bluuebunny/crossref_metadata_2025 huggingface dataset:
Accurate and Efficient Calculation of Three-Dimensional Cost Distance
Authors: Chen Yaqian , She Jiangfeng , Li Xingong , Zhang Shuhua , Tan Junzhong
Published: May 2020

Cost distance is one of the fundamental functions in geographical information systems (GISs). 3D cost distance function makes the analysis of movement in 3D frictions possible. In this paper, we propose an algorithm and efficient data structures to accurately calculate the cost distance in discrete 3D space. Specifically, Dijkstra’s algorithm is used to calculate the least cost between initial voxels and all the other voxels in 3D space. During the calculation, unnecessary bends along the travel path are constantly corrected to retain the accurate least cost. Our results show that the proposed algorithm can generate true Euclidean distance in homogeneous frictions and can provide more accurate least cost in heterogeneous frictions than that provided by several existing methods. Furthermore, the proposed data structures, i.e., a heap combined with a hash table, significantly improve the algorithm’s efficiency. The algorithm and data structures have been verified via several applications including planning the shortest drone delivery path in an urban environment, generating volumetric viewshed, and calculating the minimum hydraulic resistance.
Hypercholesterolemia Interferes with Induction of miR-125b-1-3p in Preconditioned Hearts
Authors: Szabó Márton R. , Gáspár Renáta , Pipicz Márton , Zsindely Nóra , Diószegi Petra , Sárközy Márta , Bodai László , Csont Tamás
Published: May 2020

Ischemic preconditioning (IPre) reduces ischemia/reperfusion (I/R) injury in the heart. The non-coding microRNA miR-125b-1-3p has been demonstrated to play a role in the mechanism of IPre. Hypercholesterolemia is known to attenuate the cardioprotective effect of preconditioning; nevertheless, the exact underlying mechanisms are not clear. Here we investigated, whether hypercholesterolemia influences the induction of miR-125b-1-3p by IPre. Male Wistar rats were fed with a rodent chow supplemented with 2% cholesterol and 0.25% sodium-cholate hydrate for 8 weeks to induce high blood cholesterol levels. The hearts of normo- and hypercholesterolemic animals were then isolated and perfused according to Langendorff, and were subjected to 35 min global ischemia and 120 min reperfusion with or without IPre (3 × 5 min I/R cycles applied before index ischemia). IPre significantly reduced infarct size in the hearts of normocholesterolemic rats; however, IPre was ineffective in the hearts of hypercholesterolemic animals. Similarly, miR-125b-1-3p was upregulated by IPre in hearts of normocholesterolemic rats, while in the hearts of hypercholesterolemic animals IPre failed to increase miR-125b-1-3p significantly. Phosphorylation of cardiac Akt, ERK, and STAT3 was not significantly different in any of the groups at the end of reperfusion. Based on these results we propose here that hypercholesterolemia attenuates the upregulation of miR-125b-1-3p by IPre, which seems to be associated with the loss of cardioprotection.
17-Aminogeldanamycin Inhibits Constitutive Nuclear Factor-Kappa B (NF-κB) Activity in Patient-Derived Melanoma Cell Lines
Authors: Hartman Mariusz L. , Rogut Magdalena , Mielczarek-Lewandowska Aleksandra , Wozniak Michal , Czyz Malgorzata
Published: May 2020

Melanoma remains incurable skin cancer, and targeting heat shock protein 90 (HSP90) is a promising therapeutic approach. In this study, we investigate the effect of 17-aminogeldanamycin, a potent HSP90 inhibitor, on nuclear factor-kappa B (NF-κB) activity in BRAFV600E and NRASQ61R patient-derived melanoma cell lines. We performed time-lapse microscopy and flow cytometry to monitor changes in cell confluence and viability. The NF-κB activity was determined by immunodetection of phospho-p65 and assessment of expression of NF-κB-dependent genes by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Constitutive activity of p65/NF-κB was evident in all melanoma cell lines. Differences in its level might be associated with genetic alterations in CHUK, IL1B, MAP3K14, NFKBIE, RIPK1, and TLR4, while differences in transcript levels of NF-κB-inducible genes revealed by PCR array might result from the contribution of other regulatory mechanisms. 17-Aminogeldanamycin markedly diminished the level of phospho-p65, but the total p65 protein level was unaltered, indicating that 17-aminogeldanamycin inhibited activation of p65/NF-κB. This conclusion was supported by significantly reduced expression of selected NF-κB-dependent genes: cyclin D1 (CCND1), C-X-C motif chemokine ligand 8 (CXCL8), and vascular endothelial growth factor (VEGF), as shown at transcript and protein levels, as well as secretion of IL-8 and VEGF. Our study indicates that 17-aminogeldanamycin can be used for efficient inhibition of NF-κB activity and the simultaneous diminution of IL-8 and VEGF levels in the extracellular milieu of melanoma.
Comparative Analyses of Five Complete Chloroplast Genomes from the Genus Pterocarpus (Fabacaeae)
Authors: Hong Zhou , Wu Zhiqiang , Zhao Kunkun , Yang Zengjiang , Zhang Ningnan , Guo Junyu , Tembrock Luke R. , Xu Daping
Published: May 2020

