bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of different additives on fermentation quality and aerobic stability of a total mixed ration prepared with local feed resources on Tibetan plateau
Authors: Dong Zhihao , Zhao Jie , Chen Sifan , Bao Yuhong , Tao Xuxiong , Wang Siran , Li Junfeng , Liu Qinhua , Shao Tao
Published: December 2020

To improve the utilization efficiency of total mixed ration (TMR) on Tibetan plateau, the effects of different additives on fermentation quality and aerobic stability of the ensiled TMR prepared with local feed resources were studied. A total of 150 experimental silos were prepared in a completely randomized design to evaluate the following treatments: (a) control; (b) Lactobacillus buchneri; (c) acetic acid; (d) propionic acid; (e) 1,2‐propanediol; and (f) 1‐propanol. After 90 days of ensiling, silos were opened for fermentation quality and in vitro parameters analysis, and then subjected to an aerobic stability test for 14 days. The acetic acid, 1,2‐propanediol and 1‐propanol treatments increased (p < .05) pH and acetic acid content, and lowered (p < .05) the lactic acid production in comparison to control. There were no statistically significant differences in in vitro digestibility parameters among the treatments. Treatments of acetic acid, 1,2‐propanediol and 1‐propanol substantially improved the aerobic stability of the ensiled TMR, as indicated by almost unchanged pH and lactic acid contents throughout the aerobic exposure test. These results indicated that acetic acid, 1,2‐propanediol and 1‐propanol had no adverse effect on in vitro digestibility and could be effective additives for enhancing the aerobic stability of ensiled TMR prepared on Tibetan plateau.
Combination of tumor necrosis factor‐α and epidermal growth factor induces the adrenergic‐to‐mesenchymal transdifferentiation in SH‐SY5Y neuroblastoma cells
Authors: Huang Yue , Tsubota Shoma , Nishio Nobuhiro , Takahashi Yoshiyuki , Kadomatsu Kenji
Published: December 2020

Neuroblastoma, a type of cancer that is common in children, is composed of two genetically clonal but epigenetically distinct cell types: mesenchymal (MES) and adrenergic (ADRN) types, controlled by super‐enhancer‐associated lineage‐specific transcription factor networks. Mesenchymal‐type cells are more migratory, resistant to chemotherapy, and prevalent in relapse tumors. Importantly, both cell types spontaneously transdifferentiate into one another, and this interconversion can be induced by genetic manipulations. However, the mechanisms of their spontaneous transdifferentiation and extracellular factors inducing this phenomenon have not yet been elucidated. Using a unique approach involving gene set enrichment analysis, we selected six ADRN and 10 MES candidate factors, possibly inducing ADRN and MES phenotypes, respectively. Treatment with a combination of 10 MES factors clearly induced the MES gene expression profile in ADRN‐type SH‐SY5Y neuroblastoma cells. Considering the effects on gene expression profile, migration ability, and chemoresistance, a combination of tumor necrosis factor alpha (TNF‐α) and epidermal growth factor (EGF) was sufficient to synergistically induce the ADRN‐to‐MES transdifferentiation in SH‐SY5Y cells. In addition, human neuroblastoma cohort analysis revealed that the expression of TNF and EGF receptors was strongly associated with MES gene expression signatures, supporting their important roles in transdifferentiation in vivo. Collectively, we propose a mechanism of neuroblastoma transdifferentiation induced by extracellular growth factors, which can be controlled in clinical situations, providing a new therapeutic possibility.
Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT‐1: Influence on 18F‐FDG PET Uptake
Authors: Damaraju Vijaya L. , Aminpour Maral , Kuzma Michelle , Winter Philip , Preto Jordane , Tuszynski Jack , McEwan Alexander B.J. , Sawyer Michael B.
Published: December 2020

Positron emission tomography (PET) using 2‐deoxy‐2‐[18F]fluoro‐d‐glucose ([18F]FDG), a marker of energy metabolism and cell proliferation, is routinely used in the clinic to assess patient response to chemotherapy and to monitor tumor growth. Treatment with some tyrosine kinase inhibitors (TKIs) causes changes in blood glucose levels in both nondiabetic and diabetic patients. We evaluated the interaction of several classes of TKIs with human glucose transporter‐1 (hGLUT‐1) in FaDu and GIST‐1 cells by measuring [3H]2‐deoxy‐d‐glucose ([3H]2‐DG) and [3H]FDG uptake. Uptake of both was inhibited to varying extents by the TKIs, and representative TKIs from each class showed competitive inhibition of [3H]2‐DG uptake. In GIST‐1 cells, [3H]FDG uptake inhibition by temsirolimus and nilotinib was irreversible, whereas inhibition by imatinib, gefitinib, and pazopanib was reversible. Molecular modeling studies showed that TKIs form multiple hydrogen bonds with polar residues of the sugar binding site (i.e., Q161, Q282, Q283, N288, N317, and W388), and van der Waals interactions with the H‐pocket site. Our results showed interaction of TKIs with amino acid residues at the glucose binding site to inhibit glucose uptake by hGLUT‐1. We hypothesize that inhibition of hGLUT‐1 by TKIs could alter glucose levels in patients treated with TKIs, leading to hypoglycemia and fatigue, although further studies are required to evaluate roles of other SLC2 and SLC5 members. In addition, TKIs could affect tumor [18F]FDG uptake, increasingly used as a marker of tumor response. The hGLUT‐1 inhibition by TKIs may have implications for routine [18F]FDG‐PET monitoring of tumor response in patients.
Clinical Pharmacology Studies Supporting Oligonucleotide Therapy Development: An Assessment of Therapies Approved and in Development Between 2012 and 2018
Authors: Rogers Hobart , Adeniyi Oluseyi , Ramamoorthy Anuradha , Bailey Samantha , Pacanowski Michael
Published: December 2020

