bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgery versus Balloon angioplasty for treating coarctation of aorta: A meta-analysis
Authors: Dani Avichal , Thakkar Helly , Desai Dev , Dani Jagdeepkaur S. , Dani Sameer I. 
Published: April 2023

AbstractBackgroundIn the past 50 years, therapeutic options for treating both children and adults with native aortic coarctation have significantly improved. In contrast to surgery, In 1982, balloon angioplasty (BA) was suggested as a potential alternative for the Primary treatment of CoA. Here, Surgery vs Angioplasty is compared to understand the rates of their compilations like aneurysm and recoarctation.MethodA total of 13 RCTs with a total of 877 patients (Surgery-537, Angioplasty-340) of total patients were identified following PRISMA guidelines till November 2019 and were matched for inclusion and exclusion criteria. The following search strings and MESH terms were used: ‘coarctation of aorta’, ‘surgery’, ‘balloon angioplasty, and ‘aneurysm’. Following this, Surgery and Angioplasty were evaluated for complications and recoarctation. RevMan 5.3 was used for appropriate statistical tests. Fixed and Random Effect Model tests were used and p<0.05 was considered statistically significant.ResultAngioplasty seems to be a Statistically better alternative with lesser complications (OR=1.993, CI95=1.126 to 3.527, p=0.018). It can be seen that Surgery is statistically far better in preventing the formation of an aneurysm (OR=0.291, CI95=0.141 to 0.602, p=0.001). Surgery as a treatment is statistically better than angioplasty to prevent a recoarctation (OR=0.375, CI95=0.268 to 0.524, p=<0.001).ConclusionSurgery is found to be a better treatment option for preventing complications whereas angioplasty is better in preventing the formation of aneurysms and recoarctation.
In vivoStability and Biodistribution of Liposome Coated with SlpB fromLevilactobacillus brevis
Authors: Tan Zheng Lin , Yamamoto Naoyuki 
Published: April 2023

AbstractSlpB fromLevilactobacillus brevisoffers a solution to stabilise liposome in gastrointestinal tract, and to target intestinal APCs in Peyer’s patches, rendering it a powerful tool for oral delivery of drugs, and to yield the benefits provided by oral delivery. However, the stability of SlpB-coated liposome (SlpB-LP) and its distribution in tissues were not characterized. In this study, we have demonstrated that SlpB-coating could improve the stability of liposome in gastrointestinal tract, and facilitate specific uptake of liposome into Peyer’s patches, but not intestinal, nor intestinal mucosa. Furthermore, we have shown that uptake of SlpB-LP into Peyer’s patches enhanced bioavailability of drugs, which have resulted in 427.65-fold increase in bioavailability and at least 2.41-fold decrease in retention of fluorophore in liver where drug metabolism takes places, to a degree which approximate control group. In conclusion, this study shows that SlpB could increase stability of liposome in gastrointestinal tract, increase specific uptake of liposome into Peyer’s patches, and improve bioavailability.Abstract Figure
Echoes from the last Green Sahara: whole genome analysis of Fulani, a key population to unveil the genetic evolutionary history of Africa
Authors: D’Atanasio Eugenia , Risi Flavia , Ravasini Francesco , Montinaro Francesco , Hajiesmaeil Mogge , Bonucci Biancamaria , Pistacchia Letizia , Amoako-Sakyi Daniel , Bonito Maria , Onidi Sara , Colombo Giulia , Semino Ornella , Bisol Giovanni Destro , Anagnostou Paolo , Metspalu Mait , Tambets Kristiina , Trombetta Beniamino , Cruciani Fulvio 
Published: April 2023

