bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the antimicrobial activity of the alcoholic extract ofTagetes erectaagainst bacteria and fungi of clinical importance
Authors: Martínez González Gabriel , Suárez González Frida , Chávez Alanuza Alejandro , Montes de Oca Cuenca Sandra Stephanie , Cuarto Hernández Angélica Guadalupe , de Jesús Olvera Lidia , Almeida Villegas Jorge Angel 
Published: September 2024

AbstractAntibiotic resistance is a significant global health concern, putting at risk treatment options for infectious diseases. As a result, treatments can be expensive and ineffective, so it is essential to look for new options such as the use of plant extracts with antimicrobial properties to combat these diseases.Tagetessp is a plant species that is used in folk medicine to cure various diseases and has several properties among which the antimicrobial, for this reason, the aim of this research was to evaluate the antimicrobial activity of the ethanolic extract ofTagetes erectaL against various bacteria and yeasts. The antimicrobial activity of the extract was analyzed by the Kirby-Bauer method at different concentrations. The extract showed antimicrobial activity by presenting inhibition halos mainly againstStaphylococcus, obtaining the following results:S. aureusATCC 43300 (19,400 ± 0.435 mm to 500 mg/mL);S. aureusATCC 6538 (11,206 ± 0.342 mm to 750 mg/mL);A. baumanniiATCC 19606 (10.570 ± 0.535 mm a 250 mg/mL);P. mirabilis(7.636 ± 0.196 mm a 250 mg/mL) eI. orientalisATCC 6258 (7.400 ± 0.190 mm a 250 mg/mL). Secondary metabolites such as tannins, quinones, coumarins, phenolic compounds and flavonoids were determined.Tagetes erectaL alcoholic extract has antimicrobial activity against clinically relevant strains and may be considered for further studies against multi-resistant microorganisms in the future.
The role of ERFVIIs as oxygen-sensing transducers in the evolution of land plant response to hypoxia
Authors: Carbonare Laura Dalle , van Veen Hans , Shukla Vinay , Perri Monica , Bui Liem , Holdsworth Michael J. , Licausi Francesco 
Published: September 2024

AbstractThe transcriptional response to low oxygen (hypoxia) in the flowering plantArabidopsis thalianais transduced through group VII Ethylene Response Factor (ERFVII) transcription factors, whose proteolysis is oxygen-dependent via the PLANT CYSTEINE OXIDASE (PCO) N-degron pathway. When and how this response to hypoxia evolved in land plants remains unknown. Here we investigated the conservation and divergence of transcriptional responses to hypoxia in major land plant clades. We identified induction of gene functions associated with glycolysis and fermentation as part of a conserved response across all land plant divisions. Our results indicate that ERFVIIs appeared in the last common ancestor of vascular plants with true roots, concurrently with oxygen-dependent destabilisation, to regulate hypoxia-adaptive genes. Proteins from other ERF groups have been recruited multiple times in different clades as substrates of the PCO N-degron pathway. Our results demonstrate that the response of land plants to hypoxia has been refined in derived clades through the evolution of ERFVIIs as transcriptional transducers, that occurred concomitantly with the appearance of vascular systems and roots as foraging systems through hypoxic soil.
Identification of novel components of the Ced and Ups systems inSaccharolobus islandicusREY15A
Authors: Wu Pengju , Zhang Mengqi , Kou Yanlu , Liang Shikuan , Ni Jinfeng , Huang Qihong , Shen Yulong 
Published: September 2024

