bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sestrin3 enhances macrophage-mediated generation of T helper 1 and T helper 17 cells in a mouse colitis model
Authors: Ge Liuqing , Xu Min , Brant Steven R , Liu Shaoping , Zhu Chengliang , Shang Jian , Zhao Qiu , Zhou Feng 
Published: March 2020

Abstract
Intestinal macrophages participate in the pathogenesis of inflammatory bowel diseases (IBDs) through secreting pro-inflammatory and tissue-damaging factors as well as inducing the differentiation of T helper 1 (Th1) and T helper 17 (Th17) cells. Elucidating the regulatory mechanisms of intestinal macrophage activity in IBDs is important for developing new therapeutic approaches. In the current study, the expression of Sestrins in myeloid cells and lymphocytes in colonic lamina propria (LP) was evaluated in a murine acute colitis model. We found that Sestrin3 was significantly up-regulated in LP macrophages by the colonic LP microenvironment. In the in vitro experiments, lentivirus-mediated Sestrin3 knockdown significantly reduced the production of IL-12 and IL-23 in activated macrophages, in addition to decreasing the expression of classical pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. Additionally, Sestrin3 knockdown impaired macrophage-mediated generation of Th1 and Th17 cells from CD4+ T cells, probably through up-regulating the phosphorylation of mechanistic target of rapamycin complex 1 (mTORC1) in macrophages. In the in vivo experiments, adoptive transfer of Sestrin3-deficient macrophages alleviated the generation of Th1 and Th17 cells in the colonic LP and mesenteric lymph nodes. Furthermore, the adoptive transfer mitigated the severity of colitis, as demonstrated by lower production of pro-inflammatory cytokines and fewer tissue lesions in the colon. Our study suggests that Sestrin3 might be crucial for macrophage-mediated generation of pathogenic Th1 and Th17 cells in IBDs.
Global clonal spread of mcr-3-carrying MDR ST34 Salmonella enterica serotype Typhimurium and monophasic 1,4,[5],12:i:− variants from clinical isolates
Authors: Sun Ruan-Yang , Ke Bi-Xia , Fang Liang-Xing , Guo Wen-Ying , Li Xing-Ping , Yu Yang , Zheng Si-Lin , Jiang Yu-Wei , He Dong-Mei , Sun Jian , Ke Chang-Wen , Liu Ya-Hong , Liao Xiao-Ping 
Published: March 2020

AbstractObjectivesTo investigate the prevalence and transmission of mcr-3 among Salmonella enterica serotype Typhimurium and 1,4,[5],12:i:−.MethodsA total of 4724 clinical Salmonella isolates were screened for the presence of mcr-3 in China during 2014–19. The clonal relationship of the mcr-3-positive isolates and their plasmid contents and complete sequence were also characterized based on WGS data from the Illumina and MinION platforms.ResultsWe identified 10 mcr-3-positive isolates, and all were MDR, mostly resistant to colistin, cefotaxime, ciprofloxacin, doxycycline and florfenicol. mcr-3 was co-present with blaCTX-M-55-qnrS1 on hybrid ST3-IncC-FII conjugatable plasmids (n = 6) and an ST3-IncC non-conjugatable plasmid (n = 1) and embedded into a pCHL5009T-like IncFII plasmid on the Salmonella chromosome (n = 3). Four distinctive genetic contexts surrounded mcr-3 and all but one were closely related to each other and to the corresponding region of IncFII plasmid pCHL5009T. IS15DI was most likely the vehicle for integration of mcr-3-carrying IncFII plasmids into ST3-IncC plasmids and the chromosome and for shaping the MDR regions. In addition, a phylogenetic tree based on the core genome revealed a unique Salmonella lineage (≤665 SNPs) that contained these 10 mcr-3-positive isolates and another 38 (33 from patients) mcr-3-positive Salmonella from five countries. In particular, most of the 51 mcr-3-positive isolates belonged to ST34 and harboured diverse antibiotic resistance genes (ARGs), including mcr-3-blaCTX-M-55-qnrS1, and possessed similar ARG profiles.ConclusionsOur findings revealed global clonal spread of MDR ST34 Salmonella from clinical isolates co-harbouring mcr-3 with blaCTX-M-55 and qnrS1 and a flexibility of mcr-3 co-transmittance with other ARGs mediated by mobile genetic elements.
Characteristics of drug resistance in HIV-1 CRF55_01B from ART-experienced patients in Guangdong, China
Authors: Lan Yun , Xin Ruolei , Cai Weiping , Deng Xizi , Li Linghua , Li Feng , Cai Xiaoli , Tang Xiaoping , Fan Qinghong , Hu Fengyu 
Published: March 2020

