bluuebunny/crossref_metadata_2025 huggingface dataset:
Adults With Head and Neck Burns Experience Worse Long-Term Outcomes and Require More Reconstructive Surgeries
Authors: Choe Deborah , McMullen Kara , Stewart Barclay T. , Kowalske Karen , Schneider Jeffrey C. , Ryan Colleen M. , Kazis Lewis E. , Orton Caitlin M. , Yenikomshian Haig A.
Published: December 2024

Background

Adults living with head and neck burn injuries experience psychosocial consequences due to scarring as well as functional disabilities. However, the impact of head and neck burns on long-term self-reported psychosocial outcomes, return to work, and need for reconstructive surgery has not been well described. This study investigates the unique longitudinal problems in psychosocial and functional recovery faced by adults with head and neck burn injuries.

Methods

Utilizing the multicenter Burn Model System (BMS) National Database, long-term psychosocial and functional outcomes as well as postdischarge reconstructive surgery rates between adult participants with and without head and neck burns injured after 2014 were compared.

Results

Of 1247 participants, 579 had head and neck burns and 668 had non–head and neck burns. Head and neck burn was a significant predictor of worse anxiety (β = 1.63, P = 0.049) and body image (β = −0.30, P = 0.011) at 6 months post burn; worse anxiety (β = 2.68, P = 0.004), depression (β = 2.14, P = 0.021), and body image (β = −0.41, P = 0.001) at 12 months post burn; and worse life satisfaction (β = −1.64, P = 0.036) at 24 months post burn. Head and neck burn participants reported significantly worse anxiety (P = 0.001), depression (P = 0.0026), and life satisfaction (P < 0.001) at 12 months post burn and worse body image at 6 (P < 0.001), 12 (P < 0.001), and 24 (P < 0.001) months post burn. The head-and-neck group had a significantly greater proportion of participants who had undergone contracture surgery at 12 months post burn (P < 0.001) and a smaller proportion who had returned to work by 6 (P < 0.001) and 12 (P < 0.001) months post burn.

Conclusions

This study suggests that adults with head and neck burns might strongly benefit from additional counseling, psychotherapy, and greater aftercare.
Chimeric Free Flaps Based on End-to-Side Anastomosis for Complex Lower Extremity Reconstruction
Authors: Gu Yingluo , Sun Yongyang , Xu Ke , Yi Nan , Qin Jianzhong , Zhang Yong , Zhao Jiaju , Jiang Bo
Published: December 2024

Background

Complex lower extremity defects are difficult to cover and often require multiple free tissue transfers. Chimeric anterolateral thigh free flaps (ALTF) and peroneal artery perforator free flaps (PAPF) have been designed specifically as an alternative for reconstruction with arterial end-to-side (ETS) anastomosis. We aimed to assess our institutional experience with this technique and to define its role in complex lower extremity reconstruction.

Methods

From July 2012 to March 2023, 27 patients with complex lower extremity defects underwent reconstruction with chimeric ALTF or PAPF. Patients were performed with retrograde flaps for repairing refractory wounds of tibia plateau fracture and antegrade flaps for distal 2/3 tibia and beyond. Demographic, clinical, and follow-up data on the patients were recorded with a special focus on complication profiles during a follow-up of 6 to 60 months.

Results

The mean defect size measured 121.1 ± 215.1 cm2, and the chimeric ALTF or PAPF flaps measured 143.9 ± 177.8 cm2. One patient lost the first free flap but successfully had a chimeric PAPF then. Three patients suffered partial free flap loss, and another 3 had minor complications. All 6 survived after an additional exploration, wound dressing, or antibiotics treatment. The retrograde flaps achieved similar blood flow to the antegrade flaps. Patients are all satisfied with functional and aesthetic outcomes.

Conclusions

Given the incidence of complications, utilizing chimeric ALTF and PAPF either with retrograde or antegrade flow based on arterial ETS anastomosis is a reliable surgical option for complex lower extremity reconstructions.
Effect of Autogenous Auricular Cartilage Composite Skin Graft for Bilateral Cleft Lip Nose Deformity Repair
Authors: Yuan Mei , Jin Jie , Han Yixiang , Ge Xiuyu , Zhao Shuhan , Jia Mengna , Han Zhiqiang , Tian Li , Xu Jing
Published: December 2024

Objective:

Bilateral cleft lip nose deformity often involves nasal alar retraction. The use of autogenous auricular cartilage for correction further aggravated nasal alar retraction caused by nasal lining defects after the operation. A novel graft was developed to address bilateral cleft lip nose deformity. This graft effectively addresses the lining defect and avoids nasal alar retraction following surgical intervention.

Methods:

Seventeen patients (7 males and 10 females) with bilateral cleft lip nose deformity were treated at the authors' institution. All patients underwent repair with an auricular cartilage-composite skin graft. The surgical effect was evaluated from 4 aspects: nasal flange position, postoperative appearance satisfaction, nasal aesthetic subunit index, and three-dimensional difference.

Results:

Postoperatively, 17 patients with bilateral cleft lip nose deformity were followed up from 3 months to 1 year, none of them had any obvious inward collapse or recession of the nasal margin (P > 0.05), and all of them showed satisfactory results. The satisfaction rate was above 90% (P < 0.01). The nasal tip angle and nasolabial angle were significantly smaller postoperatively than those preoperatively (P < 0.01). The nostril height and nasal columellar height were greater postoperatively than those preoperatively (P < 0.01). A comparison of the three-dimensional spatial differences revealed that the appearance of the nasal deformity was noticeably better after surgery (P < 0.01).

