bluuebunny/crossref_metadata_2025_split huggingface dataset:
Devosia rhodophyticola sp. nov. and Devosia algicola sp. nov., isolated from a marine red alga
Authors: Kim Jeong Min , Baek Woonhee , Choi Byeong Jun , Bayburt Hülya , Baek Ju Hye , Han Dong Min , Lee Sung Chul , Jeon Che Ok 
Published: January 2024

Two Gram-stain-negative, obligately aerobic, motile rod bacteria, designated as G2-5T and G20-9T, exhibiting catalase- and oxidase-positive activities, were isolated from the phycosphere of a Chondrus species, a marine red alga. Strain G2-5T exhibited optimal growth at 30 °C and pH 5.0–6.0 and in the presence of 0.5–1.0% NaCl. In contrast, strain G20-9T demonstrated optimal growth at 25 °C and pH 6.0 and in the presence of 0.5–1.5% NaCl. Both strains contained ubiquinone-10, summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c), C18 : 0 and 11-methyl-C18 : 1
ω7c, and diphosphatidylglycerol and phosphatidylglycerol as the major respiratory isoprenoid quinone, cellular fatty acids and polar lipids, respectively. The genomic DNA G+C contents were 57.2 mol% for strain G2-5T and 57.5 mol% for strain G20-9T. Strains G2-5T and G20-9T exhibited 98.2 % 16S rRNA gene sequence similarity, along with 82.3 % average nucleotide identity (ANI) and 25.0 % digital DNA–DNA hybridization (dDDH) values, indicating that they represent different species. Phylogenetic analyses based on both 16S rRNA gene and genome sequences revealed that strains G2-5T and G20-9T formed distinct phylogenic lineages within the genus

Devosia

. Strains G2-5T and G20-9T were most closely related to

Devosia limi

DSM 17137T and

Devosia beringensis

S02T with 97.7 and 96.9 % 16S rRNA gene sequence similarities, respectively. The ANI and dDDH values between strains G2-5T and G20-9T and other

Devosia

species were lower than 73.9 and 19.2 %, respectively, suggesting that they constitute novel species within the genus

Devosia

. Based on their distinct phenotypic, chemotaxonomic, and molecular characteristics, strains G2-5T and G20-9T represent two novel species of the genus

Devosia

, for which the names Devosia rhodophyticola sp. nov. (G2-5T=KACC 22601T=JCM 35404T) and Devosia algicola sp. nov. (G20-9T=KACC 22650T=JCM 35405T) are proposed, respectively.
Pharmacogenomic discovery of genetically targeted cancer therapies optimized against clinical outcomes
Authors: Truesdell Peter , Chang Jessica , Villa Doris Coto , Dai Meiou , Zhao Yulei , McIlwain Robin , Young Stephanie , Hiley Shawna , Craig Andrew W. , Babak Tomas 
Published: January 2024

ABSTRACTDespite the clinical success of dozens of genetically targeted cancer therapies, the vast majority of patients with tumors caused by loss-of-function (LoF) mutations do not have access to these treatments. This is primarily due to the challenge of developing a drug that treats a disease caused by the absence of a protein target. The success of PARP inhibitors has solidified synthetic lethality (SL) as a means to overcome this obstacle. Recent mapping of SL networks using pooled CRISPR-Cas9 screens is a promising approach for expanding this concept to treating cancers driven by additional LoF drivers. In practice, however, translating signals from cell lines, where these screens are typically conducted, to patient outcomes remains a challenge. We developed a pharmacogemic (PGx) approach called “Clinically Optimized Driver Associated PGx” (CODA-PGx) that accurately predicts genetically targeted therapies with clinical-stage efficacy in specific LoF driver contexts. Using approved targeted therapies and cancer drugs with available real-world evidence and molecular data from hundreds of patients, we discovered and optimized the key screening principles predictive of efficacy and overall patient survival. In addition to establishing basic technical conventions, such as drug concentration and screening kinetics, we found that replicating the driver perturbation in the right context, as well as selecting patients where those drivers are genuine founder mutations, were key to accurate translation. We used CODA-PGX to screen a diverse collection of clinical stage drugs and report dozens of novel LoF genetically targeted opportunities; many validated in xenografts and by real-world evidence. Notable examples include treating STAG2-mutant tumors with Carboplatin, SMARCB1-mutant tumors with Oxaliplatin, and TP53BP1-mutant tumors with Etoposide or Bleomycin.One Sentence SummaryWe identified principles of pharmacogenomic screening that predict clinical efficacy in cancer patients with specific driver mutations.
Protecting Allogeneic Pancreatic Islet Grafts by Engineered Veto
Authors: Qi Yan , Zhang Xianghua , Konigsberg Paula , Cull Janae , McCoy Patrick , Cruz Coral , Dahl Kevin , Staerz Uwe 
Published: January 2024