Abstract

Background
HIV-1 acquired drug resistance (ADR) has become a critical clinical and public health issue. Recently, HIV-1 CRF55_01B has been found more frequently in the MSM population.

Objective
To investigate the characteristics of HIV-1 drug resistance mutations (DRMs) and the extent of changes in drug susceptibility among ART-experienced CRF55_01B-infected adults of Guangdong.

Methods
ADR was tested for immediately in CRF55_01B-infected patients with virological failure. Demographic and epidemiological information was collected. DRMs and antiretroviral susceptibility were interpreted using the Stanford University HIV Drug Resistance Database HIVdb program.

Results
Overall, 162 (4.78%) CRF55_01B isolates were identified from 2013 to 2018. Among DRMs, M184V (43.83%) was the most frequent NRTI DRM, followed by K65R (23.46%), and V179E (98.77%) was the most frequent NNRTI DRM, followed by K103N (47.53%) and Y181C (14.81%). According to the HIVdb program, 79.01% of the CRF55_01B-infected patients carried mutations conferring low-level or higher drug resistance to any of the three classes of ART drugs. Among PI DRMs, only one mutation affording low-level resistance to nelfinavir was found (0.62%). Among NRTI DRMs, a high proportion of high-level resistance to lamivudine (58.64%) and emtricitabine (58.02%) was found. As regards NNRTIs, more than 75% of patients carried efavirenz and nevirapine DRMs. The percentages of high-level resistance were 70.99%, 63.58%, 22.22%, 17.90% and 4.32% for nevirapine, efavirenz, rilpivirine, doravirine and etravirine, respectively.

Conclusions
High frequencies of DRMs and resistance were observed among CRF55_01B-infected patients failing ART in Guangdong, and interventions may be considered to minimize ecological contributions to ART.
Influence of an immune-modulatory feed supplement on performance and immune function of beef cows and calves preweaning
Authors: Crook Tyler S , Beck Paul A , Gadberry Shane , Sims Michael B , Stewart C Brandon , Shelton Cody , Koltes James , Kegley Elizabeth B , Powell Jeremy , McLean Derek J , Chapman James D 
Published: March 2020