AbstractIn the cells ofSulfolobales, the Ced (Crenarchaeal system for exchange of DNA) and Ups (UV-inducible pili ofSulfolobus) systems are highly induced by DNA damages and function in chromosomal DNA exchange by mediating DNA import and cell aggregation, respectively. The Ced system is composed of CedA, CedA1, CedA2, and CedB. The Ups is composed of UpsA, UpsB, UpsE and UpsF. However, how the DNA is transported by these systems is far from clear. Here, we report two novel components of the Ced system, CedD (SiRe_1715) and CedE (SiRe_2100), which are paralogs of CedB and CedA, respectively, and one new component of the Ups system, UpsC (SiRe_1957), which is a paralog of UpsA and UpsB, inSaccharolobus islandicusREY15A. DNA exchange assay revealed thatcedD,cedE, andupsCare essential for DNA import whilecedEandupsCare also important for DNA export. Further microscopy analysis revealed thatupsCis involved in cell aggregation like other Ups genes. Besides, we found thatcedBandcedDco-occur in the genomes of crenarchaea which lackvirB4and the presence ofcedBandcedD, andvirB4is complementary. Both proteins show homology to different parts of the N-terminal domain of VirB4 in a complementary manner and form stable homo-oligomersin vitro. Collectively, our results indicate that CedD and CedE, and UpsC are essential components of the Ced and Ups systems, respectively.
Organ-specific electrophile responsivity mapping in liveC. elegans
Authors: Liu Jinmin , Kulkarni Amogh , Gao Yong-Qi , Urul Daniel A. , Hamelin Romain , Novotny Balázs Á. , Long Marcus J. C. , Aye Yimon 
Published: September 2024

AbstractProximity labeling technologies are limited to indexing localized protein residents. Such data— although valuable—cannot inform on small-molecule responsivity of local residents. We here bridge this gap by demonstrating in liveC. eleganshow electrophile-sensing propensity in specific organs can be quantitatively mapped and ranked. Using this method, >70% of tissue-specific responders exhibit novel responsivity,independentof tissue-specific abundance. One responder, cyp-33e1—for which both human and worm orthologs are electrophile responsive—marshals stress-dependent gut functions, despite manifesting uniform abundance across all tissues studied. Cyp-33e1’s localized electrophile responsivity operates site-specifically, triggering multifaceted responses: electrophile sensing through the catalytic-site cysteine results in partitioning between enzyme inhibition and localized production of a critical metabolite that governs global lipid availability, whereas a rapid dual-cysteine site-specific sensing modulates gut homeostasis. Beyond pinpointing chemical actionability within local proteomes, tissue-specific electrophile responsivity mapping illuminates otherwise intractable locale-specific metabolite signaling and stress response programs influencing organ-specific decision-making.IN BRIEFContext-specific protein reactivity is a cornerstone of biological stress responsivity, and thus has important ramifications for drug discovery; no current method can inform on these parameters. Here we debut a method that cartographs locale-specific actionability to reactive metabolites; Cyp-33e1, a gut-specific responder, emerged to partition between electrophile-driven localized enzymatic turnover that triggers gut-specific metabolite production shaping global lipid storage, and localized electrophile sensing that marshals global stress response.HIGHLIGHTSLocalis-REX maps organ-specific electrophile-responsive proteins in wormsHits are neither identified by organ-specific Ultra-ID nor biased by localized expressionHits are enriched in proteins functionally relevant to stress-related phenotypesLocalized responsivity of gut-specific hit, cyp-33e1, shapes global lipid availability
Profiling proteins involved in peroxynitrite homeostasis using ROS/RNS conditional proteomics
Authors: Zhu Hao , Uno Hiroaki , Matsuba Kyoichi , Hamachi Itaru 
Published: September 2024

AbstractPeroxynitrite (ONOO−), the product of the diffusion-controlled reaction of superoxide (O2•−) with nitric oxide (NO•), plays a crucial role in oxidative and nitrative stress and modulates key physiological processes such as redox signaling. While biological ONOO−is conventionally analyzed using 3-nitrotyrosine antibodies and fluorescent sensors, such probes lack specificity and sensitivity, making high-throughput and comprehensive profiling of ONOO−-associated proteins challenging. In this study, we used a conditional proteomics approach to investigate ONOO−homeostasis by identifying its protein neighbors in cells. We developedPeroxynitrite-responsiveproteinLabeling reagents (Porp-L) and, for the first time, discovered 2,6-dichlorophenol as an ideal moiety that can be selectively and rapidly activated by ONOO−for labeling of proximal proteins. The reaction ofPorp-Lwith ONOO−generated several short-lived reactive intermediates that can modify Tyr, His, and Lys residues on the protein surface. We have demonstrated thePorp-L-based conditional proteomics in immune-stimulated macrophages, which indeed identified proteins known to be involved in the generation and modification of ONOO−and revealed the endoplasmic reticulum (ER) as a ONOO−hot spot. Moreover, we discovered a previously unknown role for Ero1a, an ER-resident protein, in the formation of ONOO−. Overall,Porp-Lrepresent a promising research tool for advancing our understanding of the biological roles of ONOO−.
Expanding the CRISPR toolbox by engineering Cas12a orthologs of metagenomic discovery
Authors: Tao Dagang , Xu Bingrong , Li Sheng , Liu Hailong , Shi Suyu , Wang Yuan , Zhao Changzhi , Ruan Jinxue , Fu Liangliang , Huang Xingxu , Li Xinyun , Zhao Shuhong , Xie Shengsong 
Published: September 2024