Conclusions:

Auricular cartilage-composite skin graft repair is highly effective for enhancing nasal support, correcting nasal tip shape, effectively resolving nasal flange recession, and preventing nasal flange retraction in the postoperative period.

Level of Evidence:

Level IV.
Treatment of Paraclinoid Aneurysms With Stent-Assisted Coiling Versus Flow Diversion Techniques: A Systematic Review and Meta-Analysis
Authors: Tang Kai , Liu Xiao-meng , Zhang Chao , Ma Shuang-ju , Song Xiao-lei , Du Hai-long , Hu Yu-hua , Wu Jian-liang
Published: December 2024

Background:

The stent-assisted coiling (SAC) and flow-diverter stent (FDS) techniques are widely used in the endovascular treatment of paraclinoid aneurysms. This article compares the occlusion rate, periprocedural complications, and clinical outcomes of SAC and FDSs.

Methods:

Between January 2010 and December 2020, a systematic search of electronic databases identified 2283 articles for screening. After the application of inclusion and exclusion criteria, data were extracted for a meta-analysis of the proportions.

Results:

Of 23 articles containing 4 comparative studies, 27 cohorts were included, and 1208 patients with 1328 aneurysms were analyzed: In 10 cohorts, 381 (28.7%) patients were treated with SAC, whereas in 17 cohorts, 947 (71.3%) patients were treated with FDSs. In the comparative studies, no significance was observed between the 2 treatments. In the pooled cohorts, complete occlusion was achieved in 85% of aneurysms after treatment with FDSs (95% CI: 0.81–0.88, I
2=34.7%) and 76% after treatment with SAC (95% CI: 0.70–0.81, I
2=16.6%); the subgroup analysis was statistically significant (P=0.003). New visual complications were observed in 5% of the FDS-treated group (95% CI: 0.02–0.09, I
2=76.9%) and in 1% of the SAC-treated group (95% CI: 0.00–0.02, I
2=0%); the subgroup analysis was statistically significant (P=0.018). Other observational indices, including total procedure-related complications; hemorrhagic, thrombotic, and ischemic complications; permanent morbidities, and favorable neurological outcomes, showed no statistical significance between the groups.

Conclusion:

Compared with SAC, treatment with FDSs may have a higher complete occlusion rate at follow-up. The similarly low rates for procedure-related complications and permanent morbidities indicate that both treatments are safe. A higher rate of new visual complications was noted in the FDS-treated group. Further research is required for direct comparisons along with a complete ophthalmological examination.
Cutaneous Angiosarcoma With Scalp and Skull Infiltration: A Comprehensive Case Report and Treatment Considerations
Authors: Mendonca Andre L.B. , Lancellotti Carmen Lucia Penteado , de Oliveira Jean G. , Vitorino-Araujo João Luiz
Published: December 2024

Cutaneous angiosarcoma is a rare and aggressive malignancy originating from endothelial cells lining blood vessels in the skin. The authors present a comprehensive case report of cutaneous angiosarcoma with infiltration of the scalp and skull, with an abnormal presentation highlighting the clinical features, diagnostic challenges, treatment and surgical strategies, and outcomes. The case underscores the complexity of managing this aggressive disease involving critical anatomical structures and emphasizes the need for a multidisciplinary approach to optimal patient care
Strong evidence for multiple horizontal transfers of immune genes between teleost fishes
Authors: Policarpo Maxime , Salzburger Walter , Maumus Florian , Gilbert Clément
Published: December 2024

Horizontal gene transfer (HGT) is less frequent in eukaryotes than in prokaryotes, yet can have strong functional implications and was proposed as causal factor for major adaptations in several eukaryotic lineages. Most cases of eukaryote HGT reported to date are inter-domain transfers and only few studies have investigated eukaryote-to-eukaryote HGTs. Furthermore, the extent to which HGT has contributed to the gene repertoire of some lineages such as vertebrates remains unclear. Here, we performed a large-scale survey of HGT among 242 species of ray-finned fishes. We found strong evidence supporting 18 teleost-to-teleost HGT events that involve 17 different genes in 11 teleost fish orders. The genes involved in these transfers show lower synonymous divergence than expected under vertical transmission, their phylogeny is inconsistent with that of teleost fishes, and high nucleotide similarity on these genes between donor and recipient lineages extends to non-coding regions. The distribution of HGT events in the teleost tree is heterogenous, with eight of the 18 transfers occurring between the same two orders (Osmeriformes and Clupeiformes). Besides the previously reported transfer of an antifreeze protein, most transferred genes play roles in immunity, suggesting that such genes are more likely than others to confer strong selective advantage to the recipient species. Overall, our work shows that teleost-to-teleost HGT has occurred on multiple occasions and it will be worth further quantifying these transfers and evaluating their impact on teleost evolution as more genomes are being sequenced.
Biomarker panels for improved risk prediction and enhanced biological insights in patients with atrial fibrillation
Authors: Meyre Pascal B. , Aeschbacher Stefanie , Blum Steffen , Reichlin Tobias , Haller Moa , Rodondi Nicolas , Müller Andreas S. , Bernheim Alain , Beer Jürg Hans , Moschovitis Giorgio , Ziegler André , Wahrenberger Bianca , Rigamonti Elia , Conte Giulio , Krisai Philipp , Bonati Leo H. , Osswald Stefan , Kühne Michael , Conen David
Published: December 2024