Abstract
The ability to positively alter immune and stress response with nutritional compounds is of great interest and importance to the beef industry. There is a proprietary product (OmniGen-AF [OG]; Phibro Animal Health, Quincy, IL) reported to have performance-enhancing benefits by altering animal response to stress and immune challenges. The objective of this 2-yr research project was to study the effect of supplementing OG to beef cows and their calves on breeding and growth performance. One hundred and twelve multiparous beef cows and 48 primiparous cows were randomly assigned to treatment in year 1; control (CON, no OG; n = 56 multiparous and 24 primiparous) or treatment (OG fed at 8.8 g/100 kg body weight [BW]; n = 56 multiparous and 24 primiparous). Multiparous cows (mean ± SD = 6.4 ± 0.4 yr; BW = 589 ± 9.2 kg; body condition score [BCS] 6.2 ± 0.07) were used in both years of the experiment and primiparous cows (mean ± SD = 2.1 ± 0.04 yr of age, weighed 400 ± 7.5 kg, and BSC of 5.6 ± 0.06) were only used in the first year of the experiment. CON and OG supplements were offered over two production cycles beginning in December approximately 60 d prior to projected calving through pre-breeding in May of each year. Calves from treatment cows were offered treatments in a creep supplement limited to a daily rate of 1% as-fed of BW prorated for 3-d/wk feeding from mid-July through weaning with OG offered at 8.8 g/100 kg BW. Primiparous cow’s BW, BCS, and calf performance were not affected by treatment (P ≥ 0.15) in year 1. BW of multiparous OG cows tended (P = 0.10) to be heavier at weaning in year 1 and was greater (P = 0.05) at the onset of the experiment in year 2. Body condition of OG cows was greater (P ≤ 0.02) at weaning in both years 1 and 2, as well as at the onset of the experiment in year 2. Calves fed OG from the mature cows gained more (P = 0.05) BW during the creep feeding period than CON. Core body temperatures of OG heifers measured during the late summer with intravaginal temperature data loggers tended (P ≤ 0.10) to be less at 1400 and 1700 hours and were less (P = 0.05) at 1800 hours than CON heifers. Feeding OG did not result in changes (P = 0.25) in serum titer response to the BVD virus of calves during year 2. The results of the current experiment indicate feeding OG to beef cows and calves can result in improvement in BCS of cows, enhance weight gain of calves preweaning, and reduce heat loads in heifer calves during the late summer.
Bone Marrow-Derived Mesenchymal Stem Cells Combined With Simvastatin Accelerates Burn Wound Healing by Activation of the Akt/mTOR Pathway
Authors: Ramhormozi Parisa , Mohajer Ansari Javad , Simorgh Sara , Nobakht Maliheh 
Published: March 2020

Abstract
Burn wound healing is one of the most important problems in the field of medical science. Promising results have recently been reported by researchers who used bone marrow mesenchymal stem cells (BMSCs) to treat burn wounds. In this study, we investigated the effects of BMSC therapy in combination with simvastatin (SMV) on angiogenesis as well as on the activity of the Akt/mTOR signaling pathway during burn wound healing in rats. After creating second-degree burn wounds, 40 adult male Wistar rats were randomly divided into four treatment groups: the control, SMV, BMSCs, and the combination therapy group (BMSCs+SMV). Animals were killed 14 days after treatment initiation, and the wounds were removed for histological and molecular analyses. All in all, combination therapy produced better outcomes than individual therapy in terms of the wound closure area, epidermal regeneration level, collagen deposition intensity, and reepithelialization rate. In addition, the elevations of expression levels of Akt and mTOR genes, at both mRNA and protein levels, were more pronounced in the BMSCs+SMV group (P &lt; .05, at least, for both qRT-PCR and western blot assessments). qRT-PCR findings also demonstrated that the wounds treated with the combination of BMSCs and SMV had the highest expression levels of CD31 and VEGF genes (P &lt; .01 for all comparisons). These data suggest that the combined administration of BMSCs transplantation and topical SMV has a great potential in burn wound healing. According to the findings, the beneficial effects of the combination therapy are caused, at least in part, through stimulating Akt/mTOR signaling pathway.
Insecticide Resistance, and Its Effects on Bait Performance in Field-Collected German Cockroaches (Blattodea: Ectobiidae) From Taiwan
Authors: Hu I-Hsuan , Chen Shan-Min , Lee Chow-Yang , Neoh Kok-Boon 
Published: March 2020

