bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease
Authors: Omote Norihito , Sauler Maor
Published: December 2020

Cellular senescence is a cell fate implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Cellular senescence occurs in response to cellular stressors such as oxidative stress, DNA damage, telomere shortening, and mitochondrial dysfunction. Whether these stresses induce cellular senescence or an alternative cell fate depends on the type and magnitude of cellular stress, but also on intrinsic factors regulating the cellular stress response. Non-coding RNAs, including both microRNAs and long non-coding RNAs, are key regulators of cellular stress responses and susceptibility to cellular senescence. In this review, we will discuss cellular mechanisms that contribute to senescence in IPF and COPD and highlight recent advances in our understanding of how these processes are influenced by non-coding RNAs. We will also discuss the potential therapeutic role for targeting non-coding RNAs to treat these chronic lung diseases.
COVIDNet-CT: A Tailored Deep Convolutional Neural Network Design for Detection of COVID-19 Cases From Chest CT Images
Authors: Gunraj Hayden , Wang Linda , Wong Alexander
Published: December 2020

The coronavirus disease 2019 (COVID-19) pandemic continues to have a tremendous impact on patients and healthcare systems around the world. In the fight against this novel disease, there is a pressing need for rapid and effective screening tools to identify patients infected with COVID-19, and to this end CT imaging has been proposed as one of the key screening methods which may be used as a complement to RT-PCR testing, particularly in situations where patients undergo routine CT scans for non-COVID-19 related reasons, patients have worsening respiratory status or developing complications that require expedited care, or patients are suspected to be COVID-19-positive but have negative RT-PCR test results. Early studies on CT-based screening have reported abnormalities in chest CT images which are characteristic of COVID-19 infection, but these abnormalities may be difficult to distinguish from abnormalities caused by other lung conditions. Motivated by this, in this study we introduce COVIDNet-CT, a deep convolutional neural network architecture that is tailored for detection of COVID-19 cases from chest CT images via a machine-driven design exploration approach. Additionally, we introduce COVIDx-CT, a benchmark CT image dataset derived from CT imaging data collected by the China National Center for Bioinformation comprising 104,009 images across 1,489 patient cases. Furthermore, in the interest of reliability and transparency, we leverage an explainability-driven performance validation strategy to investigate the decision-making behavior of COVIDNet-CT, and in doing so ensure that COVIDNet-CT makes predictions based on relevant indicators in CT images. Both COVIDNet-CT and the COVIDx-CT dataset are available to the general public in an open-source and open access manner as part of the COVID-Net initiative. While COVIDNet-CT is not yet a production-ready screening solution, we hope that releasing the model and dataset will encourage researchers, clinicians, and citizen data scientists alike to leverage and build upon them.
Development of Combination Methods for Detecting Malignant Uptakes Based on Physiological Uptake Detection Using Object Detection With PET-CT MIP Images
Authors: Kawakami Masashi , Hirata Kenji , Furuya Sho , Kobayashi Kentaro , Sugimori Hiroyuki , Magota Keiichi , Katoh Chietsugu
Published: December 2020

Deep learning technology is now used for medical imaging. YOLOv2 is an object detection model using deep learning. Here, we applied YOLOv2 to FDG-PET images to detect the physiological uptake on the images. We also investigated the detection precision of abnormal uptake by a combined technique with YOLOv2. Using 3,500 maximum intensity projection (MIP) images of 500 cases of whole-body FDG-PET examinations, we manually drew rectangular regions of interest with the size of each physiological uptake to create a dataset. Using YOLOv2, we performed image training as transfer learning by initial weight. We evaluated YOLOv2's physiological uptake detection by determining the intersection over union (IoU), average precision (AP), mean average precision (mAP), and frames per second (FPS). We also developed a combination method for detecting abnormal uptake by subtracting the YOLOv2-detected physiological uptake. We calculated the coverage rate, false-positive rate, and false-negative rate by comparing the combination method-generated color map with the abnormal findings identified by experienced radiologists. The APs for physiological uptakes were: brain, 0.993; liver, 0.913; and bladder, 0.879. The mAP was 0.831 for all classes with the IoU threshold value 0.5. Each subset's average FPS was 31.60 ± 4.66. The combination method's coverage rate, false-positive rate, and false-negative rate for detecting abnormal uptake were 0.9205 ± 0.0312, 0.3704 ± 0.0213, and 0.1000 ± 0.0774, respectively. The physiological uptake of FDG-PET on MIP images was quickly and precisely detected using YOLOv2. The combination method, which can be utilized the characteristics of the detector by YOLOv2, detected the radiologist-identified abnormalities with a high coverage rate. The detectability and fast response would thus be useful as a diagnostic tool.
In vitro Evaluation of the Safety of Adalimumab for the Eye Under HTLV-1 Infection Status: A Preliminary Study
Authors: Kurozumi-Karube Hisako , Kamoi Koju , Ando Naoko , Uchida Minami , Hamaguchi Isao , Ohno-Matsui Kyoko
Published: December 2020

