bluuebunny/crossref_metadata_2025_split huggingface dataset:
Species delimitation and hybridization history of a hazel species complex
Authors: Lu Zhiqiang , Sun Yongshuai , Li Ying , Yang Yongzhi , Wang Gaini , Liu Jianquan 
Published: February 2021

AbstractBackground and AimsHybridization increases species adaptation and biodiversity but also obscures species boundaries. In this study, species delimitation and hybridization history were examined within one Chinese hazel species complex (Corylus chinensis–Corylus fargesii). Two species including four varieties have already been described for this complex, with overlapping distributions.MethodsA total of 322 trees from 44 populations of these four varieties across their ranges were sampled for morphological and molecular analyses. Climatic datasets based on 108 geographical locations were used to evaluate their niche differentiations. Flowering phenology was also observed for two co-occurring species or varieties.Key ResultsFour statistically different phenotypic clusters were revealed, but these clusters were highly inconsistent with the traditional taxonomic groups. All the clusters showed statistically distinct niches, with complete or partial geographical isolation. Only two clusters displayed a distributional overlap, but they had distinct flowering phenologies at the site where they co-occurred. Population-level evidence based on the genotypes of ten simple sequence repeat loci supported four phenotypic clusters. In addition, one cluster was shown to have an admixed genetic composition derived from the other three clusters through repeated historical hybridizations.ConclusionsBased on our new evidence, it is better to treat the four clusters identified here as four independent species. One of them was shown to have an admixed genetic composition derived from the other three through repeated historical hybridizations. This study highlights the importance of applying integrative and statistical methods to infer species delimitations and hybridization history. Such a protocol should be adopted widely for future taxonomic studies.
Identification of the kinanthraquinone biosynthetic gene cluster by expression of an atypical response regulator
Authors: Takao Risa , Sakai Katsuyuki , Koshino Hiroyuki , Osada Hiroyuki , Takahashi Shunji 
Published: February 2021

ABSTRACT
Recent advances in genome sequencing have revealed a variety of secondary metabolite biosynthetic gene clusters in actinomycetes. Understanding the biosynthetic mechanism controlling secondary metabolite production is important for utilizing these gene clusters. In this study, we focused on the kinanthraquinone biosynthetic gene cluster, which has not been identified yet in Streptomyces sp. SN-593. Based on chemical structure, 5 type II polyketide synthase gene clusters were listed from the genome sequence of Streptomyces sp. SN-593. Among them, a candidate gene cluster was selected by comparing the gene organization with grincamycin, which is synthesized through an intermediate similar to kinanthraquinone. We initially utilized a BAC library for subcloning the kiq gene cluster, performed heterologous expression in Streptomyces lividans TK23, and identified the production of kinanthraquinone and kinanthraquinone B. We also found that heterologous expression of kiqA, which belongs to the DNA-binding response regulator OmpR family, dramatically enhanced the production of kinanthraquinones.
LncRNA SNHG12 downregulates RAGE to attenuate hypoxia-reoxygenation-induced apoptosis in H9c2 cells
Authors: Lu Ping , Xiao Shihui , Chen Shaoze , Fu Youlin , Zhang Peng , Yao Yaner , Chen Feng 
Published: February 2021

ABSTRACTIschemia-reperfusion (I/R) injury causes cardiac dysfunction through several mechanisms including the irregular expression of some long noncoding RNA. However, the role of SNHG12 in myocardial I/R injury remains unclear. Here, we found the increase of the SNHG12 level in hypoxia-reoxygenation (H/R)-injured-H9c2 cells. SNHG12 silencing enhanced the apoptosis of H/R-injured H9c2 cells, while SNHG12 overexpression relieved the cardiomyocyte apoptosis induced by H/R stimulation. Additionally, the suppression of SNHG12 significantly boosted the H/R-induced expression and the production of TNF-α, IL-6, and IL-1β, as well as the activation of NF-κB, which were fully reversed after overexpression of SNHG12. Mechanistically, SNHG12 adversely regulated the production of receptor for advanced glycation end products (RAGE) in H/R-stimulated H9c2 cells. Antibody blocking of RAGE alleviated the apoptosis of H/R-injured H9c2 cells. Collectively, we have determined a valuable mechanism by which the high level of SNHG12 contributes to H9c2 cells against H/R injury through the reduction of RAGE expression.
Purification and characterization of cycloisomaltotetraose-forming glucanotransferases from Agreia sp. D1110 and Microbacterium trichothecenolyticum D2006
Authors: Fujita Akihiro , Kawashima Akira , Mitsukawa Yuuki , Kitagawa Noriaki , Watanabe Hikaru , Mori Tetsuya , Nishimoto Tomoyuki , Aga Hajime , Ushio Shimpei 
Published: February 2021