Abstract
Insecticide resistance in the German cockroach, Blattella germanica (L.), is a significant challenge to the pest management professionals worldwide. We collected 24 field populations of B. germanica from different localities in Taiwan island, reared them for one to two generations, and evaluated them for their resistance to deltamethrin, propoxur, and fipronil using the surface-contact method. Results showed that deltamethrin resistance ratio ranged from 1.5 to 817.5×. Among the strains, TC Supermarket, TC Sanshang Logistics, TC THSR, and TC 1Taichungsteak strains showed very high resistance to deltamethrin, which mortality ranged between 0 and 33% at 7-d post-treatment. On the other hand, resistance to propoxur and fipronil RR were 0.70–7.13× and 1.67–3.72×, respectively. Synergism studies using piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioate (DEF) suggested the major involvement of cytochrome P450 monooxygenase and minor involvement of esterases. However, deltamethrin resistance in two strains (i.e., TC Supermarket and TC THSR) was not affected by both PBO and DEF, indicating that other mechanisms are involved in the resistance, including kdr resistance. Evaluation of the field strains using commercial gel baits containing fipronil, imidacloprid, hydramethylnon, and indoxacarb for up to 7 d resulted in 24.4–100%, 11.3–78.5%, 15.8–75.5%, and 63.3–100% mortality, respectively. We found that high deltamethrin resistance in some strains could affect the performance of fipronil, imidacloprid, and indoxacarb baits, indicating the potential involvement of cytochrome P450 monooxygenase in reducing the effectiveness of the bait toxicants.
A new mouse of the Peromyscus maniculatus species complex (Cricetidae) from the highlands of central Mexico
Authors: Léon-Tapia M Ángel , Fernández Jesús A , Rico Yessica , Cervantes F A , Espinosa de los Monteros Alejandro 
Published: March 2020

AbstractThe Peromyscus maniculatus species complex is one of the most widespread group of small mammals in North America. However, the taxonomy and phylogenetic relationships among its constituent taxa remain unclear. As part of a revision of Peromyscus specimens from the highlands of the Trans-Mexican Volcanic Belt in central Mexico, we identified five individuals collected in 1968 that differed externally from other Peromyscus specimens, although morphologically similar to P. labecula and P. melanotis, both latter in the P. maniculatus species complex. Based on cranial measurements and mitochondrial DNA sequences, we aimed to more accurately determine the phylogenetic relationships and the taxonomic status of these individuals. Molecular phylogenetic analyses showed that the specimens formed a monophyletic clade sister to the P. maniculatus species complex. Pairwise genetic distances between those specimens and other species within the P. maniculatus species complex were greater than 7.91%. In addition, morphological analyses clearly distinguished the test specimens from P. melanotis and P. labecula. Based on the results of our molecular and morphological analyses, we conclude that these specimens represent an undescribed species of the P. maniculatus species complex, which we describe herein.
Merging ‘the Zephyrs of Purgatory’ and ‘Old [Chinese] K’in Music’: The Modernist as Mystic Purist in Beckett’s Dream of Fair to Middling Women
Authors: Lin Lidan 
Published: March 2020

Abstract
This article explores the global influences of Chinese mysticism latent in Chinese K’in music and Christian mysticism on Beckett’s composition of Dream of Fair to Middling Women. I argue that Beckett’s portrayal of Belacqua as a mystic purist is the direct result of his creative appropriation of K’in music, Taoism, and Christian mysticism on the one hand, and his equally creative appropriation of the modernist legacy of inner fiction exemplified by the fiction of Proust and Joyce on the other. By revealing the hybrid roots of Belacqua’s mystic quest, this essay presents a compelling case that unfolds not only Beckett’s interesting relation to China, but modernism’s ethical and aesthetic inclusion in a global context.
Determining the size of the helium core of KIC 9970396 using asteroseismology: a red giant approaching the red giant bump
Authors: Zhang Xinyi , Li Yan , Wu Tao , Su Jie 
Published: March 2020