Synthetic nucleotides that utilize RNA‐centric pharmacology can target diseases at the RNA level, thus altering protein expression in ways previously inaccessible to small molecules and therapeutic biologics. Recognizing that the unique pharmacology of oligonucleotides may require specific considerations in pre‐approval assessment, clinical and nonclinical pharmacology studies being conducted for a selected set of oligonucleotide therapies in a 6‐year period were assessed. This investigation focused primarily on the four following areas: (i) drug‐drug interaction (DDI) potential, (ii) organ impairment (i.e., renal and hepatic impairment), (iii) immunogenicity, and (iv) cardiac safety. Data were summarized and assessed from 14 Investigational New Drug programs and 7 New Drug Applications submitted to the US Food and Drug Administration (FDA) from the period of January 2012 to August 2018, encompassing 152 unique studies. The assessment of DDI potential was largely consistent with the recommendations of current DDI‐relevant guidances. Limited data were available to provide recommendations across organ impairment categories. Limited data on immunogenicity indicate impact on pharmacokinetic, the impact on safety and efficacy, although not extensively evaluated, appeared negligible. Cardiac safety evaluation indicated a potential for discordant translation of risk from nonclinical studies to clinical findings. Continued experience with synthetic oligonucleotide therapies will help inform the development of best practices to support their development and regulatory approval.
Viral panniculitis in a patient with disseminated opportunistic Enterovirus infection
Authors: Tekin Burak , Boire Nicholas , Shah Kabeer , Hanson Jennifer , Bridges Alina G.
Published: December 2020

Infection‐induced panniculitis has been described in association with a broad range of microorganisms. Among those, viral panniculitis represents a minor category, with only a few anecdotal reports in the literature documenting viral infection in the subcutaneous fat. Herein, we report a woman in her 30s with seropositive rheumatoid arthritis on rituximab and prednisone, who presented with a 6‐month history of progressive multisystem manifestations, including unintentional weight loss, fever, fatigue, myopathy, pancreatitis, and sensorineural hearing loss. She had indurated plaques on her thighs characterized by predominantly lobular panniculitis with chronic lymphohistiocytic inflammation. Molecular studies performed at the Centers for Disease Control and Prevention identified evidence of Enterovirus group with the highest identity of Coxsackievirus A9. Enterovirus RNA was also detected in the cerebrospinal fluid and muscle. Based on the findings, a diagnosis of disseminated enteroviral infection in the setting of B‐cell depletion was rendered. To the best of our knowledge, this represents the first reported case of viral panniculitis with documentation of Coxsackievirus A9 in the skin. Since rituximab may be used for the treatment of autoimmune dermatological diseases, familiarity of the potential occurrence of severe enteroviral infections in the setting of immunosuppressive treatment is important for dermatopathologists.
Conscientious objection to abortion in the developing world: The correspondence argument
Authors: Bhakuni Himani , Miotto Lucas
Published: December 2020

In this paper we extend Heidi Hurd’s “correspondence thesis” to the termination of pregnancy debate and argue that the same reasons that determine the permissibility of abortion also determine the justifiability of acts involving conscientious objection against its performance. Essentially, when abortion is morally justified, acts that prevent or obstruct it are morally unjustified. Therefore, despite conscientious objection being legally permitted in some global south countries, we argue that such permission to conscientiously object would be morally wrong in cases of morally justifiable termination of pregnancy. After presenting and defending our “correspondence argument” we suggest that conscientious objection should be denied as a matter of public health policy in developing counties, even in cases where adequate referral services are possible. Towards the end, we extend our argument to midwives, nurses, and prospective students in the field. Given their essential position in resource‐poor contexts; they too have no claim to conscientious objection.
Prognostic impact of renal dysfunction on embolic stroke of undetermined source—Role beyond CHA2DS2‐VASc score: Results from Taiwan Stroke Registry
Authors: Chua Su‐Kiat , Hsieh Fang‐I , Hu Chaur‐Jong , Wang I‐Kuan , Lee Jiunn‐Tay , Yeh Hsu‐Ling , Lin Kuan‐Yu , Lai Ta‐Chang , Sun Yu , Jeng Jiann‐Shing , Lin Cheng‐Li , Lien Li‐Ming , Hsu Chung Y. ,   Taiwan Stroke Registry Investigators
Published: December 2020

Background and purpose

The CHA2DS2‐VASc score has immense prognostic value in patients with embolic stroke of undetermined source (ESUS). We aimed to determine the usefulness of advanced renal dysfunction and its addition to the CHA2DS2‐VASc score in improving predictive accuracy.

Methods

In total, 3775 ESUS patients were enrolled from a nationwide hospital‐based prospective study. Advanced renal dysfunction was defined as estimated glomerular filtration rate <30 ml/min per 1.73 m2 or patients under dialysis. Clinical outcomes included recurrent stroke and 1‐year all‐cause mortality. Poor functional outcome was defined as a modified Rankin Scale >2 at first‐, third‐, and sixth‐month post‐stroke. The renal (R)‐CHA2DS2‐VASc score was derived by including advanced renal dysfunction in the CHA2DS2‐VASc score. Risk stratification improvement after including advanced renal dysfunction was assessed using C statistic, integrated discrimination improvement (IDI), and category‐free net reclassification index (NRI).

