bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraskeletal Osteohistovariability Reveals Complex Growth Strategies in a Late Cretaceous Enantiornithine
Authors: Atterholt Jessie , Poust Ashley W. , Erickson Gregory M. , O’Connor Jingmai K.
Published: March 2021

Most crown-birds experience rapid growth, reaching adult size within a year. Rapid growth strategies evolved within Aves multiple times during the Cretaceous, documented in the Confuciusornithiformes and the Ornithuromorpha. In contrast, osteohistological data suggest the Enantiornithes, the dominant clade of Cretaceous terrestrial birds, were characterized by much slower growth rates that were sustained longer into adulthood. Here we provide evidence for a unique growth strategy involving relatively rapid growth in the Late Cretaceous avisaurid enantiornithine,Mirarce eatoni. Multiple appendicular skeletal elements were sectioned for osteohistological analysis. These show remarkable intraskeletal variation, and high levels of variation even between individual sections. The radius is composed of parallel-fibered bone, similar to histological descriptions in other enantiornithines. Other elements, in contrast, differ markedly from other members of the clade. The humerus is composed of parallel-fibered bone with a middle layer of incipient fibrolamellar bone and several growth lines in the outer circumferential layer and near the endosteal border. The endosteal and periosteal layers of slow-growing bone indicate cyclical variation in growth rates. The femur shows regions of coarse compact cancellous bone and parallel-fibered bone with numerous secondary osteons, and only a single growth line. The tarsometatarsus is predominantly fibrolamellar in texture, with several asymmetrical growth lines located throughout the cortex; this element exhibits strong cortical drift. Growth lines in both the endosteal and periosteal portions of the cortex indicate that, like the humerus, growth rates of this bone varied cyclically. The two phalanges studied here are composed of parallel-fibered bone with extensive evidence of and remodeling over possible regions of coarse compact cancellous bone. AlthoughMirarceis one of the largest known enantiornithines, slow and protracted growth documented in similarly-sized taxa suggests this bone texture is not merely a size-related scaling effect. These findings indicate that by the Late Cretaceous, some enantiornithines had evolved absolutely higher growth rates and more complex life history strategies, in which growth rates varied across the skeleton. Furthermore, a variety of strategies were employed to achieve adult size and morphology, including cycles of slow and fast growth, asymmetrical growth within a single element, and extensive remodeling.
Climate Change and Reservoir Impacts on 21st-Century Streamflow and Fluvial Sediment Loads in the Irrawaddy River, Myanmar
Authors: Sirisena T. A. J. G. , Maskey Shreedhar , Bamunawala Janaka , Ranasinghe Roshanka
Published: March 2021

Reservoirs play a vital role in water resource management, while also contributing to alterations in downstream flow regimes and sediment load in the river. On the other hand, variations on streamflow and fluvial sediment loads can also result from climate change effects. Here, we assess future changes in streamflow and sediment load due to climate change and planned reservoirs in the Irrawaddy River Basin, Myanmar. The Soil Water Assessment Tool is used to project streamflow and sediment loads during 2046–2065 (mid-century), and 2081–2100 (end-century) periods under the two end-member Representative Concentration Pathways (i.e., RCP 2.6 and RCP 8.5) with and without planned reservoirs. Results show that compared to the baseline period (1991–2005), streamflow and sediment loads are projected to substantially increase during mid- and end-century periods when planned reservoirs are not considered (i.e., with climate change forcing only). Under RCP 2.6 and RCP 8.5, streamflow at the basin outlet is projected to increase by 8–17% and 9–45%, while sediment loads are projected to increase by 13–26% and 18–75%, respectively by the end-century period. When reservoirs are included, while annual streamflow at the basin outlet does not show a significant difference compared to the climate change only case (for any RCP and for both future time periods considered), annual sediment loads at the basin outlet are projected to slightly decrease (compared to the climate change only case) by 4–6% under RCP 8.5 during the end-century period. However, at seasonal time scales, streamflow and sediment loads at the basin outlet are significantly affected by upstream reservoirs. During the monsoon periods, the presence of planned reservoirs is projected to decrease streamflow at the basin outlet by 6–7%, while during non-monsoon periods, the reservoirs result in an increase of 32–38% in the streamflow at the outlet under RCP 8.5 during the end-century period. Similarly, for the same period and RCP 8.5, due to the planned reservoirs, sediment load is projected to decrease by 9–11% and increase by 32–44% in monsoonal and non-monsoonal periods, respectively.
Dietary Lipid Modulation of Intestinal Serotonin in Ballan Wrasse (Labrus bergylta)—In Vitro Analyses
Authors: Etayo Angela , Le Hoang T. M. D. , Araujo Pedro , Lie Kai K. , Sæle Øystein
Published: March 2021