Adalimumab (ADA), a fully human monoclonal tumor necrosis factor (TNF)-α antibody, is one of the most widely used biologics in the treatment of inflammatory diseases. However, ADA can exacerbate infectious conditions, induce paradoxical reactions such as inflammation, and cause neoplasia. Human T-cell leukemia virus type 1 (HTLV-1) is an infectious agent that induces inflammation and neoplastic infiltration in the eye. To date, numerous HTLV-1 carriers have been treated with adalimumab to suppress inflammation out of necessity, when standard anti-inflammatory drugs such as steroids and immunosuppressive agents have proven inadequate to control the inflammation. Here, we clarify the safety of adalimumab for the eye under HTLV-1 infectious conditions in vitro. We used the adult retinal pigment epithelial cell line (ARPE)-19 cell line as ocular resident cells, and used MT2 and TL-Om1 as HTLV-1-infected cells. ARPE-19 and MT2/TL-Om1 were co-cultured, and then adalimumab was administered. Production of cytokines and chemokines, TNF-α receptor (TNF-R), HTLV-1 proviral load (PVL), and apoptosis were measured to assess the effects of adalimumab. Contact between ARPE-19 and MT2/TL-Om1 produced inflammatory cytokines such as TNF, interleukin (IL)-6, IL-8 and IL-10, and transduced chemokines such as interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), monokine induced by interferon-γ (MIG), and regulated on activation, normal T cell expressed and secreted (RANTES). No inflammatory cytokines and chemokines were exacerbated by adalimumab. Expression of TNF-R on ARPE-19 and MT2/TL-Om1 cells, HTLV-1 PVLs of MT2/TL-Om1 cells, and cell growth rate and apoptotic rate of ARPE-19 were unaffected by adalimumab. In conclusion, adalimumab does not appear to exacerbate HTLV-1-associated inflammatory conditions in the eye or increase PVL in HTLV-1-infected T cells. These data suggest that adalimumab could be used safely for the eye under HTLV-1 infectious conditions from the perspective of in vitro assessment.
Liberibacter, A Preemptive Bacterium: Apoptotic Response Repression in the Host Gut at the Early Infection to Facilitate Its Acquisition and Transmission
Authors: Tang Xiao-Tian , Fortuna Kelsy , Mendoza Herrera Azucena , Tamborindeguy Cecilia
Published: December 2020

“Candidatus Liberibacter solanacearum” (Lso) is a phloem-limited Gram-negative bacterium that infects crops worldwide. In North America, two haplotypes of Lso (LsoA and LsoB) are transmitted by the potato psyllid, Bactericera cockerelli (Šulc), in a circulative and persistent manner. Both haplotypes cause damaging plant diseases (e.g., zebra chip in potatoes). The psyllid gut is the first organ Lso encounters and could be a barrier for its transmission. However, little is known about the psyllid gut immune responses triggered upon Lso infection. In this study, we focused on the apoptotic response in the gut of adult potato psyllids at the early stage of Lso infection. We found that there was no evidence of apoptosis induced in the gut of the adult potato psyllids upon infection with either Lso haplotype based on microscopic observations. However, the expression of the inhibitor of apoptosis IAPP5.2 gene (survivin-like) was significantly upregulated during the period that Lso translocated into the gut cells. Interestingly, silencing of IAPP5.2 gene significantly upregulated the expression of two effector caspases and induced apoptosis in the psyllid gut cells. Moreover, RNA interference (RNAi) of IAPP5.2 significantly decreased the Lso titer in the gut of adult psyllids and reduced their transmission efficiency. Taken together, these observations suggest that Lso might repress the apoptotic response in the psyllid guts by inducing the anti-apoptotic gene IAPP5.2 at an early stage of the infection, which may favor Lso acquisition in the gut cells and facilitate its transmission by potato psyllid.
Dietary Lipid:Protein Ratio and n-3 Long-Chain Polyunsaturated Fatty Acids Alters the Gut Microbiome of Atlantic Salmon Under Hypoxic and Normoxic Conditions
Authors: Huyben David , Roehe Beeke K. , Bekaert Michaël , Ruyter Bente , Glencross Brett
Published: December 2020

Researchers have adjusted dietary lipid:protein ratios and n-3 long-chain polyunsaturated fatty acids (LC-PUFA) to optimize the growth performance of Atlantic salmon. However, dietary impacts on the gut microbiome are lacking, especially under varying environmental conditions. To examine this response, post-smolt salmon (184 ± 5 g) were fed diets with lipid:protein ratios considered low (180, 570 g/kg) and high (230, 460 g/kg) along with low and high levels of n-3 LC-PUFA (7 or 14 g/kg) while fish were reared under low and high levels of dissolved oxygen (6.7 or 8.0 mg/L). At day 0, 35 and 116, digesta in the distal intestine were collected and analyzed for viable counts and 16S ribosomal RNA (rRNA) genes (V4 region) using Illumina MiSeq. The reduction in oxygen had negligible effects, except on viable plate counts of total bacteria and an initial effect on beta-diversity. In contrast, the high lipid (HL) diets had an increased alpha-diversity (e.g., Shannon and Chao-1) at day 0 and day 35 whereas high n-3 diets suppressed these indices at day 116. Generally, a reduction in alpha-diversity was observed over time and an interaction between lipid:protein ratio x n-3 was found. Between diets, beta-diversity and phyla abundance were similar as both Proteobacteria (44%) and Firmicutes (21%) dominated. However, at the genus level Aliivibrio, Streptococcus, Weissella, and Lactobacillus, were associated with low lipid (LL) diets while the high lipid diets were associated with less abundant bacteria, e.g., Chromohalobacter. At day 116, the relative abundance of the Tenericutes phylum increased 10-fold (36%). Fish fed the high lipid diet with high n-3 had reduced alpha-diversity, lowest abundance of lactic acid bacteria, and highest abundance of Mycoplasma, which may indicate a less healthy gut microbiome. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis revealed that saturated and unsaturated fatty acid biosynthesis pathways were several folds higher in fish fed the high lipid diet, possibly to compensate for the lack of dietary n-3. In summary, our results show that the viable plate counts, alpha-diversity, beta-diversity, and predictive function of gut bacteria in Atlantic salmon post-smolts are influenced by dietary lipid:protein ratio and n-3 LC-PUFA over several time points with little effect by dissolved oxygen.
Overexpression of Global Regulator Talae1 Leads to the Discovery of New Antifungal Polyketides From Endophytic Fungus Trichoderma afroharzianum
Authors: Ding Zhuang , Wang Xiao , Kong Fan-Dong , Huang Hui-Ming , Zhao Yan-Na , Liu Min , Wang Zheng-Ping , Han Jun
Published: December 2020