Results

After adjusting for confounding factors and CHA2DS2‐VASc score, advanced renal dysfunction showed significant associations with all‐cause mortality (HR: 2.88, 95% CI: 1.92–4.34) and poor functional outcome at third‐ (OR: 2.69, 95% CI: 1.47–4.94) and sixth‐month post‐stroke (OR: 2.67, 95% CI: 1.47–4.83). IDI and NRI showed that incorporating advanced renal dysfunction significantly improved risk discrimination over the original CHA2DS2‐VASc score. R‐CHA2DS2‐VASc score ≥2 increased risk by 1.94‐fold (95% CI: 1.15–3.27) for all‐cause mortality, and ≥4 increased risk by 1.62‐fold (95% CI: 1.05–2.50) of poor functional outcome at third‐month post‐stroke and by 1.81‐fold (95% CI: 1.19–2.75) at sixth‐month post‐stroke.

Conclusions

Advanced renal dysfunction was significantly associated with clinical and functional outcomes in ESUS patients and may improve prognostic impact of the CHA2DS2‐VASc score.
Cystatin C is a potential predictor of unfavorable outcomes for cerebral ischemia with intravenous tissue plasminogen activator treatment: A multicenter prospective nested case–control study
Authors: Chang Zihan , Zou Haiqiang , Xie Zhenchao , Deng Bin , Que Rongfang , Huang Zifeng , Weng Guomei , Wu Zhihuan , Pan Ying , Wang Yanping , Li Mengyan , Xie Huifang , Zhu Shuzhen , Xiong Li , CT Mok Vincent , Jin Kunlin , Yenari Midori A. , Wei Xiaobo , Wang Qing
Published: December 2020

Background and purpose

The aim of this study was to explore whether cystatin C (CysC) could be used as a potential predictor of clinical outcomes in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV‐tPA).

Methods

We performed an observational study including a retrospective analysis of data from 125 AIS patients with intravenous thrombolysis. General linear models were applied to compare CysC levels between groups with different outcomes; logistic regression analysis and receiver‐operating characteristic curves were adopted to identify the association between CysC and the therapeutic effects.

Results

Compared with the "good and sustained benefit" (GSB) outcome group (defined as ≥4‐point reduction in National Institutes of Health Stroke Scale or a score of 0–1 at 24 h and 7 days) and the "good functional outcome" (GFO) group (modified Rankin Scale score 0–2 at 90 days), serum CysC baseline levels were increased in the non‐GSB and non‐GFO groups. Logistic regression analysis found that CysC was an independent negative prognostic factor for GSB (odds ratio [OR] 0.010; p = 0.005) and GFO (OR 0.011; p = 0.021) after adjustment for potential influencing factors. Receiver‐operating characteristic curves showed the CysC‐involved combined models provided credible efficacy for predicting post‐90‐day favorable clinical outcome (area under the curve 0.86; p < 0.001).

Conclusions

Elevated serum CysC is independently associated with unfavorable clinical outcomes after IV‐tPA therapy in AIS. Our findings provide new insights into discovering potential mediators for neuropathological process or treatment in stroke.
Retrospective analysis of lameness localisation in Western Performance Horses: A ten‐year review
Authors: Johnson Sherry A. , Donnell Josh R. , Donnell Alan D. , Frisbie David D.
Published: December 2020

Background

Similar to other high‐level athletic disciplines, the western performance horse experiences a variety of orthopaedic conditions as a result of rigorous sport‐specific physical demands. While musculoskeletal injury rates have been quantified in other equine disciplines, these data are lacking for the western performance athlete.

Objectives

To identify the most common anatomical regions of lameness in western performance horses being evaluated at the nation's largest sanctioned shows over a 10‐year study period.

Study design

Retrospective review of clinical records.

Methods

Records of diagnostic analgesia of western performance horses competing at nationally sanctioned shows were retrospectively reviewed over a 10‐year period to identify affected limb(s) and lameness localisation patterns.

Results

A total of 2267 lameness examinations on 2512 horses were included. The average lameness grade was 2.21/5 with 1504/2267 (56%) cases being primarily forelimb in origin while 1173/2267 (44%) were hindlimb related. Forelimb lameness localised to the distal limb in 40% of cases. The proximal metatarsus/distal tarsus was an identified source of lameness in 16% of cases, followed by the stifle in 9% of cases. All‐around western performance horses most commonly presented with a single hindlimb lameness (315/1188, 26.5%) in contrast to reining horses that presented with a single forelimb lameness (135/616, 22%).

Discussion

Determining the source of lameness through diagnostic analgesia remains challenging, but the continued assessment of response to diagnostic analgesia may help characterise discipline‐specific injuries in western performance horses.

Main limitations

Retrospective review of subjective responses to diagnostic analgesia.

Conclusions

The distal forelimb and distal tarsus/proximal metatarsus were the two most common anatomical regions of lameness based on response to diagnostic analgesia.
Head Start and Families' Recovery From Economic Recession: Policy Recommendations for COVID‐19
Authors: Scarborough William J. , Collins Caitlyn , Ruppanner Leah , Landivar Liana Christin
Published: December 2020

Objective

This article examines whether the availability of Head Start during the Great Recession mitigated the impact of this crisis on poverty rates among families with young children.

Background

The first 2 decades of the 21st century have witnessed two major economic crises: the Great Recession and the COVID‐19 pandemic. Poverty rates among families with young children grew substantially during the Great Recession. Families with young children are also more vulnerable to instability during the COVID‐19 pandemic because job losses have been steeper and childcare availability has been significantly curtailed. Programs such as Head Start that support at‐risk families may mitigate such negative consequences.