AbstractCas12a (Cpf1) is a CRISPR-associated nuclease with broad utility in genome editing and molecular diagnostic applications. However, the widespread adoption of CRISPR-Cas12a nucleases and their variants has been hindered by the requirement for a specific protospacer adjacent motif (PAM), relatively low CRISPR RNA (crRNA) activity and the inability to multiplex nucleic acid detection alone. To overcome these limitations, we employed a comprehensive framework combined with AlphaFold2 tode novomine 1,261 previously unexploited Cas12a orthologs from the global microbiome. Following experimental analysis, we identified the most promising 21 Cas12a nuclease orthologs and designated them “Genie scissor 12” (Gs12). Our analysis uncovered two exceptional variants among these newly identified orthologs: Gs12-10, a first natural PAM-less Cas12a ortholog, which can recognize 52 distinct PAM types, representing a significant 1.8-fold expansion in recognition range compared to the relative LbCas12a PAM; and Gs12-7MAX, an engineered variant of Gs12-7 that exhibited 1.27-fold higher editing efficiency than enAsCas12a-HF. Furthermore, we harnessed Gs12-1, Gs12-4, Gs12-9, and Gs12-18, along with their corresponding engineered crRNAs, to develop a powerful four-channel multiplexed CRISPR-based nucleic acid detection system. The discovery of diverse functions in Cas12a offers a deeper understanding of the CRISPR/Cas12a family. Also, it holds great promise for expanding its applications and uncovering the untapped potential of other CRISPR/Cas systems.Graphical Abstract
TvAP65 inTrichomonas vaginalisPromotes HPV Infection by Interacting with Host Molecules
Authors: Mei Xuefang , Sheng Wanxin , Zhang Yani , Tian Wenjie , Tian Xiaowei , Yang Zhenke , Wang Shuai , Zhang Zhenchao 
Published: September 2024

AbstractCervical cancer induced by human papillomavirus (HPV) infection poses a serious threat to women’s health. Studies have shown thatTrichomonas vaginalis(T. vaginalis), which is widely prevalent globally, can facilitate HPV infection. However, the underlying mechanism remains unclear. This study found thatT. vaginalissignificantly enhanced HPV infection in HaCaT cells and mouse vaginas throughin vivoandin vitroexperiments, and promoted the expression of HPV membrane receptor molecules CD151 and HSPG2. The HPV infection rate and CD151/HSPG2 expression levels were significantly decreased after reducing the expression ofT. vaginalisadhesion protein 65 (TvAP65). In contrast, both HPV infection rates and CD151/HSPG2 expression were significantly increased in HaCaT cells over-expressing TvAP65. When both TvAP65 inT. vaginalisand CD151/HSPG2 in HaCaT cells were knocked down simultaneously, the infection rate of HPV in HaCaT cells was further reduced. These results suggest that TvAP65 promotes HPV infection by up-regulating the expression of CD151 and HSPG2. Furthermore, this study knocked down the 12 interacting molecules of TvAP65 in HaCaT cells one by one, and found that the HPV infection rate was significantly reduced afterT. vaginalisinfected HaCaT cells with low expression of FTH1, SPCS1, ATP5MC3, ITGB7, PMEPA1 or REEP5. Among them, SPCS1 played the most significant role. Simultaneous knockdown of TvAP65 and SPCS1 further significantly down-regulated the infection rate of HPV in HaCaT cells. Moreover, this molecule also down-regulated the promoting effect ofT. vaginalison HSPG2/CD151 expression. These results imply that SPCS1 plays an important role inT. vaginalispromoting HSPG2/CD151 expression and HPV infection. This study not only further proved thatT. vaginaliscan promote HPV infection but also explores the molecular mechanism by which TvAP65, through its interaction with SPCS1, up-regulates the expression of HSPG2 and CD151, thereby facilitating HPV infection. This provides a theoretical basis for clarifying the mechanism of co-infection betweenT. vaginalisand HPV.
Entorhinal grid-like codes for visual space during memory formation
Authors: Graichen Luise P. , Linder Magdalena S. , Keuter Lars , Jensen Ole , Doeller Christian F. , Lamm Claus , Staudigl Tobias , Wagner Isabella C. 
Published: September 2024