Atrial fibrillation (AF) is associated with an increased risk of adverse cardiovascular events, but the underlying biological mechanisms remain incompletely understood. Here we evaluated a panel of 12 circulating biomarkers representing diverse pathophysiological pathways in a cohort of 3,817 AF patients to assess their association with adverse cardiovascular outcomes. We identified 5 biomarkers—d-dimer, growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTropT)—that were independently associated with cardiovascular death, stroke, myocardial infarction, and systemic embolism, significantly enhancing predictive accuracy. Additionally, GDF-15, insulin-like growth factor-binding protein-7 (IGFBP-7), NT-proBNP, and hsTropT were strong predictors of heart failure hospitalization, while GDF-15 and IL-6 were associated with major bleeding events. Incorporating IL-6, NT-proBNP, and hsTropT to the CHA₂DS₂-VASc score improved stroke risk prediction. Machine learning models incorporating these biomarkers demonstrated consistent improvements in risk stratification across all outcomes. Our results highlight the potential of integrating biomarkers related to myocardial injury, inflammation, oxidative stress, and coagulation into both conventional and machine learning-based models refine prognosis and guide clinical decision-making in AF patients.
Mitochondrial damage triggers therapy-induced senescence
Authors: Baltira Chrysiida , Alkan Ferhat , Mayayo-Peralta Isabel , Guillen-Navarro Miriam , Thijssen Bram , Lempers Rose , Pello Kimberley , Fedorushkova Daria M. , Their Anna , Jochems Fleur , Rozing Kicky , Bleijerveld Onno B. , Janssen Hans , Kuil Laura E. , Beijnen Jos H. , Faller William J. , Silva Joana , Bernards Rene , van Tellingen Olaf , de Gooijer Mark C.
Published: December 2024

Glioblastoma (GBM) is a fatal brain tumor with a critical need for better therapies. It is known that the PI3K, MAPK, and CDK4/6 signaling pathways are hyper-activated in these tumors; however, previous studies have used very high concentration of inhibitors to assess their importance, with mixed results. Here we developed PMCi, a combination approach that targets all three pathways simultaneously, at clinically-relevant doses. PMCi effectively suppresses GBM cell proliferation in vitro and in vivo, and outperforms monotherapies and dual combinations. PMCi acts by inducing cellular senescence, which is mediated solely by the mitochondria, and, unlike other forms of senescence, is independent of nuclear damage. This phenotype is caused by a reactive oxygen species (ROS)\cGAS-STING\senescence-associated secretory phenotype (SASP) signaling cascade, that acts in a paracrine manner to establish and maintain senescence. Our results demonstrate that mitochondrial damage is sufficient to drive senescence, and that this can be leveraged to target GBM cells.
The last resort antibiotic daptomycin exhibits two independent antibacterial mechanisms of action
Authors: Buttress Jessica A. , Schäfer Ann-Britt , Koh Alan , Wheatley Jessica , Mickiewicz Katarzyna , Wenzel Michaela , Strahl Henrik
Published: December 2024

Daptomycin is a lipopeptide antibiotic, commonly used as last resort treatment against multidrug resistant Gram-positive pathogens. Despite its clinical success, the mechanism through which daptomycin exerts its antibacterial properties has remained controversial. Much of the debate is focused around daptomycin’s ability to depolarise the cytoplasmic membrane, potential formation of large membrane pores, and its more recently discovered capability to inhibit cell wall synthesis and disturb membrane lipid domain organisation through interactions with cell wall precursor lipids. Here we show that, rather than representing different facets of a single underlying activity, daptomycin exhibits two independent antibacterial mechanisms of action: (i) targeting of cell wall precursor lipids that leads to cell wall synthesis inhibition and (ii) membrane depolarisation that does not rely on interactions with cell wall precursor lipids. This dual mechanism of action provides an explanation for the frequently disagreeing findings obtained throughin vivoandin vitrostudies and explains why resistance development towards daptomycin is slow and multifactorial. In a broader context, this demonstrates that dual mechanism antibiotics can be clinically successful and exhibit favourable characteristics in terms of real-world, clinically relevant resistance development.
WWOX deficiency impairs neurogenesis and neuronal function in human organoids
Authors: Steinberg Daniel J. , Zonca Asia , Rosh Idan , Kustanovich Irina , Maroun Kian , Stern Shani , Davila-Velderrain Jose , Aqeilan Rami I.
Published: December 2024

WOREE and SCAR12 syndromes are rare neurodevelopmental disorders caused by WWOX mutations, severely impairing brain development. The pleiotropic nature of WWOX complicates identifying specific mechanisms. Using neural organoids and single-cell transcriptomics, we identified radial glial cells (RGs) as preferentially affected, with disrupted cell cycle dynamics leading to an accumulation of cells in the G2/M and S phases, overexpression of the proto-oncogene MYC, and concomitant reduction in neuronal generation. Patient-derived organoids exhibited milder phenotypes compared to knockout organoids, showing functional neuronal impairments like hyperexcitability and delayed differentiation rather than RG dysfunction. Remarkably, gene therapy restored neuronal function, normalizing hyperexcitability and promoting maturation, without disturbing RG populations. We propose a model in which WWOX mutations impair neurogenesis via RG through cell-type specific dysregulation of the MYC and Wnt signaling pathways. These insights highlight potential therapeutic strategies for WWOX-related disorders and open avenues for interventions targeting these key molecular pathways.