Method

This study used data from the American Community Survey from 2006 through 2016 and state‐level data on Head Start availability from Program Information Reports. Growth curve modeling was used to examine how the availability of Head Start predicted poverty growth during the Great Recession and the speed of recovery post‐recession.

Results

States with higher rates of Head Start enrollment had a smaller increase in family poverty during the Great Recession and a more stable recovery than states with lower Head Start enrollment.

Conclusions

These findings suggest that greater access to Head Start programs prevented many families from falling into poverty and helped others exit poverty during the Great Recession.

Implications

The findings provide clear, evidence‐based policy recommendations. Increased federal funding for Head Start is needed to support families during a COVID‐19 recession. States should supplement these allocations to expand Head Start enrollment for all eligible families.
Teshima pyroclastics: Onset of characteristic Setouchi magmatism induced by slab melting at 14.8 Ma
Authors: Nakaoka Reina , Kado Soko , Hasegawa Shuichi , Suzuki‐Kamata Keiko , Ishizuka Osamu , Sekimoto Shun , Kawabata Hiroshi , Tatsumi Yoshiyuki
Published: December 2020

Ar‐Ar ages, and petrographical and geochemical characteristics of pyroclastics and an overlying lava from Teshima Island, southwest Japan are presented. Although previous geological and age data suggested Teshima pyroclastics were products of magmatism > 3 my prior to lava flows of Setouchi volcanic rocks generated in association with southward migration of the southwest Japan arc sliver during opening of the Sea of Japan backarc basin at ~ 15 Ma, the present results led to the conclusion that a sequence of Setouchi volcanism, induced by slab melting and subsequent melt‐mantle reactions, produced both pyroclastics and lava at 14.6–14.8 Ma. This age is oldest among those reported so far and may represent the timing of onset of characteristic Setouchi magmatism immediately posterior to and hence as a result of the mega‐tectonic event including rotation of the southwest Japan arc sliver.
Histomorphometric and immunohistochemical study shows that tricalcium silicate cement associated with zirconium oxide or niobium oxide is a promising material in the periodontal tissue repair of rat molars with perforated pulp chamber floors
Authors: Barbosa D. D. , Delfino M. M. , Guerreiro‐Tanomaru J. M. , Tanomaru‐Filho M. , Sasso‐Cerri E. , Silva G. F. , Cerri P. S.
Published: December 2020

Aim

To evaluate the periodontium response to tricalcium silicate (TCS) with zirconium oxide (ZrO2) or niobium oxide (Nb2O5) used in the sealing of perforated pulp chamber floors in rat maxillary molars.

Methodology

In eighty rats, the perforations in right maxillary molars were filled with either TCS + ZrO2, TCS + Nb2O5, White MTA (used as a gold standard material) or no repair material was placed (Sham Group, SG); the left molars of SG, were used as controls (CG). Sections of maxillary fragments following 7, 15, 30 and 60 days were used to evaluate the volume densities of inflammatory cells (VvIC) and fibroblasts (VvFb), width of the periodontal space, amount of collagen, number of osteoclasts and number of IL‐6‐immunostained cells. The data were subjected to two‐way ANOVA followed by Tukey’s test (P ≤ 0.05).

Results

At all periods, significant differences in VvIC were not detected among TCS + ZrO2, TCS + Nb2O5 and MTA groups, which had values significantly lower (P < 0.05) than the SG. Significant differences in the number of IL‐6‐immunolabelled cells were not observed among TCS + ZrO2, TCS + Nb2O5 and MTA groups (P > 0.05) at 15, 30 and 60 days. At 7, 15 and 30 days, the number of osteoclast was significantly greater in TCS + ZrO2, TCS + Nb2O5 and MTA (P < 0.05) than in the CG; no significant difference was detected after 60 days (P > 0.05). The width of the periodontal space and amount of collagen in TCS + ZrO2 and TCS + Nb2O5 groups were similar to the CG at 30 and 60 days while SG specimens had a significant reduction (P < 0.05) in the amount of collagen and significant increase (P < 0.05) in the width of the periodontal space.

Conclusions

TCS + ZrO2 and TCS + Nb2O5 were associated with periodontium repair since these materials allowed the reestablishment of periodontal space width and collagen formation when used in the filling of uninfected perforations in the pulp chamber floor of maxillary rat molars. Furthermore, the significant reduction in the periodontal space of TCS + ZrO2 and TCS + Nb2O5 specimens after 60 days confirmed that the experimental materials were associated with a more rapid recovery of the injured tissues than MTA.
Media framing of social media addiction in the UK and the US
Authors: Lundahl Outi
Published: December 2020

As extant literature on social media has generally focused on investigating the psychological factors, which makes a person more susceptible to social media addiction, it has not yet investigated how social media addiction is portrayed by the media. However, the media framing of addictions can have considerable implications for consumers, as extant literature has shown them to use media texts as cultural resources through which they attempt to understand and justify their behaviour. The media can also have more indirect effects by, for instance, driving stigmatization or public policy initiatives. Thus, this study compares the media framing of social media addiction in the United Kingdom and the United States through longitudinal, mixed‐methods frame analysis. It then extends the extant literature by showing how social media addiction has been framed in both the United Kingdom and United States. It shows that concern regarding the issue has increased in both countries. In addition, the findings show that while previously social media addiction has been seen as an individual, psychological problem, concerns about the addictiveness and, thereby, about the lacking public policy measures have also increased in both countries. Implications for individual consumers, public policy and managers are considered.
Therapy for advanced cholangiocarcinoma: Current knowledge and future potential
Authors: Wang Mingxun , Chen Ziyan , Guo Pengyi , Wang Yi , Chen Gang
Published: December 2020