ABSTRACT
Mixed modes are less affected by the surface effect and carry internal information of a star. Asteroseismic modelling of mixed modes can constrain the size of the helium core of a star. Previous work has shown that the evolution stage of KIC 9970396 may be near the red giant bump phase, which is one of the most interesting regions in the red giant evolution stage. It is known that there is a clear relation between the core and mass luminosity, following homological principles on the low-luminosity giant branch. Our aim in this paper is to determine the size of the helium core and constrain the internal structure of the star. Our approach is first to identify the most p-dominated frequencies in the observational mixed modes. The calculated frequencies are then fitted to the observational frequencies, which we choose not to correct for surface effect offsets. We have computed a grid of theoretical models to fit the l = 1 modes of KIC 9970396. The size of the helium core of KIC 9970396 is determined to be MHe = 0.229 ± 0.001 M⊙ and RHe = 0.03055 ± 0.00015 R⊙. The best-fitting model shows that KIC 9970396 is undergoing a stage that is between the first dredge-up event and the red giant bump. Compared with the results of our model, the previous core–mass luminosity relation overestimates the helium core mass by 0.009 M⊙ when the stellar luminosity of a red giant star is known.
Long-term variation of trochid populations in an Irish sea lough
Authors: Little Colin , Trowbridge Cynthia D , Pilling Graham M , Williams Gray A , Morritt David , Stirling Penny 
Published: March 2020

AbstractSnapshot assessments of species, which live for a number of years, are often misleading if they are conducted at an inappropriately short temporal scale. Densities of the trochid gastropods Steromphala umbilicalis (da Costa, 1778) and S. cineraria (Linnaeus, 1758) fluctuated widely between 1996 and 2014 at ten rocky-shore sites within Lough Hyne, southwest Ireland. Between 2014 and 2019, the abundance of S. cineraria decreased to levels not seen in the previous two decades. This significant reduction was possibly in response to extreme dissolved oxygen fluctuations related to eutrophication of the semi-enclosed lough. Steromphala umbilicalis showed low density in 2018 and 2019, but this was within the limits of interannual fluctuations. The Lusitanian trochid Phorcus lineatus (da Costa, 1778) was first recorded by us in the lough in the early 2000s, just as it was establishing a flourishing population with densities of c. 6 snails/0.25 m2. Although this native trochid survived the cold winters of 2009–2012, the population suffered high adult mortality and little recruitment. Between 2013 and 2019, the population increased and the population density stabilized. The increase in P. lineatus reflects its position high on the shore, where air temperatures have risen over the last two decades. It may, therefore, be a sentinel species to detect the effects of climate change. By contrast, the decrease in S. cineraria was related to its shallow subtidal habitat where hypoxia and superoxia have recently become marked in the lough. This trochid, therefore, offers potential as an indicator of eutrophication-associated stress. These temporal variations in trochid species emphasize the need for longer term assessments when estimating the importance of any one species to the ecosystem.
Structural basis of UCUU RNA motif recognition by splicing factor RBM20
Authors: Upadhyay Santosh Kumar , Mackereth Cameron D 
Published: March 2020

Abstract
The vertebrate splicing factor RBM20 (RNA binding motif protein 20) regulates protein isoforms important for heart development and function, with mutations in the gene linked to cardiomyopathy. Previous studies have identified the four nucleotide RNA motif UCUU as a common element in pre-mRNA targeted by RBM20. Here, we have determined the structure of the RNA Recognition Motif (RRM) domain from mouse RBM20 bound to RNA containing a UCUU sequence. The atomic details show that the RRM domain spans a larger region than initially proposed in order to interact with the complete UCUU motif, with a well-folded C-terminal helix encoded by exon 8 critical for high affinity binding. This helix only forms upon binding RNA with the final uracil, and removing the helix reduces affinity as well as specificity. We therefore find that RBM20 uses a coupled folding-binding mechanism by the C-terminal helix to specifically recognize the UCUU RNA motif.
Phase I trial of convection-enhanced delivery of nimustine hydrochloride (ACNU) for brainstem recurrent glioma
Authors: Saito Ryuta , Kanamori Masayuki , Sonoda Yukihiko , Yamashita Yoji , Nagamatsu Kenichi , Murata Takaki , Mugikura Shunji , Kumabe Toshihiro , Wembacher-Schröder Eva , Thomson Rowena , Tominaga Teiji 
Published: March 2020