AbstractBackgroundThe Sahelian Fulani are the largest nomadic pastoral ethnic group. Their origins are still largely unknown and their Eurasian genetic component is usually explained by recent admixture events with northern African groups. However, it has also been proposed that Fulani may be the descendants of ancient groups settled in the Sahara during its last Green phase (12000-5000 BP), as also suggested by Y chromosome results.ResultsWe produced 23 high-coverage (30 ×) whole genomes from Fulani individuals from 8 Sahelian countries, plus 17 samples from other African groups and 3 Europeans as controls, for a total of 43 new whole genome sequences. These data have been compared with 814 published modern whole genomes and analyzed together with relevant published ancient individuals (for a total of > 1800 samples). These analyses showed that the non-sub-Saharan genetic ancestry component of Fulani cannot be only explained by recent admixture events, but it could be shaped at least in part by older events by events more ancient than previously reported, possibly tracing its origin to the last Green Sahara.ConclusionsAccording to our results, Fulani may be the descendants of Saharan cattle herders settled in that area during the last Green Sahara. The exact ancestry composition of such ghost Saharan population(s) cannot be completely unveiled from modern genomes only, but the joint analysis with the available African ancient samples suggested a similarity between ancient Saharans and Late Neolithic Moroccans.
Modeling neurodevelopmental disorder-associatedhAGO1mutations inC. elegansArgonauteALG-1
Authors: Duan Ye , Li Li , Panzade Ganesh Prabhakar , Piton Amélie , Zinovyeva Anna , Ambros Victor 
Published: April 2023

ABSTRACTMicroRNAs (miRNA) are endogenous non-coding RNAs important for post-transcriptional regulation of gene expression. miRNAs associate with Argonaute proteins to bind to the 3’ UTR of target genes and confer target repression. Recently, multiplede novocoding variants in the human Argonaute geneAGO1(hAGO1) have been reported to cause a neurodevelopmental disorder (NDD) with intellectual disability (ID). Most of the altered amino acids are conserved between the miRNA-associated Argonautes inH. sapiensandC. elegans, suggesting thehAGO1mutations could disrupt evolutionarily conserved functions in the miRNA pathway. To investigate how thehAGO1mutations may affect miRNA biogenesis and/or functions, we genetically modeled four of thehAGO1 de novovariants (referred to as NDD mutations) by introducing the identical mutations to theC. elegans hAGO1 homolog, alg-1. This array of mutations caused distinct effects onC. elegansmiRNA functions, miRNA populations, and downstream gene expression, indicative of profound alterations in aspects of miRNA processing and miRISC formation and/or activity. Specifically, we found that thealg-1NDD mutations cause allele-specific disruptions in mature miRNA profiles both in terms of overall abundances and association with mutant ALG-1. We also observed allele-specific profiles of gene expression with altered translational efficiency and/or mRNA abundance. The sets of perturbed genes include human homologs whose dysfunction is known to cause NDD. We anticipate that these cross-clade genetic studies may advance the understanding of fundamental Argonaute functions and provide insights into the conservation of miRNA-mediated post-transcriptional regulatory mechanisms.
The minus end depolymerase KIF2A drives flux-like treadmilling of γTuRC-uncapped microtubules
Authors: Henkin Gil , Brito Cláudia , Thomas Claire , Surrey Thomas 
Published: April 2023

ABSTRACTDuring mitosis, a functional spindle requires high microtubule turnover. Such turnover is highlighted by the multiple functions of spindle poles, where microtubule minus ends are concentrated, and where microtubule nucleation and depolymerization happen side by side. How these seemingly antagonistic processes are coordinated during poleward microtubule flux is not understood. Here we reconstitute this coordinationin vitrocombining different pole localized activities. We find that the spindle pole-localized kinesin-13 KIF2A is a microtubule minus-end depolymerase, in contrast to its paralog MCAK. Due to its asymmetric activity, KIF2A still allows microtubule nucleation by plus-end growth from the γ-tubulin ring complex (γTuRC), which in turn serves as a protective cap that shields the minus end against KIF2A binding. Efficient γTuRC-uncapping requires the combined action of KIF2A and a microtubule severing enzyme, then leading to treadmilling of the uncapped microtubule driven by KIF2A. Together these results provide insight into the molecular mechanisms by which a minimal protein module coordinates microtubule nucleation and depolymerization at spindle poles consistent with their role in poleward microtubule flux.
WITHDRAWN: Progranulin inhibits phospholipase sPLA2-IIA to control neuroinflammation
Authors: Du Huan , Yang Cha , Nana Alissa L. , Seeley William W. , Smolka Marcus , Hu Fenghua 
Published: April 2023

Withdrawal StatementThe authors have withdrawn this manuscript because more work is needed to fully define the role of sPLA2-IIA. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Intestinal transit amplifying cells require METTL3 for growth factor signaling, KRAS expression, and cell survival
Authors: Danan Charles H. , Naughton Kaitlyn E. , Hayer Katharina E. , Vellappan Sangeevan , McMillan Emily A. , Zhou Yusen , Matsuda Rina , Nettleford Shaneice K. , Katada Kay , Parham Louis R. , Ma Xianghui , Chowdhury Afrah , Wilkins Benjamin J. , Shah Premal , Weitzman Matthew D. , Hamilton Kathryn E. 
Published: April 2023

