bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxic Pretreatment Adipose-derived Stem Cell Exosomes Improve Cognition by Delivery Circ-Epc1 and Shifting Microglial M1/M2 Polarization in Alzheimer’s Disease Mice Model
Authors: Liu Haining , Jin Mingming , Ji Minxiu , Zhang Wei , Liu An , Wang Tao 
Published: August 2021

Abstract
Background: Alzheimer’s disease (AD) is the most major dementia in the globe. Increasing evidence informs that exosomes from hypoxic pretreatment adipose-derived stem cells (ADSCs) could therapeutically affect cognitive function in AD-associated pathophysiology. However, their role and regulatory mechanism remain largely unknown. Methods: High-throughput sequencing was used to identify differentially expressed exosomal circRNAs from ADSCs or hypoxia pretreated ADSCs. Luciferase reporter assays and RT-qPCR were used to investigate the relationships between circ-Epc1, miR-770-3p, and TREM2. APP/PS1 double transgenic AD model mice were then utilized to study therapeutic effect regarding circ-Epc1 in ADSCs exosomes. BV2 cells were used to understand the regulatory relationship between circ-Epc1, miR-770-3p, and TREM2 and how these interactions modulated phenotypic transformation and inflammatory cytokine expression in microglia. Results: The result show that exosomes from hypoxia pretreatment ADSCs had a greater therapeutic effect at improving cognitive function by decreasing neuronal damage in the hippocampus. High-throughput sequencing found that circ-Epc1 played an important role in hypoxia pretreated ADSC exosomes regarding their ability to improve cognitive function. Luciferase reporter assays showed that TREM2 and miR-770-3p were downstream targets of circ-Epc1. Overexpressing miR-770-3p or downregulating TREM2 reversed the effects of circ-Epc1 on M2 microglia under LPS treatment. In vivo experiments showed that circ-Epc1-containing ADSC exosomes increased the therapeutic effect of exosome at improving cognitive function by decreasing neuronal damage and shifting hippocampal microglia from M1 to M2 polarization. Conclusions: Taken together, the data found that hypoxic pretreatment ADSCs exosomes improve cognition by delivery circ-Epc1 and shifting microglial M1/M2 polarization in alzheimer’s disease mice model.
SEAM-ECM Jet Milling TC4 Titanium Alloy Using Gas-Liquid Mixed Medium
Authors: Zhang Shengsheng , Wang Lizhong , Zhou Jianping , Dai Xiangyu , Xu Yan , Qiu Weixing , Wang Shuaishuai , Hu Guoyu 
Published: August 2021

Abstract
A novel combined machining approach combining short electric arc machining and electrochemical machining (SEAM-ECM) is proposed in this study. It aims to improve the surface integrity of TC4 titanium alloy by adding compressed air and electrolyte into the SEAM. This approach can change the material removal mechanism of the conventional SEAM and improve the gap flow field distribution and discharge state using the dual fluid properties of electrolyte and air mixed medium. The effects of gas addition on the state of the gap flow field and the electrical conductivity of the mixed medium are illustrated by flow field simulation. The effects of the presence or absence of air and the electrical conductivity of the solution on the machining performance are compared by experiments. The results show that the recast layer is weakened by using electrolyte and air mixed medium in SEAM-ECM compared to SEAM alone. The addition of high-speed air reduces defects such as melt drops, particles, holes. It performs with higher precision and finishes than ECM alone, the overall surface integrity has been significantly improved.
Known But Not Called by name: Recreational Fishers’ Ecological Knowledge of Freshwater Plants in Hungary
Authors: Löki Viktor , Nagy Jenő , Nagy András , Babai Dániel , Molnár Zsolt , Lukács Balázs András 
Published: August 2021

