bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of post-activation potentiation on the sports performance of athletes: a systematic review
Authors: Li Jiazhe , Soh Kim Goek , Loh Su Peng , Luo Shengyao , Bashir Marrium , Yu Xiao 
Published: September 2023

BackgroundThis study aimed to investigate the effects of post-activation potentiation (PAP) on sport performance.MethodsThe data used in this study were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Researchers extracted relevant randomized controlled trials from the available literature using prominent scientific indexing databases such as EBSCOhost, PubMed, Scopus, Web of Science, as well as Google Scholar. Ten of the 125 studies that met the inclusion criteria were included. The overall quality of each study was determined using the PEDro scale. Ten studies had scores ranging from 3 to 5.ResultsIn PAP interventions, power (n = 4) was the primary aspect of sports performance, followed by endurance (n = 1), speed (n = 2), and jumping ability (n = 2). Meanwhile, PAP significantly affects the power, endurance, speed, and jumping abilities of athletes in basketball, volleyball, track and field, and soccer.ConclusionCompared with conventional training, PAP is a relatively novel dynamic warm-up routine that can greatly enhance the sports performance of athletes in terms of endurance, power, speed, and jumping ability. As a phenomenon of rapid increase in muscle strength and power caused by high-intensity warm-up activities, PAP can help athletes quickly adjust the physical condition to the best state in the pre-match warm- up. However, since some study findings did not reflect the effect of PAP on the sports performance of athletes, more high-quality randomized controlled trials are required to further prove the effect of PAP. Additionally, the existing evidence does not consider the effect of PAP on agility and flexibility performance. In formulating the PAP induction program, it is also necessary to consider the impact of the gender and age of the inducer, exercise level, pre-stimulation load, and interval time on PAP.Systematic Review Registration:[https://inplasy.com/], identifier: [INPLASY202330120].
The Impact of Social Determinants of Health and Lifestyle on the Association of Lipoprotein(a) with Myocardial Infarction and Stroke
Authors: Brandt Eric J. , Kirch Matthias , Patel Nimai , Chennareddy Chaitanya , Murthy Venkatesh L. , Goonewardena Sascha N. 
Published: September 2023

AbstractBackgroundIn European cohorts, a higher Mediterranean diet or Life’s Simple 7 (LS7) score abolished or attenuated the risk associated with increasing Lipoprotein(a) [Lp(a)] on cardiovascular outcomes. This is unstudied in US cohorts. The impact of social determinants of health (SDOH) on the association of Lp(a) with cardiovascular outcomes remains unstudied. We sought to test if a SDOH score and LS7 score impacts the association of Lp(a) with myocardial infarction (MI) or stroke.MethodsObservational Cohort of US Adults from the Atherosclerosis Risk in Communities (ARIC) and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts. We performed sequential multivariable Cox proportional hazard analysis, first adjusting for age, gender, non-HDL-C, race and ethnicity, then added SDOH and LS7 scores sequentially. The primary outcomes were time until first fatal or nonfatal MI or stroke.ResultsARIC (n=15,072; median Lp(a)=17.3 mg/dL) had 16.2 years average follow up. MESA (n=6,822; median Lp(a)=18.3 mg/dL had 12.3 years average follow-up. In multivariable analyses adjusted for age, gender, race and ethnicity, and non-HDL-C, Lp(a) was associated (HR, p-value) with MI in ARIC (1.10, <0.001) and MESA (1.09, <0.001), and stroke in ARIC (1.08, <0.001) but not MESA (0.97, 0.50). With SDOH and LS7 added to the model associations remained similar (association of Lp(a) with MI in ARIC 1.09, <0.001 and in MESA 1.10, 0.001, with stroke in ARIC 1.06, <0.003 and in MESA 0.96, 0.39). In models with all covariates, each additional SDOH correlated positively with MI (ARIC 1.13, <0.001; MESA 1.11, <0.001) and stroke (ARIC 1.17, <0.001; HR 1.07, p=0.11) and each additional LS7 score point correlated negatively with MI (ARIC 0.81, <0.001; MESA 0.84, <0.001) and stroke (ARIC 0.82, <0.001; MESA 0.84, <0.001).Conclusions and RelevanceSDOH and lifestyle factors were predictors for MI and stroke that did not impact the association between Lp(a) and cardiovascular events. Our findings support that Lp(a) is an independent risk factor for MI and possibly stroke.
Respective contribution of Appl to mushroom body axon growth and long-term memory inDrosophila
Authors: Marquilly Claire , Boulanger Ana , Busto Germain U. , Pasquer Laure , Zinzen Robert P , Hassan Bassem A , Fradkin Lee G , Preat Thomas , Dura Jean-Maurice 
Published: September 2023