Teaser

WWOX mutations disrupt radial glial function and neurogenesis via MYC dysregulation, with gene therapy offering targeted restoration.
microGalaxy: A gateway to tools, workflows, and training for reproducible and FAIR analysis of microbial data
Authors: Nasr Engy , Amato Pierre , Bhardwaj Anshu , Blankenberg Daniel , Brites Daniela , Cumbo Fabio , Do Katherine , Ferrari Emanuele , Griffin Timothy J. , Gruening Bjoern , Hiltemann Saskia , Jagtap Pratik , Mehta Subina , Métris Kimberly L. , Momin Saim , Oba Asime , Pavloudi Christina , Pechlivanis Nikos , Péguilhan Raphaëlle , Psomopoulos Fotis , Rosic Nedeljka , Schatz Michael C , Schiml Valerie Claudia , Siguret Clea , Soranzo Nicola , Stubbs Andrew , Van Heusden Peter , Vohra Mustafa ,   microGalaxy Community, Zierep Paul , Batut Bérénice
Published: December 2024

Microbial research generates vast and complex data from diverse omics technologies, necessitating innovative analytical solutions. microGalaxy (Galaxy for Microbiology) addresses these needs with a user-friendly platform that integrates 220+ tool suites and 65+ curated workflows for microbial analyses, including taxonomic profiling, assembly, annotation, and functional analysis. Hosted on the main EU Galaxy server (microgalaxy.usegalaxy.eu), it supports workflow creation & customization, sharing, and updates across public and private Galaxy servers, ensuring flexibility and reproducibility. The platform also offers 45+ tutorials, 15+ instructional videos, and structured learning pathways, empowering researchers to conduct advanced analyses. Backed by a community-driven approach, microGalaxy prioritizes tool testing, semi-automatic updates, and multi-omics integration to meet global research demands. With its focus on rapid workflow prototyping and high-throughput processing, microGalaxy provides scalable resources for researchers at all expertise levels, enabling them to tackle challenges in microbial data analysis with confidence and efficiency.
SHEN-LONG, a novel cardiac regulatory locus, regulates cardiac master transcription factor NKX2-5 in pluripotent stem cell derived cardiomyocytes
Authors: Scarafía María Agustina , Halek Julia , Smucler Joaquín , Waisman Ariel , Moro Lucía , Sevlever Gustavo , Miriuka Santiago , La Greca Alejandro
Published: December 2024

Cardiac development is a finely regulated process, transforming undifferentiated cells into the specialized cell components of the heart. Super-Enhancers (SE), clusters of enhancers densely populated with transcription factors, play a central role in cell fate decisions, including cardiogenesis. In this work, we studied a cardiac SE in chr3q25.31. This locus also contains a cardiac specific long non-coding RNA: LINC00881 (LINC881). We termed this region of interest SHEN-LONG (SuperHeartENhancer andLONGnon-coding LINC881), and selected it for further functional characterization. Our analysis revealed SHEN-LONG is a hotspot of cardiac kernel transcription factor binding sites. Cardiac differentiation of human iPSC with partial Knock Out of SHEN-LONG resulted in cardiomyocytes with reduced NKX2-5 expression, a master cardiac transcription factor, suggesting a significant role of SHEN-LONG in this process. Whole transcriptome sequencing of SHEN-LONG KO cardiomyocytes produced 134 differentially expressed genes located at great distances (>4Mb) emphasizing its long-range functional impact. A regulation mediated essentially by the SE and not by LINC881 was confirmed when LINC881 overexpression did not recover NKX2-5 expression. These findings provide insights into a novel NKX2-5 regulatory mechanism. The knowledge gained in this work may pave the way for advances in therapeutic interventions for cardiovascular disorders.
IL-1β-driven NF-κB transcription of ACE2 as a Mechanism of Macrophage Infection by SARS-CoV-2
Authors: Lee Cadence , Khan Rachel , Mantsounga Chris S. , Sharma Sheila , Pierce Julia , Amelotte Elizabeth , Butler Celia A. , Farinha Andrew , Parry Crystal , Caballero Olivya , Morrison Jeremi A. , Uppuluri Saketh , Whyte Jeffrey J. , Kennedy Joshua L. , Zhang Xuming , Choudhary Gaurav , Olson Rachel M. , Morrison Alan R.
Published: December 2024

Coronavirus disease 2019 (COVID-19), caused by infection with the enveloped RNA betacoronavirus, SARS-CoV-2, led to a global pandemic involving over 7 million deaths. Macrophage inflammatory responses impact COVID-19 severity; however, it is unclear whether macrophages are infected by SARS-CoV-2. We sought to identify mechanisms regulating macrophage expression of ACE2, the primary receptor for SARS-CoV-2, and to determine if macrophages are susceptible to productive infection. We developed a humanizedACE2(hACE2) mouse wherebyhACE2cDNA was cloned into the mouseACE2locus under control of the native promoter. We validated the susceptibility ofhACE2mice to SARS-CoV-2 infection relative to wild-type mice and an establishedK18-hACE2model of acute fulminating disease. Intranasal exposure to SARS-CoV-2 led to pulmonary consolidations with cellular infiltrate, edema, and hemorrhage, consistent with pneumonia, yet unlike theK18-hACE2model,hACE2mice survived and maintained stable weight. InfectedhACE2mice also exhibited a unique plasma chemokine, cytokine, and growth factor inflammatory signature relative toK18-hACE2mice. InfectedhACE2mice demonstrated evidence of viral replication in infiltrating lung macrophages, and infection of macrophages in vitro revealed a transcriptional profile indicative of altered RNA and ribosomal processing machinery as well as activated cellular antiviral defense. Macrophage IL-1β-driven NF-κB transcription of ACE2 was an important mechanism of dynamic ACE2 upregulation, promoting macrophage susceptibility to infection. Experimental models of COVID-19 that make use of native hACE2 expression will allow for mechanistic insight into factors that can either promote host resilience or increase susceptibility to worsening severity of infection.
Asynchronous Transitions from Hepatoblastoma to Carcinoma in High-Risk Pediatric Tumors
Authors: Yu Xinjian , Sarabia Stephen , Urbicain Martin , Somvanshi Sonal , Patel Roma , Tran Tuan M , Yeh Yen-Ping , Chang Keng-Shih , Lo Yi-Tzu , Epps Jessica , Scorsone Kathleen A. , Chiu Hua-Sheng , Hollingsworth Emporia Faith , Perez Cintia R. , Najaf Panah Mohammad Javad , Zorman Barry , Finegold Milton , Goss John A. , Alaggio Rita , Roy Angshumoy , Fisher Kevin E. , Heczey Andras , Woodfield Sarah , Vasudevan Sanjeev , Patel Kalyani , Chen Ting-Wen , Lopez-Terrada Dolores , Sumazin Pavel
Published: December 2024