Pterocarpus is a genus of trees mainly distributed in tropical Asia, Africa, and South America. Some species of Pterocarpus are rosewood tree species, having important economic value for timber, and for some species, medicinal value as well. Up to now, information about this genus with regard to the genomic characteristics of the chloroplasts has been limited. Based on a combination of next-generation sequencing (Illumina Hiseq) and long-read sequencing (PacBio), the whole chloroplast genomes (cp genomes) of five species (rosewoods) in Pterocarpus (Pterocarpus macrocarpus, P. santalinus, P. indicus, P. pedatus, P. marsupium) have been assembled. The cp genomes of five species in Pterocarpus have similar structural characteristics, gene content, and sequence to other flowering plants. The cp genomes have a typical four-part structure, containing 110 unique genes (77 protein coding genes, 4 rRNAs, 29 tRNAs). Through comparative genomic analysis, abundant simple sequence repeat (SSR)loci (333–349) were detected in Pterocarpus, among which A /T single nucleotide repeats accounted for the highest proportion (72.8–76.4%). In the five cp genomes of Pterocarpus, eight hypervariable regions, including trnH-GUG_psbA, trnS-UGA_psbC, accD-psaI, ndhI-exon2_ndhI-exon1, ndhG_ndhi-exon2, rpoC2-exon2, ccsA, and trnfM-CAU, are proposed for use as DNA barcode regions. In the comparison of gene selection pressures (P. santalinus as the reference genome), purifying selection was inferred as the primary mode of selection in maintaining important biological functions. Phylogenetic analysis shows that Pterocarpus is a monophyletic group. The species P. tinctorius is resolved as early diverging in the genus. Pterocarpus was resolved as sister to the genus Tipuana.
A Fatal Alliance between Microglia, Inflammasomes, and Central Pain
Authors: Hoffmann Stefanie , Beyer Cordian
Published: May 2020

Microglia are the resident immune cells in the CNS, which survey the brain parenchyma for pathogens, initiate inflammatory responses, secrete inflammatory mediators, and phagocyte debris. Besides, they play a role in the regulation of brain ion homeostasis and in pruning synaptic contacts and thereby modulating neural networks. More recent work shows that microglia are embedded in brain response related to stress phenomena, the development of major depressive disorders, and pain-associated neural processing. The microglia phenotype varies between activated-toxic-neuroinflammatory to non-activated-protective-tissue remodeling, depending on the challenges and regulatory signals. Increased inflammatory reactions result from brain damage, such as stroke, encephalitis, as well as chronic dysfunctions, including stress and pain. The dimension of damage/toxic stimuli defines the amplitude of inflammation, ranging from an on-off event to low but continuous simmering to uncontrollable. Pain, either acute or chronic, involves inflammasome activation at the point of origin, the different relay stations, and the sensory and processing cortical areas. This short review aimed at identifying a sinister role of the microglia-inflammasome platform for the development and perpetuation of acute and chronic central pain and its association with changes in CNS physiology.
Transcriptional Activity and Stability of CD39+CD103+CD8+ T Cells in Human High-Grade Endometrial Cancer
Authors: Workel Hagma H. , van Rooij Nienke , Plat Annechien , Spierings Diana C.J. , Fehrmann Rudolf S. N. , Nijman Hans W. , de Bruyn Marco
Published: May 2020