ABSTRACT
Glucanotransferases that can synthesize cyclo-{→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→} (CI4) from dextran were purified to homogeneity from the culture supernatant of Agreia sp. D1110 and Microbacterium trichothecenolyticum D2006. The molecular mass of both enzymes was estimated to be 86 kDa by SDS-PAGE. The glucanotransferase, named CI4-forming enzyme, from Agreia sp. exhibited the highest activity at pH 6.0 and 40 °C. The enzyme was stable on the pH range of 4.6-9.9 and up to 40 °C. On the other hand, the enzyme from M. trichothecenolyticum exhibited the highest activity at pH 5.7 and 40 °C. The enzyme was stable on the pH range of 5.0-6.9 and up to 35 °C. Both enzymes catalyzed 4 reactions, namely, intramolecular α-1,6-transglycosylation (cyclization), intermolecular α-1,6-transglycosylation, hydrolysis of CI4, and coupling reaction. Furthermore, the CI4-forming enzyme produced CI4 from α-1,6-linked glucan synthesized from starch by 6-α-glucosyltransferase. These findings will enable the production of CI4 from starch.
Knockdown of p62/sequestosome enhances ginsenoside Rh2-induced apoptosis in cervical cancer HeLa cells with no effect on autophagy
Authors: Bian Shuai , Zhao Yue , Li Fangyu , Lu Shuyan , Yang Song , Liu Meichen , Wang Siming , Zhao Daqing , Zhang Wei , Wang Jiawen 
Published: February 2021

ABSTRACTp62/sequestosome is a multifunctional adaptor protein that participates in a wide variety of cellular processes. 20(S)-Ginsenoside Rh2 (G-Rh2) has various biological effects, including anticancer activity. We found that G-Rh2 can induce apoptosis and autophagy in HeLa cells. G-Rh2 significantly enhanced the transcriptional level of p62. A siRNA was constructed to knock down p62 and assess its effect on apoptosis induced by G-Rh2. p62 protein levels were successfully downregulated in cells transfected with the p62-specific siRNA. Silencing of p62 further decreased cell viability while also enhancing cell apoptosis, reactive oxygen species generation, the ratio of Bax to Bcl-2, and the cleavage of PARP. p62 knockdown decreased expression levels of Nrf2. Moreover, silencing of p62 had no significant effect on autophagy induced by G-Rh2. These results suggest that combining G-Rh2 treatment with inhibition of p62 may be a potential treatment strategy for cervical cancer.
MMRFBiolinks: an R-package for integrating and analyzing MMRF-CoMMpass data
Authors: Settino Marzia , Cannataro Mario 
Published: February 2021

Abstract
In order to understand the mechanisms underlying the onset and the drug responses in multiple myeloma (MM), the second most frequent hematological cancer, the use of appropriate bioinformatic tools for integrative analysis of publicly available genomic data is required. We present MMRFBiolinks, a new R package for integrating and analyzing datasets from the Multiple Myeloma Research Foundation (MMRF) CoMMpass (Clinical Outcomes in MM to Personal Assessment of Genetic Profile) study, available at MMRF Researcher Gateway (MMRF-RG), and from the National Cancer Institute Genomic Data Commons (NCI-GDC) Data Portal. The package provides several methods for integrative analysis (array–array intensity correlation, Kaplan–Meier survival analysis) and visualization (response to treatments plot) of MMRF data, for performing an easily comprehensible analysis workflow. MMRFBiolinks extends the TCGABiolinks package by providing 13 new functions to analyze MMRF-CoMMpass data: six dealing with MMRF-RG data and seven with NCI-GDC data. As validation of the tool, we present two cases studies for searching, downloading and analyzing MMRF data. The former presents a workflow for identifying genes involved in survival depending on treatment. The latter presents an analysis workflow for analyzing the Best Overall (BO) response through correlation plots between the BO Response with respect to treatments, time, duration of treatment and annotated variants, as well as through Kaplan–Meier survival curves. The case studies demonstrate how MMRFBiolinks is able of overcoming the limitations of the analysis tools available at NCI-GDC and MMRF-RG, facilitating and making more comprehensive the retrieval, downloading and analysis of MMRF data.
NPI-GNN: Predicting ncRNA–protein interactions with deep graph neural networks
Authors: Shen Zi-Ang , Luo Tao , Zhou Yuan-Ke , Yu Han , Du Pu-Feng 
Published: February 2021