SummaryIn today’s clinical practice, general immune suppression regimens are used to prevent transplant rejection. Though highly effective, they impair a patient’s protection against infectious challenges. Strategies are being sought that prevent graft rejection without inhibiting beneficial immune functions. One such approach is based on the classical veto effect that employs donor-derived CD8+T cells to inhibit cellular immune responses. Yet, allogeneic grafts may only be partially protected by classical veto as CD8+T cells may fail to remove organ-specific alloreactive T cells. To induce transplant specific immune unresponsiveness, if not tolerance, it may be necessary to endow grafted tissues with veto. Adenoviral vectors were designed that expressed the CD8 α-chain as transgene and thus conferred the immune inhibitory veto function to cells of grafted tissues. In the present model, adenoviral vector vectors protected transduced allogeneic pancreatic islets from rejection in fully immune competent recipients. These studies demonstrated that a tissue-engineering approached could be used to create universally acceptable transplants.
Effect of Artificial Lung Fiber Bundle Geometric Design on Micro- and Macro-scale Clot Formation
Authors: Lai Angela , Omori Natsuha , Napolitano Julia E. , Antaki James F. , Cook Keith E. 
Published: January 2024

AbstractThe hollow fiber membrane bundle is the functional component of artificial lungs, transferring oxygen and carbon dioxide to and from the blood. It is also the primary location of blood clot formation and propagation in these devices. The geometric design of fiber bundles is defined by a narrow range of parameters that determine gas exchange efficiency and blood flow resistance, such as fiber packing density, path length, and frontal area. However, these parameters also affect thrombosis. This study investigated the effect of these parameters on clot formation using 3-D printed flow chambers that mimic the geometry and blood flow patterns of fiber bundles. Hollow fibers were represented by an array of vertical micro-rods (380 micron diameter) arranged with varying packing densities (40, 50, and 60%) and path lengths (2 and 4 cm). Blood was pumped through the device corresponding to three mean blood flow velocities (16, 20, and 25 cm/min). Results showed that (1) clot formation decreases dramatically with decreasing packing density and increasing blood flow velocity, (2) clot formation at the outlet of fiber bundle enhances deposition upstream, and consequently (3) greater path length provides more clot-free fiber surface area for gas exchange than a shorter path length. These results can be used to create less thrombogenic, more efficient artificial lung designs.Translational Impact SentenceFiber bundle parameters, such as decreased packing density, increased blood flow velocity, and a longer path length, can be used to design a less thrombogenic, more efficient artificial lung to extend functionality.
Development and validation of a subject-specific integrated finite element musculoskeletal model of human trunk with ergonomic and clinical applications
Authors: Ghezelbash Farshid , Eskandari Amir Hossein , Shirazi-Adl Aboulfazl , Larivière Christian 
Published: January 2024

AbstractBackground and ObjectivesBiomechanical modeling of the human trunk is crucial for understanding spinal mechanics and its role in ergonomics and clinical interventions. Traditional models have been limited by only considering the passive structures of the spine in finite element (FE) models or incorporating active muscular components in multi-body musculoskeletal (MS) models with an oversimplified spine. This study aimed to develop and validate a subject-specific coupled FE-MS model of the trunk that integrates detailed representation of both the passive and active components for biomechanical simulations.MethodsWe constructed a parametric FE model of the trunk, incorporating a realistic muscle architecture, personalized through imaging datasets and statistical shape models. To validate the model, we compared tissue-level responses with in vitro experiments, and muscle activities and intradiscal pressures versus in vivo measurements during various physical activities. We further demonstrated the versatility of the proposed personalized integrated framework through additional applications in ergonomics (i.e., wearing an exoskeleton) and surgical interventions (e.g., nucleotomy and spinal fusion).ResultsThe model demonstrated satisfactory agreement with experimental data, showcasing its validity to predict tissue- and disc-level responses accurately, as well as muscle activity and intradiscal pressures. When simulating ergonomics scenarios, the exoskeleton-wearing condition resulted in lower intradiscal pressures (1.9 MPa vs. 2.2 MPa at L4-L5) and peak von Mises stresses in the annulus fibrosus (2.2 MPa vs. 2.9 MPa) during forward flexion. In the context of surgical interventions, spinal fusion at L4-L5 led to increased intradiscal pressure in the adjacent upper disc (1.72 MPa vs. 1.58 MPa), whereas nucleotomy minimally influenced intact disc pressures but significantly altered facet joint loads and annulus fibrosus radial strains.ConclusionsThe integrated FE-MS model of the trunk represents a significant advancement in biomechanical simulations, providing insights into the intricate interplay between active and passive spinal components. Its predictive capability extends beyond that of conventional models, enabling detailed risk analysis and the simulation of varied surgical outcomes. This comprehensive tool has potential implications for the design of ergonomic interventions and the optimization of surgical techniques to minimize detrimental effects on spinal mechanics.
A universal molecular mechanism driving aging
Authors: Jin Wan , Zheng Jing , Xiao Yu , Ju Lingao , Chen Fangjin , Fu Jie , Jiang Hui , Zhang Yi 
Published: January 2024