Abstract

Background
Treatment options for patients suffering brainstem gliomas are quite limited as surgery is not an option against intrinsic tumors at brainstem and chemotherapy generally failed to demonstrate its efficacy. Intracerebral convection-enhanced delivery (CED) is a novel approach for administering chemotherapy to patients with brain tumors. We present the results of phase I trial of CED of nimustine hydrochloride (ACNU), designed to determine the maximum tolerable concentration of ACNU, for patients with recurrent brainstem gliomas.

Methods
Sixteen patients, aged 3–81 years old, suffering from recurrent brainstem gliomas, including diffuse intrinsic pontine glioma patients as well as patients with recurrent gliomas that originated from non-brainstem sites, were enrolled in this trial between February 2011 and April 2016. The dose/concentration escalation trial included 3 dose/concentration groups (0.25, 0.5, and 0.75 mg/mL, all at 7 mL) to determine the safety and tolerability of CED of ACNU. Real-time monitoring of drug distribution was performed by mixing gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA) in the infusion solution. CED of ACNU was given in combination with oral or intravenous temozolomide chemotherapy.

Results
CED of ACNU demonstrated antitumor activity, as assessed by radiographic changes and prolonged overall survival. The recommended dosage was 0.75 mg/mL. Drug-associated toxicity was minimal.

Conclusions
Intracerebral CED of ACNU under real-time monitoring of drug distribution, in combination with systemic temozolomide, was well tolerated among patients with recurrent brainstem gliomas. The safety and efficacy observed suggest the clinical benefits of this strategy against this devastating disease. Based on this phase I study, further clinical development of ACNU is warranted.
Elevated plasma levels of selective cytokines in COVID-19 patients reflect viral load and lung injury
Authors: Liu Yingxia , Zhang Cong , Huang Fengming , Yang Yang , Wang Fuxiang , Yuan Jing , Zhang Zheng , Qin Yuhao , Li Xiaoyun , Zhao Dandan , Li Shunwang , Tan Shuguang , Wang Zhaoqin , Li Jinxiu , Shen Chenguang , Li Jianming , Peng Ling , Wu Weibo , Cao Mengli , Xing Li , Xu Zhixiang , Chen Li , Zhou Congzhao , Liu William J , Liu Lei , Jiang Chengyu 
Published: March 2020

Abstract
A recent outbreak of pneumonia in Wuhan, China was found to be caused by a 2019 novel coronavirus (2019-nCoV or SARS-CoV-2 or HCoV-19). We previously reported the clinical features of 12 patients with 2019-nCoV infections in Shenzhen, China. To further understand the pathogenesis of COVID-19 and find better ways to monitor and treat the disease caused by 2019-nCoV, we measured the levels of 48 cytokines in the blood plasma of those 12 COVID-19 patients. Thirty-eight out of the 48 measured cytokines in the plasma of 2019-nCoV-infected patients were significantly elevated compared to healthy individuals. Seventeen cytokines were linked to 2019-nCoV loads. Fifteen cytokines, namely M-CSF, IL-10, IFN-α2, IL-17, IL-4, IP-10, IL-7, IL-1ra, G-CSF, IL-12, IFN-γ, IL-1α, IL-2, HGF and PDGF-BB, were strongly associated with the lung-injury Murray score and could be used to predict the disease severity of 2019-nCoV infections by calculating the area under the curve of the receiver-operating characteristics. Our results suggest that 2019-nCoV infections trigger extensive changes in a wide array of cytokines, some of which could be potential biomarkers of disease severity of 2019-nCoV infections. These findings will likely improve our understanding of the immunopathologic mechanisms of this emerging disease. Our results also suggest that modulators of cytokine responses may play a therapeutic role in combating the disease once the functions of these elevated cytokines have been characterized.