Abstract
Noncoding RNAs (ncRNAs) play crucial roles in many biological processes. Experimental methods for identifying ncRNA–protein interactions (NPIs) are always costly and time-consuming. Many computational approaches have been developed as alternative ways. In this work, we collected five benchmarking datasets for predicting NPIs. Based on these datasets, we evaluated and compared the prediction performances of existing machine-learning based methods. Graph neural network (GNN) is a recently developed deep learning algorithm for link predictions on complex networks, which has never been applied in predicting NPIs. We constructed a GNN-based method, which is called Noncoding RNA–Protein Interaction prediction using Graph Neural Networks (NPI-GNN), to predict NPIs. The NPI-GNN method achieved comparable performance with state-of-the-art methods in a 5-fold cross-validation. In addition, it is capable of predicting novel interactions based on network information and sequence information. We also found that insufficient sequence information does not affect the NPI-GNN prediction performance much, which makes NPI-GNN more robust than other methods. As far as we can tell, NPI-GNN is the first end-to-end GNN predictor for predicting NPIs. All benchmarking datasets in this work and all source codes of the NPI-GNN method have been deposited with documents in a GitHub repo (https://github.com/AshuiRUA/NPI-GNN).
Social organization of otters in relation to their ecology
Authors: Lélias Marie-Loup , Lemasson Alban , Lodé Thierry 
Published: February 2021

AbstractOtter species are known to fluctuate intraspecifically from a solitary lifestyle to group-living arrangements. By examining what is known about habitat use and foraging style in otters of 13 different species, based on 93 studied sites, we assessed (1) the relationship between social habits and preferred habitats, (2) the relationship between species and prey preferences, and (3) the effect of predator avoidance on their social organization in order to assess the socio-ecological factors influencing otters. Females remain the core of their social stability. We show the major influence of habitats and feeding strategies (i.e. socio-ecology) of otters. The different species of solitary otters most often inhabit linear environments, such as freshwater ecosystems or wave-exposed marine coasts, and their habitat is often subject to disturbances that fragment their functional continuity. Social otters are more often found in extensive habitats with high plant cover, regular food resources and in areas with large predators compared to solitary species. The maintenance of regular resources and the fact that the main trophic resources are replenished rapidly might be determining factors driving sociality. Group-living and bachelor congregations among otters can also respond to pressure from large predators. This suggests that foraging, habitat use and the presence of large predators may be the drivers of sociality in otters. We conclude that most otters have a greater social potential than previously assumed, which is confirmed by their various vocalizations recently described.
G protein-coupled receptor kinase 5 (GRK5) contributes to impaired cardiac function and immune cell recruitment in post-ischemic heart failure
Authors: de Lucia Claudio , Grisanti Laurel A , Borghetti Giulia , Piedepalumbo Michela , Ibetti Jessica , Lucchese Anna Maria , Barr Eric W , Roy Rajika , Okyere Ama Dedo , Murphy Haley Christine , Gao Erhe , Rengo Giuseppe , Houser Steven R , Tilley Douglas G , Koch Walter J 
Published: February 2021

Abstract

Aims
Myocardial infarction (MI) is the most common cause of heart failure (HF) worldwide. G protein-coupled receptor kinase 5 (GRK5) is upregulated in failing human myocardium and promotes maladaptive cardiac hypertrophy in animal models. However, the role of GRK5 in ischemic heart disease is still unknown. In this study, we evaluated whether myocardial GRK5 plays a critical role post-MI in mice and included the examination of specific cardiac immune and inflammatory responses.

Methods and results
Cardiomyocyte-specific GRK5 overexpressing transgenic mice (TgGRK5) and non-transgenic littermate control (NLC) mice as well as cardiomyocyte-specific GRK5 knockout mice (GRK5cKO) and wild type (WT) were subjected to MI and, functional as well as structural changes together with outcomes were studied. TgGRK5 post-MI mice showed decreased cardiac function, augmented left ventricular dimension and decreased survival rate compared to NLC post-MI mice. Cardiac hypertrophy and fibrosis as well as fetal gene expression were increased post-MI in TgGRK5 compared to NLC mice. In TgGRK5 mice, GRK5 elevation produced immuno-regulators that contributed to the elevated and long-lasting leukocyte recruitment into the injured heart and ultimately to chronic cardiac inflammation. We found an increased presence of pro-inflammatory neutrophils and macrophages as well as neutrophils, macrophages and T-lymphocytes at 4-days and 8-weeks respectively post-MI in TgGRK5 hearts. Conversely, GRK5cKO mice were protected from ischemic injury and showed reduced early immune cell recruitment (predominantly monocytes) to the heart, improved contractility and reduced mortality compared to WT post-MI mice. Interestingly, cardiomyocyte-specific GRK2 transgenic mice did not share the same phenotype of TgGRK5 mice and did not have increased cardiac leukocyte migration and cytokine or chemokine production post-MI.