Serotonin (5-HT) is pivotal in the complex regulation of gut motility and consequent digestion of nutrients via multiple receptors. We investigated the serotonergic system in an agastric fish species, the ballan wrasse (Labrus bergylta) as it represents a unique model for intestinal function. Here we present evidence of the presence of enterochromaffin cells (EC cells) in the gut of ballan wrasse comprising transcriptomic data on EC markers like adra2a, trpa1, adgrg4, lmxa1, spack1, serpina10, as well as the localization of 5-HT and mRNA of the rate limiting enzyme; tryptophan hydroxylase (tph1) in the gut epithelium. Second, we examined the effects of dietary marine lipids on the enteric serotonergic system in this stomach-less teleost by administrating a hydrolyzed lipid bolus in ex vivo guts in an organ bath system. Modulation of the mRNA expression from the tryptophan hydroxylase tph1 (EC cells isoform), tph2 (neural isoform), and other genes involved in the serotonergic machinery were tracked. Our results showed no evidence to confirm that the dietary lipid meal did boost the production of 5-HT within the EC cells as mRNA tph1 was weakly regulated postprandially. However, dietary lipid seemed to upregulate the post-prandial expression of tph2 found in the serotonergic neurons. 5-HT in the intestinal tissue increased 3 hours after “exposure” of lipids, as was observed in the mRNA expression of tph2. This suggest that serotonergic neurons and not EC cells are responsible for the substantial increment of 5-HT after a lipid-reach “meal” in ballan wrasse. Cells expressing tph1 were identified in the gut epithelium, characteristic for EC cells. However, Tph1 positive cells were also present in the lamina propria. Characterization of these cells together with their implications in the serotonergic system will contribute to broad the scarce knowledge of the serotonergic system across teleosts.
Evaluation Method of Wind Power Consumption Capacity Based on Multi-Fractal Theory
Authors: Li Hongzhong , Wang Yao , Zhang Xinyu , Fu Guo
Published: March 2021

An analysis model of wind power consumption capacity is established with the multi-fractal theory. Firstly, the fluctuation characteristics of wind power are described through multi-fractal parameters, and the correlation between wind power fluctuation characteristics and consumption capacity are analyzed. Afterwards, the swinging door algorithm (SDA) is applied to divide the wind power curve in the evaluation period, and the fluctuation process with similar characteristics is clustered. Further, a functional analysis model to evaluate wind power consumption capacity is mentioned based on the fluctuation clustering results. Finally, the effectiveness of the method is verified by an example of a regional power grid in China, and the influence of adjustable parameters in the model on the consumption capacity is quantitatively analyzed.
Integrated Analysis of ceRNA Regulatory Network Associated With Tumor Stage in Cervical Cancer
Authors: Ma Xiaojie , Zhang Qian , Du Jiayu , Tang Jie , Tan Bangxian
Published: March 2021

Objective

To analyze the abnormally expressed genes involved in cervical cancer occurrence and development.

Materials and Methods

Integrated bioinformatics methods were used to analyze differentially expressed (DE) RNAs, including mRNAs, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), in stage I, II, III, and IV cervical cancer patients from the TCGA database to fully reveal the dynamic changes caused by cervical cancer.

Results

First, DE RNAs in cervical cancer tissues from stage I, II, III, and IV patients and normal cervical tissues were identified and divided into different profiles. Several DE RNA profiles were down-regulated or up-regulated in stage I, III, and IV patients. GO and KEGG analysis of DE mRNA profile 1, 2, 4, 5, 6 and 22 which were significantly down-regulated or up-regulated showed that DE mRNAs are involved in cell division, DNA replication, cell adhesion, the positive and negative regulation of RNA polymerase ll promoter transcription. Besides, DE RNA profiles with significant differences in patient stages were analyzed to perform a competing endogenous RNA (ceRNA) regulatory network of lncRNA, miRNA, and mRNA. The protein-protein interaction (PPI) network of DE mRNAs in the ceRNA regulatory network was also constructed. The network had nine central genes (up-regulated genes: CDKN2A, GSK3B, BIRC5, CYCS, MAD2L1; down-regulated genes: PTEN, FOXO3, CCND2, TGFBR2). Survival analysis found that 5 lncRNAs, 9 mRNAs, and 4 miRNAs can be used as prognostic indicators of cervical cancer. Finally, combined with cluster analysis results, we further screened 2 DE RNAs (AMZ2P1 and HDAC5) using clinical samples, suggesting that AMZ2P1, and HDAC5 may act as diagnostic biomarkers for the development of cervical cancer.

Conclusion

This research provides new effective targets and reliable biological markers for the diagnosis and prognosis of cervical cancer.
Nanoparticles for Enhanced Adoptive T Cell Therapies and Future Perspectives for CNS Tumors
Authors: Balakrishnan Preethi Bala , Sweeney Elizabeth E.
Published: March 2021

Adoptive T cell therapy has emerged as a revolutionary immunotherapy for treating cancer. Despite immense promise and clinical success in some hematologic malignancies, limitations remain that thwart its efficacy in solid tumors. Particularly in tumors of the central nervous system (CNS), T cell therapy is often restricted by the difficulty in intratumoral delivery across anatomical niches, suboptimal T cell specificity or activation, and intratumoral T cell dysfunction due to immunosuppressive tumor microenvironments (TMEs). Nanoparticles may offer several advantages to overcome these limitations of T cell therapy, as they can be designed to robustly and specifically activate T cells ex vivo prior to adoptive transfer, to encapsulate T cell stimulating agents for co-localized stimulation, and to be conjugated onto T cells for added functionality. This perspective highlights recent preclinical advances in using nanoparticles to enhance T cell therapy, and discusses the potential applicability and constraints of nanoparticle-enhanced T cells as a new platform for treating CNS tumors.
Antigenic Challenge Influences Epigenetic Changes in Antigen-Specific T Regulatory Cells
Authors: Iwaszkiewicz-Grzes Dorota , Piotrowska Magdalena , Gliwinski Mateusz , Urban-Wójciuk Zuzanna , Trzonkowski Piotr
Published: March 2021

Background

Human regulatory T cells (Tregs) are the fundamental component of the immune system imposing immune tolerance via control of effector T cells (Teffs). Ongoing attempts to improve Tregs function have led to the creation of a protocol that produces antigen-specific Tregs, when polyclonal Tregs are stimulated with monocytes loaded with antigens specific for type 1 diabetes. Nevertheless, the efficiency of the suppression exerted by the produced Tregs depended on the antigen with the best results when insulin β chain peptide 9-23 was used. Here, we examined epigenetic modifications, which could influence these functional differences.