Tumor-infiltrating CD8+ T cells (TIL) are of the utmost importance in anti-tumor immunity. CD103 defines tumor-resident memory T cells (TRM cells) associated with improved survival and response to immune checkpoint blockade (ICB) across human tumors. Co-expression of CD39 and CD103 marks tumor-specific TRM with enhanced cytolytic potential, suggesting that CD39+CD103+ TRM could be a suitable biomarker for immunotherapy. However, little is known about the transcriptional activity of TRM cells in situ. We analyzed CD39+CD103+ TRM cells sorted from human high-grade endometrial cancers (n = 3) using mRNA sequencing. Cells remained untreated or were incubated with PMA/ionomycin (activation), actinomycin D (a platinum-like chemotherapeutic that inhibits transcription), or a combination of the two. Resting CD39+CD103+ TRM cells were transcriptionally active and expressed a characteristic TRM signature. Activated CD39+CD103+ TRM cells differentially expressed PLEK, TWNK, and FOS, and cytokine genes IFNG, TNF, IL2, CSF2 (GM-CSF), and IL21. Findings were confirmed using qPCR and cytokine production was validated by flow cytometry of cytotoxic TIL. We studied transcript stability and found that PMA-responsive genes and mitochondrial genes were particularly stable. In conclusion, CD39+CD103+ TRM cells are transcriptionally active TRM cells with a polyfunctional, reactivation-responsive repertoire. Secondly, we hypothesize that differential regulation of transcript stability potentiates rapid responses upon TRM reactivation in tumors.
Characterization and Analysis of the Mitochondrial Genome of Common Bean (Phaseolus vulgaris) by Comparative Genomic Approaches
Authors: Bi Changwei , Lu Na , Xu Yiqing , He Chunpeng , Lu Zuhong
Published: May 2020

The common bean (Phaseolus vulgaris) is a major source of protein and essential nutrients for humans. To explore the genetic diversity and phylogenetic relationships of P. vulgaris, its complete mitochondrial genome (mitogenome) was sequenced and assembled. The mitogenome is 395,516 bp in length, including 31 unique protein-coding genes (PCGs), 15 transfer RNA (tRNA) genes, and 3 ribosomal RNA (rRNA) genes. Among the 31 PCGs, four genes (mttB, nad1, nad4L, and rps10) use ACG as initiation codons, which are altered to standard initiation codons by RNA editing. In addition, the termination codon CGA in the ccmFC gene is converted to UGA. Selective pressure analysis indicates that the ccmB, ccmFC, rps1, rps10, and rps14 genes were under evolutionary positive selection. The proportions of five amino acids (Phe, Leu, Pro, Arg, and Ser) in the whole amino acid profile of the proteins in each mitogenome can be used to distinguish angiosperms from gymnosperms. Phylogenetic analyses show that P. vulgaris is evolutionarily closer to the Glycininae than other leguminous plants. The results of the present study not only provide an important opportunity to conduct further genomic breeding studies in the common bean, they also provide valuable information for future evolutionary and molecular studies of leguminous plants.
Expanded Screening of One Million Swedish Babies with R4S and CLIR for Post-Analytical Evaluation of Data
Authors: Sörensen Lene , von Döbeln Ulrika , Åhlman Henrik , Ohlsson Annika , Engvall Martin , Naess Karin , Backman-Johansson Carolina , Nordqvist Yvonne , Wedell Anna , Zetterström Rolf H.
Published: May 2020

Sweden has one neonatal screening laboratory, receiving 115 to 120 thousand samples per year. Among the one million babies screened by tandem mass spectrometry from November 2010 until July 2019, a total of 665 babies were recalled and 311 verified as having one of the diseases screened for with this methodology, giving a positive predictive value (PPV) of 47% and an incidence of 1:3200. The PPV was high (41%) already in the first year after start of screening, thanks to the availability of the collaborative project Region 4 Stork database. The PPV is presently 58%. This improvement was achieved by the implementation of second-tier analyses in the screening for methylmalonic aciduria, propionic aciduria, isovaleric aciduria, and homocystinuria, and the employment of various post analytical tools of the Region 4 Stork, and its successor the collaborative laboratory integrated reports.
Arrhythmogenic Cardiomyopathy: Molecular Insights for Improved Therapeutic Design
Authors: Stevens Tyler L. , Wallace Michael J. , El Refaey Mona , Roberts Jason D. , Koenig Sara N. , Mohler Peter J.
Published: May 2020

Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder characterized by structural and electrical cardiac abnormalities, including myocardial fibro-fatty replacement. Its pathological ventricular substrate predisposes subjects to an increased risk of sudden cardiac death (SCD). ACM is a notorious cause of SCD in young athletes, and exercise has been documented to accelerate its progression. Although the genetic culprits are not exclusively limited to the intercalated disc, the majority of ACM-linked variants reside within desmosomal genes and are transmitted via Mendelian inheritance patterns; however, penetrance is highly variable. Its natural history features an initial “concealed phase” that results in patients being vulnerable to malignant arrhythmias prior to the onset of structural changes. Lack of effective therapies that target its pathophysiology renders management of patients challenging due to its progressive nature, and has highlighted a critical need to improve our understanding of its underlying mechanistic basis. In vitro and in vivo studies have begun to unravel the molecular consequences associated with disease causing variants, including altered Wnt/β-catenin signaling. Characterization of ACM mouse models has facilitated the evaluation of new therapeutic approaches. Improved molecular insight into the condition promises to usher in novel forms of therapy that will lead to improved care at the clinical bedside.
The Hypopiezotolerant Bacterium, Serratia liquefaciens, Failed to Grow in Mars Analog Soils under Simulated Martian Conditions at 7 hPa
Authors: Schuerger Andrew C. , Mickol Rebecca L. , Schwendner Petra
Published: May 2020