AbstractIntestinal epithelial transit amplifying cells are essential stem progenitors required for intestinal homeostasis, but their rapid proliferation renders them vulnerable to DNA damage from radiation and chemotherapy. Despite their critical roles in intestinal homeostasis and disease, few studies have described genes that are essential to transit amplifying cell function. We report that the RNA methyltransferase, METTL3, is required for survival of transit amplifying cells in the murine small intestine. Transit amplifying cell death after METTL3 deletion was associated with crypt and villus atrophy, loss of absorptive enterocytes, and uniform wasting and death in METTL3-depleted mice. Ribosome profiling and sequencing of methylated RNAs in enteroids andin vivodemonstrated decreased translation of hundreds of unique methylated transcripts after METTL3 deletion, particularly transcripts involved in growth factor signal transduction such asKras. Further investigation confirmed a novel relationship between METTL3 andKrasmethylation and protein levelsin vivo. Our study identifies METTL3 as an essential factor supporting the homeostasis of small intestinal tissue via direct maintenance of transit amplifying cell survival. We highlight the crucial role of RNA modifications in regulating growth factor signaling in the intestine, with important implications for both homeostatic tissue renewal and epithelial regeneration.
Patterns of host plant use do not explain mushroom body expansion in Heliconiini butterflies
Authors: Young Fletcher J. , Monllor Monica , McMillan W. Owen , Montgomery Stephen H. 
Published: April 2023

AbstractThe selective pressures leading to the elaboration of downstream, integrative processing centres, such as the mammalian neocortex or insect mushroom bodies, are often unclear. InHeliconiusbutterflies, the mushroom bodies are three to four times larger than their Heliconiini, and the largest known in Lepidoptera. Heliconiini lay almost exclusively onPassiflora, which exhibit a remarkable diversity of leaf shape, and it has been suggested that the mushroom body expansion ofHeliconiusmay have been driven by the cognitive demands of recognising and learning the leaf shapes of local host plants. We test this hypothesis using two complementary methods: i) phylogenetic comparative analyses to test whether variation in mushroom body size is associated with the morphological diversity of host plants exploited across the Heliconiini; and ii) shape learning experiments using six Heliconiini species. We found that variation in the range of leaf morphologies used by Heliconiini was not associated with mushroom body volume. Similarly, we find interspecific differences in shape learning ability, butHeliconiusare not overall better shape learners than other Heliconiini. Together these results suggest that the visual recognition and learning of host plants was not a main factor driving the diversity of mushroom body size in this tribe.
Sequence-specific interactions determine viscoelasticity and aging dynamics of protein condensates
Authors: Alshareedah Ibraheem , Borcherds Wade M. , Cohen Samuel R. , Singh Anurag , Posey Ammon E. , Farag Mina , Bremer Anne , Strout Gregory W. , Tomares Dylan T. , Pappu Rohit V. , Mittag Tanja , Banerjee Priya R. 
Published: April 2023

AbstractBiomolecular condensates are viscoelastic materials. Here, we report results from investigations into molecular-scale determinants of sequence-encoded and age-dependent viscoelasticity of condensates formed by prion-like low-complexity domains (PLCDs). The terminally viscous forms of PLCD condensates are Maxwell fluids. Measured viscoelastic moduli of these condensates are reproducible using a Rouse-Zimm model that accounts for the network-like organization engendered by reversible physical crosslinks among PLCDs in the dense phase. Measurements and computations show that the strengths of aromatic inter-sticker interactions determine the sequence-specific amplitudes of elastic and viscous moduli as well as the timescales over which elastic properties dominate. PLCD condensates also undergo physical aging on sequence-specific timescales. This is driven by mutations to spacer residues that weaken the metastability of terminally viscous phases. The aging of PLCD condensates is accompanied by disorder-to-order transitions, leading to the formation of non-fibrillar, beta-sheet-containing, semi-crystalline, terminally elastic, Kelvin-Voigt solids. Our results suggest that sequence grammars, which refer to the identities of stickers versus spacers in PLCDs, have evolved to afford control over the metastabilities of terminally viscous fluid phases of condensates. This selection can, in some cases, render barriers for conversion from metastable fluids to globally stable solids to be insurmountable on functionally relevant timescales.
Interferon-gamma is Quintessential for NOS2 and COX2 Expression in ER-Breast Tumors that Lead to Poor Outcome
Authors: Cheng Robert YS. , Ridnour Lisa A. , Wink Adelaide L. , Gonzalez Ana L. , Femino Elise L. , Rittscher Helene , Somasundarum Veena , Heinz William F. , Coutinho Leandro , Cristina Rangel M. , Edmondson Elijah F. , Butcher Donna , Kinders Robert J. , Li Xiaoxian , Wong Stephen T.C. , McVicar Daniel W. , Anderson Steven K. , Pore Milind , Hewitt Stephen M. , Billiar Timothy R. , Glynn Sharon , Chang Jenny C. , Lockett Stephen J. , Ambs Stefan , Wink David A. 
Published: April 2023