AbstractEye movements, such as saccades, allow us to gather information about the environment and, in this way, can shape memory. In non-human primates, saccades are associated with the activity of grid cells in the entorhinal cortex. Grid cells are essential for spatial navigation, but whether saccade-based grid-like signals play a role in human memory formation is currently unclear. Here, human participants underwent functional magnetic resonance imaging (fMRI) and continuous eye gaze monitoring while studying scene images. Recognition memory was probed immediately thereafter. Results revealed saccade-based grid-like codes in the left entorhinal cortex while participants studied the scene images, a finding that was replicated with an independent data set reported here. The grid-related effects were time-locked to activation increases in the frontal eye fields. Most importantly, saccade-based grid-like codes were associated with recognition memory, such that grid-like codes were lower the better participants performed in subsequently recognizing the scene images. Collectively, our findings suggest an entorhinal map of visual space that is timed with neural activity in oculomotor regions, supporting memory formation.
Purkinje cell intrinsic activity shapes cerebellar development and function
Authors: Osório Catarina , White Joshua J. , Solé Paula Torrents , Mandemaker Nienke , Olivero Federico , Kirwan Freya , de Winter Fred , Regolo Eleonora , Fiocchi Francesca Romana , Serra Inês , Tjon Saffira , Ozgur Zeliha , van den Hout Mirjam C.G.N. , van Ijcken Wilfred F. J. , López-Bendito Guillermina , Badura Aleksandra , Lim Lynette , van Woerden Geeske , Schonewille Martijn 
Published: September 2024

AbstractThe emergence of functional cerebellar circuits is heavily influenced by activity-dependent processes. However, the role of intrinsic activity in Purkinje neurons, independent of external input, in driving cerebellar development remains less understood. Here, we demonstrate that before synaptic networks mature, Purkinje cell intrinsic activity is essential for regulating dendrite growth, establishing connections with cerebellar nuclei, and ensuring proper cerebellar function. Disrupting this activity during the postnatal period impairs motor function, with earlier disruptions causing more severe effects. Importantly, only disruptions during early development lead to pronounced defects in cellular morphology, highlighting key temporal windows for dendritic growth and maturation. Transcriptomic analysis revealed that early intrinsic activity drives the expression of activity-dependent genes, such asPrkcgandCar8, which are essential for dendritic growth. Our findings emphasize the importance of temporally-specific intrinsic activity in Purkinje cells for guiding cerebellar circuit development, providing a potential common mechanism underlying cerebellum-related disorders.
The wheat NLR protein PM3b localizes to endoplasmic reticulum-plasma membrane contact sites and interacts with AVRPM3b2/c2through its LRR domain
Authors: Isaksson Jonatan , Kunz Lukas , Flückiger Simon , Widrig Victoria , Keller Beat 
Published: September 2024