Transcription regulation caused by global regulators exerts important effects on fungal secondary metabolism. By overexpression of the global regulator Talae1 in a Ficus elastica-associated fungus Trichoderma afroharzianum, two structurally new polyketides (1 and 2) that were newly produced in the transformant were isolated and identified. Their structures, including the absolute configurations, were elucidated through a combination of high resolution mass spectrometer (HRMS), NMR, and electronic circular dichroism (ECD) calculations. The growth inhibitory activities of compounds 1 and 2 were evaluated against four bacteria and six plant-pathogenic fungi. Compound 1 showed the highest antifungal activity against Botrytis cinerea and Fusarium oxysporum f. sp. nicotianae with MIC of 8 μg/ml. To the best of our knowledge, this is the first study to report on the application of the global regulator in T. afroharzianum to activate the biosynthesis of bioactive secondary metabolites.
Ancestral Sequence Reconstructions of MotB Are Proton-Motile and Require MotA for Motility
Authors: Islam Md Imtiazul , Lin Angela , Lai Yu-Wen , Matzke Nicholas J. , Baker Matthew A. B.
Published: December 2020

The bacterial flagellar motor (BFM) is a nanomachine that rotates the flagellum to propel many known bacteria. The BFM is powered by ion transit across the cell membrane through the stator complex, a membrane protein. Different bacteria use various ions to run their BFM, but the majority of BFMs are powered by either proton (H+) or sodium (Na+) ions. The transmembrane (TM) domain of the B-subunit of the stator complex is crucial for ion selectivity, as it forms the ion channel in complex with TM3 and TM4 of the A-subunit. In this study, we reconstructed and engineered thirteen ancestral sequences of the stator B-subunit to evaluate the functional properties and ionic power source of the stator proteins at reconstruction nodes to evaluate the potential of ancestral sequence reconstruction (ASR) methods for stator engineering and to test specific motifs previously hypothesized to be involved in ion-selectivity. We found that all thirteen of our reconstructed ancient B-subunit proteins could assemble into functional stator complexes in combination with the contemporary Escherichia coli MotA-subunit to restore motility in stator deleted E. coli strains. The flagellar rotation of the thirteen ancestral MotBs was found to be Na+ independent which suggested that the F30/Y30 residue was not significantly correlated with sodium/proton phenotype, in contrast to what we had reported previously. Additionally, four among the thirteen reconstructed B-subunits were compatible with the A-subunit of Aquifex aeolicus and able to function in a sodium-independent manner. Overall, this work demonstrates the use of ancestral reconstruction to generate novel stators and quantify which residues are correlated with which ionic power source.
Biased Influences of Low Tumor Purity on Mutation Detection in Cancer
Authors: Cheng Jun , He Jun , Wang Shanshan , Zhao Zhangxiang , Yan Haidan , Guan Qingzhou , Li Jing , Guo Zheng , Ao Lu
Published: December 2020

The non-cancerous components in tumor tissues, e.g., infiltrating stromal cells and immune cells, dilute tumor purity and might confound genomic mutation profile analyses and the identification of pathological biomarkers. It is necessary to systematically evaluate the influence of tumor purity. Here, using public gastric cancer samples from The Cancer Genome Atlas (TCGA), we firstly showed that numbers of mutation, separately called by four algorithms, were significant positively correlated with tumor purities (all p < 0.05, Spearman rank correlation). Similar results were also observed in other nine cancers from TCGA. Notably, the result was further confirmed by six in-house samples from two gastric cancer patients and five in-house samples from two colorectal cancer patients with different tumor purities. Furthermore, the metastasis mechanism of gastric cancer may be incorrectly characterized as numbers of mutation and tumor purities of 248 lymph node metastatic (N + M0) samples were both significantly lower than those of 121 non-metastatic (N0M0) samples (p < 0.05, Wilcoxon rank-sum test). Similar phenomena were also observed that tumor purities could confound the analysis of histological subtypes of cancer and the identification of microsatellite instability status (MSI) in both gastric and colon cancer. Finally, we suggested that the higher tumor purity, such as above 70%, rather than 60%, could be better to meet the requirement of mutation calling. In conclusion, the influence of tumor purity on the genomic mutation profile and pathological analyses should be fully considered in the further study.
Single Domain Antibodies Targeting Receptor Binding Pockets of NadA Restrain Adhesion of Neisseria meningitidis to Human Brain Microvascular Endothelial Cells
Authors: Kulkarni Amod , Mochnáčová Evelína , Majerova Petra , Čurlík Ján , Bhide Katarína , Mertinková Patrícia , Bhide Mangesh
Published: December 2020