Methods

The analysis was pefromed in the sorted specific (SPEC, proliferating) and unspecific (UNSPEC, non-proliferating) subsets of Tregs and Teffs generated by the stimulation with monocytes loaded with either whole insulin (INS) or insulin β chain peptide 9-23 (B:9-23) or polyclonal cells stimulated with anti-CD3/anti-CD28 beads (POLY). A relative expression of crucial Tregs genes was determined by qRT-PCR. The Treg-specific demethylated region (TSDR) in FoxP3 gene methylation levels were assessed by Quantitative Methylation Specific PCR (qMSP). ELISA was used to measure genomic DNA methylation and histone H3 post-translational modifications (PTMs).

Results

Tregs SPECB:9-23 was the only subset expressing all assessed genes necessary for regulatory function with the highest level of expression among all analyzed conditions. The methylation of global DNA as well as TSDR were significantly lower in Tregs SPECB:9-23 than in Tregs SPECINS. When compared to Teffs, Tregs were characterized by a relatively lower level of PTMs but it varied in respective Tregs/Teffs pairs. Importantly, whenever the difference in PTM within Tregs/Teffs pair was significant, it was always low in one subset from the pair and high in the other. It was always low in Tregs SPECINS and high in Teffs SPECINS, while it was high in Tregs UNSPECINS and low in Teffs UNSPECINS. There were no differences in Tregs/Teffs SPECB:9-23 pair and the level of modifications was low in Tregs UNSPECB:9-23 and high in Teffs UNSPECB:9-23. The regions of PTMs in which differences were significant overlapped only partially between particular Tregs/Teffs pairs.

Conclusions

Whole insulin and insulin β chain peptide 9-23 affected epigenetic changes in CD4+ T cells differently, when presented by monocytes. The peptide preferably favored specific Tregs, while whole insulin activated both Tregs and Teffs.
Polyethylene Glycol Ointment Alleviates Psoriasis-Like Inflammation Through Down-Regulating the Function of Th17 Cells and MDSCs
Authors: Lu Yan , Xiao Yi , Yin Ming-Zhu , Zhou Xing-Chen , Wu Li-Sha , Chen Wang-Qing , Luo Yan , Kuang Ye-Hong , Zhu Wu
Published: March 2021

Objective: To explore the possible mechanism of improving the imiquimod (IMQ)-induced psoriasis-like inflammation by using polyethylene glycol (PEG) ointment.

Methods: We evaluated the appearance of psoriasis lesions by Psoriasis Area and Severity Index (PASI), observed the epidermal proliferation by histopathological staining and immunohistochemical staining, and explored the key molecules and signaling pathways of improving psoriasis-like inflammation treated with PEG ointment by RNA sequencing. Finally, we verified the expression of inflammatory cells and inflammatory factors by flow cytometry, immunohistochemical staining, and Q-PCR.

Results: PEG ointment could improve the appearance of psoriasis lesions and the epidermis thickness of psoriasis mouse, inhibit the proliferation of keratinocytes, and down-regulate the relative mRNA levels of IL-23, IL-22, IL-6, IL-17C, IL-17F, S100A7, S100A8, S100A9, CXCL1, CXCL2, and IL-1β in the skin lesions of psoriasis mouse by down-regulating the numbers of myeloid-derived suppressor cells (MDSCs) and T helper 17 (Th17) cells.

Conclusion: PEG ointment could improve the IMQ-induced psoriasis-like inflammation by down-regulating the functions of Th17 cells and MDSCs.
Bone Erosions Detected by Ultrasound Are Prognostic for Clinical Arthritis Development in Patients With ACPA and Musculoskeletal Pain
Authors: Ziegelasch Michael , Eloff Emma , Hammer Hilde B. , Cedergren Jan , Martinsson Klara , Reckner Åsa , Skogh Thomas , Magnusson Mattias , Kastbom Alf
Published: March 2021

Anti-citrullinated protein antibodies (ACPA) often precede onset of rheumatoid arthritis (RA) by years, and there is an urgent clinical need for predictors of arthritis development among such at-risk patients. This study assesses the prognostic value of ultrasound for arthritis development among ACPA-positive patients with musculoskeletal pain. We prospectively followed 82 ACPA-positive patients without clinical signs of arthritis at baseline. Ultrasound at baseline assessed synovial hypertrophy, inflammatory activity by power Doppler, and erosions in small joints of hands and feet. We applied Cox regression analyses to examine associations with clinical arthritis development during follow-up (median, 69 months; range, 24–90 months). We also compared the ultrasound findings among the patients to a control group of 100 blood donors without musculoskeletal pain. Clinical arthritis developed in 39/82 patients (48%) after a median of 6 months (range, 1–71 months). One or more ultrasound erosions occurred in 13/82 patients (16%), with none in control subjects (p < 0.001). Clinical arthritis development was more common among patients with baseline ultrasound erosions than those without (77 vs. 42%, p = 0.032), and remained significant in a multivariable Cox regression analysis that included previously described prognostic factors (HR 3.9, 95% CI 1.6–9.4, p = 0.003). Ultrasound-detected tenosynovitis was more frequent among the patients and associated with clinical arthritis development in a univariable analysis (HR 2.5, 95% CI 1.1–5.7, p = 0.031), but did not remain statistically significant in multivariable analysis. Thus, bone erosions detected by ultrasound are independent predictors of clinical arthritis development in an ACPA-positive at-risk population.