SummaryThe Amyloid Precursor Protein (APP) is linked to Alzheimer’s disease.Applis the singleDrosophilaAPP ortholog and is expressed in all neurons throughout development. Appl was previously shown to modulate, cell-autonomously, axon outgrowth in the mushroom bodies (MBs), the fly olfactory memory center. Furthermore,Applknockdown in the MBs results in loss of memory following the association of odorants with electric shocks. Nevertheless, the memory defects of flies devoid of Appl remains unknown becauseAppldflies, carrying the only known null allele, show an abnormal response to electric shock. We found thatAppldaffects the normal function ofvnd, the gene just proximal toAppl. We report here thatvndis required for MB β-branch axon outgrowth. Moreover,vndis expressed in neurons close to, but not within, the MB during development and is required non-cell-autonomously for MB axon outgrowth. To decipher developmental and memory defects specifically due to a loss of onlyApplfunction, we generated a preciseApplnull allele (ApplC2.1) by CRISPR/Cas9 genomic engineering. WithApplC2.1, we confirmed the partial requirement forApplin MB axon outgrowth but found no defects of electric shock avoidance, allowing us to test for potential memory defects.ApplC2.1flies showed a complete loss of long-term memory which was fully rescued by MB-restricted expression ofAppl+only during the adult stage. Therefore, we demonstrate that the complete lack of Appl affects memory independently from structural developmental defects.
In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma
Authors: Liu S. John , Pak Joanna , Zou Christopher , Casey-Clyde Timothy , Borah Ashir A. , Wu David , Seo Kyounghee , O’Loughlin Thomas , Lim Daniel A. , Ozawa Tomoko , Berger Mitchel S. , Weiss William A. , Raleigh David R. , Gilbert Luke A. 
Published: September 2023

AbstractGenetic perturbation screens with single cell readouts have enabled rich phenotyping of gene function and regulatory networks. These approaches have been challengingin vivo,especially in adult disease models such as cancer, which include mixtures of malignant and microenvironment cells. Glioblastoma (GBM) is a fatal cancer, and methods of systematically interrogating gene function and therapeutic targetsin vivo, especially in combination with standard of care treatment such as radiotherapy, are lacking. Here, we iteratively develop a multiplexin vivoperturb-seq CRISPRi platform for single cell genetic screens in cancer and tumor microenvironment cells that leverages intracranial convection enhanced delivery (CED) of sgRNA libraries into models of GBM. Our platform enables potent silencing of drivers ofin vivogrowth and tumor maintenance, as well as genes that sensitize GBM to radiotherapy. We find radiotherapy rewires transcriptional responses to genetic perturbations in anin vivodependent manner, revealing heterogenous patterns of treatment sensitization or resistance in GBM. Furthermore, we demonstrate targeting of genes that function in the tumor microenvironment, enabling alterations of ligand-receptor interactions between immune/stromal cells followingin vivoCRISPRi perturbations. In sum, we demonstrate the utility of multiplexed perturb-seq forin vivosingle cell dissection of adult cancer and normal tissue biology across multiple cell types in the context of therapeutic intervention, a platform with potential for broad application.
Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis
Authors: Wilken Madison B , Fonar Gennadiy , Nations Catriana , Pavani Giulia , Tsao Victor , Garifallou James , Tober Joanna , Bennett Laura , Maguire Jean Ann , Gagne Alyssa , Okoli Nkemdilim , Gadue Paul , Chou Stella T , Speck Nancy A , French Deborah L , Thom Christopher S 
Published: September 2023

AbstractTropomyosins coat actin filaments and impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linkedTropomyosin 1(TPM1) with human blood trait variation. Prior work suggested thatTPM1regulated blood cell formation in vitro, but it was unclear how or whenTPM1affected hematopoiesis. Using gene-edited induced pluripotent stem cell (iPSC) model systems,TPM1knockout was found to augment developmental cell state transitions, as well as TNFα and GTPase signaling pathways, to promote hemogenic endothelial (HE) cell specification and hematopoietic progenitor cell (HPC) production. Single-cell analyses showed decreasedTPM1expression during human HE specification, suggesting thatTPM1regulated in vivo hematopoiesis via similar mechanisms. Indeed, analyses of aTPM1gene trap mouse model showed thatTPM1deficiency enhanced the formation of HE during embryogenesis. These findings illuminate novel effects ofTPM1on developmental hematopoiesis.
Mechanisms used for cDNA synthesis and site-specific integration of RNA into DNA genomes by a reverse transcriptase-Cas1 fusion protein
Authors: Mohr Georg , Yao Jun , Park Seung Kuk , Markham Laura M. , Lambowitz Alan M. 
Published: September 2023

