesis, knock-down of the canonical Wnt pathway effectorSpol β-catenin-1,a posterior determinant, induces precocious head regeneration under conditions that are normally head regeneration incompetent. Our results suggest that regeneration competence emerges through interactions between cycling stem-like cells, the cellular source of new tissue, and developing adult tissue(s) harboring axial patterning information.
In-uterorescue of neurological dysfunction in a mouse model of Wiedemann-Steiner syndrome
Authors: Reynisdottir Tinna , Anderson Kimberley Jade , Brinn Andrew , Franklin Katie , Ouyang Juan , Snorradottir Asbjorg Osk , Lutz Cathleen M. , Zuberi Aamir R. , DeLeon Valerie Burke , Bjornsson Hans Tomas 
Published: July 2024

AbstractWiedemann-Steiner syndrome (WDSTS) is a rare genetic cause of intellectual disability primarily caused by heterozygous loss of function variants in the gene encoding the histone methyltransferase KMT2A. Prior studies have shown successful postnatal amelioration of disease phenotypes for Rett, Rubinstein-Taybi and Kabuki syndromes, related Mendelian disorders of the epigenetic machinery. To explore whether the neurological phenotype in WDSTS is treatablein-utero, we created a novel mouse model carrying a loss of function variant in between two loxP sites.Kmt2a+/LSLmice demonstrate core features of WDSTS including growth retardation, craniofacial abnormalities, and hypertrichosis as well as hippocampal memory defects. The neurological phenotypes show rescue upon restoration ofKMT2A in-uterofollowing breeding to a nestin-Cre. Together, our data provide a novel mouse model to explore the therapeutic window in WDSTS. Our work suggests that WDSTS has a window of opportunity extending at least until the mid-point ofin-uterodevelopment, making WDSTS an ideal candidate for future therapeutic strategies.Abstract FigureGraphical abstract