Trial Registration: Regional Ethics Committee in Linköping, Sweden, Dnr M220-09. Registered 16 December 2009, https://etikprovningsmyndigheten.se/.
Metagenomic Data Assembly – The Way of Decoding Unknown Microorganisms
Authors: Lapidus Alla L. , Korobeynikov Anton I.
Published: March 2021

Metagenomics is a segment of conventional microbial genomics dedicated to the sequencing and analysis of combined genomic DNA of entire environmental samples. The most critical step of the metagenomic data analysis is the reconstruction of individual genes and genomes of the microorganisms in the communities using metagenomic assemblers – computational programs that put together small fragments of sequenced DNA generated by sequencing instruments. Here, we describe the challenges of metagenomic assembly, a wide spectrum of applications in which metagenomic assemblies were used to better understand the ecology and evolution of microbial ecosystems, and present one of the most efficient microbial assemblers, SPAdes that was upgraded to become applicable for metagenomics.
Research on the Interaction Mechanism Between α Mino-Phosphonate Derivative Q-R and Harpin-Binding Protein 1 in Tobacco (Nicotiana tabacum) Plants
Authors: Huang Maoxi , Yan Yunlong , Wang Li , Chen Jun , Liu Tao , Xie Xin , Li Xiangyang
Published: March 2021

Amino-phosphonate derivative R-diphenyl-1-(4-methylbenzothiazole-2-amino)-1-(thiphene-2-yl)-methylphosphonate (Q-R) has a high protective anti-tobacco mosaic virus (TMV) activity. However, the mechanism responsible for Q-R’s effect on TMV infection is largely unknown. Here, we studied the expression levels of harpin-binding protein 1 (HrBP1) and pathogenesis-related protein-1a (PR-1a) in TMV-infected tobacco plants by using reverse transcription quantitative real-time PCR. Then, we verified the interactions between Q-R and the HrBP1 protein from Escherichia coli using isothermal titration calorimetry and studied the Q-R-associated assembly of HrBP1 using size-exclusion chromatography. The results showed that the expression levels of HrBP1 and PR-1a genes were significantly increased by Q-R at the transcriptional level in TMV-infected tobacco plants, and the E. coli-expressed HrBP1 protein was assembled into oligomers by Q-R via binding to HrBP1 with a dissociation constant of 1.19 μM. We, therefore, concluded that Q-R activated the HrBP1 and PR-1a genes and enhanced the ability of HrBP1 to assemble in tobacco plants.
Fatty Acid Methyl Esters From the Coral-Associated Bacterium Pseudomonas aeruginosa Inhibit Virulence and Biofilm Phenotypes in Multidrug Resistant Staphylococcus aureus: An in vitro Approach
Authors: Vijay Karuppiah , Kiran George Seghal , Divya S. , Thangavel Kavitha , Thangavelu Sathiamoorthi , Dhandapani Ranjithkumar , Selvin Joseph
Published: March 2021

In an attempt to study the antibacterial, antivirulence and antibiofilm potentials of bacteria residing the tissue and surface mucus layers of the pristine corals, we screened a total of 43 distinct bacterial morphotypes from the coral Favites sp. Among the isolates, Pseudomonas aeruginosa strain CBMGL12 with showed antibacterial, antivirulence and antibiofilm activity against multidrug resistant pathogenic strains of Staphylococcus aureus (reference strain: MTCC96; community-acquired methicillin resistant strain: CA-MRSA). Extracellular products (ECP) from the coral-associated bacterium P. aeruginosa were solvent extracted, fractionated by chromatographic techniques such as silica column and HPLC-UV with concomitant bioassays guiding the fractionation of metabolites. Identification of bioactive chemical moieties was performed by FT-IR analysis, GC-MS/MS equipped with NIST library, 1H and 13C NMR spectral studies. We report the differential production of extracellular and cell-associated virulence and biofilm phenotypes in multi-drug resistant strains of S. aureus, post-treatment with the ECP containing aromatic fatty acid methyl esters (FAME) such as methyl benzoate and methyl phenyl acetate produced by a coral-associated bacterium. In conclusion, this study has identified antibacterial, antibiofilm and antivirulent FAME from the coral-associated P. aeruginosa for its ability to attenuate virulence and biofilms phenotypes in multi-drug resistant pathogenic strains of S. aureus.
Predominant Microbial Colonizers in the Root Endosphere and Rhizosphere of Turfgrass Systems: Pseudomonas veronii, Janthinobacterium lividum, and Pseudogymnoascus spp.
Authors: Xia Qing , Rufty Thomas , Shi Wei
Published: March 2021