SUMMARYReverse transcriptase-Cas1 (RT-Cas1) fusion proteins found in some CRISPR systems enable spacer acquisition from both RNA and DNA, but the mechanism of RNA spacer acquisition has remained unclear. Here, we foundMarinomonas mediterraneaRT-Cas1/Cas2 adds short 3’-DNA (dN) tails to RNA protospacers enabling their direct integration into CRISPR arrays as 3’-dN-RNA/cDNA duplexes or 3’-dN-RNAs at rates comparable to similarly configured DNAs. Reverse transcription of RNA protospacers occurs by multiple mechanisms, including recently describedde novoinitiation, protein priming with any dNTP, and use of short exogenous or synthesized DNA oligomer primers, enabling synthesis of cDNAs from diverse RNAs without fixed sequence requirements. The integration of 3’-dN-RNAs or single-stranded (ss) DNAs is favored over duplexes at higher protospacer concentrations, potentially relevant to spacer acquisition from abundant pathogen RNAs or ssDNA fragments generated by phage-defense nucleases. Our findings reveal novel mechanisms for site-specifically integrating RNA into DNA genomes with potential biotechnological applications.
Transgenic expression ofcifgenes fromWolbachiastrainwAlbB recapitulates cytoplasmic incompatibility inAedes aegypti
Authors: McNamara Cameron J , Ant Thomas H , Harvey-Samuel Tim , White-Cooper Helen , Martinez Julien , Alphey Luke , Sinkins Steven P 
Published: September 2023

AbstractThe endosymbiotic bacteriaWolbachiacan invade insect populations by modifying host reproduction through cytoplasmic incompatibility (CI), an effect that results in embryonic lethality whenWolbachia-carrying males mate withWolbachia-free females. Here we describe a transgenic system for recreating CI in the major arbovirus vectorAedes aegyptiusing CI factor (cif) genes fromwAlbB, aWolbachiastrain currently being deployed to reduce dengue transmission. CI-like sterility was induced whencifAandcifBwere co-expressed in testes; this sterility could be rescued by maternalcifAexpression, thereby reproducing the pattern ofWolbachia-induced CI. Expression ofcifBalone was associated with extensive DNA damage and disrupted spermatogenesis. The strength of rescue by maternalcifAexpression was dependent on the comparative levels ofcifA/cifBexpression in males. These findings are consistent with CifB acting as a toxin and CifA as an antitoxin, with CifA attenuating CifB toxicity in both the male germline and in developing embryos.
Dual α-globin and truncated EPO receptor knockin restores hemoglobin production in α-thalassemia-derived red blood cells
Authors: Chu Simon N. , Soupene Eric , Wienert Beeke , Yin Han , Sharma Devesh , McCreary Travis , Jia Kun , Homma Shota , Hampton Jessica P. , Gardner James M. , Conklin Bruce R. , MacKenzie Tippi C. , Porteus Matthew H. , Cromer M. Kyle 
Published: September 2023

AbstractAlpha-thalassemia is an autosomal recessive disease with increasing worldwide prevalence. The molecular basis is due to mutation or deletion of one or more duplicated α-globin genes, and disease severity is directly related to the number of allelic copies compromised. The most severe form, α-thalassemia major (αTM), results from loss of all four copies of α-globin and has historically resulted in fatalityin utero. However,in uterotransfusions now enable survival to birth. Postnatally, patients face challenges similar to β-thalassemia, including severe anemia and erythrotoxicity due to imbalance of β-globin and α-globin chains. While curative, hematopoietic stem cell transplantation (HSCT) is limited by donor availability and potential transplant-related complications. Despite progress in genome editing treatments for β-thalassemia, there is no analogous curative option for patients suffering from α-thalassemia. To address this, we designed a novel Cas9/AAV6-mediated genome editing strategy that integrates a functional α-globin gene into the β-globin locus in αTM patient-derived hematopoietic stem and progenitor cells (HSPCs). Incorporation of a truncated erythropoietin receptor transgene into the α-globin integration cassette dramatically increased erythropoietic output from edited HSPCs and led to the most robust production of α-globin, and consequently normal hemoglobin. By directing edited HSPCs toward increased production of clinically relevant RBCs instead of other divergent cell types, this approach has the potential to mitigate the limitations of traditional HSCT for the hemoglobinopathies, including low genome editing and low engraftment rates. These findings support development of a definitiveex vivoautologous genome editing strategy that may be curative for α-thalassemia.Graphical abstract
Finding Expression of MUC1 and MUC4 in the Respiratory System of the Iraqi Common Quail (Coturnix coturnix)
Authors: Murad AL-Mamoori Nabeel Abd , Almhanna Hazem , Kadhim Abdulrazzaq B , Kilroy David , Kumar Arun HS 
Published: September 2023