Neisseria adhesin A (NadA), one of the surface adhesins of Neisseria meningitides (NM), interacts with several cell types including human brain microvascular endothelial cells (hBMECs) and play important role in the pathogenesis. Receptor binding pockets of NadA are localized on the globular head domain (A33 to K69) and the first coiled-coil domain (L121 to K158). Here, the phage display was used to develop a variable heavy chain domain (VHH) that can block receptor binding sites of recombinant NadA (rec-NadA). A phage library displaying VHH was panned against synthetic peptides (NadA-gdA33−K69 or NadA-ccL121−K158), gene encoding VHH was amplified from bound phages and re-cloned in the expression vector, and the soluble VHHs containing disulfide bonds were overexpressed in the SHuffle E. coli. From the repertoire of 96 clones, two VHHs (VHHF3–binding NadA-gdA33−K69 and VHHG9–binding NadA-ccL121−K158) were finally selected as they abrogated the interaction between rec-NadA and the cell receptor. Preincubation of NM with VHHF3 and VHHG9 significantly reduced the adhesion of NM on hBMECs in situ and hindered the traversal of NM across the in-vitro BBB model. The work presents a phage display pipeline with a single-round of panning to select receptor blocking VHHs. It also demonstrates the production of soluble and functional VHHs, which blocked the interaction between NadA and its receptor, decreased adhesion of NM on hBMECs, and reduced translocation of NM across BBB in-vitro. The selected NadA blocking VHHs could be promising molecules for therapeutic translation.
Identification and Development of a Novel 4-Gene Immune-Related Signature to Predict Osteosarcoma Prognosis
Authors: Cao Mingde , Zhang Junhui , Xu Hualiang , Lin Zhujian , Chang Hong , Wang Yuchen , Huang Xusheng , Chen Xiang , Wang Hua , Song Yancheng
Published: December 2020

Osteosarcoma (OS) is a malignant disease that develops rapidly and is associated with poor prognosis. Immunotherapy may provide new insights into clinical treatment strategies for OS. The purpose of this study was to identify immune-related genes that could predict OS prognosis. The gene expression profiles and clinical data of 84 OS patients were obtained from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. According to non-negative matrix factorization, two molecular subtypes of immune-related genes, C1 and C2, were acquired, and 597 differentially expressed genes between C1 and C2 were identified. Univariate Cox analysis was performed to get 14 genes associated with survival, and 4 genes (GJA5, APBB1IP, NPC2, andFKBP11) obtained through least absolute shrinkage and selection operator (LASSO)-Cox regression were used to construct a 4-gene signature as a prognostic risk model. The results showed that highFKBP11expression was correlated with high risk (a risk factor), and that highGJA5, APBB1IP, orNPC2expression was associated with low risk (protective factors). The testing cohort and entire TARGET cohort were used for internal verification, and the independent GSE21257 cohort was used for external validation. The study suggested that the model we constructed was reliable and performed well in predicting OS risk. The functional enrichment of the signature was studied through gene set enrichment analysis, and it was found that the risk score was related to the immune pathway. In summary, our comprehensive study found that the 4-gene signature could be used to predict OS prognosis, and new biomarkers of great significance for understanding the therapeutic targets of OS were identified.
Inhibition of Cathepsin S Induces Mitochondrial Apoptosis in Glioblastoma Cell Lines Through Mitochondrial Stress and Autophagosome Accumulation
Authors: Fei Maoxing , Zhang Li , Wang Handong , Zhu Yihao , Niu Wenhao , Tang Ting , Han Yanling
Published: December 2020

Cathepsin S (CTSS), a lysosomal cysteine protease, is overexpressed in various cancers, including glioblastoma (GB). A high level of CTSS is associated with tumor progression and poor outcome in GB. However, the underlying mechanisms of its role in the biological characteristics of G5B remain to be elucidated. Here, we uncovered a potential role of CTSS in the lysosomes and mitochondria of GB cells (GBCs). Downregulation of CTSS in GBCs could increase the expression of autophagy-related proteins; however, there was no significant change in p62, suggesting autophagy blockade. Moreover, inhibition of CTSS increased the expression of mitochondrial calcium uniporter (MCU) and enhanced mitochondrial Ca2+ uptake ability, causing mitochondrial Ca2+ overload, the generation of copious reactive oxygen species (ROS) and eventual mitochondrial apoptosis. Additionally, elevated damage to mitochondria exacerbated the burden of autophagy. Finally, we found that silence of MCU could alleviate the inhibition of CTSS-induced autophagosome accumulation and mitochondrial stress. Collectively, these results demonstrate that CTSS plays an important role in the process of autophagic flux and mitochondrial functions in GBCs.
Detection of Recurrent Prostate Cancer With 18F-Fluciclovine PET/MRI
Authors: Selnæs Kirsten Margrete , Krüger-Stokke Brage , Elschot Mattijs , Johansen Håkon , Steen Per Arvid , Langørgen Sverre , Aksnessæther Bjørg Yksnøy , Indrebø Gunnar , Sjøbakk Torill Anita Eidhammer , Tessem May-Britt , Moestue Siver Andreas , Knobel Heidi , Tandstad Torgrim , Bertilsson Helena , Solberg Arne , Bathen Tone Frost
Published: December 2020

Objective

Simultaneous PET/MRI combines soft-tissue contrast of MRI with high molecular sensitivity of PET in one session. The aim of this prospective study was to evaluate detection rates of recurrent prostate cancer by 18F-fluciclovine PET/MRI.

