bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental variability can promote parasite diversity within hosts and transmission among hosts
Authors: Jarvis-Cross Madeline , Krkosek Martin 
Published: June 2023

AbstractWhile the mechanisms that govern disease emergence and spread among hosts are increasingly well-described, the mechanisms that promote parasite diversity within-hosts, affecting host outcomes and spillover potential, have been comparatively understudied. Furthermore, while attention has been paid to the effects of increasing temperatures on disease systems, the effects of environmental variability have been left underexplored, despite rising climatic variability. To investigate the impacts of environmental variability on parasite diversity within-hosts, we analyzed a model of within-host population dynamics wherein two parasites indirectly compete through the host’s immune response. We simulated the model under constant, demographically stochastic, environmentally stochastic, and demographically and environmentally stochastic conditions, and analysed the viability and longevity of non-equilibrium parasite co-occurrence. We found that environmental stochasticity increased the viability and longevity of parasite co-occurrence, suggesting that thermal variability arising from climatic change and as a physiological trait may promote parasite diversity within ectotherms and help explain bats’ propensity to support diverse communities of parasites. Further, we found that under certain conditions, the transmissibility of co-occurring parasites can surpass the transmissibility of single parasites, suggesting that thermal variability may increase the transmissibility of co-occurring parasites.
Electrocatalytic on-site oxygenation for transplanted cell-based-therapies
Authors: Lee Inkyu , Surendran Abhijith , Fleury Samantha , Gimino Ian , Curtiss Alexander , Fell Cody , Shiwarski Daniel , El-Refy Omar , Rothrock Blaine , Jo Seonghan , Schwartzkopff Tim , Mehta Abijeet Singh , John Sharon , Ji Xudong , Nikiforidis Georgios , Feinberg Adam , Hester Josiah , Weber Douglas J. , Veiseh Omid , Rivnay Jonathan , Karni Tzahi Cohen- 
Published: June 2023

AbstractImplantable cell therapies and tissue transplants require sufficient oxygen supply to function and are limited by a delay or lack of vascularization from the transplant host1, 2. Exogenous oxygen production can support cells and tissues, such as pancreatic islets and engineered therapeutic cells. Previous oxygenation strategies have targeted gas circulation or decomposition of solid peroxides. These strategies however require bulky implants, transcutaneous supply lines, and are limited in their total oxygen production or regulation3, 4. Readily integrated and controlled production of oxygen has eluded cell therapy devices. Here, we show an electrocatalytic approach that enables bioelectronic control of oxygen generation in complex cellular environments to sustain engineered cell viability and therapy production under hypoxic stress and at high cell densities. Nanostructured sputtered iridium oxide serves as an ideal catalyst for oxygen evolution reaction (OER) at neutral pH. It enables a lower OER onset and shows selective oxygen production without evolution of toxic side products over a 300 mV window of operation. This electrocatalytic on site oxygenator (ecO2) can sustain high cell loadings (>60k cells/mm3) in hypoxic conditions in vitro and in vivo. Our results demonstrate that exogenous oxygen production devices can be readily integrated into bioelectronic platforms and enable high cell loadings in smaller device footprints with broad applicability.
The Multifaceted Effects of Short-Term Acute Hypoxia Stress: Insights into the tolerance mechanism ofPropsilocerus akamusi(Diptera: Chironomidae)
Authors: Zhang Yao , Zhang Qing-Ji , Xu Wen-Bin , Zou Wei , Xiang Xian-Ling , Gong Zhi-Jun , Cai Yong-Jiu 
Published: June 2023