Abstract
Background: Documenting local ecological knowledge (LEK) has recently became a topic of considerable interest. LEK can contribute to various areas of ecology, including habitat management and conservation biology. It has been recently revealed that recreational fishers’ ecological knowledge (FEK) can also provide valuable information about different organisms and habitats, while recreational fishers’ ecological knowledge is understudied in many aspects and regions of the world. Methods: We aimed to record Hungarian recreational FEK on plant species related to freshwater habitats. Our research was conducted in three regularly fished water bodies in Hungary, namely Lake Velence, Keleti Main Canal, and Lake Látóképi, where a total of 72 interviews were conducted with recreational anglers. During interviews, 24 plant species occurring at freshwater habitats with common or sporadic distribution were shown to anglers as single species or in congeneric pairs. Miscellaneous plant related knowledge of anglers was also collected. Results: Anglers identified a total of 16 plant species. They used 45 botanical or folk names. An angler knew the name of 4.6 plants on average, and recognized 7.4 other species without naming it. According to our detailed analysis, anglers were able to name or at least recognise those plant species which are somehow related to fishing activities, are salient and/or common. Moreover, anglers at Lake Velence recognized less plant species, however, they also had less years of fishing experience compared to anglers of the other two locations. Conclusion: We found that recreational FEK exist even in the case of freshwater plants which are not the main focus of anglers. It is highly presumable that recreational fishers would be able to provide reliable ecologically related data for scientific research establishing future citizen science projects of nature conservation.
Intercellular Propagation and Aggregate Seeding of Mutant Ataxin-1
Authors: Huang Haoyang , Toker Nicholas , Burr Eliza , Okoro Jeff , Moog Maia , Hearing Casey , Lagalwar Sarita 
Published: August 2021

Abstract
Intercellular propagation of aggregated protein inclusions along actin-based tunneling nanotubes (TNTs) has been reported as a means of pathogenic spread in Alzheimer’s, Parkinson’s and Huntington’s Disease. Propagation of oligomeric-structured polyglutamine-expanded ataxin-1 (Atxn1[154Q]) has been reported in the cerebellum of a Spinocerebellar ataxia type 1 (SCA1) knock-in mouse to correlate with disease propagation. In this study, we investigated whether a physiologically-relevant polyglutamine-expanded ATXN1 protein (ATXN1[82Q]) could propagate intercellularly. Using a cerebellar-derived live cell model, we observed ATXN1 aggregates form in the nucleus, export out of the nucleus into the cytoplasm, and finally, propagate to neighboring cells along actin-based intercellular connections. Additionally, we observed the facilitation of aggregate-resistant proteins into aggregates given the presence of aggregation-prone proteins within a cell. Taken together, our results support a pathogenic role of intercellular propagation of polyglutamine-expanded ATXN1 inclusions.
The Potential Role of Naproxen in Promoting Rivastigmine Effect Against Aluminum Chloride-Induced Alzheimer-Like Model in Rats
Authors: Abdel-Aal Raafat A. , Hussein Ola A. , Elsaady Reham G. , Abdelzaher Lobna 
Published: August 2021

Abstract
Alzheimer’s disease (AD) is one of the leading causes of dependence and disability among the elderly worldwide. The traditional anti-Alzheimer medication, rivastigmine, one of the cholinesterase inhibitors (ChEIs), fails to achieve a definitive cure. Neuroinflammation plays a central role in AD pathogenesis. We tested the hypothesis that naproxen, a non-steroidal anti-inflammatory drug (NSAID), administration to the rivastigmine-treated aluminum chloride (AlCl3), Alzheimer's rat model, could provide an additive neuroprotective effect compared to rivastigmine alone. The studied groups were control (Cont), AlCl3 treated (Al), rivastigmine treated (RIVA), naproxen treated (Napro), and combined rivastigmine and naproxen treated (RIVA + Napro). Rats’ memory, spatial learning, and cognitive behavior were assessed followed by evaluation of hippocampal acetylcholinesterase (AChE) activity. Hippocampal and cerebellar histopathology were thoroughly examined. A marker of astroglial injury; glial fibrillary acidic protein (GFAP), the apoptosis maker; activated caspase-3 and the neuroepithelial stem cells marker; nestin expressions were immunohistochemically assayed. AD rats displayed significantly impaired memory and cognitive function, augmented hippocampal AChE activity, massive neurodegeneration associated with enhanced astrogliosis, apoptosis, and impaired neurogenesis. Rivastigmine, naproxen, and their combination decreased hippocampal AChE activity, mitigated behavioral and neuropathological changes in Al-intoxicated rats, possibly through downregulation of activated caspase-3 and upregulation of nestin. Except for the enhancement of neurogenesis and suppression of apoptosis, the combination therapy had no additional neuroprotective benefit over rivastigmine-only therapy. Naproxen's efficacy was demonstrated by its ability to act at the cellular level, enhance neurogenesis, and suppress apoptosis without having an additional mitigating impact in Al-induced cognitive impairment.
Bone marrow derived stem cells facilitate axonal regeneration in a rat model of 2, 5-hexanedione-induced neuropathy via miRNA-dependent and independent routes
Authors: Zuo Enjun , Hu Shuhai , Zhang Cong , Shi Xiaoxia , Yang Zhaofei , Li Shuangyue , Bai Qiufang , Gong Guanyu , Wang Ruoyu , Piao Fengyuan 
Published: August 2021