Methods

Patients with biochemical recurrence (BCR) or persistently detectable prostate specific antigen (PSA), were examined with simultaneous 18F-fluciclovine PET/MRI. Multiparametric MRI (mpMRI) and PET/MRI were scored on a 3-point scale (1-negative, 2-equivocal, 3-recurrence/metastasis) and detection rates (number of patients with suspicious findings divided by total number of patients) were reported. Detection rates were further stratified based on PSA level, PSA doubling time (PSAdt), primary treatment and inclusion criteria (PSA persistence, European Association of Urology (EAU) Low-Risk BCR and EAU High-Risk BCR). A detailed investigation of lesions with discrepancy between mpMRI and PET/MRI scores was performed to evaluate the incremental value of PET/MRI to mpMRI. The impact of the added PET acquisition on further follow-up and treatment was evaluated retrospectively.

Results

Among patients eligible for analysis (n=84), 54 lesions were detected in 38 patients by either mpMRI or PET/MRI. Detection rates were 41.7% for mpMRI and 39.3% for PET/MRI (score 2 and 3 considered positive). There were no significant differences in detection rates for mpMRI versus PET/MRI. Disease detection rates were higher in patients with PSA≥1ng/mL than in patients with lower PSA levels but did not differ between patients with PSAdt above versus below 6 months. Detection rates in patients with primary radiation therapy were higher than in patients with primary surgery. Patients categorized as EAU Low-Risk BCR had a detection rate of 0% both for mpMRI and PET/MRI. For 15 lesions (27.8% of all lesions) there was a discrepancy between mpMRI score and PET/MRI score. Of these, 10 lesions scored as 2-equivocal by mpMRI were changed to a more definite score (n=4 score 1 and n=6 score 3) based on the added PET acquisition. Furthermore, for 4 of 10 patients with discrepancy between mpMRI and PET/MRI scores, the added PET acquisition had affected the treatment choice.

Conclusion

Combined 18F-fluciclovine PET/MRI can detect lesions suspicious for recurrent prostate cancer in patients with a range of PSA levels. Combined PET/MRI may be useful to select patients for appropriate treatment, but is of limited use at low PSA values or in patients classified as EAU Low-Risk BCR, and the clinical value of 18F-fluciclovine PET/MRI in this study was too low to justify routine clinical use.
Oral Administration of Penicillin or Streptomycin May Alter Serum Serotonin Level and Intestinal Motility via Different Mechanisms
Authors: Zhu Cuihong , Gong Huashan , Luo Ping , Dong Li , Zhang Guohua , Shi Xueyin , Rong Weifang
Published: December 2020

Background/Aims

Enterochromaffin cells (EC cells) constitute the largest population of enteroendocrine cells and release serotonin (5-HT) in response to mechanical and chemical cues of the gastrointestinal tract (GIT). How EC cells respond to altered microbiota such as due to antibiotic treatments remain poorly understood. We hypothesized that the pacemaker channel HCN2 might contribute to the regulation of EC cells functions and their responses to antibiotics-induced changes in intestinal flora.

Methods

Mice were given either penicillin or streptomycin or both in drinking water for 10 consecutive days. The changes in the profile of short chain fatty acids (SCFAs) in the cecum following penicillin or streptomycin treatments were tested by GC-MS. Serum 5-HT content, whole intestinal transit time, fecal water content, cecum weight and expression of HCN2 and TPH1 in cecal mucosa were measured. Ivabradine (a HCN channels blocker) was used to explore the role of HCN2 in penicillin-induced changes in 5-HT availability and intestinal motility.

Results

HCN2 immunofluorescence was detected on intestinal EC cells. Both penicillin and streptomycin caused significant reduction in total SCFAs in the cecum, with the penicillin-treated group showing greater reductions in butyrate, isobutyrate and isovalerate levels than the streptomycin group. The expression of HCN2 was increased in the mice treated with penicillin, whereas TPH1 expression was increased in the mice treated with streptomycin. Mice treated with antibiotics all had larger and heavier cecum, elevated serum 5-HT level and increased fecal water content. Besides, mice treated with penicillin had prolonged intestinal transit time. Intraperitoneal injection of Ivabradine attenuated the effect of penicillin on serum 5-HT level, cecum size and weight, intestinal motility, and fecal water content.

Conclusion

Disruptions of the intestinal flora structure due to oral administration of penicillin may significantly increase serum 5-HT level and inhibit intestinal motility, at least partially through up-regulating the expression of HCN2. Oral administration of streptomycin may alter 5-HT availability by up-regulating TPH1 expression thus increasing synthesis of 5-HT. Alterations of intestinal flora composition due to exposure to different antibiotics may regulate 5-HT availability and intestinal motility through different mechanisms.
Temperature-Dependent Lipid Accumulation in the Polar Marine Microalga Chlamydomonas malina RCC2488
Authors: Morales-Sánchez Daniela , Schulze Peter S. C. , Kiron Viswanath , Wijffels Rene H.
Published: December 2020