Microbes can colonize plant roots to modulate plant health and environmental fitness. Thus, using microbes to improve plant adaptation to biotic and abiotic stresses will be promising to abate the heavy reliance of management systems on synthetic chemicals and limited resource. This is particularly important for turfgrass systems because intensive management for plant available nutrients (e.g., nitrogen), water, and pest control is necessary to maintain a healthy and aesthetic landscape. However, little is known on microbial species and host compatibility in turfgrass root endosphere and rhizosphere. Here, by using marker gene high throughput sequencing approaches we demonstrated that a few bacterial and fungal species prevailed the root endosphere and rhizosphere and were of a broad host spectrum. Irrespective of turfgrass species (bermudagrass, ultradwarf bermudagrass, creeping bentgrass, and tall fescue), defoliation intensities (i.e., mowing height and frequency), turfgrass sites, and sampling time, Pseudomonas veronii was predominant in the root endosphere, constituting ∼38% of the total bacterial community, which was much higher than its presence in the bulk soil (∼0.5%) and rhizosphere (∼4.6%). By contrast, Janthinobacterium lividum and fungal species of the genus Pseudogymnoascus were more abundant in the rhizosphere, constituting ∼15 and ∼ 39% of the total bacterial and fungal community, respectively, compared to their respective presence in the bulk soil (∼ 0.1 and 5%) and root endosphere (∼ 0.8 and 0.3%). Such stark contrasts in the microbiome composition between the root endosphere, rhizosphere, and bulk soil were little influenced by turfgrass species, suggesting the broad turfgrass host compatibility of these bacterial and fungal species. Further, their dominance in respective niches were mutually unaffected, implying the possibility of developing a multiple species formula for coping turfgrass with environmental stresses. These species were likely involved in controlling pests, such as infectious nematodes and fungi, decomposing root debris, and helping turfgrass water and nutrient uptake; yet these possibilities need to be further examined.
Genetic Evolution and Implications of the Mitochondrial Genomes of Two Newly Identified Taenia spp. in Rodents From Qinghai-Tibet Plateau
Authors: Wu Yao-Dong , Li Li , Fan Yan-Lei , Ni Xing-Wei , Ohiolei John Asekhaen , Li Wen-Hui , Li Jian-Qiu , Zhang Nian-Zhang , Fu Bao-Quan , Yan Hong-Bin , Jia Wan-Zhong
Published: March 2021

The larva of Taeniidae species can infect a wide range of mammals, causing major public health and food safety hazards worldwide. The Qinghai-Tibet Plateau (QTP), a biodiversity hotspot, is home to many species of rodents, which act as the critical intermediate hosts of many Taeniidae species. In this study, we identified two new larvae of Taenia spp., named T. caixuepengi and T. tianguangfui, collected from the plateau pika (Ochotona curzoniae) and the Qinghai vole (Neodon fuscus), respectively, in QTP, and their mitochondrial genomes were sequenced and annotated. Phylogenetic trees based on the mitochondrial genome showed that T. caixuepengi has the closest genetic relationship with T. pisiformis, while T. tianguangfui was contained in a monophyletic group with T. crassiceps, T. twitchelli, and T. martis. Biogeographic scenarios analysis based on split time speculated that the speciation of T. caixuepengi (∼5.49 Mya) is due to host switching caused by the evolution of its intermediate host. Although the reason for T. tianguangfui (∼13.11 Mya) speciation is not clear, the analysis suggests that it should be infective to a variety of other rodents following the evolutionary divergence time of its intermediate host and the range of intermediate hosts of its genetically close species. This study confirms the species diversity of Taeniidae in the QTP, and speculates that the uplift of the QTP has not only a profound impact on the biodiversity of plants and animals, but also that of parasites.
Morpho-Phylo Taxonomy of Novel Dothideomycetous Fungi Associated With Dead Woody Twigs in Yunnan Province, China
Authors: Mortimer Peter E. , Jeewon Rajesh , Xu Jian-Chu , Lumyong Saisamorn , Wanasinghe Dhanushka N.
Published: March 2021

Within the field of mycology, macrofungi have been relatively well-studied when compared to microfungi. However, the diversity and distribution of microfungi inhabiting woody material have not received the same degree of research attention, especially in relatively unexplored regions, such as Yunnan Province, China. To help address this knowledge gap, we collected and examined fungal specimens from different plants at various locations across Yunnan Province. Our investigation led to the discovery of four species that are clearly distinct from extant ones. These taxonomic novelties were recognized based on morphological comparisons coupled with phylogenetic analyses of multiple gene sequences (non-translated loci and protein-coding regions). The monotypic genus Neoheleiosa gen. nov. (type: N. lincangensis) is introduced in Monoblastiaceae (Monoblastiales) for a woody-based saprobic ascomycete that possesses globose to subglobose or obpyriform ascomata with centric or eccentric, papillate ostioles, an ascomatal wall with thin-walled cells of textura globulosa, cylindric, pedicellate asci with an ocular chamber, and 1-septate, brown, guttulate, longitudinally striated, bicellular ascospores. Neoheleiosa has a close phylogenetic affinity to Heleiosa, nevertheless, it is morphologically dissimilar by its peridium cells and ornamented ascospores. Acrocalymma hongheense and A. yuxiense are described and illustrated as new species in Acrocalymmaceae. Acrocalymma hongheense is introduced with sexual and asexual (coelomycetous) features. The sexual morph is characterized by globose to subglobose, ostiolate ascomata, a peridium with textura angularis cells, cylindric-clavate asci with a furcate to truncate pedicel and an ocular chamber, hyaline, fusiform, 1-septate ascospores which are surrounded by a thick, distinct sheath, and the asexual morph is featured by pycnidial conidiomata, subcylindrical, hyaline, smooth, annelledic, conidiogenous cells, hyaline, guttulate, subcylindrical, aseptate conidia with mucoid ooze at the apex and with a rounded hilum at the base. Acrocalymma yuxiense is phylogenetically distinct from other extant species of Acrocalymma and differs from other taxa in Acrocalymma in having conidia with three vertical eusepta. Magnibotryascoma kunmingense sp. nov. is accommodated in Teichosporaceae based on its coelomycetous asexual morph which is characterized by pycnidial, globose to subglobose, papillate conidiomata, enteroblastic, annelledic, discrete, cylindrical to oblong, hyaline conidiogenous cells arising from the inner layer of pycnidium wall, subglobose, oval, guttulate, pale brown and unicelled conidia.
Norepinephrine-Induced Calcium Signaling and Store-Operated Calcium Entry in Olfactory Bulb Astrocytes
Authors: Fischer Timo , Prey Jessica , Eschholz Lena , Rotermund Natalie , Lohr Christian
Published: March 2021