Most malignant hepatocellular tumors in children are classified as either hepatoblastoma (HB) or hepatocellular carcinoma (HCC), but some tumors demonstrate features of both HB and HCC1–3. These tumors have been recognized under a provisional diagnostic category by the World Health Organization and are distinguished from HB and HCC by a combination of histological, immunohistochemical, and molecular features4–6. Their outcomes and cellular composition remain an open question7–9. The heterogeneous histological and molecular profiles of hepatoblastomas with carcinoma features (HBCs)4may result from cells with combined HB and HCC characteristics (HBC cells) or from mixtures of cells displaying either HB or HCC signatures. We used multiomics profiling to show that HBCs are mixtures of HB, HBC, and HCC cell types. HBC cells are more chemoresistant than HB cells, and their chemoresistance—a driver of poor outcomes10–12—is determined by their cell types, genetic alterations, and embryonic differentiation stages. We showed that the prognosis of HBCs is significantly worse than that of HBs. We also showed that HBC cells are derived from HB cells at early hepatoblast differentiation stages, that aberrant activation of WNT-signaling initiates HBC transformation, and that WNT inhibition promotes differentiation and increases sensitivity to chemotherapy. Furthermore, our analysis revealed that each HBC is the product of multiple HB-to-HBC and HBC-to-HCC transitions. Thus, multiomics profiling of HBCs provided key insights into their biology and resolved major questions regarding the etiology of these childhood liver tumors.
High-resolution mastigoneme structure reveals 5’,5’-phosphodiesters stabilized glycan folding
Authors: Huang Junhao , Tao Hui , Chen Jikun , Pan Junmin , Yan Chuangye , Yan Nieng
Published: December 2024

Glycans play a crucial role in structure organization, energy metabolism, and signal transduction in living organisms. Compared with proteins and nucleic acids, glycans exhibit remarkable molecular heterogeneity, extensive conformational flexibility, and diverse linkages. These properties pose significant challenges for obtaining high-resolution structure of glycans. Here, we report a cryo-EM structure of the heavily glycosylatedChlamydomonasmastigoneme at 2.3-2.5 Å resolutions. In addition to enabling analysis of accurate interactions for glycosyl packing, the high resolution map reveals an unprecedented 5’,5’-phosphodiester bond that links adjacent glycan chains attached to hydroxyproline (Hyp) residues n and n+3. Structural analysis reveals a secondary structural element for glycoconjugates, which we name the poly-Hyp (pHP) glycohelix. Our work represents an important advancement in deciphering glycan folding.
DOMON domain-containing proteins control root development upon phosphate deficiency and ammonium stress by modulating iron dynamics
Authors: Clúa Joaquín , Poirier Yves
Published: December 2024

Phosphorous and nitrogen are the main nutrients limiting plant growth in natural and agricultural systems. Plants typically uptake phosphorous in the form of inorganic phosphate, whereas the main nitrogen sources are nitrate and ammonium. Roots show a high degree of developmental plasticity in response to nutritional stresses, directly influencing plant fitness and stress resilience. InArabidopsis thaliana, phosphate deficiency and high levels of ammonium in the media triggers a strong inhibition of the primary root growth. This developmental response is initiated by the accumulation of apoplastic iron in specific cell types, which triggers the inhibition of meristem maintenance and cell elongation. In this report, we show that DOMON domain-containing proteins are key molecular players controlling root development upon phosphate deficiency and ammonium toxicity via iron dynamics.
Enhancing Collagen Biosynthesis in Mammalian Cells Through Hypoxia-Mimetic Prolyl Hydroxylase Inhibition
Authors: Shahar Bar , Kilimnik Itay , Lifshits Lucia Adriana , Netti Francesca , Sova Marina , Rosin-Grunewald Dalia , Gal Maayan , Adler-Abramovich Lihi
Published: December 2024

Collagen, the most abundant protein in the extracellular matrix of mammalian cells, is extensively needed in various biotechnological and therapeutic applications, such as tissue engineering and regeneration, cosmetics, and cultivated meat. Despite the increasing demand for natural collagen from non-animal sources, it is mainly produced from animal connective tissues. Recent research has highlighted that under hypoxia, the activation of the hypoxia-inducible factor (HIF) leads to enhanced collagen type I biosynthesis. However, under normal oxygen conditions, HIF activity is downregulated by the HIF-prolyl hydroxylase (PHD) enzyme. We, therefore, hypothesized that inhibiting PHD could elevate HIF transcriptional activity and enhance collagen biosynthesis under normoxia. Our study demonstrates that inhibiting PHD using exogenous small molecules boosts HIF activity and upregulates the key enzymes, collagen prolyl 4-hydroxylases and lysyl hydroxylases, resulting in up to 29-fold increase in collagen type I in embryonic mouse fibroblast NIH/3T3 cells. These findings suggest that targeting PHD can effectively enhance collagen production in mammalian cells. Therefore, modulating key protein signaling pathways presents a promising strategy for enhancing the production of high-yield natural collagen.
Inhibition of Mitochondrial Fission Protein Drp1 Ameliorates Myopathy in the D2-mdx Model of Duchenne Muscular Dystrophy
Authors: Rosen H. Grace , Berger Nicolas J. , Hodge Shantel N. , Fujishiro Atsutaro , Lourie Jared , Kapadia Vrusti , Linden Melissa A. , Jee Eunbin , Kim Jonghan , Kim Yuho , Zou Kai
Published: December 2024