The exploration of cold-adapted microalgae offers a wide range of biotechnological applications that can be used for human, animal, and environmental benefits in colder climates. Previously, when the polar marine microalgaChlamydomonas malinaRCC2488 was cultivated under both nitrogen replete and depleted conditions at 8°C, it accumulated lipids and carbohydrates (up to 32 and 49%, respectively), while protein synthesis decreased (up to 15%). We hypothesized that the cultivation temperature had a more significant impact on lipid accumulation than the nitrogen availability inC. malina. Lipid accumulation was tested at three different temperatures, 4, 8, and 15°C, under nitrogen replete and depleted conditions. At 4°C under the nitrogen replete conditionC. malinahad the maximal biomass productivity (701.6 mg L–1day–1). At this condition, protein content was higher than lipids and carbohydrates. The lipid fraction was mainly composed of polyunsaturated fatty acids (PUFA) in the polar lipid portion, achieving the highest PUFA productivity (122.5 mg L–1day–1). At this temperature, under nitrogen deficiency, the accumulation of carbohydrates and neutral lipids was stimulated. At 8 and 15°C, under both nitrogen replete and depleted conditions, the lipid and carbohydrate content were higher than at 4°C, and the nitrogen stress condition did not affect the algal biochemical composition. These results suggest thatC. malinais a polar marine microalga with a favorable growth temperature at 4°C and is stressed at temperatures ≥8°C, which directs the metabolism to the synthesis of lipids and carbohydrates. Nevertheless,C. malinaRCC2488 is a microalga suitable for PUFA production at low temperatures with biomass productivities comparable with mesophilic strains.
Unmasking Reflexivity in HR Managers During the COVID-19 Lockdown in Italy
Authors: Ripamonti Silvio Carlo , Galuppo Laura , Provasoli Giulia , Benozzo Angelo
Published: December 2020

This paper explores how some Italian HR managers narrate the changes imposed by the COVID-19 threat in the workplace. Events since December 2019 have presented exceptional circumstances to which HR managers have reacted in very different ways. This study explored how HR managers came to introduce organizational changes aimed at coping with the emergency, as well as how employees were involved in those organizational changes. The article is based on a thematic analysis of some interviews with Italian HR managers whose companies decided to switch working from home on a massive scale. We wanted to offer some reflections on the actions taken by a few HR managers and Italian companies to keep working at a time when most workers were forced to respect the lockdown.
Cognitive Control in Suicide Ideators and Suicide Attempters
Authors: Brokke Silje Støle , Landrø Nils Inge , Haaland Vegard Øksendal
Published: December 2020

There is a need to understand more of the risk factors involved in the process from suicide ideation to suicide attempt. Cognitive control processes may be important factors in assessing vulnerability to suicide. A version of the Stroop procedure, Delis–Kaplan Executive Function System (D-KEFS) Color–Word Interference Test (CWIT) and Behavior Rating Inventory of Executive Function (BRIEF-A) were used in this study to test attention control and cognitive shift, as well as to assess everyday executive function of 98 acute suicidal psychiatric patients. The Columbia Suicide History Form (CSHF) was used to identify a group of suicide ideators and suicide attempters. Results showed that suicide attempters scored lower on attention control than suicide ideators who had no history of attempted suicide. The self-report in the BRIEF-A inventory did not reflect any cognitive differences between suicide ideators and suicide attempters. A logistic regression analysis showed that a poorer attention control score was associated with the suicide attempt group, whereas a poorer cognitive shift score was associated with the suicide ideation group. The results found in this study suggest that suicide attempters may struggle with control of attention or inhibiting competing responses but not with cognitive flexibility.
How to Investigate the Effects of Groups on Changes in Longitudinal Patient-Reported Outcomes and Response Shift Using Rasch Models
Authors: Hammas Karima , Sébille Véronique , Brisson Priscilla , Hardouin Jean-Benoit , Blanchin Myriam
Published: December 2020

In order to investigate patients’ experience of healthcare, repeated assessments of patient-reported outcomes (PRO) are increasingly performed in observational studies and clinical trials. Changes in PRO can however be difficult to interpret in longitudinal settings as patients’ perception of the concept being measured may change over time, leading to response shift (longitudinal measurement non-invariance) and possibly to erroneous interpretation of the observed changes in PRO. Several statistical methods for response shift analysis have been proposed, but they usually assume that response shift occurs in the same way in all individuals within the sample regardless of their characteristics. Many studies aim at comparing the longitudinal change of PRO into two groups of patients (treatment arm, different pathologies, …). The group variable could have an effect on PRO change but also on response shift effect and the perception of the questionnaire at baseline. In this paper, we propose to enhance the ROSALI algorithm based on Rasch Measurement Theory for the analysis of longitudinal PRO data to simultaneously investigate the effects of group on item functioning at the first measurement occasion, on response shift and on changes in PRO over time. ROSALI is subsequently applied to a longitudinal dataset on change in emotional functioning in patients with breast cancer or melanoma during the year following diagnosis. The use of ROSALI provides new insights in the analysis of longitudinal PRO data.
Genetic Fuzzy Based Scalable System of Distributed Robots for a Collaborative Task
Authors: Sathyan Anoop , Cohen Kelly , Ma Ou
Published: December 2020

This paper introduces a new genetic fuzzy based paradigm for developing scalable set of decentralized homogenous robots for a collaborative task. In this work, the number of robots in the team can be changed without any additional training. The dynamic problem considered in this work involves multiple stationary robots that are assigned with the goal of bringing a common effector, which is physically connected to each of these robots through cables, to any arbitrary target position within the workspace of the robots. The robots do not communicate with each other. This means that each robot has no explicit knowledge of the actions of the other robots in the team. At any instant, the robots only have information related to the common effector and the target. Genetic Fuzzy System (GFS) framework is used to train controllers for the robots to achieve the common goal. The same GFS model is shared among all robots. This way, we take advantage of the homogeneity of the robots to reduce the training parameters. This also provides the capability to scale to any team size without any additional training. This paper shows the effectiveness of this methodology by testing the system on an extensive set of cases involving teams with different number of robots. Although the robots are stationary, the GFS framework presented in this paper does not put any restriction on the placement of the robots. This paper describes the scalable GFS framework and its applicability across a wide set of cases involving a variety of team sizes and robot locations. We also show results in the case of moving targets.
What Determines the Entrepreneurial Intentions of Highly-Skilled Women with Refugee Experience? An Empirical Analysis in the Context of Sweden
Authors: Lazarczyk-Bilal Nina , Glinka Beata
Published: December 2020