The search for life on Mars is predicated on the idea that Earth and Mars life (if present) should be both carbon- and water-based with similar forms of evolution. However, the astrobiology community can currently only investigate plausible Martian microbial ecosystems by using Terran life-forms as proxies. In order to examine how life might persist on Mars, we used a hypopiezotolerant bacterium (def., able to grow at 7–10 hPa)—Serratia liquefaciens—in growth assays with four Mars analog soils conducted under a subset of simulated Martian conditions including 7 hPa, 0 °C, and a CO2-enriched anoxic atmosphere (called low-PTA conditions). The four Mars analog soils included an Aeolian dust analog, the Mars JSC-1 analog, a Phoenix lander-site simulant, and a high-Salts analog. Serratia liquefaciens cells were able to grow at 30 °C in a liquid minimal basal medium (MBM) supplemented with 10- or 20-mM sucrose, Spizizen salts, and micronutrients. When the four analog soils were doped with both MBM and cells of S. liquefaciens, and subsequently incubated at 30 °C for 72 h, cell densities increased between 2-logs (Phoenix analog) and 4-logs (Aeolian and JSC-1 analogs); the Salts analog led to complete inactivation of S. liquefaciens within 24 h. In contrast, when the experiment was repeated, but incubated under low-PTA conditions, S. liquefaciens cells were either killed immediately by the Salts analog, or decreased by >5 logs over 28 d by the Aeolian, JSC-1, and Phoenix analogs. The failure of S. liquefaciens to grow in the analog soils under low-PTA conditions was attributed to the synergistic interactions among six factors (i.e., low pressure, low temperature, anoxic atmosphere (i.e., the low-PTA conditions), low-pH in the Salts soil, dissolved salts in all analogs, and oligotrophic conditions) that increased the biocidal or inhibitory conditions within the analog soils. Results suggest that even if a hypopiezotolerant Terran microbe is displaced from a spacecraft surface on Mars, and lands in a hydrated and nutrient-rich niche, growth in the Martian regolith is not automatically assured.
Decompositions of Weakly Compact Valued Integrable Multifunctions
Authors: Piazza Luisa Di , Musiał Kazimierz
Published: May 2020

We give a short overview on the decomposition property for integrable multifunctions, i.e., when an “integrable in a certain sense” multifunction can be represented as a sum of one of its integrable selections and a multifunction integrable in a narrower sense. The decomposition theorems are important tools of the theory of multivalued integration since they allow us to see an integrable multifunction as a translation of a multifunction with better properties. Consequently, they provide better characterization of integrable multifunctions under consideration. There is a large literature on it starting from the seminal paper of the authors in 2006, where the property was proved for Henstock integrable multifunctions taking compact convex values in a separable Banach space X. In this paper, we summarize the earlier results, we prove further results and present tables which show the state of art in this topic.
Autoimmune Thyroid Disease is Associated with a Lower Prevalence of Diabetic Retinopathy in Patients with Type 1 Diabetic Mellitus
Authors: Stefanowicz-Rutkowska Magdalena Maria , Matuszewski Wojciech , Bandurska-Stankiewicz Elżbieta Maria
Published: May 2020

Background and objectives: The aim of the study was to assess the correlation of autoimmune thyroid diseases (AITD) in patients with diabetes mellitus type 1 (DM1) with the occurrence of diabetic retinopathy (DR). Materials and Methods: The inclusion criteria for the study were: type 1 diabetes diagnosed on the basis of WHO criteria lasting at least a year, presence of AITD for at least a year, and age over 18 years. The control group consisted of patients without diagnosed AITD (DM1noAITD), selected according to age, BMI and DM1 duration. Anthropometric parameters, metabolic risk factors such as glycated hemoglobin (HbA1c), lipids and blood pressure, thyroid status and the presence of DR were assessed. Results: The study involved 200 patients with type 1 diabetes aged 36 ± 12 years, 70 men and 130 women. Patients from the study group (DM1AITD) had significantly lower creatinine concentration, significantly lower systolic blood pressure (SBP), glycated hemoglobin (HbA1c) percentage and triglyceride (TG) concentration, and higher high-density lipoprotein (HDL-cholesterol) concentration than the control group (DM1noAITD). There was a significantly lower chance of non-proliferative diabetic retinopathy (NPDR) among DM1AITD than in the control group. Conclusions: Patients with DM1 and AITD were metabolically better balanced, as evidenced by a significantly lower SBP, percentage of HbA1c and TG, as well as significantly higher HDL-cholesterol in this group. Patients with DM1 and AITD were significantly less likely to have NPDR than the control group.
Microbiome of the Queensland Fruit Fly through Metamorphosis
Authors: Majumder Rajib , Sutcliffe Brodie , Taylor Phillip W. , Chapman Toni A.
Published: May 2020