Abstract
Background

Peripheral polyneuropathies are clinically difficult situations and can be caused by exposure to occupational hazardous materials, such as N-hexane, which is still being used in developing countries. Autologous transplantation with bone marrow-mesenchymal stem cells (BMSCs) could be a promising therapeutical approach but its effect on toxic chemical-induced neuropathy remains undetermined. The present study sought to understand whether BMSCs could improve axon regeneration in Hexane-caused polyneuropathies and attempted to understand the associated molecular mechanisms.
Methods

A rat model of 2,5-hexanedine (HD)-induced polyneuropathy was established by intraperitoneally injection of 400 mg/kg/day HD, 5 times/week for 5 weeks. After the development of characteristic phenotypes, rats were given a single bolus tail-vein injection of BMSCs (5×107 cells/kg) and followed-up for 5 weeks. Sciatic nerves of HD/HD + BMSCs treated rats, as a representative tissue for peripheral nerve, were analyzed using electron microscopy, immunohistochemistry, western blotting and RNA sequencing. To further dissect the underlying mechanism, cultured DRG neurons +/- Schwann cells were challenged with HD/BMSC-derived conditional medium (BMSC-CM), in the presence or absence of NGF/Akt/mTOR inhibitors, recombinant NGF, miRNA mimics or miRNA inhibitors and further tested for changes in cellular and molecular levels.
Results

BMSCs engrafting significantly improved motor function recovery. Accelerated axon regeneration in sciatic nerves was evidenced by transmission electron microscopy, GAP43 western blotting and MBP/SMI312 immunostaining. Increased NGF expression and signaling activation was evidenced in response to BMSC/BMSC-CM treatment. In cultured cells, BMSC-CM’s effect was abolished by anti-NGF antibody or TrkA inhibitor K252a but reinforced by recombinant NGF. The activation of PI3K-Akt-mTOR-CREB signaling was observed and Akt and mTOR inhibitors were shown to attenuate BMSCS-promoted axon regeneration. While NGF was shown to be secreted by BMSCs in culture medium, miRNA array suggested certain miRNAs might also participate to regulate NGF expression. Three let-7 family miRNAs, including let-7a-5p, let-7d-5p and let-7e-5p, and 69 other miRNAs were found to be differentially expressed in HD and HD/BMSC groups. The regulatory effect of let-7e-5p on NGF expression was examined using miRNA mimics and inhibitors.
Conclusions

Together, our study demonstrated that BMSC transplantation significantly improve axon regeneration in hexane-induced polyneuropathy by activating NGF-PI3K-Akt-mTOR-CREB signaling via two independent mechanisms.
Social complexity, life-history and lineage influence the molecular basis of caste in a major transition in evolution
Authors: Wyatt Christopher , Bentley Michael , Taylor Daisy , Favreau Emeline , Brock Ryan , Taylor Benjamin , Bell Emily , Leadbeater Ellouise , Sumner Seirian 
Published: August 2021

Abstract
Major evolutionary transitions describe how biological complexity arises; e.g. in the evolution of complex multicellular bodies, and superorganismal insect societies. Such transitions involve the evolution of division of labour, e.g. as queen and worker castes in insect societies. A key mechanistic hypothesis for the evolution of division of labour is that a shared set of genes co-opted from a common solitary ancestral ground plan - a so-called genetic toolkit for sociality - regulate insect castes across different levels of social complexity. The vespid wasps represent an excellent system in which to test this. Here, using conventional and machine learning analyses of brain transcriptome data from nine species of vespid wasps, we find evidence of a shared genetic toolkit across species representing different levels of social complexity, with a large suite of genes classifying castes correctly across species. However, we also found evidence of additional fine-scale differences in predictive gene sets, functional enrichment and rates of gene evolution that were related to level of social complexity, but also life-history traits (e.g. mode of colony founding). Thus, there appear to be shifts in the gene networks regulating social behaviour and rates of gene evolution that are influenced by innovations in both social complexity and life-history. These results suggest that the concept of a shared genetic toolkit for sociality may be too simplistic to fully describe the process of the major transition to sociality, even within a single lineage. Diversity in lineage, social complexity and life-history traits must be taken into account in the quest to uncover the molecular bases of the major transition to sociality.
Identification of Genes Associated with Human-Canine Communication in Canine Evolution.
Authors: Tonoike Akiko , Otaki Ken-ichi , Terauchi Go , Ogawa Misato , Katayama Maki , Sakata Hikari , Miyasako Fumina , Mogi Kazutaka , Kikusui Takefumi , Nagasawa Miho 
Published: August 2021