One of the main challenges faced by refugee hosting states is the labour market integration of newcomers, which can be achieved to some extent through the creation of small businesses. This paper analyses the individual level determinants of the entrepreneurial intentions of highly-skilled women with refugee experience. The study adds a new perspective to the conversation about highly-skilled migrant women analysed so far, mostly as family reunion migrants joining economic migrants. It also contributes to the relatively new research on refugee entrepreneurship by adopting an unusual perspective for looking at highly skilled women. The empirical analysis embedded in the context of Sweden is two-fold. First, it is done in SPSS on the sample (N = 98) drawn from the 2017 Swedish Invandrarindex data set with the use of binary logistic regression. Second, the findings from the quantitative analysis are nuanced with the analysis of two case studies based on SSI with Syrian women having refugee experience. The results show that the gender variable does not predict the effect on entrepreneurial intentions. The findings confirm the importance of previous self-employment and leadership experience and indicate the potential importance of entrepreneurial role models, the cultural aspect of entrepreneurial intentions and the role of an encouraging environment in the host country.
The Challenge of Environmental Samples for PCR Detection of Phytopathogenic Bacteria: A Case Study of Citrus Huanglongbing Disease
Authors: Morán Félix , Barbé Silvia , Bastin Saskia , Navarro Inmaculada , Bertolini Edson , López María M. , Hernández-Suárez Estrella , Urbaneja Alberto , Tena Alejandro , Siverio Felipe , Marco-Noales Ester
Published: December 2020

Huanglongbing (HLB) is the most devastating citrus disease and is associated with three bacterial species of the genus ‘Candidatus Liberibacter’ transmitted by insect vectors. The early detection of HLB is based on PCR methods, and it is one of the cornerstones for preventing incursion into disease-free countries. However, the detection of phytopathogenic bacteria with PCR-based methods is problematic in surveys that include a variety of samples of different origins. Here, we first report the proportion of amplifications obtained by two standardized real-time PCR methods for the diagnosis of HLB in various environmental samples that include plants, psyllid vectors, and parasitic wasps of the psyllids. The results of 4915 samples showed that 9.3% of them were amplified by the first rapid screening test and only 0.3% by the more specific tests. Most of the amplifications were associated with parasitic wasps. We designed the primers external to the target regions of both real-time PCR protocols to determine if amplifications belonged to one of three ‘Ca. Liberibacter’ species associated with HLB. The bioinformatic analysis of the sequences obtained with these primers revealed that all these amplifications came from the presence of other prokaryotic organisms in the samples. The primers developed in this study overcome the problem of undesired amplification in environmental samples. Thus, they could be used in future survey protocols to prevent the eradication of negative trees and the generation of unjustified alarms.
Evaluating Irrigation and Farming Systems with Solar MajiPump in Ethiopia
Authors: Assefa Tewodros T. , Adametie Temesgen F. , Yimam Abdu Y. , Belay Sisay A. , Degu Yonas M. , Hailemeskel Solomon T. , Tilahun Seifu A. , Reyes Manuel R. , Prasad P. V. Vara
Published: December 2020

Small-scale irrigation in Ethiopia is a key strategy to improve and sustain the food production system. Besides the use of surface water for irrigation, it is essential to unlock the groundwater potential. It is equally important to use soil management and water-saving systems to overcome the declining soil fertility and the temporal water scarcity in the region. In this study, the solar MajiPump was introduced to enable dry season crop production in Ethiopia using shallow groundwater sources. The capacity of the MajiPumps (MP400 and MP200) was tested for the discharge head and discharge using three types of solar panels (150 W and 200 W rigid, and 200 W flexible). Besides, drip irrigation and conservation agriculture (CA) farming systems were evaluated in terms of water productivity and crop yield in comparison to the farmers’ practice (overhead irrigation and tilled farming system). Results indicated that the maximum discharge head capacity of the MajiPumps was 18 m, 14 m, 10 m when using MP400 with 200 W rigid, MP400 with 200 W flexible, and MP200 with 150 W rigid solar panels, respectively. The corresponding MajiPump flow rates ranged from 7.8 L/min to 24.6 L/min, 3 L/min to 25 L/min, and 3.6 L/min to 22.2 L/min, respectively. Compared to farmer’s practice, water productivity was significantly improved under the CA farming and the drip irrigation systems for both irrigated vegetables (garlic, onion, cabbage, potato) and rainfed maize production. The water productivity of garlic, cabbage, potato, and maize was increased by 256%, 43%, 53%, and 9%, respectively, under CA as compared to conventional tillage (CT) even under overhead irrigation. Thus, farmers can obtain a significant water-saving benefit from CA regardless of water application systems. However, water and crop productivity could be further improved in the combined use of MajiPump with CA and drip irrigation (i.e., 38% and 33% water productivity and 43% and 36% crop productivity improvements were observed for potato and onion, respectively). Similarly, compared to CT, the use of CA significantly increased garlic, cabbage, potato, and maize yield by 170%, 42%, 43%, and 15%, respectively under the MajiPump water-lifting system. Overall, the solar-powered drip irrigation and CA farming system were found to be efficient to expand small-scale irrigation and improve productivity and livelihoods of smallholder farmers in Ethiopia.
Identification of Mutations Conferring Tryptanthrin Resistance to Mycobacterium smegmatis
Authors: Frolova Svetlana G. , Klimina Ksenia M. , Kumar Ravinder , Vatlin Aleksey A. , Salunke Deepak B. , Kendrekar Pravin , Danilenko Valery N. , Maslov Dmitry A.
Published: December 2020