Bactrocera tryoni (Froggatt) (Queensland fruit fly, or “Qfly”) is a highly polyphagous tephritid fruit fly and a serious economic pest in Australia. Qfly biology is intimately linked to the bacteria and fungi of its microbiome. While there are numerous studies of the microbiome in larvae and adults, the transition of the microbiome through the pupal stage remains unknown. To address this knowledge gap, we used high-throughput Next-Generation Sequencing (NGS) to examine microbial communities at each developmental stage in the Qfly life cycle, targeting the bacterial 16S rRNA and fungal ITS regions. We found that microbial communities were similar at the larval and pupal stage and were also similar between adult males and females, yet there were marked differences between the larval and adult stages. Specific bacterial and fungal taxa are present in the larvae and adults (fed hydrolyzed yeast with sugar) which is likely related to differences in nutritional biology of these life stages. We observed a significant abundance of the Acetobacteraceae at the family level, both in the larval and pupal stages. Conversely, Enterobacteriaceae was highly abundant (>80%) only in the adults. The majority of fungal taxa present in Qfly were yeasts or yeast-like fungi. In addition to elucidating changes in the microbiome through developmental stages, this study characterizes the Qfly microbiome present at the establishment of laboratory colonies as they enter the domestication process.
Viral Bone Infection: A Neglected Disease?
Authors: Drago Lorenzo , Romanò Carlo L. , Morelli Ilaria , Benzakour Thami
Published: May 2020

Bone structures reveal viral DNA/RNA, but little is known of the interaction and pathogenesis of viruses and bone diseases. Their detection and identification is often overlooked and not considered by many clinicians and researchers. In this Editorial, we suggest the role of viruses in some inflammatory bone conditions and their possible role as aetiological agents in bone and joint infections.
Inhibiting Methanogenesis Stimulated de novo Synthesis of Microbial Amino Acids in Mixed Rumen Batch Cultures Growing on Starch but not on Cellulose
Authors: Ungerfeld Emilio M. , Aedo M. Fernanda , Muñoz Camila , Urrutia Natalie L. , Martínez Emilio D. , Saldivia Marcelo
Published: May 2020

Ameliorating methane (CH4) emissions from ruminants would have environmental benefits, but it is necessary to redirect metabolic hydrogen ([H]) toward useful sinks to also benefit animal productivity. We hypothesized that inhibiting rumen methanogenesis would increase de novo synthesis of microbial amino acids (AA) as an alternative [H] sink if sufficient energy and carbon are provided. We examined the effects of inhibiting methanogenesis with 9, 10-anthraquione (AQ) on mixed rumen batch cultures growing on cellulose or starch as sources of energy and carbon contrasting in fermentability, with ammonium (NH4+) or trypticase (Try) as nitrogen (N) sources. Inhibiting methanogenesis with AQ inhibited digestion with cellulose but not with starch, and decreased propionate and increased butyrate molar percentages with both substrates. Inhibiting methanogenesis with 9, 10-anthraquinone increased de novo synthesis of microbial AA with starch but not with cellulose. The decrease in the recovery of [H] caused by the inhibition of methanogenesis was more moderate with starch due to an enhancement of butyrate and AA as [H] sinks. There may be an opportunity to simultaneously decrease the emissions of CH4 and N with some ruminant diets and replace plant protein supplements with less expensive non-protein nitrogen sources such as urea.
A Review of Arguments for the Existence of Latent Infections of Bacillus anthracis, and Research Needed to Understand Their Role in the Outbreaks of Anthrax
Authors: Gainer Robert S. , Vergnaud Gilles , Hugh-Jones Martin E.
Published: May 2020