It is well-established that astrocytes respond to norepinephrine with cytosolic calcium rises in various brain areas, such as hippocampus or neocortex. However, less is known about the effect of norepinephrine on olfactory bulb astrocytes. In the present study, we used confocal calcium imaging and immunohistochemistry in mouse brain slices of the olfactory bulb, a brain region with a dense innervation of noradrenergic fibers, to investigate the calcium signaling evoked by norepinephrine in astrocytes. Our results show that application of norepinephrine leads to a cytosolic calcium rise in astrocytes which is independent of neuronal activity and mainly mediated by PLC/IP3-dependent internal calcium release. In addition, store-operated calcium entry (SOCE) contributes to the late phase of the response. Antagonists of both α1- and α2-adrenergic receptors, but not β-receptors, largely reduce the adrenergic calcium response, indicating that both α-receptor subtypes mediate norepinephrine-induced calcium transients in olfactory bulb astrocytes, whereas β-receptors do not contribute to the calcium transients.
Drug Repurposing in the Treatment of Traumatic Brain Injury
Authors: Ghiam Michael K. , Patel Shrey D. , Hoffer Alan , Selman Warren R. , Hoffer Barry J. , Hoffer Michael E.
Published: March 2021

Traumatic brain injury (TBI) is the most common cause of morbidity among trauma patients; however, an effective pharmacological treatment has not yet been approved. Individuals with TBI are at greater risk of developing neurological illnesses such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The approval process for treatments can be accelerated by repurposing known drugs to treat the growing number of patients with TBI. This review focuses on the repurposing of N-acetyl cysteine (NAC), a drug currently approved to treat hepatotoxic overdose of acetaminophen. NAC also has antioxidant and anti-inflammatory properties that may be suitable for use in therapeutic treatments for TBI. Minocycline (MINO), a tetracycline antibiotic, has been shown to be effective in combination with NAC in preventing oligodendrocyte damage. (−)-phenserine (PHEN), an anti-acetylcholinesterase agent with additional non-cholinergic neuroprotective/neurotrophic properties initially developed to treat AD, has demonstrated efficacy in treating TBI. Recent literature indicates that NAC, MINO, and PHEN may serve as worthwhile repositioned therapeutics in treating TBI.
Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats
Authors: Yang Huajun , Zhang Yifan , Chen Hongqun , Zhu Yingwu , Li Yuan , Ouyang Fu , Chu Lan , Liu Daishun
Published: March 2021

Our previous study revealed that miR-184 expression is significantly altered in the brain following ischemic stroke in rats. However, it is unknown whether this alteration in miR-184 expression contributes to brain injury after ischemic stroke. Here, we aim to address the potential of miR-184 to impact nerve injury following ischemia and reperfusion. Rats received ICV injection of miR-184 adenovirus or empty vector and were subjected to right middle cerebral artery occlusion (MCAO) to establish an ischemic stroke model. We cultured SH-SY5Y cells under oxygen-glucose deprivation/reoxygenation (OGD/R) and transfected them with miR-184 lentivirus to explore the primary mechanisms. To evaluate miR-184 expression, neurological function deficits, the cerebral infarct volume, cell viability, and apoptosis, qRT-PCR analysis of miR-184 expression, the modified neurological severity score (mNSS) system, TTC staining, the CCK-8 assay, flow cytometry, and dual-luciferase reporter assays were utilized. We found that miR-184 expression was downregulated and that the cerebral infarct volume and mNSSs were increased following ischemic stroke; however, increasing the level of miR-184 alleviated brain damage. Overexpression of miR-184 resulted in increased viability and reduced apoptosis of SH-SY5Y cells following OGD/R in vitro. We identified the phosphatidic acid phosphatase type 2B (PPAP2B) gene as a direct target gene of miR-184. In summary, our results reveal that attenuation of miR-184 levels in ischemic stroke contributes to ischemic injury through targeting PPAP2B mRNA-mediated apoptosis, which may be a promising therapeutic target for ischemic stroke.
Gluten-Free Foods Cooked in Shared Fryers With Wheat: A Pilot Study Assessing Gluten Cross Contact
Authors: Thompson Tricia , Lyons Trisha Bury , Keller Amy , Jaffe Nancee , Emerson-Mason Luke
Published: March 2021

Introduction: Consumers with celiac disease are discouraged from eating fried foods cooked in shared fryers with wheat-containing foods at restaurants based on presumed gluten exposure. The purpose of the present study is to assess gluten levels of fries free of gluten-containing ingredients cooked in shared fryers with wheat.

Methods: 20 orders of fries were purchased from 10 different restaurants. Restaurants confirmed that fries and oil were free of gluten-containing ingredients. All restaurants confirmed that their fryers were used to cook wheat-containing foods. Fries were sent to Bia Diagnostics and tested in 1-gram duplicates using the R7001 sandwich R5 ELISA and the R7021 competitive R5 ELISA. A microwave control also was run.