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a global burden, responsible for over 1 million deaths annually. The emergence and spread of drug-resistant M. tuberculosis strains (MDR-, XDR- and TDR-TB) is the main challenge in global TB-control, requiring the development of novel drugs acting on new biotargets, thus able to overcome the drug-resistance. Tryptanthrin is a natural alkaloid, with great therapeutic potential due to its simple way of synthesis and wide spectrum of biological activities including high bactericidal activity on both drug-susceptible and MDR M. tuberculosis strains. InhA was suggested as the target of tryptanthrins by in silico modeling, making it a promising alternative to isoniazid, able to overcome drug resistance provided by katG mutations. However, neither the mechanism of action of tryptanthrin nor the mechanism of resistance to tryptanthrins was ever confirmed in vitro. We show that the MmpS5-MmpL5 efflux system is able to provide resistance to tryptanthrins using an in-house test-system. Comparative genomic analysis of spontaneous tryptanthrin-resistant M. smegmatis mutants showed that mutations in MSMEG_1963 (EmbR transcriptional regulator) lead to a high-level resistance, while those in MSMEG_5597 (TetR transcriptional regulator) to a low-level one. Mutations in an MFS transporter gene (MSMEG_4427) were also observed, which might be involved in providing a basal level of tryptanthrins-resistance.
Melatonin Mitigates the Infection of Colletotrichum gloeosporioides via Modulation of the Chitinase Gene and Antioxidant Activity in Capsicum annuum L.
Authors: Ali Muhammad , Tumbeh Lamin-Samu Anthony , Muhammad Izhar , Farghal Mohamed , Khattak Abdul Mateen , Jan Ibadullah , ul Haq Saeed , Khan Abid , Gong Zhen-Hui , Lu Gang
Published: December 2020

Anthracnose, caused by Colletotrichum gloeosporioides, is one of the most damaging pepper (Capsicum annum L.) disease. Melatonin induces transcription of defense-related genes that enhance resistance to pathogens and mediate physiological activities in plants. To study whether the melatonin-mediated pathogen resistance is associated with chitinase gene (CaChiIII2), pepper plants and Arabidopsis seeds were treated with melatonin, then CaChiIII2 activation, hydrogen peroxide (H2O2) levels, and antioxidant enzymes activity during plant–pathogen interactions were investigated. Melatonin pretreatment uncoupled the knockdown of CaChiIII2 and transiently activated its expression level in both control and CaChiIII2-silenced pepper plants and enhanced plant resistance. Suppression of CaChiIII2 in pepper plants showed a significant decreased in the induction of defense-related genes and resistance to pathogens compared with control plants. Moreover, melatonin efficiently enabled plants to maintain intracellular H2O2 concentrations at steady-state levels and enhanced the activities of antioxidant enzymes, which possibly improved disease resistance. The activation of the chitinase gene CaChiIII2 in transgenic Arabidopsis lines was elevated under C. gloeosporioides infection and exhibited resistance through decreasing H2O2 biosynthesis and maintaining H2O2 at a steady-state level. Whereas melatonin primed CaChiIII2-overexpressed (OE) and wild-type (WT) Arabidopsis seedlings displayed a remarkable increase in root-length compared to the unprimed WT plants. Using an array of CaChiIII2 knockdown and OE, we found that melatonin efficiently induced CaChiIII2 and other pathogenesis-related genes expressions, responsible for the innate immunity response of pepper against anthracnose disease.
Risk Analysis of Road Tunnels: A Computational Fluid Dynamic Model for Assessing the Effects of Natural Ventilation
Authors: Caliendo Ciro , Genovese Gianluca , Russo Isidoro
Published: December 2020

We have developed an appropriate Computational Fluid Dynamics (CFD) model for assessing the exposure to risk of tunnel users during their evacuation process in the event of fire. The effects on escaping users, which can be caused by fire from different types of vehicles located in various longitudinal positions within a one-way tunnel with natural ventilation only and length less than 1 km are shown. Simulated fires, in terms of maximum Heat Release Rate (HRR) are: 8, 30, 50, and 100 MW for two cars, a bus, and two types of Heavy Goods Vehicles (HGVs), respectively. With reference to environmental conditions (i.e., temperatures, radiant heat fluxes, visibility distances, and CO and CO2 concentrations) along the evacuation path, the results prove that these are always within the limits acceptable for user safety. The exposure to toxic gases and heat also confirms that the tunnel users can safely evacuate. The evacuation time was found to be higher when fire was related to the bus, which is due to a major pre-movement time required for leaving the vehicle. The findings show that mechanical ventilation is not necessary in the case of the tunnel investigated. It is to be emphasized that our modeling might represent a reference in investigating the effects of natural ventilation in tunnels.