AbstractPlant nucleotide-binding leucine-rich repeat (NLR) proteins are intracellular immune receptors that directly or indirectly perceive pathogen derived effector proteins to induce an immune response. NLRs display diverse sub-cellular localizations, which are associated with the capacity of the immune receptor to confer disease resistance and recognize its corresponding avirulence effector. In wheat, the NLR PM3b recognizes the wheat powdery mildew effector AVRPM3b2/c2and we examined the molecular mechanism underlying this recognition. We show that PM3b and other PM3 variants localize to endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (EPCS) while AVRPM3b2/c2localizes to the nucleocytoplasmic space. Additionally, we found that PM3b interacts in planta with AVRPM3b2/c2through its LRR domain. We further demonstrate that full length PM3b interaction with AVRPM3b2/c2is considerably weaker than for the isolated PM3b LRR domain or the susceptible PM3 variant PM3CS, indicating that activation of PM3b leads to dissociation of the complex. In line with this: We observed a strong interaction between PM3b and AVRPM3b2/c2in a P-loop mutant of PM3b which was unable to initiate a cell death response, or when an inactive variant of AVRPM3b2/c2was used. We propose that PM3b transiently interacts with AVRPM3b2/c2through residues in the LRR which are conserved among PM3 variants while the amino acids necessary for full activation and cell death signaling are unique to PM3b. Our data suggests that PM3b localization and interaction with AVRPM3b2/c2differs from other well studied NLRs and further highlights the mechanistic diversity in NLR-mediated responses against pathogens in plants.
End of preservation normothermic machine perfusion of porcine kidneys after ischaemic injury reprograms metabolism and induces fibrosis after transplant despite unchanged function: insights from the renal proteome
Authors: Mulvey John Francis , Snashall Corinna , Rozenberg Kaithlyn , Lo Faro M. Letizia , Eijken Marco , Lohmann Stine , Moers Cyril , Leuvenink Henri , Baan Carla , Hoogduijn Martin , Keller Anna Krarup , Sutton Chris , Hunter James , Jespersen Bente , Ploeg Rutger , Shaheed Sadr 
Published: September 2024

AbstractNormothermic machine perfusion (NMP) after initial hypothermic preservation of donor kidneys prior to transplantation is becoming a clinical reality, but the precise molecular mechanisms through which the graft is impacted remain only partially characterised. Using an unbiased proteomic methodology, we found that auto transplantation of is chaemically injured porcine kidneys resulted in an activation of the stress response 14 days after transplantation, as well as in selective changes in the proteins responsible for the metabolism of organic acids. The addition of 4 hours of NMP at the end of organ preservation (endNMP) resulted in coordinated changes to the renal proteome at 14 days when compared with the effect of transplant after preservation by hypothermic machine perfusion alone: most notably increased fibrosis and widespread additional reprogramming of metabolism. These findings were supported by intersection with single cell transcriptomics data which suggested an enrichment of proteins predominantly expressed in fibroblasts in kidneys with end of preservation NMP 14 days post-transplant compared to healthy kidneys. Our data showed that the addition of endNMP to existing preservation strategies resulted in a different molecular phenotype after transplantation, despite unchanged filtration function. In addition to potentially conferring benefits, NMP may also result in potentially detrimental molecular changes and thus protocols should be carefully evaluated to derive optimal clinical outcomes.
Plant Mobile Domain protein-DNA motif modules counteract Polycomb silencing to stabilize gene expression
Authors: Pélissier Thierry , Jarry Lucas , Olivier Margaux , Dajoux Gabin , Pélissier Marie-Noëlle Pouch- , Courtois Charles , Descombin Julie , Picault Nathalie , Moissiard Guillaume , Mathieu Olivier 
Published: September 2024

AbstractIn plants and animals, Polycomb group (PcG) proteins are crucial for development, regulating gene expression through H3K27me3 deposition and subsequent gene silencing. While Polycomb silencing target specification is increasingly understood, it remains unclear how certain genes with apparent silencing-attracting features escape this process. Here, we show that the plant mobile domain C (PMD-C) containing proteins MAINTENANCE OF MERISTEMS (MAIN), MAIN-LIKE 1 (MAIL1) and MAIL2 oppose Polycomb silencing at numerous actively transcribed genes in Arabidopsis. Mutations inMAIN,MAIL1orMAIL2result in PcG-dependent ectopic H3K27me3 deposition, often associated with transcriptional repression. We show that MAIL1, which functions in concert with MAIN, and MAIL2 target distinct gene sets and associate with chromatin at specific DNA sequence motifs. We demonstrate that the integrity of these motif sequences is essential for promoting expression and antagonizing H3K27me3 deposition. Our results unveil a novel system opposing Polycomb silencing involving PMD-C protein-DNA motif modules, expanding our understanding of eukaryotic gene regulation mechanisms.