Hugh-Jones and Blackburn and Turnbull’s collective World Health Organization (WHO) report did literature reviews of the theories and the bases for causes of anthrax outbreaks. Both comment on an often-mentioned suspicion that, even though unproven, latent infections are likely involved. Hugh-Jones suggested Gainer do an updated review of our present-day knowledge of latent infections, which was the basis for Gainer’s talk at the Biology of Anthrax Conference in Bari, Italy 2019. At the Conference Gainer met Vergnaud who presented anthrax genome studies that implied that the disease might have spread throughout Asia and from Europe to North America in a short time span of three or four centuries. Vergnaud wondered if latent infections might have played a role in the process. Several other presenters at the Conference also mentioned results that might suggest the existence of latent infections. Vergnaud subsequently looked into some of the old French literature about related observations, results, and discussions of early Pasteur vaccine usage (late 1800′s) and found mentions of suspected latent infections. The first part of the paper is a focused summary and interpretation of Hugh-Jones and Blackburn’s and Turnbull’s reviews specifically looking for suggestions of latent infections, a few additional studies with slightly different approaches, and several mentions made of presentations and posters at the Conference in Italy. In general, many different investigators in different areas and aspects of the anthrax study at the Conference found reasons to suspect the existence of latent infections. The authors conclude that the affected species most studied, including Homo sapiens, provide circumstantial evidence of latent infections and modified host resistance. The last part of the review explores the research needed to prove or disprove the existence of latent infections.
Immune-modulatory Properties of the Octapeptide NAP in Campylobacter jejuni Infected Mice Suffering from Acute Enterocolitis
Authors: Heimesaat Markus M. , Mousavi Soraya , Kløve Sigri , Genger Claudia , Weschka Dennis , Giladi Eliezer , Bereswill Stefan , Gozes Illana
Published: May 2020

Human infections with the food-borne zoonotic pathogen Campylobacter jejuni are progressively rising and constitute serious global public health and socioeconomic burdens. Hence, application of compounds with disease-alleviating properties are required to combat campylobacteriosis and post-infectious sequelae. In our preclinical intervention study applying an acute C. jejuni induced enterocolitis model, we surveyed the anti-pathogenic and immune-modulatory effects of the octapeptide NAP which is well-known for its neuroprotective and anti-inflammatory properties. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and intraperitoneally treated with synthetic NAP from day 2 until day 5 post-infection. NAP-treatment did not affect gastrointestinal C. jejuni colonization but could alleviate clinical signs of infection that was accompanied by less pronounced apoptosis of colonic epithelial cells and enhancement of cell regenerative measures on day 6 post-infection. Moreover, NAP-treatment resulted in less distinct innate and adaptive pro-inflammatory immune responses that were not restricted to the intestinal tract but could also be observed in extra-intestinal and even systemic compartments. NAP-treatment further resulted in less frequent translocation of viable pathogens from the intestinal tract to extra-intestinal including systemic tissue sites. For the first time, we here provide evidence that NAP application constitutes a promising option to combat acute campylobacteriosis.
Advances in Molecular Tools and In Vivo Models for the Study of Human Fungal Pathogenesis
Authors: Malavia Dhara , Gow Neil A. R. , Usher Jane
Published: May 2020

Pathogenic fungi represent an increasing infectious disease threat to humans, especially with an increasing challenge of antifungal drug resistance. Over the decades, numerous tools have been developed to expedite the study of pathogenicity, initiation of disease, drug resistance and host-pathogen interactions. In this review, we highlight advances that have been made in the use of molecular tools using CRISPR technologies, RNA interference and transposon targeted mutagenesis. We also discuss the use of animal models in modelling disease of human fungal pathogens, focusing on zebrafish, the silkworm, Galleria mellonella and the murine model.
Anti-Inflammatory Effects of Vitamin E in Response to Candida albicans
Authors: Barros Silvana , D. Ribeiro Ana Paula , Offenbacher Steven , Loewy Zvi G.
Published: May 2020

Oral mucositis, inflammation, and ulceration that occur in the oral cavity can manifest in significant pain. A formulation was designed to investigate the potential of vitamin E to ameliorate inflammation resulting from Candida albicans in cell-based systems. Human gingival fibroblasts and THP1 cells were stimulated with heat killed C. albicans and Porphyromonas gingivalis LPS (agonists). Unstimulated cells were included as controls. Cells were also simultaneously treated with a novel denture adhesive formulation that contains vitamin E (antagonist). The experimental conditions included cells exposed to the experimental formulation or the vehicle for 2 h for mRNA extraction and analysis, and cells left for 24 h under those experimental conditions for analysis of protein expression by ELISA. ssAffymetrix expression microarray pathway analyses demonstrated that the tested formulation exhibited a statistically significant (p < 0.05) inhibition of the following key inflammatory pathways: TLR 6, IL-1 signaling (IRAK, A20), NF-kappaB, IL-6 signaling (gp130, JK2 and GRB2), TNF signaling (TNF receptor) and Arachidonic acid metabolism (PLA2). Quantitative PCR array analysis confirmed the downregulation of key inflammatory genes when cells under adhesive treatment were challenged with heat killed C. albicans. PGE2 secretion was inhibited by the tested formulation only on THP1 cells after 24 h stimulation with C. albicans. These results suggest that the active formulation containing vitamin E acetate can modulate inflammatory responses, through anti-inflammatory actions as indicated by in vitro experimental conditions.
Evidence for Common Horizontal Transmission of Wolbachia among Ants and Ant Crickets: Kleptoparasitism Added to the List
Authors: Tseng Shu-Ping , Hsu Po-Wei , Lee Chih-Chi , Wetterer James K. , Hugel Sylvain , Wu Li-Hsin , Lee Chow-Yang , Yoshimura Tsuyoshi , Yang Chin-Cheng Scotty
Published: May 2020