AbstractA strong correlation between NOS2 and COX2 tumor expression and poor clinical outcomes in ER-breast cancer has been established. However, mechanisms of tumor induction of these enzymes are unclear. Analysis of The Cancer Genome Atlas (TCGA) revealed correlations between NOS2 and COX2 expression and Th1 cytokines. Herein, single cell RNAseq analysis of TNBC cells shows potent NOS2 and COX2 induction by IFNγ combined with IL1β or TNFα. Given that IFNγ is secreted by cytolytic lymphocytes, which improve clinical outcomes, this role of IFNγpresents a dichotomy. To explore this conundrum, tumor NOS2, COX2, and CD8+T cells were spatially analyzed in aggressive ER-, TNBC, and HER2+ breast tumors. High expression and clustering of NOS2-expressing tumor cells occurred at the tumor/stroma interface in the presence of stroma-restricted CD8+T cells. High expression and clustering of COX2-expressing tumor cells extended into immune desert regions in the tumor core where CD8+T cell penetration was limited or absent. Moreover, high NOS2-expressing tumor cells were proximal to areas with increased satellitosis suggestive of cell clusters with a higher metastatic potential. Furtherin vitroexperiments revealed that IFNγ+IL1β/TNFα increased elongation and migration of treated tumor cells. This spatial analysis of the tumor microenvironment provides important insight of distinct neighborhoods where stroma-restricted CD8+T cells exist proximal to NOS2-expressing tumor niches that could have increased metastatic potential.
Resistance Training Diminishes Mitochondrial Adaptations to Subsequent Endurance Training
Authors: Mesquita Paulo H. C. , Godwin Joshua S. , Ruple Bradley A. , Sexton Casey L. , McIntosh Mason C. , Mueller Breanna J. , Osburn Shelby C. , Mobley C. Brooks , Libardi Cleiton A. , Young Kaelin C. , Gladden L. Bruce , Roberts Michael D. , Kavazis Andreas N. 
Published: April 2023

ABSTRACTWe investigated the effects of performing a period of resistance training (RT) on the performance and molecular adaptations to a subsequent period of endurance training (ET). Twenty-five young adults were divided into RT+ET (n=13), which underwent seven weeks of RT followed by seven weeks of ET, and ET-only (n=12), which performed seven weeks of ET. Body composition, endurance performance, and muscle biopsies were collected before RT (T1, baseline for RT+ET), before ET (T2, post RT for RT+ET and baseline for ET), and after ET (T3). Immunohistochemistry was performed to determine fiber cross-sectional area (fCSA), myonuclear content, myonuclear domain size, satellite cell number, and mitochondrial content. Western blots were used to quantify markers of mitochondrial remodeling. Citrate synthase activity and markers of ribosome content were also investigated. Resistance training improved body composition and strength, increased vastus lateralis thickness, mixed and type II fCSA, myonuclear number, markers of ribosome content, and satellite cell content (p<0.050). In response to ET, both groups similarly decreased body fat percentage and improved endurance performance (e.g., VO2max, and speed at which the onset of blood lactate accumulation occurred during the VO2max test). Levels of mitochondrial complexes I-IV in the ET-only group increased 32-66%, while the RT+ET group increased 1-11%. Additionally, mixed fiber relative mitochondrial content increased 15% in the ET-only group but decreased 13% in the RT+ET group. In conclusion, RT performed prior to ET had no additional benefits to ET adaptations. Moreover, prior RT seemed to impair mitochondrial adaptations to ET.KEY POINTS SUMMARYResistance training is largely underappreciated as a method to improve endurance performance, despite reports showing it may improve mitochondrial function.Although several concurrent training studies are available, in this study we investigated the effects of performing a period resistance training on the performance and molecular adaptations to subsequent endurance training.Prior resistance training did not improve endurance performance and impaired most mitochondrial adaptations to subsequent endurance training, but that seemed to be a result of detraining from resistance training.
Identification of LMAN1 and SURF4 dependent secretory cargoes
Authors: Tang Vi T. , Abbineni Prabhodh S. , Veiga Leprevost Felipe da , Basrur Venkatesha , Emmer Brian T. , Nesvizhskii Alexey I. , Ginsburg David 
Published: April 2023