Cholangiocarcinoma (CCA) is a biliary epithelial tumour that can emerge at any point in the biliary tree. It is commonly classified based on its anatomical site of development into intrahepatic cholangiocarcinoma (ICC), perihilar cholangiocarcinoma (PCC) and distal cholangiocarcinoma (DCC), each of which is associated with varying patient demographics, molecular characteristics and treatment options. CCA patients have poor overall prognoses and 5‐year survival rates. Additionally, CCA is often diagnosed at an advanced stage, with surgical treatment restricted to early‐stage disease. Owing to an increase in the incidence of ICC, that of CCA is also on the rise, with a corresponding increase in the associated mortality, particularly in South America and Asia. Therefore, the development of an effective treatment is crucial to improve the survival of CCA patients. We aimed to systematically review the current understanding of advanced CCA treatment and discuss potential effective strategies.
Overexpression of c‐Fos reverses osteoprotegerin‐mediated suppression of osteoclastogenesis by increasing the Beclin1‐induced autophagy
Authors: Tong Xishuai , Chen Miaomiao , Song Ruilong , Zhao Hongyan , Bian Jianchun , Gu Jianhong , Liu Zongping
Published: December 2020

Osteoclastogenesis requires the involvement of transcription factors and degrading enzymes, and is regulated by upstream and downstream signalling. However, c‐Fos how regulates osteoclastogenesis through autophagy remain unclear. This study aimed to explore the role of c‐Fos during osteoprotegerin (OPG)‐mediated suppression of osteoclastogenesis. We found that the number of osteoclasts and the expression of c‐Fos, MMP‐9, CAⅡ, Src and p62 were decreased after treated with OPG, including attenuation the PI3K/Akt and the TAK1/S6 signalling pathways, but the expression of Beclin1 and LC3Ⅱ were increased. Knockdown of Beclin1 could reverse the expression of c‐Fos and MMP‐9 by activating the PI3K/Akt signalling pathway, but inhibiting the autophagy and the TAK1/S6 signalling pathway. In addition, inhibition of autophagy using the PI3K inhibitor LY294002 did not rescues OPG‐mediated suppression of osteoclastogenesis, but caused reduction of the expression of c‐Fos and CAⅡ by attenuating the autophagy, as well as the PI3K/Akt and the TAK1/S6 signalling pathways. Furthermore, continuous activation of c‐Fos could reverse OPG‐mediated suppression of osteoclastogenesis by activating the autophagy and the PI3K/Akt and the TAK1/S6 signalling pathways. Thus, overexpression of c‐Fos could reverse OPG‐mediated suppression of osteoclastogenesis via activation of Beclin1‐induced autophagy, indicating c‐Fos might serve as a new candidate for bone‐related basic studies.
CD63 negatively regulates hepatocellular carcinoma development through suppression of inflammatory cytokine‐induced STAT3 activation
Authors: Yu Shijun , Chen Jingde , Quan Ming , Li Li , Li Yandong , Gao Yong
Published: December 2020

Tetraspanin CD63 has been widely implicated in tumour progression of human malignancies. However, its role in the tumorigenesis and metastasis of hepatocellular carcinoma (HCC) remains unclear yet. In the present study, we aimed to investigate the specific function and underlying mechanisms of CD63 in HCC progression. CD63 expression in HCC tissues was detected using immunohistochemistry and quantitative real‐time PCR analyses; effects of CD63 on HCC cell proliferation and migration were investigated by CCK‐8 assay, colony formation assay, transwell assay and a xenograft model of nude mice. RNA‐sequencing, bioinformatics analysis, dual‐luciferase reporter assay and Western blot analysis were performed to explore the underlying molecular mechanisms. Results of our experiments showed that CD63 expression was frequently reduced in HCC tissues compared with adjacent normal tissues, and decreased CD63 expression was significantly associated with larger tumour size, distant site metastasis and higher tumour stages of HCC. Overexpression of CD63 inhibited HCC cell proliferation and migration, whereas knockdown of CD63 promoted these phenotypes. IL‐6, IL‐27 and STAT3 activity was regulated by CD63, and blockade of STAT3 activation impaired the promotive effects of CD63 knockdown on HCC cell growth and migration. Our findings identified a novel CD63‐IL‐6/IL‐27‐STAT3 axis in the development of HCC and provided a potential target for the diagnosis and treatment of this disease.
Identification and Characterization of a Novel Apical Membrane Antigen 3 in Eimeria tenella
Authors: Wang Qingjie , Zhu Shunhai , Zhao Qiping , Huang Bing , Yu Shuilan , Yu Yu , Liang Shanshan , Wang Haixia , Zhao Huanzhi , Han Hongyu , Dong Hui
Published: December 2020