While Wolbachia, an intracellular bacterial symbiont, is primarily transmitted maternally in arthropods, horizontal transmission between species has been commonly documented. We examined kleptoparasitism as a potential mechanism for Wolbachia horizontal transmission, using ant crickets and their host ants as the model system. We compared prevalence and diversity of Wolbachia across multiple ant cricket species with different degrees of host specificity/integration level. Our analyses revealed at least three cases of inter-ordinal Wolbachia transfer among ant and ant crickets, and also showed that ant cricket species with high host-integration and host-specificity tend to harbor a higher Wolbachia prevalence and diversity than other types of ant crickets. This study provides empirical evidence that distribution of Wolbachia across ant crickets is largely attributable to horizontal transmission, but also elucidates the role of intimate ecological association in successful Wolbachia horizontal transmission.
Atomic Force Microscopy and Raman Microspectroscopy Investigations of the Leaching of Chalcopyrite (112) Surface
Authors: Qian Gujie , Gibson Christopher T. , Harmer-Bassell Sarah , Pring Allan
Published: May 2020

The aim of this study was to determine the reactivity of the chalcopyrite (112) surface under industrially relevant leaching conditions. Leaching of the chalcopyrite (112) surface was carried out at approximately pH 1 and in the presence of 0.01 M ferric or ferrous. The atomic force microscopy (AFM) and Raman microspectroscopy analyses suggested that the chalcopyrite (112) surface was relatively inert, with no formation of elemental sulfur observed over 42 days of leaching. In addition, it was found that the distribution of Fe-S and Cu-S bonds was always negatively correlated, as revealed by Raman analysis. This suggested that the breakage of the Fe-S and Cu-S bonds did not occur concurrently at a specific reaction site. The rate of variation of surface roughness, as reflected by AFM data, also suggested that leaching of the chalcopyrite (112) surface in the ferric or ferrous solution medium likely occurred more rapidly in the initial stage (fewer than seven days) than in the later stage (after seven days).
HOX Transcript Antisense RNA HOTAIR Abrogates Vasculogenic Mimicry by Targeting the AngiomiR-204/FAK Axis in Triple Negative Breast Cancer Cells
Authors: Lozano-Romero Allan , Astudillo-de la Vega Horacio , Terrones-Gurrola María Cruz del Rocío , Marchat Laurence A. , Hernández-Sotelo Daniel , Salinas-Vera Yarely M. , Ramos-Payan Rosalío , Silva-Cázares Macrina B. , Nuñez-Olvera Stephanie I. , Hernández-de la Cruz Olga N. , López-Camarillo César
Published: May 2020