Abstract
The dog (Canis familiaris) was the first domesticated animal and hundreds of breeds exist today. During domestication, dogs experienced strong selection for temperament, behaviour, and cognitive ability. However, the genetic basis of these abilities is not well-understood. We focused on ancient dog breeds to investigate breed-related differences in social cognitive abilities. In a problem-solving task, ancient breeds showed a lower tendency to look back at humans than other European breeds. In a two-way object choice task, they showed no differences in correct response rate or ability to read human communicative gestures. We examined gene polymorphisms in oxytocin, oxytocin receptor, melanocortin 2 receptor, and a Williams–Beuren syndrome-related gene (WBSCR17), as candidate genes of dog domestication. The single-nucleotide polymorphisms on melanocortin 2 receptor were related to both tasks, while other polymorphisms were associated with the unsolvable task. This indicates that glucocorticoid functions are involved in the cognitive skills acquired during dog domestication.
Plastidial Wax Ester Biosynthesis As A Tool To Synthesize Shorter And More Saturated Wax Esters
Authors: Vollheyde Katharina , Hornung Ellen , Herrfurth Cornelia , Ischebeck Till , Feussner Ivo 
Published: August 2021

Abstract
Background: Wax esters (WE) are neutral lipids that consist of a fatty alcohol esterified to a fatty acid. WE are valuable feedstocks in industry for producing lubricants, coatings and cosmetics. They can be produced chemically from fossil fuel or plant derived triacylglycerol. As fossil fuel resources are finite, the synthesis of WE in transgenic plants may serve as an alternative source. As chain length and desaturation degree of the alcohol and acyl moieties determine the physicochemical properties of WE and their field of application, a tightly controlled tailor-made WE synthesis in plants is aimed for. Here, we report the generation of ten combinations of WE producing transgenes expressed in Arabidopsis thaliana. In order to study their suitability for WE production in planta, we analyzed WE amount and synthesized WE species in the transgenic plants.Results: The transgenes consisted of different combinations of a fatty acyl-CoA/ACP reductase (FAR) and two wax synthases/acyl-CoA:diacylglycerol O-acyltransferases (WSD) namely WSD2 and WSD5 from the bacterium Marinobacter aquaeoleoi. We generated constructs with and without plastidial transit peptides to access diverse alcohol and acyl substrate pools within A. thaliana. We observed WE formation with plastid and cytosol-localized FAR and WSD in seeds. A comparative WE analysis revealed the production of shorter and more saturated WE by plastid-localized WE biosynthesis compared to cytosolic WE synthesis.Conclusions: A shift of WE formation into seed plastids is a suitable approach for tailor-made WE production and can be used to synthesize WE mainly derived from mid and long chain saturated and monounsaturated substrates.
Incorporating temporal distribution of population-level viral load enables real-time estimation of COVID-19 transmissibility
Authors: Lin Yun , Yang Bingyi , Cobey Sarah , Lau Eric , Adam Dillon , Wong Jessica , Bond Helen , Cheung Justin K. , Ho Faith , Gao Huizhi , Ali Sheikh Taslim , Leung Nancy , Tsang Tim , Wu Peng , Leung Gabriel , Cowling Benjamin 
Published: August 2021