Eimeria tenella is an obligate intracellular parasite in the phylum Apicomplexa. As described for other members of Apicomplexa, apical membrane antigen 1 (AMA1) has been shown to be critical for sporozoite invasion of host cells by E. tenella. Recently, an E. tenella paralogue of AMA1 (EtAMA1), dubbed sporoAMA1 (EtAMA3), was identified in proteomic and transcriptomic analyses of E. tenella, but not further characterized. Here, we show that EtAMA3 is a type I integral membrane protein that has 24% −38% identity with other EtAMAs. EtAMA3 has the same pattern of Cys residues in domains I and II of AMA1 orthologs from apicomplexan parasites, but high variance in domain III, with all six invariant Cys residues absent. EtAMA3 expression was developmentally regulated at the mRNA and protein levels. EtAMA3 protein was detected in sporulated oocysts and sporozoites, but not in the unsporulated oocysts or second‐generation merozoites. EtAMA3 is secreted by micronemes and is primarily localized to the apical end of sporozoites during host‐cell invasion. Additionally, pretreatment of sporozoites with rEtAMA3‐specific antibodies substantially impeded their invasion into host cells. These results suggest EtAMA3 is a sporozoite‐specific protein that is involved in host‐cell sporozoite invasion.
A new species of Chaetostoma (Siluriformes: Loricariidae) from the Orinoco basin with comments on Amazonian species of the genus in Colombia
Authors: Urbano‐Bonilla Alexander , Ballen Gustavo A.
Published: December 2020

Chaetostoma chimu sp. nov. is described from 119 specimens collected in the Andean foothills of the Orinoco River in Colombia. The new species can be distinguished from congeners by a combination of characters, including shape of cheek odontodes, presence of a supraoccipital excrescence, sexual dimorphism characters and colour pattern. In addition, this species can be distinguished from the sympatric and geographically close congeners of the Orinoco that have curved cheek odontodes (i.e., Chaetostoma anale, Chaetostoma formosae and Chaetostoma joropo), by presenting a generally larger orbital diameter and interorbital distance, details of sexual dimorphism and colour pattern. The type locality of specimens collected by Kjell von Sneidern in the mid‐twentieth century in the Colombian Amazon is also clarified. Chaetostoma alternifasciatum and Chaetostoma vagum are proposed as junior synonyms of C. anale. An identification key for the species of Chaetostoma from cis‐Andean drainages in Colombia is provided. The new species is herein categorized as Vulnerable (Vu) B1a (i, iii), following the IUCN criteria.
Revealing the functional traits linked to hidden environmental factors in community assembly
Authors: Pillar Valério D. , Sabatini Francesco Maria , Jandt Ute , Camiz Sergio , Bruelheide Helge
Published: December 2020

Aim

To identify functional traits that best predict community assembly without knowing the underlying environmental drivers.

Methods

We propose a new method based on the correlation r(XY) between two matrices of potential community composition: the matrix X is fuzzy‐weighted by trait similarities of species, and the matrix Y is derived by Beals smoothing using the probabilities of species co‐occurrences. Since X is based on one or more traits, r(XY) measures how well the traits used for fuzzy‐weighting reflect the species co‐occurrence patterns in Y. We developed an optimisation algorithm to identify the traits maximising this correlation, together with an appropriate permutational test for significance. Using metacommunity data generated by a stochastic, individual‐based, spatially explicit model, we assessed the type I error and the power of our method across different simulation scenarios, varying environmental filtering parameters, number of traits and trait correlation structures. Then, we applied the method to real‐world community and trait data of dry calcareous grassland communities across Germany to identify, out of 49 traits, the combination of traits that maximised r(XY).

Results

The method correctly identified the relevant traits involved in the assembly mechanisms of simulated communities, showing high power and accurate type I error. It proved to be robust against confounding aspects related to interactions between environmental factors, strength of limiting factors, and trait collinearity. In the grassland dataset, the method identified five traits that best explained community assembly. These traits reflect the size and the leaf economics spectrum, which are related to succession and resource supply, factors that may not be always measured in real‐world situations.

Conclusions

Our method successfully identified the relevant traits mediating community assembly, therefore providing insights on the underlying environmental and biotic factors, even if these are hidden, unmeasured or not accessible at the spatial or temporal scale of the study.
Total FLC transcript dynamics from divergent paralogue expression explains flowering diversity in Brassica napus
Authors: Calderwood Alexander , Lloyd Andrew , Hepworth Jo , Tudor Eleri H. , Jones D. Marc , Woodhouse Shannon , Bilham Lorelei , Chinoy Catherine , Williams Kevin , Corke Fiona , Doonan John H. , Ostergaard Lars , Irwin Judith A. , Wells Rachel , Morris Richard J.
Published: December 2020

Flowering time is a key adaptive and agronomic trait. In Arabidopsis, natural variation in expression levels of the floral repressor FLOWERING LOCUS C (FLC) leads to differences in vernalization. In Brassica napus there are nine copies of FLC. Here, we study how these multiple FLC paralogues determine vernalization requirement as a system.

We collected transcriptome time series for Brassica napus spring, winter, semi‐winter, and Siberian kale crop types. Modelling was used to link FLC expression dynamics to floral response following vernalization.

We show that relaxed selection pressure has allowed expression of FLC paralogues to diverge, resulting in variation of FLC expression during cold treatment between paralogues and accessions. We find that total FLC expression dynamics best explains differences in cold requirement between cultivars, rather than expression of specific FLC paralogues.