Results: The sandwich ELISA found gluten in 9/20 fry orders (7 to > 80 ppm). The competitive ELISA found gluten in 3/20 fry orders (14 to > 270 ppm). In the microwave control (60-ppm gluten mixture of wheat flour and canola oil), the unheated mixture tested at a mean level of 64 ppm gluten using the sandwich ELISA and 137 ppm gluten using the competitive ELISA. The mixture heated to 190°C tested at a mean level of 55 ppm gluten using the sandwich ELISA and < 10 ppm and 16 ppm gluten using the competitive ELISA.

Discussion: Based on test results, 25% of fry orders would not be considered gluten-free.

Summary: Gluten cross contact may occur when gluten-free foods are cooked in shared fryers with wheat. ELISAs may underperform when analyzing for gluten that has been heated.
Tumor Microenvironment Proteomics: Lessons From Multiple Myeloma
Authors: Fernando Rodrigo Carlini , de Carvalho Fabrício , Leme Adriana Franco Paes , Colleoni Gisele Wally Braga
Published: March 2021

Although the “seed and soil” hypothesis was proposed by Stephen Paget at the end of the 19th century, where he postulated that tumor cells (seeds) need a propitious medium (soil) to be able to establish metastases, only recently the tumor microenvironment started to be more studied in the field of Oncology. Multiple myeloma (MM), a malignancy of plasma cells, can be considered one of the types of cancers where there is more evidence in the literature of the central role that the bone marrow (BM) microenvironment plays, contributing to proliferation, survival, migration, and drug resistance of tumor cells. Despite all advances in the therapeutic arsenal for MM treatment in the last years, the disease remains incurable. Thus, studies aiming a better understanding of the pathophysiology of the disease, as well as searching for new therapeutic targets are necessary and welcome. Therefore, the present study aimed to evaluate the protein expression profiling of mononuclear cells derived from BM of MM patients in comparison with these same cell types derived from healthy individuals, in order to fill this gap in MM treatment. Proteomic analysis was performed using the mass spectrometry technique and further analyses were done using bioinformatics tools, to identify dysregulated biological pathways and/or processes in the BM microenvironment of patients with MM as a result of the disease. Among the pathways identified in this study, we can highlight an upregulation of proteins related to protein biosynthesis, especially chaperone proteins, in patients with MM. Additionally, we also found an upregulation of several proteins involved in energy metabolism, which is one of the cancer hallmarks. Finally, with regard to the downregulated proteins, we can highlight mainly those involved in different pathways of the immune response, corroborating the data that has demonstrated that the immune system of MM is impaired and, therefore, the immunotherapies that have been studied recently for the treatment of the disease are extremely necessary in the search for a control and a cure for these patients who live with the disease.
The Efficacy and Safety of Programmed Death-1 and Programmed Death Ligand 1 Inhibitors for the Treatment of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis
Authors: He Shukang , Jiang Weichao , Fan Kai , Wang Xiaobei
Published: March 2021

Background

Hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage where only systemic treatment can be offered. The emergence of immune checkpoint inhibitors (ICIs) provides hope for the treatment of HCC. In this study, we performed a meta-analysis to provide evidence for the efficacy and safety of ICIs in the treatment of HCC.

Methods

The following databases and websites were searched: Embase, PubMed, Cochrane Library and ClinicalTrials.gov. The primary endpoints were response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS).

Results

Finally, twelve studies were included in this meta-analysis. When the corresponding outcome indicators and their 95% confidence intervals (CIs) were pooled directly, the overall RR, DCR, PFS and OS were 0.17 (0.15-0.19, I2 = 56.2%, P=0.009), 0.58 (0.55-0.61, I2 = 75.9%, P<0.001), 3.27 months (2.99-3.55, I2 = 73.0%, P=0.001), 11.73 months (10.79-12.67, I2 = 90.3%, P<0.001). Compared to the control group, treatment with ICIs significantly improved RR, PFS and OS, the OR and HRs were 3.11 (2.17-4.44, P<0.001), 0.852 (0.745-0.974, P=0.019) and 0.790 (0.685-0.911, P=0.001), respectively. However, no significant improvement in DCR was found in ICIs treatment in this meta-analysis.

Conclusion

HCC patients would benefit from ICIs treatment, however, more studies are needed in the future to provide more useful evidence for the treatment of HCC by programmed death-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors.
The Acute and Late Toxicities of MRI-Guided External Beam Partial Breast Irradiation Delivered Using a Once-Per-Day Regimen
Authors: Lee Hye In , Kim Kyubo , Kim Jin Ho , Chang Ji Hyun , Shin Kyung Hwan
Published: March 2021

Background and Purpose

The use of external beam accelerated partial breast irradiation (APBI) using a twice-per-day regimen has raised concerns about increase rates of late toxicities. We compared toxicity outcomes of external beam APBI using a once-per-day regimen and accelerated hypofractionated whole breast irradiation (AWBI) in patients with early-stage breast cancer.

Materials and Methods

This was a single-institution, retrospective cohort study. Patients aged ≥50 years with pTisN0 or pT1N0 breast cancer who underwent breast-conserving surgery and adjuvant radiotherapy were included. APBI was delivered at 38.5 Gy in 10 fractions once daily using magnetic resonance imaging (MRI)-guided radiotherapy only to patients who were strictly “suitable”, according to the ASTRO-APBI guidelines. AWBI was delivered at 40.5–43.2 Gy in 15 or 16 fractions with or without a boost.