AbstractHow cell replication ultimately results in aging and the Hayflick limit are not fully understood. Here we show that clock-like accumulation of DNA G-quadruplexes (G4s) throughout cell replication drives conserved aging mechanisms. G4 stimulates transcription-replication interactions to delay genome replication and impairs DNA re-methylation and histone modification recovery, leading to loss of heterochromatin. This creates a more permissive local environment for G4 formation in subsequent generations. As a result, G4s gradually accumulate on promoters throughout mitosis, driving clock-like DNA hypomethylation and chromatin opening. In patients andin vitromodels, loss-of-function mutations in the G4-resolving enzymes WRN, BLM and ERCC8 accelerate the erosion of the epigenomic landscape around G4. G4-driven epigenomic aging is strongly correlated with biological age and is conserved in yeast, nematodes, insects, fish, rodents, and humans. Our results revealed a universal molecular mechanism of aging and provided mechanistic insight into how G-quadruplex processor mutations drive premature aging.
Shaping up genomes: Prokaryotic roots and eukaryotic diversification of SMC complexes
Authors: van Hooff Jolien J.E. , Raas Maximilian W.D. , Tromer Eelco C. , Eme Laura 
Published: January 2024

SummaryAcross the tree of life, SMC complexes organize, segregate and regulate DNA. In contrast to prokaryotes, which often possess one SMC complex, eukaryotes usually have four such complexes. This expanded set is involved in managing the considerably larger nuclear genomes of eukaryotes, which are distributed across multiple chromosomes. Despite their essential functions, SMC complexes exhibit variations across model eukaryotes, suggesting an even greater variety of these complexes that remains unexplored. Here, we aimed to uncover the diversity and evolution of SMC complexes across eukaryotes, and their deeper, prokaryotic evolutionary origins. For this, we conducted in-depth comparative genomic and phylogenetic analyses of SMC complexes. We show that the last eukaryotic common ancestor (LECA) likely had fully-fledged versions of all four complexes and that the condensin II complex was later lost at least 30 times in eukaryotes. We report evidence that proteins previously designated as functional analogs in various model organisms (e.g., Sororin, Securin, Nse5 and Nse6) are in fact genuine orthologs. Finally, we traced the prokaryotic origins of these complexes and propose that a single SMC complex duplicated in an early archaeon. Altogether, we provide a comprehensive overview of eukaryotic SMC complex diversity and evolution, both addressing and generating questions about their functioning in ancestral and contemporary organisms.
Reprogramming neuroblastoma by diet-enhanced polyamine depletion
Authors: Cherkaoui Sarah , Yang Lifeng , McBride Matthew , Turn Christina S. , Lu Wenyun , Eigenmann Caroline , Allen George E. , Panasenko Olesya O. , Zhang Lu , Vu Annette , Liu Kangning , Li Yimei , Gandhi Om H. , Surrey Lea , Wierer Michael , White Eileen , Rabinowitz Joshua D. , Hogarty Michael D. , Morscher Raphael J. 
Published: January 2024