AbstractPlenty of freshwater species, especially macroinvertebrates that are essential to the provision of numerous ecosystem functions, encountered higher mortality due to acute hypoxia. However, within the family Chironomidae, a wide range of tolerance to hypoxia/anoxia is displayed andPropsilocerus akamusidepends on this great endurance to become a dominant species in eutrophic lakes. To further understand howP. akamusiresponds to acute hypoxic stress, we used multi-omics analysis in combination with histomorphological characteristics and physiological indicators. To evaluate enzyme activity, the transcriptome and metabolome, and histomorphological characteristics, we set up two groups: a control group (DO 8.4mg/L) and a hypoxic group (DO 0.39mg/L). With blue-black chromatin, cell tightness, cell membrane invagination, and the production of apoptotic vesicles, tissue cells displayed typical apoptotic features. While lactate dehydrogenase (LDH), (Alcohol dehydrogenase) ADH, catalase (CAT), and Na+/K+ -ATPase (NKA) activities were dramatically enhanced under hypoxic stress, glycogen content, and superoxide dismutase (SOD) activities were significantly reduced compared to the control group. The above results were further supported by the joint analysis of the transcriptome and metabolome, which further revealed that in addition to carbohydrates, including glycogen, the energy metabolism of the fatty acid, trehalose, and glyoxylate cycles is also included. Furthermore, we also revealed the ethanol tested in hypoxic stress should derive from symbiodinium ofP akamusi.Understanding the processes which enableP. akamusito survive lengthy periods of hypoxia in eutrophic lakes might help to design sensitive biomonitoring procedures, and this species has the potential to be used as an effective eutrophication indicator.
Single Nuclei RNA Sequencing of the Gastrocnemius Muscle in Peripheral Artery Disease
Authors: Pass Caroline , Palzkill Victoria , Tan Jianna , Kim Kyoungrae , Thome Trace , Yang Qingping , Fazzone Brian , Robinson Scott T. , O’Malley Kerri A. , Yue Feng , Scali Salvatore T. , Berceli Scott A. , Ryan Terence E. 
Published: June 2023

ABSTRACTBackgroundLower extremity peripheral artery disease (PAD) is a growing epidemic with limited effecOve treatment options. Herein, we provide a single nuclei atlas of PAD limb muscle to facilitate a better understanding of the composition of cells and transcriptional differences that comprise the diseased limb muscle.MethodsWe obtained gastrocnemius muscle specimens from 20 PAD patients and 12 non-PAD controls. Nuclei were isolated and single nuclei RNA sequencing (snRNAseq) was performed. The composition of nuclei was characterized by iteraOve clustering via principal component analysis, differenOal expression analysis, and the use of known marker genes. BioinformaOcs analysis was performed to determine differences in gene expression between PAD and non-PAD nuclei, as well as subsequent analysis of intercellular signaling networks. Additional histological analyses of muscle specimens accompany the snRNAseq atlas.ResultssnRNAseq analysis indicated a fiber type shim with PAD paOents having fewer Type I (slow/oxidaOve) and more Type II (fast/glycolyOc) myonuclei compared to non-PAD, which was confirmed using immunostaining of muscle specimens. Myonuclei from PAD displayed global upregulation of genes involved in stress response, autophagy, hypoxia, and atrophy. Subclustering of myonuclei also idenOfied populations that were unique to PAD muscle characterized by metabolic dysregulation. PAD muscles also displayed unique transcriptional profiles and increased diversity of transcriptomes in muscle stem cells, regeneraOng myonuclei, and fibro-adipogenic progenitor (FAPs) cells. Analysis of intercellular communication networks revealed FAPs as a major signaling hub in PAD muscle, as well as deficiencies in angiogenic and bone morphogeneOc protein signaling which may contribute to poor limb function in PAD.ConclusionsThis reference snRNAseq atlas provides a comprehensive analysis of the cell composition, transcriptional signature, and intercellular communication pathways that are altered in the PAD condition.
Tissue-bound hyaluronan molecular weight as a regulator of dendritic cell immune potency
Authors: Quartey Brian Chesney , Sapudom Jiranuwat , ElGindi Mei , Alatoom Aseel , Teo Jeremy 
Published: June 2023