AbstractBackgroundThis study focused on the major components of mucus, known as mucins, within the mucosal epithelium of the respiratory system in Iraqi Common Quail. Six quail were utilized in accordance with animal ethics guidelines from the College of Veterinary Medicine at the University of Al-Qadisiyah. Histological analysis, utilizing H&E staining, aimed to identify key respiratory system structures. PAS plus Alcian blue stains were employed to identify specific carbohydrates in the trachea, bronchi, and lungs. RT-qPCR was used to assess the gene expression levels of MUC1 and MUC4.ResultsThe trachea and bronchi encompassed four distinct layers: tunica mucosa, tunica submucosa, hyaline cartilage, and tunica adventitia. The mucosa consisted of pseudostratified epithelium that transitioned into simple columnar cells toward the primary and secondary bronchioles. This transition further progressed into simple cuboidal and squamous epithelium at smaller tertiary branches of the secondary bronchioles. Notably, the bronchial tunica submucosa was thinner than the trachea. While hyaline cartilage was prominently present in the trachea, it became fragmented in the bronchi and diminished towards the lungs and secondary bronchioles. Lung tissue was characterized by numerous lobules housing alveoli connected to alveolar ducts and sacs, alongside an intricate network of blood vessels. The respiratory tissues, including the trachea, bronchi, and lungs, exhibited a strong affinity for PAS-combined Alcian blue stains. This confirmed the substantial presence of both acidic and neutral mucins within the epithelial cells and glands. The trachea demonstrated significantly elevated levels of acidic mucins and a concentrated amount? of neutral mucins. Transcriptome analysis indicated the expression of both MUC1 and MUC4 genes. Importantly, MUC4 expression surpassed that of MUC1 in the trachea, bronchi, and lungs.ConclusionThis study highlights the similarity of histological structures in the trachea, bronchi, and lungs of quail to typical avian species. Moreover, it underscored the substantial presence of both acidic and neutral mucins, with MUC4 being the predominant mucin, potentially playing a pivotal role in regulating mucosal barrier functions and interacting with pathogens. Nonetheless, further investigation is warranted to elucidate MUC4’s role in respiratory epithelial cells.
Novel substrate prediction for the TAM family of RTKs using phosphoproteomics and structure-based modeling
Authors: Widstrom Naomi E. , Andrianov Grigorii V. , Heier Jason L. , Heier Celina , Karanicolas John , Parker Laurie L. 
Published: September 2023

ABSTRACTThe TAM family of receptor tyrosine kinases is implicated in multiple distinct oncogenic signaling pathways. However, to date there are no FDA-approved small molecule inhibitors for the TAM kinases. Inhibitor design and screening rely on tools to study kinase activity. Our goal was to address this gap by designing a set of synthetic peptide substrates for each of the TAM family members: Tyro3, Axl and Mer. We used an in vitro phosphoproteomics workflow to determine the substrate profile of each TAM kinase and input the identified substrates into our data processing pipeline, KINATEST-ID, producing a position-specific scoring matrix for each target kinase and generating a list of candidate synthetic peptide substrates. We synthesized and characterized a set of those substrate candidates, systematically measuring their initial phosphorylation rate with each TAM kinase by LC-MS. We also used the multimer modeling function of AlphaFold2 to predict peptide-kinase interactions at the active site for each of the novel candidate peptide sequences against each of the TAM family kinases, and observed that remarkably, every sequence for which it predicted a putatively catalytically competent interaction was also demonstrated biochemically to be a substrate for one or more of the TAM kinases. This work shows that kinase substrate design can be achieved using a combination of preference motifs and structural modeling, and it provides the first demonstration of peptide-protein interaction modeling for predicting likelihood of constructive catalytic interactions.
Lipid levels correlate with neuronal and dopaminergic markers during the differentiation of SH-SY5Y cells
Authors: Marlet Frederik Ravnkilde , Muñoz Sonia Sanz , Sotiraki Nefeli , Eliasen Jannik Nicklas , Woessmann Jakob Paul , Weicher Jan , Dreier Jesper Elmsted , Schoof Erwin , Kohlmeier Kristi A , Maeda Kenji , Galvagnion Céline 
Published: September 2023