SummaryNeuroblastoma is a highly lethal childhood tumor derived from differentiation-arrested neural crest cells1,2. Like all cancers, its growth is fueled by metabolites obtained from either circulation or local biosynthesis3,4. Neuroblastomas depend on local polyamine biosynthesis, with the inhibitor difluoromethylornithine showing clinical activity5. Here we show that such inhibition can be augmented by dietary restriction of upstream amino acid substrates, leading to disruption of oncogenic protein translation, tumor differentiation, and profound survival gains in the TH-MYCNmouse model. Specifically, an arginine/proline-free diet decreases the polyamine precursor ornithine and augments tumor polyamine depletion by difluoromethylornithine. This polyamine depletion causes ribosome stalling, unexpectedly specifically at adenosine-ending codons. Such codons are selectively enriched in cell cycle genes and low in neuronal differentiation genes. Thus, impaired translation of these codons, induced by the diet-drug combination, favors a pro-differentiation proteome. These results suggest that the genes of specific cellular programs have evolved hallmark codon usage preferences that enable coherent translational rewiring in response to metabolic stresses, and that this process can be targeted to activate differentiation of pediatric cancers.Graphical AbstractHighlights- Extra-tumoral conversion of arginine feeds tumor ornithine via uptake from circulation in MYCN-neuroblastoma.- A proline and arginine free diet enhances pharmacological polyamine depletion via reduced ornithine substrate availability.- Polyamine depletion disrupts oncogenic translation to induce a pro-differentiation proteome causing neuroblast differentiation and prolonged survival in the TH-MYCN mouse model.- Genes of specific cellular programs have evolved codon usage preferences that enable coherent translational rewiring in response to metabolic stress, such as polyamine depletion.
The conserved σDstress response monitors multiple aspects of envelope integrity in corynebacteria
Authors: Hart Elizabeth M. , Lyerly Evan , Bernhardt Thomas G. 
Published: January 2024

ABSTRACTThe cell envelope fortifies bacterial cells against antibiotics and other insults. Species in theMycobacterialesorder have a complex envelope that includes an outer layer of mycolic acids called the mycomembrane (MM) and a cell wall composed of peptidoglycan and arabinogalactan. This envelope architecture is unique among bacteria and contributes significantly to the virulence of pathogenicMycobacterialeslikeMycobacterium tuberculosis. Characterization of pathways that govern envelope biogenesis in these organisms is therefore critical in understanding their biology and for identifying new antibiotic targets. To better understand MM biogenesis, we developed a cell sorting-based screen for mutants defective in the surface exposure of a porin normally embedded in the MM of the model organismCorynebacterium glutamicum.The results revealed a requirement for the conserved σDenvelope stress response in porin export and identified MarPas the site-1 protease, respectively, that activate the response by cleaving the membrane-embedded anti-sigma factor. A reporter system revealed that the σDpathway responds to defects in mycolic acid and arabinogalactan biosynthesis, suggesting that the stress response has the unusual property of being induced by activating signals that arise from defects in the assembly of two distinct envelope layers. Our results thus provide new insights into howC. glutamicumand related bacteria monitor envelope integrity and suggest a potential role for members of the σDregulon in protein export to the MM.AUTHOR SUMMARYBacteria within theMycobacterialesorder, which includes the pathogenMycobacterium tuberculosis,have a unique multilayered cell surface architecture. How they sense and respond to defects in the construction of this distinct envelope to maintain homeostasis remains poorly understood. Here, we used the model organismCorynebacterium glutamicumto reveal that the conserved σDenvelope stress response pathway responds to two distinct signals resulting from defects in different envelope layers. The results provide new insight into how members of theMycobacterialesmonitor the integrity of their surface and pave the way for the identification of novel vulnerabilities in envelope biogenesis that may be useful for targeting with antibiotics.
“Ca. Nitrosocosmicus” members are the dominant archaea associated with pepper (Capsicum annuumL.) and ginseng (Panax ginsengC.A. Mey.) plants’ rhizospheres
Authors: Lee Ui-Ju , Gwak Joo-Han , Choi Seungyeon , Jung Man-Young , Lee Tae Kwon , Ryu Hojin , Awala Samuel Imisi , Wanek Wolfgang , Wagner Michael , Quan Zhe-Xue , Rhee Sung-Keun 
Published: January 2024