AbstractHyaluronic acid (HA) is a major glycosaminoglycan found in the extracellular matrix (ECM) and exhibits immunoregulatory properties depending on its molecular weight (MW). However, the impact of tissue bound HA on dendritic cell (DC) functions is not well understood due to the varying distribution of HA MW under different physiological and pathological conditions. To investigate DCs in defined biosystems, we used three-dimensional (3D) collagen matrices modified with HA of specific MW, while maintaining similar microstructure and HA levels. Using these matrices, we examined the influence of HA on cytokine binding and observed distinct properties depending on the presence and MW of HA, suggesting modulation of cytokine availability by the different MW of HA. Our studies on DC immune potency revealed that low molecular weight HA (LMW-HA; 8-15 kDa) enhances immature DC (iDC) differentiation and antigen uptake, while medium (MMW-HA; 500-750 kDa) and high molecular weight HA (HMW-HA; 1250-1500 kDa) increase cytokine secretion in matured DCs (mDCs). Interestingly, the modulation of DCs surface marker expression and cytokine secretion by different MW of HA appeared to be independent of CD44. However, we found that cytokine secretion of DCs was dependent on the CD44 receptor regardless of the presence or absence of HA in the matrix. Additionally, we observed reduced migratory capacity of iDCs and mDCs when cultured on MMW- and HMW-HA matrices, and this effect was dependent on CD44. In summary, our findings provide new insights into the MW-dependent effects of tissue-bound HA on DCs, opening avenues for the design of DC-modulating materials to enhance DC-based therapy.
Iron Oxide Nanoparticles Coated with Biodegradable Block-Copolymer PDMAEMA-b-PMPC and Functionalized with Aptamer for HER2 Breast Cancer Cell Identification
Authors: de Valega Negrão Cyro von Zuben , Cerize Natália Neto Pereira , Justo-Junior Amauri da Silva , Liszbinski Raquel Bester , Meneguetti Giovanna Pastore , Araujo Larissa , Rocco Silvana Aparecida , Gonçalves Kaliandra de Almeida , Cornejo Daniel Reinaldo , Leo Patrícia , Perecin Caio , Adamoski Douglas , Dias Sandra Martha Gomes 
Published: June 2023

AbstractHybrid nanoparticles have shown promise in biomedical applications; however, their seamless integration into clinical settings remains challenging. Here, we introduce a novel metal oxide polymer hybrid nanoparticle (NP) with a high affinity for nucleic acids. Iron oxide nanoparticles (IONP) were initially synthesized via the co-precipitation method and subjected to comprehensive characterization. Subsequently, block copolymers were synthesized using the Reversible Addition−Fragmentation Chain Transfer (RAFT) technique, employing the zwitterionic PMPC (Poly (2 Methacryloyloxyethyl Phosphorylcholine)) and the cationic PDMAEMA (Poly(2 (Dimethylamino) Ethyl Methacrylate)) with varying degrees of polymerization. In vitro cytotoxicity studies demonstrated the biocompatibility of the synthesized nanoparticles, with no observed toxicity up to a concentration of 150 µg/mL. The cationic polymer PDMAEMA facilitated the facile coating of IONP, forming the IONPP complex, consisting of a 13.27 metal core and a 3.1 nm block-copolymer coating. Subsequently, the IONPP complex was functionalized with a DNA aptamer specifically targeting the human epidermal growth factor receptor 2 (HER2) in breast cancer, forming IONPPP. The block-copolymer exhibited an EC50of 7.07 µg/mL and demonstrated enhanced recognition efficiency in HER2-amplified SKBR3 cells. Our study presents a comprehensive IONPPP characterization capable of binding short DNA sequences and targeting proteins such as HER2. This newly developed nanoparticle holds significant potential for cancer cell identification and isolation, offering promising prospects in cancer research and clinical applications.1.Statement of significanceDespite recent advancements in biomedical research, developing sensitive and specific tools for recognizing biological motifs, such as cell receptors and proteins in complex biological solutions, remains a challenge. Furthermore, current approaches often rely on complex biological derivatives like antibodies, lacking a cost-effective delivery strategy. Our study proposes creating and characterizing a novel hybrid metal oxide polymer nanoparticle named IONPPP, functionalized with a DNA aptamer designed to recognize HER2-positive cells. HER2 is a clinically actionable marker for gastric, gastroesophageal, and, particularly, breast cancers. This unique combination of a metal core with an external polymeric structure offers the potential for identification, isolation, and even theragnostic applications, benefiting from its low toxicity and high specificity.2.Graphical Abstract
ATP binding cassette transporters and uridine diphosphate glycosyltransferases are ancient protein families that evolved roles in herbicide resistance through exaptation
Authors: Caygill Samuel , Dolan Liam 
Published: June 2023