Conclusions
Our study shows that myocyte GRK5 has a crucial and GRK-selective role on the regulation of leucocyte infiltration into the heart, cardiac function and survival in a murine model of post-ischemic HF, supporting GRK5 inhibition as a therapeutic target for HF.
Subclinical Pulmonary Involvement in Active IBD Responds to Biologic Therapy
Authors: Ellrichmann M , Bethge J , Boesenkoetter J , Conrad C , Noth R , Bahmer T , Nikolaus S , Aden K , Zeissig S , Schreiber S 
Published: February 2021

Abstract

Objective
Increased mortality from respiratory diseases was observed in epidemiological studies of patients with ulcerative colitis [UC] as a potentially underestimated extraintestinal manifestation. We therefore investigated the presence of pulmonary manifestations of inflammatory bowel disease [IBD] and the potential effect of tumour necrosis factor alpha [TNF-α] inhibitors on pulmonary function tests [PFT] in a prospective, longitudinal study.

Methods
In all, 92 consecutive patients with IBD (49 Crohn´s disease [CD], 43 UC) and 20 healthy controls were recruited. Fifty patients with IBD were in remission, and 42 had active disease with 22 of these being examined before and 6 weeks after initiating anti-TNF therapy. Pulmonary function tests [PFT] were evaluated using the Medical Research Council [MRC] dyspnoea index and a standardized body plethysmography. IBD activity was assessed using Harvey-Bradshaw index for CD and partial Mayo score for UC. Data are presented as mean ± standard error of the mean [SEM].

Results
Patients with active IBD showed significant reduction of PFT. Forced expiration [Tiffeneau index] values [FEV1%] were significantly reduced in IBD patients with active disease [78.8 ± 1.1] compared with remission [86.1 ± 0.9; p = 0.0002] and with controls [87.3 ± 1.3; p = 0.001]. Treatment with anti-TNF induced a significant relief in obstruction [p = 0.003 for FEV1% in comparison with baseline levels]. The level of pulmonary obstruction significantly correlated with clinical inflammation scores [HBI or Mayo].

Conclusions: Patients
with active IBD present with significant obstructive abnormalities in their PFTs. Obstruction is related to inflammatory activity, with anti-TNF improving PFTs. Pulmonary obstruction and possibly chronic bronchopulmonary inflammation is an overlooked problem in active IBD that is probably obscured by intestinal symptoms.
The Effect of Diet Interacting With Temperature on the Development Rate of a Noctuidae Quinoa Pest
Authors: Quispe-Tarqui Reinaldo , Yujra Pari Janneth , Callizaya Condori Franz , Rebaudo François 
Published: February 2021

Abstract
The quinoa pest Copitarsia incommoda (Walker, Lepidoptera: Noctuidae) is a cause of significant damage, and it is thus critical for Andean countries to have access to phenological models to maintain production and food safety. These models are key components in pest control strategies in the context of global warming and in the development of sustainable production integrating agroecological concepts. Phenological models are mainly based on outlining the relationship between temperature and development rate. In this study, we investigated the combined effect of protein content within the diet (artificial diet; artificial diet with −20% protein; artificial diet with +20% protein; natural quinoa diet) and temperature (12, 16.9, 19.5, 22.7, 24.6°C) as drivers of the development rate. Our study supports the literature, since temperature was found to be the main driver of the development rate. It highlights the significant role played by protein content and its interaction with temperature (significant effects of temperature, diet, and diet:temperature on development time using GLMs for all foraging life stages). We discuss the implications of such drivers of the development rate for implementing and applying phenological models that may benefit from including factors other than temperature. While performance curves such as development rate curves obtained from laboratory experiments are still a useful basis for phenological development, we also discuss the need to take into account the heterogeneity of the insect response to environmental factors. This is critical if pest control practices are to be deployed at the optimal time.
Severe tricuspid regurgitation: prognostic role of right heart remodelling and pulmonary hypertension
Authors: Schneider Matthias , König Andreas , Geller Welf , Dannenberg Varius , Winter Max-Paul , Binder Thomas , Hengstenberg Christian , Mascherbauer Julia , Goliasch Georg 
Published: February 2021