Results

Between October 2015 and December 2018, 173 and 300 patients underwent APBI and AWBI, respectively. At a median follow-up of 34.9 months (range 7.1 to 55.4 months), the 3-year recurrence-free survival rates of the APBI and AWBI groups were both 99.2% (p=0.63). Acute toxicities were less frequent in the APBI than AWBI group (grade 1: 95 [54.9%] vs. 233 [77.7%] patients; grade 2: 7 [4.0%] vs. 44 [14.7%] patients; no grade ≥3 toxicities were observed in either group, p<0.001). Late toxicities were less common in the APBI than AWBI group (grade 1: 112 [64.7%] vs. 197 [65.7%] patients; grade 2: 9 [5.2%] vs. 64 [21.3%] patients; grade 3: 0 vs. 5 [1.7%] patients, p<0.001). Multivariate analysis showed that APBI was significantly associated with fewer late toxicities of grade ≥2 compared with AWBI (odds ratio 4.17, p=0.006).

Conclusion

Once-per-day APBI afforded excellent locoregional control and fewer toxicities compared with AWBI. This scheme could be an attractive alternative to AWBI in patients who meet the ASTRO-APBI guidelines.
Interactive Effects of Mycorrhizae, Soil Phosphorus, and Light on Growth and Induction and Priming of Defense in Plantago lanceolata
Authors: Qu Laiye , Wang Minggang , Biere Arjen
Published: March 2021

Increasing demands to reduce fertilizer and pesticide input in agriculture has triggered interest in arbuscular mycorrhizal fungi (AMF) that can enhance plant growth and confer mycorrhiza-induced resistance (MIR). MIR can be based on a variety of mechanisms, including induction of defense compounds, and sensitization of the plant’s immune system (priming) for enhanced defense against later arriving pests or pathogens signaled through jasmonic acid (JA). However, growth and resistance benefits of AMF highly depend on environmental conditions. Low soil P and non-limiting light conditions are expected to enhance MIR, as these conditions favor AMF colonization and because of observed positive cross-talk between the plant’s phosphate starvation response (PSR) and JA-dependent immunity. We therefore tested growth and resistance benefits of the AMFFunneliformis mosseaeinPlantago lanceolataplants grown under different levels of soil P and light intensity. Resistance benefits were assessed in bioassays with the leaf chewing herbivoreMamestra brassicae. Half of the plants were induced by jasmonic acid prior to the bioassays to specifically test whether AMF primed plants for JA-signaled defense under different abiotic conditions. AMF reduced biomass production but contrary to prediction, this reduction was not strongest under conditions considered least optimal for carbon-for-nutrient trade (low light, high soil P). JA application induced resistance toM. brassicae, but its extent was independent of soil P and light conditions. Strikingly, in younger plants, JA-induced resistance was annulled by AMF under high resource conditions (high soil P, ample light), indicating that AMF did not prime but repressed JA-induced defense responses. In older plants, low soil P and light enhanced susceptibility toM. brassicaedue to enhanced leaf nitrogen levels and reduced leaf levels of the defense metabolite catalpol. By contrast, in younger plants, low soil P enhanced resistance. Our results highlight that defense priming by AMF is not ubiquitous and calls for studies revealing the causes of the increasingly observed repression of JA-mediated defense by AMF. Our study further shows that in our system abiotic factors are significant modulators of defense responses, but more strongly so by directly modulating leaf quality than by modulating the effects of beneficial microbes on resistance.
Exploring Biocontrol Agents From Microbial Keystone Taxa Associated to Suppressive Soil: A New Attempt for a Biocontrol Strategy
Authors: Zheng Yanfen , Han Xiaobin , Zhao Donglin , Wei Keke , Yuan Yuan , Li Yiqiang , Liu Minghong , Zhang Cheng-Sheng
Published: March 2021

Recent studies have observed differing microbiomes between disease-suppressive and disease-conducive soils. However, it remains unclear whether the microbial keystone taxa in suppressive soil are critical for the suppression of diseases. Bacterial wilt is a common soil-borne disease caused by Ralstonia solanacearum that affects tobacco plants. In this study, two contrasting tobacco fields with bacterial wilt disease incidences of 0% (disease suppressive) and 100% (disease conducive) were observed. Through amplicon sequencing, as expected, a high abundance of Ralstonia was found in the disease-conducive soil, while large amounts of potential beneficial bacteria were found in the disease-suppressive soil. In the fungal community, an abundance of the Fusarium genus, which contains species that cause Fusarium wilt, showed a positive correlation (p < 0.001) with the abundance of Ralstonia. Network analysis revealed that the healthy plants had more complex bacterial networks than the diseased plants. A total of 9 and 13 bacterial keystone taxa were identified from the disease-suppressive soil and healthy root, respectively. Accumulated abundance of these bacterial keystones showed a negative correlation (p < 0.001) with the abundance of Ralstonia. To complement network analysis, culturable strains were isolated, and three species belonging to Pseudomonas showed high 16S rRNA gene similarity (98.4–100%) with keystone taxa. These strains displayed strong inhibition on pathogens and reduced the incidence of bacterial wilt disease in greenhouse condition. This study highlighted the importance of keystone species in the protection of crops against pathogen infection and proposed an approach to obtain beneficial bacteria through identifying keystone species, avoiding large-scale bacterial isolation and cultivation.