Abstract
Many locations around the world have used real-time estimates of the time-varying effective reproductive number (\({R}_{t}\)) of COVID-19 to provide evidence of transmission intensity to inform control strategies. Estimates of \({R}_{t}\) are typically based on statistical models applied to case counts and typically suffer lags of more than a week because of the incubation period and reporting delays. Noting that viral loads tend to decline over time since illness onset, analysis of the distribution of viral loads among confirmed cases can provide insights into epidemic trajectory. Here, we analyzed viral load data on confirmed cases during two local epidemics in Hong Kong, identifying a strong correlation between temporal changes in the distribution of viral loads (measured by cycle threshold values) and estimates of \({R}_{t}\) based on case counts. We demonstrate that cycle threshold values could be used to improve real-time \({R}_{t}\) estimation, enabling more timely tracking of epidemic dynamics.
Rational Medicine Prescription and Adherence to Prescription Format: A Description of Practices in the Private Sector in Addis Ababa, Ethiopia
Authors: Mekuria Getahun Asmamaw , Ejigu Nahu , Tewihubo Dinksew , Ayenew Wondim 
Published: August 2021

Abstract
Background: In Ethiopia, despite the private health sector's role in healthcare delivery is growing, studies on private health sector prescribing practices are uncommon. The main aim of this study was to evaluate the private health sector's rational prescribing practices and adherence to prescription format, using some of the World Health Organization (WHO) core drug use indicators in Addis Ababa, Ethiopia. Method: A retrospective cross sectional study design was used to collect quantitative data from prescriptions prescribed and dispensed by private health sectors in the Lemi-kura sub-city, Addis Ababa. The study was conducted from June to July, 2021. The WHO criteria were used to evaluate prescribing and prescription completeness indicators. Prescriptions, kept for the last 1-year that prescribed between January 1, 2020 to January 1, 2021 by private drug outlets, were analyzed. A combination of simple random sampling and systematic sampling procedures were employed. All the statistical calculations were performed using SPSS® V 20.0 software. Result: Off total of 1,200 prescriptions, 2,192 drugs were prescribed and the average number of drugs per prescription was 1.83 (Standard Deviation (SD)=0.9). Generic names, antibiotics, injections, and issued from national essential medicines list accounted for 77.4%, 63.8%, 11.5%, and 80.6% of all prescriptions, respectively. The patients' full names, ages, and sexes were mentioned in 99%, 95.3%, and 96.3% of prescriptions, respectively. The patient's card number (54.3%) and weight (2.3%) were not adhered to properly. The drug name, strength, dose, frequency, duration, and how to use, ranges from 85 to 99% of the prescriptions. Dosage forms (35.5%) and diagnoses (31.7%) were less likely to be completed. Only 36.6% and 25.8% of prescriptions, respectively, contained names and qualifications of prescribers. Obtaining prescription papers with the full name (9%), qualification (1.3%), and signature (26.8%) of the dispenser, and date of dispensing (0.7%), is extremely difficult. Interestingly, no dispenser filled out all of this information on a single prescription. Conclusion: The study's findings indicated rational prescribing and prescription completeness indicators were all considerably deviate from WHO standards and hence unsuitable. To promote rational medication use, health practitioners in the private sector should be given regulatory interventions, ongoing monitoring from relevant bodies, and regular training on good prescribing and dispensing practices.
Metabolic engineering strategies to produce medium-chain oleochemicals via acyl-ACP:CoA transacylase activity
Authors: Yan Qiang , Cordell William , Jindra Michael , Courtney Dylan , Kuckuk Madeline , Chen Xuanqi , Pfleger Brian 
Published: August 2021

Abstract
Microbial lipid metabolism is an attractive route for producing aliphatic chemicals, commonly referred to as oleochemicals. The predominant metabolic engineering strategy centers on heterologous thioesterases capable of producing fatty acids of desired size. To convert acids to desired oleochemicals (e.g. fatty alcohols, ketones), metabolic engineers modify cells to block beta-oxidation, reactivate fatty acids as coenzyme-A thioesters, and redirect flux towards termination enzymes with broad substrate utilization ability. These genetic modifications narrow the substrate pool available for the termination enzyme but cost one ATP per reactivation - an expense that could be saved if the acyl-chain was directly transferred from ACP- to CoA-thioester. In this work, we demonstrate an alternative acyl-transferase strategy for producing medium-chain oleochemicals. Through bioprospecting, mutagenesis, and metabolic engineering, we developed strains of Escherichia coli capable of producing over 1 g/L of medium-chain free fatty acids, fatty alcohols, and methyl ketones using the transacylase strategy.