Abstract

Aims
Left heart diseases (LHDs) are the main driving forces for the development of functional tricuspid regurgitation (TR). Therefore, in most cases, the true prognostic value of TR remains concealed by concomitant LHD. This study aimed to analyse right heart remodelling in patients with TR without other valve disease and with normal systolic left ventricular function (sysLVF), and to stratify its prognostic value in the presence (dPH, maximal TR velocity signal (TRVmax) ≥ 3.5 m/s in echocardiography) or absence (nsPH, TRVmax &lt; 3.5m/s) of concomitant pulmonary hypertension (PH).

Methods and results
We performed an observational analysis of all patients diagnosed with TR in the absence of other valve disease and reduced sysLVF at our institution between 1 January 2003 and 31 December 2013. Five-year mortality was chosen as endpoint. The final cohort entailed 29 979 consecutive patients (median age 60 years, interquartile range 46–70), 49.9% were male, mean follow-up was 95±49 months. Severe TR was present in 790 patients (2.6%). In dPH and in nsPH, severe TR was associated with an excess 5-year mortality that was even more pronounced in the dPH group (58.2% vs. 43.6%, P = 0.001). In nsPH, right ventricular dysfunction predicted mortality. In dPH, mortality was independent of presence or absence of right heart dilatation or dysfunction.

Conclusion
Severe TR without concomitant left heart valve disease or LV systolic dysfunction was a rare disease in this large-scale all-comer population and is associated with an unfavourable prognosis. The differentiation of patients with nsPH and dPH is essential as they present with different patterns of right heart remodelling and with different long-time outcomes.
Efficacy of Miniscrew-Assisted Rapid Palatal Expansion (MARPE) in late adolescents and adults: a systematic review and meta-analysis
Authors: Kapetanović Aldin , Theodorou Christina I , Bergé Stefaan J , Schols Jan G J H , Xi Tong 
Published: February 2021

SummaryBackgroundMiniscrew-Assisted Rapid Palatal Expansion (MARPE) is a non-surgical treatment for transverse maxillary deficiency. However, there is limited evidence concerning its efficacy.ObjectivesThis systematic review aims to evaluate the efficacy of MARPE in late adolescents and adults by assessing success rate and skeletal and dental transverse maxillary expansion, as well as treatment duration, dental and periodontal side effects and soft tissue effects.Search methodsSeven electronic databases were searched (MEDLINE, Embase, Cochrane Library, Web of Science, Scopus, ProQuest and ClinicalTrials.gov) without limitations in November 2020.Selection criteriaRandomized and non-randomized clinical trials and observational studies on patients from the age of 16 onwards with transverse maxillary deficiency who were treated with MARPE and which included any of the predefined outcomes.Data collection and analysisInclusion eligibility screening, data extraction and risk of bias assessment were performed independently in duplicate. When possible, exploratory meta-analyses of mean differences (MDs) with their 95% confidence intervals (CIs) were conducted, followed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis of the evidence quality.ResultsEight articles were included: two prospective and six retrospective observational studies. One study had a moderate risk of bias, whereas seven studies had a serious risk of bias. GRADE quality of evidence was very low. MARPE showed a high success rate (mean: 92.5%; 95%CI: 88.7%–96.3%), resulting in a significant skeletal width increase (MD: 2.33 mm; 95%CI: 1.63 mm–3.03 mm) and dental intermolar width increase (MD: 6.55 mm; 95%CI: 5.50 mm–7.59 mm). A significant increase in dental tipping, a decrease in mean buccal bone thickness and buccal alveolar height, as well as nasal soft tissue change was present (P &lt; 0.05). The mean duration of expansion ranged from 20 to 126 days.LimitationsOne of the main drawbacks was the lack of high-quality prospective studies in the literature.Conclusions and implicationsMARPE is a treatment modality that is associated with a high success rate in skeletal and dental maxillary expansion. MARPE can induce dental and periodontal side effects and affect peri-oral soft tissues. Given the serious risk of bias of the included studies, careful data interpretation is necessary and future research of higher quality is strongly recommended.RegistrationPROSPERO (CRD42020176618).FundingNo grants or any other support funding were received.