AbstractATP-binding cassette (ABC) transporters actively transport various substances across membranes, while uridine diphosphate (UDP) glycosyltransferases (UGTs) are proteins that catalyse the chemical modification of various organic compounds. Both of these protein superfamilies have been associated with conferring herbicide resistance in weeds. Little is known about the evolutionary history of these protein families in the Archaeplastida. To infer the evolutionary histories of these protein superfamilies, we compared protein sequences collected from 10 species which represent distinct lineages of the Archaeplastida – the lineage including glaucophyte algae, rhodophyte algae, chlorophyte algae and the streptophytes – and generated phylogenetic trees. We show that ABC transporters were present in the last common ancestor of the Archaeplastida which lived 1.6 billion years ago, and the major clades identified in extant plants were already present then. Conversely, we only identified UGTs in members of the streptophyte lineage, which suggests a loss of these proteins in earlier diverging Archaeplastida lineages or arrival of UGTs into a common ancestor of the streptophyte lineage through horizontal gene transfer from a non-Archaeplastida eukaryote lineage. We found that within the streptophyte lineage, most diversification of the UGT protein family occurred in the vascular lineage, with 17 of the 20 clades identified in extant plants present only in vascular plants. Based on our findings, we conclude that ABC transporters and UGTs are ancient protein families which diversified during Archaeplastida evolution, which may have evolved to for developmental functions as plants began to occupy new environmental niches and are now being selected to confer resistance to a diverse range of herbicides in weeds.
Neurobehavioral effects of fungicides in zebrafish: a systematic review and meta-analysis
Authors: Reis Carlos G. , Bastos Leonardo M. , Chitolina Rafael , Gallas-Lopes Matheus , Zanona Querusche K. , Becker Sofia Z. , Herrmann Ana P. , Piato Angelo 
Published: June 2023

AbstractWith the aim of yielding high productivity levels, pesticides are widely used in global agriculture. Among them, fungicides are compounds intended to inhibit fungal proliferation in crops and seeds. Their application often leads to environmental contamination, with these chemicals persistently being detected in surface waters. This presence may threaten non-target organisms that dwell in the affected ecosystems, including humans. In toxicologic research, the zebrafish (Danio rerio) is the most used fish species to assess the potential effects of fungicide exposure, generating numerous and sometimes conflicting findings. We conducted a systematic review and meta-analysis aiming to synthesize the neurobehavioral effects of fungicides in zebrafish. The search was performed in three databases (PubMed, Scopus, and Web of Science) and the screening was based on a two-stage process guided by pre-defined inclusion/exclusion criteria. Qualitative and quantitative data, as well as reporting quality, were extracted from the included studies (n = 60). Meta-analyses were performed for the outcomes of distance traveled in larvae and adults, and spontaneous movements in embryos. We found an overall significant effect of fungicide exposure on distance, which was lower in exposed versus control groups (SMD −0.44 [−0.74; −0.13], p = 0.0055). No effect was observed for spontaneous movements. The overall heterogeneity for distance and spontaneous movements was considered high (I2= 80%) and moderate (I2= 74%), respectively. This can be explained by substantial methodological variation between protocols, whereas a poor reporting practice hinders the proper critical evaluation of the findings. However, a sensitivity analysis did not indicate any study skewing the meta-analyses. This review demonstrates the need for better-designed and reported experiments in this field.Highlights-We systematically reviewed the behavioral effects of fungicides in zebrafish-Fungicides decrease the distance traveled-Fungicide exposure has no significant effects on spontaneous movements-Moderate to high levels of heterogeneity were found-The results showed a need for better-designed studies with clarity of report
The zinc transporter Slc30a1 in macrophages plays a protective role againstSalmonellainfection
Authors: Na-Phatthalung Pinanong , Sun Shumin , Xie Enjun , Wang Jia , Min Junxia , Wang Fudi 
Published: June 2023