The combination of multiple FLC paralogues with different expression dynamics leads to rich behaviour in response to cold and a wide range of vernalization requirements in B. napus. We find evidence for different strategies to determine the response to cold in existing winter rapeseed accessions.
When food‐delivery platform workers consent to algorithmic management: a Foucauldian perspective
Authors: Galière Sophia
Published: December 2020

This paper extends research on algorithmic management by examining mechanisms of compliance. Algorithmic management has predominantly been analysed in terms of the exercise of disciplinary power over workers and rational control of labour. Facing algorithms, platform workers would be in a situation of fear, passivity and frustration. In this paper, we utilise the Foucauldian framework of ‘dispositive’ in order to reconceptualise platforms as exerting both rational and normative control. Based on a qualitative case study of the food‐delivery platform Deliveroo, we underscore that algorithmic rational control, although fallible, is being reinforced by techniques of subjectification. Several dispositives on the platform, such as the pay‐per‐delivery and shift picker systems, generate an active mobilisation of workers. Our discussion highlights the governmentality power of algorithmic management, which builds consent by promoting a hyper‐meritocratic ideal of justice.
Evaluation of Chemo‐ and Photo‐toxicity of a Live Fluorescent Dye for Cell Analysis
Authors: Reyes Lua Alejandra Magaly , Tonnicchia Simone , Giampietro Costanza , Mazza Edoardo , Ferrari Aldo
Published: December 2020

Live cell imaging is used to track the dynamic adaptation of cell size and motility to various external factors. Bright‐field configuration can be used for these experiments; however, the analysis can be challenging and difficult to automate. In this direction, a superior alternative is represented by the use of live cell dyes, which provide intense fluorescence from subcellular structures of living cells. Yet, the potential chemo‐ and photo‐toxicity of the fluorophores poses the necessity of an accurate protocol optimization to avoid artefacts. Toxicity studies generally focus on cell proliferation and apoptosis, neglecting the cellular activities under investigation. Here, we present the case of SYTO 13 in combination with primary endothelial cells. The optimization of the staining procedure is tested comparing cell proliferation and motility rate. In addition, the combined effect of staining and fluorescent illumination, reporting for photochemical toxicity, is evaluated. We demonstrate that while cell viability and proliferation are mainly unaffected by the staining and imagining protocols, a significant reduction of the motility rate is induced both by the chemical dye alone and in combination with fluorescent illumination. The general implications for this procedure are discussed.
Prophage region and short tandem repeats of “Candidatus Liberibacter asiaticus” reveal significant population structure in China
Authors: Zheng Yongqin , Huang Hongxia , Huang Zhenhui , Deng Xiaoling , Zheng Zheng , Xu Meirong
Published: December 2020

Whole‐genome sequencing of “Candidatus Liberibacter asiaticus” (Las) indicated some polymorphic gene regions enabling the molecular characterization of this bacterium. Although the population diversity of Las in China has been previously studied, no reports have used a combination of a prophage region and short tandem repeat (STR) loci for phylogenetic relationship characterization. In this study, we investigated the genetic diversity and structure of 667 Las strains from nine provinces in southern China using multiple genetic loci including three type‐specific prophage loci, two STR loci, and a miniature inverted‐repeat transposable element (MITE) region. The results indicated that the genetic diversity varied according to the gene loci used. The prophage regions, including the MITEs, revealed significant genetic differences of Las populations in Yunnan and Guizhou from other provinces, while the STR loci only indicated a difference of Las population in Guizhou from those of other provinces. In particular, the Las population shown to be diverse in Jiangxi at the CLIBASIA_01215_STR locus was not diverse when measured using the other loci. Considering all loci, the Las populations from Yunnan and Guizhou were different, those from Guangdong and Guangxi were complex, while the Las population in Jiangxi was comparatively simple. Las populations from five neighbouring provinces, including Guangdong, Guangxi, Hunan, Fujian, and Jiangxi were grouped in a big cluster. The Las population structure changed with age according to the prophage type. This study evaluated the method used for studying the molecular diversity of Las populations and provided more detailed information on the geographical origin and epidemic trend of Chinese Las populations.
Distinguishing the neural mechanism of attentional control and working memory in feature‐based attentive tracking
Authors: Hu Luming , Wang Chundi , Talhelm Thomas , Zhang Xuemin
Published: December 2020

Surface features are an important component in attentive tracking. However, the neural mechanisms underlying how features affect attentive tracking remain unknown. The present fMRI study addressed this issue by manipulating the intragroup feature complexity and intergroup feature similarity. In particular, this study distinguished the different neural mechanisms of intragroup feature complexity and intergroup feature similarity by investigating the roles of attentional control and working memory in dynamic feature‐based attentive tracking. Behavioral and neuroimaging evidence showed that when targets are distinct from distractors, the intragroup feature complexity of the targets, rather than that of the distractors, mainly increases the visual working memory load and significantly activates the frontoparietal cortical circuit. Thus, the involvement of working memory in feature‐based attentive tracking is modulated by goal‐directed attention control. In addition, when targets are similar to distractors, the intergroup feature similarity (i.e., target‐distractor similarity) mainly affects the allocation of attention. Specifically, target‐distractor similarity affects the goal‐directed attention toward the targets in a stimulus‐driven way and induces an interaction between the ventral and dorsal attention networks.
Mixed carbonate–siliciclastic sedimentation at the margin of a late Miocene tidal strait, lower Colorado River Valley, south‐western USA
Authors: Gardner Kevin , Dorsey Rebecca J.
Published: December 2020