AbstractMost proteins secreted into the extracellular space are first recruited from the endoplasmic reticulum into coat protein complex II (COPII)-coated vesicles or tubules that facilitate their transport to the Golgi apparatus. Although several secreted proteins have been shown to be actively recruited into COPII vesicles/tubules by the cargo receptors LMAN1 and SURF4, the full cargo repertoire of these receptors is unknown. We now report mass spectrometry analysis of conditioned media and cell lysates from HuH7 cells CRISPR targeted to inactivate theLMAN1orSURF4gene. We found that LMAN1 has limited clients in HuH7 cells whereas SURF4 traffics a broad range of cargoes. Analysis of putative SURF4 cargoes suggests that cargo recognition is governed by complex mechanisms rather than interaction with a universal binding motif.
Controlling morpho-electrophysiological variability of neurons with detailed biophysical models
Authors: Arnaudon Alexis , Reva Maria , Zbili Mickael , Markram Henry , Van Geit Werner , Kanari Lida 
Published: April 2023

AbstractVariability is a universal feature among biological units such as neuronal cells as they enable a robust encoding of a high volume of information in neuronal circuits and prevent hyper synchronizations such as epileptic seizures. While most computational studies on electrophysiological variability in neuronal circuits were done with simplified neuron models, we instead focus on the variability of detailed biophysical models of neurons. With measures of experimental variability, we leverage a Markov chain Monte Carlo method to generate populations of electrical models able to reproduce the variability from sets of experimental recordings. By matching input resistances of soma and axon initial segments with the one of dendrites, we produce a compatible set of morphologies and electrical models that faithfully represent a given morpho-electrical type. We demonstrate our approach on layer 5 pyramidal cells with continuous adapting firing type and show that morphological variability is insufficient to reproduce electrical variability. Overall, this approach provides a strong statistical basis to create detailed models of neurons with controlled variability.
The microbiota and immune system non-genetically affect offspring phenotypes transgenerationally
Authors: Harris Jordan C. , Trigg Natalie A. , Goshu Bruktawit , Yokoyama Yuichi , Dohnalová Lenka , White Ellen K. , Harman Adele , Thaiss Christoph A. , Grice Elizabeth A. , Conine Colin C. , Kambayashi Taku 
Published: April 2023

Summary paragraphThe host-microbiota relationship has evolved to shape mammalian processes, including immunity, metabolism, and development1–3. Host phenotypes change in direct response to microbial exposures by the individual. Here we show that the microbiota induces phenotypic change not only in the individual but also in their succeeding generations of progeny. We found that germ-free mice exhibit a robust sebum secretion defect and transcriptional changes in various organs, persisting across multiple generations despite microbial colonization and breeding with conventional mice. Host-microbe interactions could be involved in this process, since T cell-deficient mice, which display defective sebum secretion4, also transgenerationally transmit their phenotype to progeny. These phenotypes are inherited by progeny conceived duringin vitrofertilization using germ-free sperm and eggs, demonstrating that epigenetic information in the gametes is required for phenotypic transmission. Accordingly, small non-coding RNAs that can regulate embryonic gene expression5were strikingly and similarly altered in gametes of germ-free and T cell-deficient mice. Thus, we have uncovered a novel mechanism whereby the microbiota and immune system induce phenotypic changes in successive generations of offspring. This epigenetic form of inheritance could be advantageous for host adaptation to environmental perturbation, where phenotypic diversity can be introduced more rapidly than by genetic mutation.