AbstractThe zinc transporter Slc30a1 plays an essential role in maintaining cellular zinc homeostasis; however, its functional role in macrophages remains largely unknown. Here, we systematically examined the expression and function of Slc30a1 in macrophages uponSalmonellainfection in both Slc30a1 reporter mice and in macrophage-specificSlc30a1knockout (Slc30a1fl/flLysMCre) mice. We found thatSlc30a1fl/flLysMCremice have an increased susceptibility toSalmonellainfection compared to control littermates. Mechanistically, we found that loss of Slc30a1 in macrophages reduced their bactericidal activity via reduced iNOS and NO production due to intracellular zinc accumulation. In addition, we observed significantly increased expression ofMt1(metallothionein 1) inSalmonella-infectedSlc30a1-deficient macrophages, suggesting that Mt1 may serve as a compensatory zinc reservoir. Interestingly, macrophages lacking bothMt1andSlc30a1expression (Slc30a1fl/flLysMCre; Mt1-/-) had increased cell death uponSalmonellainfection due to excess zinc-induced oxidative stress. Taken together, our results show that Slc30a1 in macrophages can protect againstSalmonellainfection, providing mechanistic insights into the role of Slc30a1-mediated zinc homeostasis in macrophages in response to infectious disease.
Unpredictable soil conditions affect the prevalence of a microbial symbiosis
Authors: Scott Trey J. , Stephenson Calum J. , Rao Sandeep , Queller David C. , Strassmann Joan E. 
Published: June 2023

AbstractThe evolution of symbiotic interactions may be affected by unpredictable conditions. However, a link between prevalence of symbiosis and these conditions has not been widely demonstrated. We test for these associations usingDictyostelium discoideumsocial amoebae and their bacterial symbionts.D. discoideumare host to endosymbiotic bacteria from three taxa:Paraburkholderia, AmoebophilusandChlamydiae. Three species of facultativeParaburkholderiasymbionts are the best studied and give hosts the ability to carry food bacteria through the dispersal stage to new environments.AmoebophilusandChlamydiaeare obligate endosymbionts with no measurable impact on host fitness. We test whether the frequency of both single infections and coinfections of these symbionts are associated with the unpredictability of their soil environments by using symbiont presence-absence data from soil isolates from 21 locations across the eastern United States. We find that thatAmoebophilusandChlamydiaeobligate endosymbionts and coinfections are not associated with any of our mean measures, but that unpredictable precipitation can promote or hinder symbiosis depending on the species ofParaburkholderiasymbiont.
Accelerating Cancer Vaccine Development for Human T-Lymphotropic Virus (HTLV) Using a High-Throughput Molecular Dynamics Approach
Authors: Moin Abu Tayab , Rani Nurul Amin , Ullah Md. Asad , Patil Rajesh B. , Robin Tanjin Barketullah , Nawal Nafisa , Zubair Talha , Mahamud Syed Iftakhar , Sakib Mohammad Najmul , Islam Nafisa Nawal , Khaleque Md. Abdul , Absar Nurul , Shohael Abdullah Mohammad 
Published: June 2023

AbstractHuman T-lymphotropic virus (HTLV), a retrovirus belonging to the oncovirus family, has long been linked to be associated with various inflammatory and immunosuppressive disorders. To combat the devastating impact of this virus, our study employed a reverse vaccinology approach to design a multi-epitope-based vaccine targeting the highly virulent subtypes of HTLV. We conducted a comprehensive analysis of the molecular interactions between the vaccine and Toll-like receptors (TLRs), providing valuable insights for future research on preventing and managing HTLV-related diseases and any possible outbreaks. The vaccine was designed by focusing on the envelope glycoprotein gp62, a crucial protein involved in the infectious process and immune mechanisms of HTLV inside the human body. Epitope mapping identified T cell and B cell epitopes with low binding energies, ensuring their immunogenicity and safety. Linkers and adjuvants were incorporated to enhance the vaccine’s stability, antigenicity, and immunogenicity. Two vaccine constructs were developed, both exhibiting high antigenicity and conferring safety. Vaccine construct 2 demonstrated expected solubility and structural stability after disulfide engineering. Molecular docking analyses revealed strong binding affinity between the vaccine construct 2 and both TLR2 and TLR4. Molecular dynamics simulations indicated that the TLR2-vaccine complex displayed enhanced stability, compactness, and consistent hydrogen bond formation, suggesting a favorable affinity. Contact analysis, Gibbs free energy landscapes, and DCC analysis further supported the stability of the TLR2-vaccine complex, while DSSP analysis confirmed stable secondary structures. MM-PBSA analysis revealed a more favorable binding affinity of the TLR4-vaccine complex, primarily due to lower electrostatic energy. In conclusion, our study successfully designed a multi-epitope-based vaccine targeting HTLV subtypes and provided valuable insights into the molecular interactions between the vaccine and TLRs. These findings should contribute to the development of effective preventive and treatment approaches against HTLV-related diseases.