Although current treatments for Duchenne Muscular Dystrophy (DMD) have proven to be effective in delaying myopathy, there remains a strong need to identify novel targets to develop additional therapies. Mitochondrial dysfunction is an early pathological feature of DMD. A fine balance of mitochondrial dynamics (fission and fusion) is crucial to maintain mitochondrial function and skeletal muscle health. Excessive activation of Dynamin-Related Protein 1 (Drp1)-mediated mitochondrial fission was reported in animal models of DMD. However, whether Drp1-mediated mitochondrial fission is a viable target for treating myopathy in DMD remains unknown. Here, we treated a D2-mdx model of DMD (9-10 weeks old) with Mdivi-1, a selective Drp1 inhibitor, every other day (i.p. injection) for 5 weeks. We demonstrated that Mdivi-1 effectively improved skeletal muscle strength and reduced serum creatine kinase concentration. Mdivi-1 treatment also effectively inhibited mitochondrial fission regulatory protein markers, Drp1(Ser616) phosphorylation and Fis1 in skeletal muscles from D2-mdx mice, which resulted in reduced content of damaged and fragmented mitochondria. Furthermore, Mdivi-1 treatment attenuated lipid peroxidation product, 4-HNE, in skeletal muscle from D2-mdx mice, which was inversely correlated with muscle grip strength. Finally, we revealed that Mdivi-1 treatment downregulated Alpha 1 Type I Collagen (Col1a1) protein expression, a marker of fibrosis, and Interleukin-6 (IL-6) mRNA expression, a marker of inflammation. In summary, these results demonstrate that inhibition of Drp1-mediated mitochondrial fission by Mdivi-1 is effective in improving muscle strength and alleviating muscle damage in D2-mdx mice. These improvements are associated with improved skeletal muscle mitochondrial integrity, leading to attenuated lipid peroxidation.
Modulation of hippocampal sharp-wave ripples by behavioral states and body movements in head-fixed rodents
Authors: Rios Alain , Minori Usui , Isomura Yoshikazu
Published: December 2024

Hippocampal sharp-wave ripples (SWRs) are critical events implicated in memory consolidation, planning, and the reactivation of recent experiences. Under freely moving conditions, a well-established dichotomy exists: hippocampal networks predominantly generate theta oscillations during periods of reward pursuit (preparatory behaviors) and exhibit pronounced SWR activity once the reward is achieved (consummatory behaviors). Here, we examined how SWRs are modulated by reward delivery and subtle movements in head-fixed rats. Contrary to the canonical view established in freely moving settings, we found that the dominant and more enduring effect was a sustained suppression of SWR activity immediately following water delivery. Moreover, even minor, localized movements (such as whisking or body adjustments) decreased SWR occurrence, demonstrating that hippocampal ripple generation is highly sensitive to motor engagement, irrespective of reward timing. Such movement-induced suppression of ripples persisted during both sleep-like states and quiet wakefulness, suggesting that while large-scale brain states modulate the overall likelihood of SWR generation, local motor-related influences exert a state-independent inhibitory effect on hippocampal ripples. Our results show that SWR modulation by behavioral states and body movements is more context-dependent than previously appreciated.
Population genomics reveals an ancient origin of heartworms in canids
Authors: Power Rosemonde I. , Abdullah Swaid , Walden Heather S. , Verocai Guilherme G. , Sanders Tiana L. , Luksovsky Joe L. , Moorhead Andrew R. , Dzimianski Michael T. , Foster Jeremy M. , Michalski Michelle L. , Rojas Alicia , Chacón Samuel C. , Deak Georgiana , Mihalca Andrei D. , Danesi Patrizia , Papadopoulos Elias , Taweethavonsawat Piyanan , Bui Dung Thi , Ngoc Anh Do , Sharma Reuben S.K. , Ho Simon Y.W. , Doyle Stephen R. , Šlapeta Jan
Published: December 2024

Heartworms (Dirofilaria immitis) are parasitic nematodes that cause significant cardiopulmonary-associated morbidity and mortality in canids worldwide. The global dissemination of heartworms is believed to have occurred alongside the dispersal of domesticated dogs. To test this theory, we performed the largest population genetics study of heartworms to date, based on whole-genome sequencing of 127 modern adult individuals collected from mammalian carnivore hosts across four continents. Population structure and demographic analyses of the nuclear genome reveal distinct genetic differences between heartworms from different continents, indicating a deeper ancient origin and dispersal in canid hosts than previously recognised. Using admixture analyses, we find an Asian origin for Australian heartworms consistent with the arrival of dingoes thousands of years ago. Finally, the genetic relatedness between European and Central American heartworms suggests that modern dispersal, likely associated with human colonisation of the Americas by Europeans, occurred with domesticated dogs. Our findings shed light on the global population dynamics and evolutionary history of heartworms, which can aid future surveillance and control efforts for this important veterinary parasite.
CRISPR-Cas supervises diverse anti-phage defense systems
Authors: Shu Xian , Wang Rui , Cheng Feiyue , Li Zhihua , Wu Aici , Xue Qiong , Liu Chao , Cao Xifeng , Feng Yue , Li Ming
Published: December 2024