AbstractParkinson’s Disease (PD) is characterized by the loss of dopaminergic neurons and the deposition in the remaining cells of protein inclusions called Lewy Bodies (LBs). LBs are heterogeneous structures composed of protein and lipid molecules and their main constituent is the presynaptic protein α-synuclein. SH-SY5Y cells are neuroblastoma cells commonly used to model PD because they express dopaminergic markers and α-synuclein and they can be differentiated into neuronal cells using established protocols. Despite increasing evidence pointing towards a role of lipids in the initiation of PD, limited knowledge is available on the lipidome of undifferentiated and differentiated SH-SY5Y cells. In this study, we show that the levels and chemical properties of negatively charged phospholipids, diacyl glycerol and sphingolipids are specifically altered along the differentiation process of SH-SY5Y cells and that the levels of these lipids’ species correlate with those of dopaminergic and neuronal markers. These results are supported by proteomic data showing that the main biological processes affected by the differentiation of SH-SY5Y cells are lipid metabolism and processes associated with neuron maturation. Finally, our results show that electrophysiological activity can be detected in differentiated SH-SY5Y cells at a stage where most of the lipid changes have reached their maximal value. These results provide the first complete and quantitative characterisation of the changes in lipidome associated with the differentiation of SH-SY5Y cells into more neuronal and dopaminergic-like phenotype and serve as a basis for further characterisation of lipid disruptions in association with PD and its risk factors in this dopaminergic-like neuronal cell model.
Characterization of erythroferrone oligomerization and its impact on BMP antagonism
Authors: Mast Jacob F , Leach Edmund A E , Thompson Thomas B 
Published: September 2023

AbstractHepcidin, a peptide hormone that negatively regulates iron metabolism, is expressed by bone morphogenetic protein (BMP) signaling. Erythroferrone (ERFE) is an extracellular protein that binds and inhibits BMP ligands, thus positively regulating iron import by indirectly suppressing hepcidin. This allows for rapid erythrocyte regeneration after blood loss. ERFE belongs to the C1Q/TNF related protein (CTRP) family and is suggested to adopt multiple oligomeric forms: a trimer, a hexamer, and a high molecular weight species. The molecular basis for how ERFE binds BMP ligands and how the different oligomeric states impact BMP inhibition are poorly understood. In this study, we demonstrated that ERFE activity is dependent on the presence of stable dimeric or trimeric ERFE, and that larger species are dispensable for BMP inhibition. Additionally, we used anin-silicoapproach to identify a helix, termed the ligand binding domain (LBD), that was predicted to bind BMPs and occlude the type I receptor pocket. We provide evidence that the LBD is crucial for activity through luciferase assays and surface plasmon resonance (SPR) analysis. Our findings provide new insight into how ERFE oligomerization impacts BMP inhibition, while identifying critical molecular features of ERFE essential for binding BMP ligands.
Pseudorabies virus causes splenic injury via inducing the oxidative stress and apoptpsos related factors in mice
Authors: Sun Wei , Liu Shanshan , Yan Yi , Wang Qingyan , Fan Yu , Okyere Samuel Kumi 
Published: September 2023

AbstractPseudorabies virus (PRV) is an immunosuppressive disease that causes significant damage to the pig industry. This study aimed to detect the effects of PRV on oxidative stress related factors and cell apoptosis in the spleen, providing a basis for the research on the pathogenesis of PRV in mice model. Pathological observation was performed by hematoxylin and eosin Y staining. Biochemical and Flow cytometry method were performed to determine the reactive oxygen species profile of the spleen post-infection and apoptosis detection. In addition, q-PCR and Western blot were adopted to measure the apoptotic conditions of the spleen infected with PRV. The results indicated that the ROS level in the PRV infection group was remarkedly increased (p<0 01) at a time-dependent pattern. Furthermore, the Malondialdehyde levels in the spleen of mice in the infection group increased significantly (p<0.01) in a time-dependent mode. However, the Catalase, Superoxide dismutase, and Glutathione activity and expression levels in the infection group were significantly decreased with the control group (p<0 01) in a time-dependent manner. Furthermore, the ratio of splenocyte apoptosis in the infection group significantly increased (p<0 05,p<0 01) in a time-dependent manner. In conclusion, PRV infection causes apoptosis of the spleen via oxidative stress in mice.