AbstractBackgroundAlthough archaea are widespread in terrestrial environments, little is known about the selection forces that shape their composition, functions, survival, and proliferation strategies in the rhizosphere. The ammonia-oxidizing archaea (AOA), which are abundant in soil environments, catalyze the first step of nitrification and have the potential to influence plant growth and development significantly.ResultsBased on archaeal 16S rRNA andamoAgene (encoding the ammonia monooxygenase subunit A) amplicon sequencing analysis, distinct archaeal communities dominated by AOA were found to be associated with the root systems of pepper (Capsicum annuumL.) and ginseng (Panax ginsengC.A. Mey.) plants compared to bulk soil not penetrated by roots. AOA related to “CandidatusNitrosocosmicus”, which, unlike most other AOA, harbor genes encoding manganese catalase (MnKat), dominated rhizosphere soils, and thus contributed to the development of distinct archaeal communities in rhizospheres. Accordingly, for both plant species, the copy number ratios of AOA MnKat genes toamoAgenes were significantly higher in rhizosphere soils than in bulk soils. In contrast to MnKat-negative strains from other AOA clades, the catalase activity of a representative isolate of “Ca.Nitrosocosmicus” was demonstrated. Members of this clade were enriched in H2O2-amended bulk soils, and constitutive expression of their MnKat gene was observed in both bulk and rhizosphere soils.ConclusionsDue to their abundance, “Ca.Nitrosocosmicus” members can be considered key players mediating the nitrification process in rhizospheres. The selection of this MnKat-containing AOA in rhizospheres of several agriculturally important plants hints at a previously overlooked AOA-plant interaction. For additional mechanistic analyses of the interaction, this key clade of AOA with cultured representatives can be employed.
Fibronectin 1 is a novel biomarker of obstetric antiphospholipid syndrome
Authors: Xu Jinfeng , Chung Tenchi , Hu Zhe , Tian Yuan , Ling Qiao , Wang Xiaodong , Peng Bing 
Published: January 2024

AbstractObjectiveTo investigate novel biomarkers and the mechanism of obstetric antiphospholipid syndrome (OAPS).MethodsHTR8/SVneo cells line were treated with plasma from OAPS (OAPS group) and healthy (NC group) pregnant women, respectively. The changes induced by plasma treatment at the transcriptome level were examined by RNA sequencing of the cells. Results were analyzed with bioinformatics tools to elucidate the potential biomarkers. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, hematoxylin and eosin (HE), immunohistochemistry (IHC), and immunofluorescence (IF) were used for subsequent validation.ResultsBioinformatic analysis revealed the expression of Fibronectin 1 (FN1) was significantly increased in OAPS group. On analyzing molecular function, OAPS plasma exposure mainly affected the expression of the genes related to extracellular matrix (ECM) structural constituent. Compared to the NC group, differently expressed genes were mainly annotated to the collagen-containing ECM matrix and the ECM organization. In OAPS group, the protein expression of FN1 was also increased in blood (p<0 .05). The mRNA and protein expression of FN1 in placenta tissue were increased (p<0 .05) in OAPS group. Massive degeneration and atrophy can be seen in placental villi, with a significant reduction or disappearance of syncytiotrophoblasts and excessive fibrinoid deposition in the villous stroma of OAPS placenta. Both IHC and IF results showed the staining area and intensity of FN1 in the placental villi and stroma were significantly higher in OAPS group.ConclusionsFN1 may play a potential role in the pathogenic mechanisms of OAPS.Highlights
Employees' perceptions of responsible leadership in private security: a mediation model
Authors: Üzüm Burcu , Özkan Osman Seray , Huertas-Valdivia Irene 
Published: January 2024

PurposeA quantitative study sought to better understand responsible leadership (RL) style in the private security sector. The authors analyzed RL’s mediating role in the relationship between rules climate (RC) and employees' perceived organizational support (POS).Design/methodology/approachThe data were collected through an online questionnaire administered to full-time private guards in Ankara (Turkey). A mediation model was proposed, and research hypotheses were tested with structural equation modeling (SEM).FindingsThe results indicate a significant positive relationship between the company’s RC and managers' RL, and a positive significant relationship between managers' RL and employees' POS. RL mediates the relationship between company’s RC and employees' POS.Research limitations/implicationsThe theoretical framework draws on conservation of resources (COR) theory to consider RL an effective resource. The organization’s RC was a key factor the affecting leader’s responsible behaviors.Originality/valueThis study explores a thriving leadership style, gaining research attention across fields. To the authors' knowledge, no prior research has studied this leadership style in the security sector. The authors use COR to increase understanding of an important antecedent (company’s RC) and consequence (employees' POS) of RL, highlighting this emerging style’s mediating role.