A variety of bacterial anti-phage systems have recently been discovered1–3, but how these systems synergize to defend against diverse phages remains poorly understood. Here, we report that the adaptive immune system CRISPR-Cas supervises the expression of diverse immune systems by exploiting the regulatory CRISPR RNA-like RNAs (crlRNAs). The crlRNAs target and inhibit the promoters of various immune systems, including the newly characterized Nezha and Gabija, as well as eight previously unrecognized systems that feature distinct defensive domains. Notably, CRISPR regulation balances the expression level of these systems to ensure effective anti-phage activity while avoiding their autoimmunity risks. In return, the supervised immune systems trigger abortive infections when CRISPR-Cas is inhibited by viral anti-CRISPR proteins, thereby offering an anti-anti-CRISPR protection at the population level. Moreover, these systems complement CRISPR immunity with a differing anti-phage profile. These findings highlight the pivotal role of CRISPR-Cas in orchestrating a diverse range of immune systems and showcase the delicate synergy among the multilayered defense strategies in prokaryotes.
Network vulnerability of cattle movement in Minas Gerais, Brazil, from 2013 to 2022
Authors: Costa Anna Cecília Trolesi Reis Borges , Savini Lara , de Oliveira Luciana Faria , Lage Andrey Pereira , Dorneles Elaine Maria Seles , Candeloro Luca
Published: December 2024

The aim of this study was to analyze the network vulnerability of cattle movements from 2013 to 2022, in Minas Gerais, Brazil and to identify the spatial spreaders into the network to improve infectious disease control programs by targeted risk-based surveillance and intervention. The vulnerability was calculated considering the graphs diameter and the spatial spreaders with a threshold distance of 300 km, for incoming (IN) and outgoing (OUT) movements. Additionally, a risk-based analysis was performed in the more vulnerable region. The results showed Triângulo Mineiro / Alto Paranaíba with higher vulnerability and many IN spatial spreaders, as well as Vale do Mucurí region with many OUT spatial spreaders. The risk-based analysis revealed betweenness and out degree as the most effective measures to be considered for intervention. Therefore, the vulnerability analysis and the spatial spreader were observed as great tools for risk-based interventions and surveillance. Furthermore, Triângulo Mineiro / Alto Paranaíba and Vale do Mucuri regions were important regions, considering restriction of animal infectious disease spread in Minas Gerais, Brazil.
Phylogenetic variation of immature neurons in mammalian amygdala: high prevalence in primate expanded nuclei projecting to neocortex
Authors: Ghibaudi Marco , La Rosa Chiara , Telitsyn Nikita , Graic Jean-Marie , Faulkes Chris , Sherwood Chet , Bonfanti Luca
Published: December 2024

Structural changes involving new neurons can occur through stem cell-driven neurogenesis and late-maturing immature neurons, namely undifferentiated neuronal precursors frozen in a state of arrested maturation. The latter exist in the cerebral cortex, being particularly abundant in large-brained mammals. Similar cells have been described in the amygdala of some species, although their interspecies variation remain poorly understood. Here, their occurrence, number, molecular expression, and morphology were systematically analyzed in eight diverse mammalian species widely differing in neuroanatomy, brain size, lifespan, and socioecology. We show remarkable phylogenetic variation of the immature neurons in the amygdala, with a significantly greater prevalence in primates. The cells are associated with the amygdala basolateral complex that in evolution has expanded in primates in conjunction with cortical projections, thus mimicking the general trend of the neocortex. These results support the emerging view that large brains performing complex socio-cognitive functions rely on wide reservoirs of immature neurons.
Decoupling the electronic gap from the spin Chern number in spin-resolved topological insulators
Authors: Tyner Alexander C. , Grindall Cormac , Pixley J. H.
Published: December 2024

In two-dimensional topological insulators, a disorder-induced topological phase transition is typically identified with an Anderson localization transition at the Fermi energy. However, in Z2 trivial, spin-resolved topological insulators it is the spectral gap of the spin spectrum, in addition to the bulk mobility gap, which protects the nontrivial topology of the ground state. In this work, we show that these two gaps, the bulk electronic and spin gap, can evolve distinctly on the introduction of quenched short-ranged disorder and that an odd-quantized spin Chern number topologically protects states below the Fermi energy from localization. This decoupling leads to a unique situation in which an Anderson localization transition occurs below the Fermi energy at the topological transition. Furthermore, the presence of topologically protected extended bulk states nontrivial bulk topology typically implies the existence of protected boundary modes. We demonstrate the absence of protected boundary modes in the Hamiltonian and yet the edge modes in the eigenstates of the projected spin operator survive. Our work thus provides evidence that a nonzero spin-Chern number, in the absence of a nontrivial Z2 index, does not demand the existence of protected boundary modes at finite or zero energy.

Published by the American Physical Society
2024
Heavy-light quark systems from the QCD instanton vacuum:
Nf=1
light flavor case
Authors: Hong Ki-Hoon , Kim Hyun-Chul , Musakhanov M. M. , Rakhimov N.
Published: December 2024

We investigate heavy-light quark systems within the framework of the QCD instanton vacuum, focusing on the Nf=1 light flavor case. We derive an effective heavy-light quark interaction from the low-energy QCD partition function and construct a heavy-meson effective Lagrangian. The physical residual mass of heavy mesons, Λ, is determined by employing compositeness and normalization conditions. We calculate the masses of D and B mesons and their weak decay constants to the leading order and next-to-leading order in the 1/mQ expansion. The current results for fD and fB are in good agreement with recent lattice QCD data and Particle Data Group (PDG) average values.