The processes and deposits of tide‐dominated river deltas and estuaries are well‐understood, but the sedimentary dynamics of tide‐dominated straits and seaways are relatively little studied. Although recent depositional models have started to fill this gap, many aspects of tidal strait sedimentation such as interaction with strait‐margin alluvial fans and marginal marine systems remain poorly understood. This paper presents a study of the late Miocene basal carbonate member of the Bouse Formation exposed along the lower Colorado River, where prior studies have suggested a tidal influence on deposition. This study explores the applicability of tidal strait models in a continental oblique‐rift setting, and tests hypotheses for depositional processes and environments through detailed analysis of sedimentary facies, cross‐bedding architecture and palaeocurrent data. Mixed carbonate–siliciclastic facies on the west margin of the southern Blythe Basin record sedimentation in alluvial fans and fan‐fringing tidal flats at the retreating margin of a transgressive tidal strait. Pre‐Bouse normal faults established a narrow, tectonically confined basin architecture that led to amplification of tidal currents. Basin‐margin deposits pass laterally and up‐section into high‐energy cross‐bedded grainstone facies that record southward migration of compound dunes in the dune‐bedded strait zone of a shallow (ca 25 m) tidal strait. These findings provide the basis for recognition of strait‐margin facies in other settings where complex facies associations result from along‐strike variations in palaeobathymetry and current velocity. The results support a tidal origin for the southern Bouse Formation and provide new evidence for post‐Miocene uplift of the lower Colorado River Valley and adjacent areas.
Comparison of improved shear strength of biotreated sand using different ureolytic strains and sterile conditions
Authors: Sharma Meghna , Satyam Neelima , Reddy Krishna R.
Published: December 2020

The present study aims to improve shear strength of poorly graded sand using microbially induced calcite precipitation (MICP) technique. Two soil‐based bacteria, namely Sporosarcina pasteurii (SP) and Bacillus sphaericus (BS), were bioaugmented in sand. The cementation solutions of 0.50 M concentration were prepared using distilled water (DWCS) and tap water (TWCS), maintaining sterile and non‐sterile conditions, respectively. The biotreatment was carried out in direct shear test (DST) moulds using 12‐hr treatment cycles up to 14 days. The biotreated sand samples were subjected to DST to determine shear strength parameters, and results were statistically explored using analysis of variance (ANOVA). The amount of calcite precipitation, XRD and SEM was used to interpret biocementation. The non‐sterile treatment using TWCS showed significant strength. Additional biotreatment samples were prepared in DST and cylindrical PVC moulds using TWCS for 18 days but adopting different treatment cycles of 12, 24, 48 and 72 hr to explore inexpensive treatment option. All of these biotreated samples were tested for hydraulic conductivity, shear strength (based on DST and triaxial consolidated undrained (CU) tests) and three‐layer calcite contents. In CU tests, stress‐strain response of biocemented sands showed initial brittle behaviour followed by strain‐softening, analogous to rock‐like behaviour similar to sandstone. The maximum increase in strength was achieved with 12‐hr treatment cycle. The 24‐hr treatment cycle showed 1.7–1.8 times lesser strength than 12‐hr treatment cycle specimens. However, a significant amount of calcite precipitation and strength in 24‐hr treatment cycle showed its effectiveness in achieving cost reduction for large‐scale field applications.
First record of OSL‐dated fluvial sands in a tropical Andean cave reveals rapid late Quaternary tectonic uplift
Authors: Baby Patrice , Viveen Willem , Sanjurjo‐Sanchez Jorge , Bigot Jean‐Yves , Dosseto Antony , Villegas‐Lanza Juan C. , Apaéstegui James , Guyot Jean‐Loup
Published: December 2020

We present the first results of OSL‐dated fluvial sands extracted from a riverside cave in the tropical Andes. The excellent agreement between the ages of the various samples allowed the calculation of a late Quaternary valley incision rate forced by ongoing uplift of an active Subandean fault‐propagation fold in NE Peru. A structural cross‐section was constructed to understand the relationship between the geometry of the fault‐propagation fold, historical damaging earthquakes and the cave system. The calculated uplift rate is 2.3 to 2.6 mm a−1 over the past 70 ka and can be directly linked to active propagation of west‐verging basement thrusts. It is similar to uplift rates calculated from fluvial terraces in the Subandes of Colombia and Venezuela. The results will help to better assess the seismic hazard and confirm that OSL dating of fluvial sands in caves is a powerful tool to quantify uplift rates of active mountain fronts.
Enabling accurate measurement of activated factor XI (FXIa) in therapeutic immunoglobulin products
Authors: Wilmot Helen V. , Gray Elaine
Published: December 2020

Background and objectives

In 2010, an intravenous immunoglobulin (IVIG) product was removed from the market due to an association with serious thromboembolic events. Investigations revealed that factor XIa (FXIa) was present as a process‐related impurity. This study investigated the ability of two commercial FXIa assays to measure FXIa in immunoglobulin preparations and conducted a survey of FXIa activity in marketed immunoglobulin products.

Materials and methods

Factor XIa assays were modified to include spiking of samples with FXIa before testing. An immunoglobulin product and its excipient were used to assess the ability of the assays to recover the spiked FXIa levels.

Results

The Biophen FXIa assay required a high pre‐dilution of the sample to obtain statistically valid results and complete FXIa recovery. The ROX FXIa assay was more sensitive, giving statistically valid results at a lower sample pre‐dilution and FXIa spike level. This modified ROX FXIa assay was used to assay 17 lots of immunoglobulin products for FXIa. Two product lots had measurable FXIa levels without the need for spiking. A further 3 lots produced detectable but not statistically valid FXIa results when left unspiked. Spiking produced statistically valid assays and recoveries above 100%, demonstrating inherent FXIa.

Conclusion

This study shows marketed immunoglobulin products can contain detectable levels of FXIa. Spiking brings the FXIa levels into the quantifiable range of the assay, allowing measurement of inherent FXIa. Accurate measurement is important to inform on ‘safe’ levels of FXIa in these products and allow future safety guidelines to be set.