Published by the American Physical Society
2024
Q
-ball collisions and their gravitational waves
Authors: Hong Deog Ki , Lonsdale Stephen J.
Published: December 2024

Sydney Coleman’s Q-ball remains a compelling instance of the formation of localized objects within classical field theory, independently of the quantum evolution. The theoretical possibility of such objects forming and colliding in the early Universe from models such as Affleck-Dine fragmentation, or from a number of mechanisms where they are produced copiously with various sizes and charges to constitute dark matter in the Universe, makes it important to study in detail Q-ball collision phenomenology. In this work, we present certain results from the study of Q-ball collisions and their generation of gravitational waves, using a new general code package for scalar fields coupled to gravity. We then comment on the possibility of future gravitational wave detectors searching for signals of Q-ball collisions.

Published by the American Physical Society
2024
Cherednik-Mehta-Macdonald formula as a superintegrability property of a unitary model
Authors: Mironov A. , Morozov A. , Popolitov A.
Published: December 2024

A typical example of superintegrability is provided by expression of the Hopf link hyperpolynomial in an arbitrary representation through a pair of the Macdonald polynomials at special points. In the simpler case of the Hopf link HOMFLY-PT polynomial and a pair of the Schur functions, it is a relation in the unitary matrix model. We explain that the Cherednik-Mehta-Macdonald identity for bilinear Macdonald residues with an elliptic weight function is nothing but a reformulation of these same formulas. Their lifting to arbitrary knots and links, even torus ones, remains obscure.

Published by the American Physical Society
2024
Playful TikTok videos: investigating the role of mental imagery in customers’ social media sharing and destination attitude
Authors: Yuan Yanzhe , Surachartkumtonkun Jiraporn , Shao Wei
Published: December 2024

Purpose

This research explores how playful TikTok video content influences customers’ attitudes towards travel destinations and their intention to share. It examines the role of mental imagery in shaping these responses and investigates how perceived novelty moderates the relationship between playfulness and mental imagery.

Design/methodology/approach

We conducted a scenario-based online survey using an actual video from a real Chinese influencer, with 701 tourists participating. In the second study, we used an experimental research design and created a video specifically for the experiment, where we manipulated the playfulness of the content, involving 402 participants.

Findings

The results show that the playfulness of TikTok videos enhances mental imagery, which mediates the positive effect on customers’ attitudes and sharing intentions. Novelty further strengthens the impact of playfulness on mental imagery, highlighting the importance of both factors in destination marketing.

Research limitations/implications

Data were collected in mainland China, where the travel short video content was shared by the blogger. Future research should validate these findings with travellers from different countries and destinations, expanding the understanding of consumer engagement on social media for destination marketing.

Practical implications

This research has significant implications for creating destination marketing strategies on TikTok. Marketing managers and influencers should prioritise crafting playful video content while considering the unique appeal and novelty of the travel destination. This approach is crucial for fostering active customer engagement online.

Originality/value

This research advances our understanding of how playfulness and novelty in TikTok videos influence mental imagery, impacting consumer attitudes and behaviour. It contributes to destination marketing by highlighting the mediating role of mental imagery and the moderating effect of novelty in shaping customer responses and sharing intentions.
Global insights on public sector accounting reforms: a comprehensive study on the adoption, implementation, and impact of IFRS and IPSAS
Authors: Masoud Najeb
Published: December 2024

Purpose

This paper aims to investigate the adoption of International Financial Reporting Standards (IFRS) and International Public Sector Accounting Standards (IPSAS) and their impact on financial transparency, public sector accountability and economic performance across 173 jurisdictions from 2000 to 2022.

Design/methodology/approach

A robust quantitative approach using econometric panel data analysis with fixed- and random-effects models evaluates the effects of IFRS and IPSAS adoption. This study compares 69 adopting countries with 104 non-adopting or partially adopting nations, examining cross-country and temporal dynamics.

Findings

This paper provides compelling evidence that adopting IFRS and IPSAS significantly improves financial transparency and public sector accountability. Countries adopting these standards, mainly developed economies, experience increased foreign direct investment and improved sovereign credit ratings. The impact is more pronounced in nations with solid institutional frameworks while developing countries benefit from enhanced governance and reduced corruption, though to a lesser extent. These findings contribute to the literature by demonstrating how international accounting standards enhance governance quality and economic performance.

Research limitations/implications

The study’s limitations include the availability and reliability of financial data in jurisdictions with weaker institutional systems. Future research should include longitudinal case studies and stakeholder analyses to explore the nuanced effects of IFRS and IPSAS adoption in different regions.

Practical implications

The results emphasise the need for tailored implementation strategies, especially for developing countries. Strengthening institutional frameworks, investing in capacity-building programmes and enhancing financial literacy are essential to maximising the benefits of IFRS and IPSAS adoption. Policymakers can leverage these standards to improve transparency, attract investment and promote economic stability.

Social implications

By improving financial transparency and accountability, IFRS and IPSAS foster better governance, reduce corruption and promote more equitable resource distribution. These reforms have a particularly positive impact on developing countries, enhancing public trust, supporting social equity and encouraging sustainable economic development.

Originality/value

This paper provides a unique contribution to the discourse on global financial standards. It offers a comprehensive quantitative analysis of IFRS and IPSAS adoption over 23 years and valuable insights for policymakers and financial regulators seeking to strengthen governance and promote global economic integration.