HOX transcript antisense RNA (HOTAIR) is an oncogenic long non-coding RNA frequently overexpressed in cancer. HOTAIR can enhance the malignant behavior of tumors by sponging microRNAs with tumor suppressor functions. Vasculogenic mimicry is a hypoxia-activated process in which tumor cells form three-dimensional (3D) channel-like networks, resembling endothelial blood vessels, to obtain nutrients. However, the role of HOTAIR in vasculogenic mimicry and the underlying mechanisms are unknown in human cancers. In the current study, we investigated the relevance of HOTAIR in hypoxia-induced vasculogenic mimicry in metastatic MDA-MB-231 and invasive Hs-578t triple negative breast cancer cells. Analysis of The Cancer Genome Atlas (TCGA) database using cBioPortal confirmed that HOTAIR was upregulated in clinical breast tumors relative to normal mammary tissues. Our quantitative RT-PCR assays showed a significant increase in HOTAIR levels after 48 h hypoxia relative to normoxia in breast cancer cell lines. Remarkably, knockdown of HOTAIR significantly abolished the hypoxia-induced vasculogenic mimicry which was accompanied by a reduction in the number of 3D channel-like networks and branch points. Likewise, HOTAIR silencing leads to reduced cell migration abilities of cancer cells. Bioinformatic analysis predicted that HOTAIR has a potential binding site for tumor suppressor miR-204. Luciferase reporter assays confirmed that HOTAIR is a competitive endogenous sponge of miR-204. Congruently, forced inhibition of HOTAIR in cells resulted in augmented miR-204 levels in breast cancer cells. Further bioinformatic analysis suggested that miR-204 can bind to the 3′ untranslated region of focal adhesion kinase 1 (FAK) transcript involved in cell migration. Western blot and luciferase reporter assays confirmed that FAK is a novel target of miR-204. Finally, silencing of HOTAIR resulted in low levels of cytoplasmic FAK protein and alterations in the organization of cellular cytoskeleton and focal adhesions. In summary, our results showed, for the first time, that HOTAIR mitigates cell migration and vasculogenic mimicry by targeting the miR-204/FAK axis in triple negative breast cancer cells.
Effects of Olive Oil on Blood Pressure: Epidemiological, Clinical, and Mechanistic Evidence
Authors: Massaro Marika , Scoditti Egeria , Carluccio Maria Annunziata , Calabriso Nadia , Santarpino Giuseppe , Verri Tiziano , De Caterina Raffaele
Published: May 2020

The increasing access to antihypertensive medications has improved longevity and quality of life in hypertensive patients. Nevertheless, hypertension still remains a major risk factor for stroke and myocardial infarction, suggesting the need to implement management of pre- and hypertensive patients. In addition to antihypertensive medications, lifestyle changes, including healthier dietary patterns, such as the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet, have been shown to favorably affect blood pressure and are now recommended as integrative tools in hypertension management. An analysis of the effects of nutritional components of the Mediterranean diet(s) on blood pressure has therefore become mandatory. After a literature review of the impact of Mediterranean diet(s) on cardiovascular risk factors, we here analyze the effects of olive oil and its major components on blood pressure in healthy and cardiovascular disease individuals and examine underlying mechanisms of action. Both experimental and human studies agree in showing anti-hypertensive effects of olive oil. We conclude that due to its high oleic acid and antioxidant polyphenol content, the consumption of olive oil may be advised as the optimal fat choice in the management protocols for hypertension in both healthy and cardiovascular disease patients.
Qualitative Exploration of Pharmacists’ Feedback Following the Implementation of an “Allergic Rhinitis Clinical Management Pathway (AR-CMaP)” in Australian Community Pharmacies
Authors: Cvetkovski Biljana , Cheong Lynn , Tan Rachel , Kritikos Vicky , Rimmer Janet , Bousquet Jean , Yan Kwok , Bosnic-Anticevich Sinthia
Published: May 2020

Allergic Rhinitis (AR) is both a common and high burden disease, with the majority of AR sufferers purchasing suboptimal/inappropriate AR medication from community pharmacies. Unfortunately, it is still a challenge to translate the AR management guidelines that are available at both a global and national level into practice. This study aimed to explore the experiences and perceptions of community pharmacists with regards to the implementation of AR management guidelines in real-life everyday practice. This exploration took the form of a qualitative research study in which pharmacists were interviewed following the implementation of a guideline-driven AR management pathway in their pharmacies. Fifteen pharmacists from six pharmacies agreed to participate in a telephone interview. Five themes were identified that encompassed the sentiment of the pharmacists during the interviews: (1) impact of training on pharmacists’ approach to patients and AR management recommendations; (2) patient engagement and the importance of appropriate tools; (3) patient barriers to change in practice; (4) physical, logistical, and inter-professional barriers to change within the pharmacy environment; and (5) recommendations for improvement. The results of this study indicate that, following the implementation of an AR management pathway, pharmacists believe that their interactions with patients around their AR were enhanced through the use of appropriate tools and education. However, if optimal AR management is to be delivered within the community pharmacy setting, the undertaking needs to be collaborative with both pharmacy assistants and general practitioners.
Benchmark Dataset Based on Category Maps with Indoor–Outdoor Mixed Features for Positional Scene Recognition by a Mobile Robot
Authors: Madokoro Hirokazu , Woo Hanwool , Nix Stephanie , Sato Kazuhito
Published: May 2020

This study was conducted to develop original benchmark datasets that simultaneously include indoor–outdoor visual features. Indoor visual information related to images includes outdoor features to a degree that varies extremely by time, weather, and season. We obtained time-series scene images using a wide field of view (FOV) camera mounted on a mobile robot moving along a 392-m route in an indoor environment surrounded by transparent glass walls and windows for two directions in three seasons. For this study, we propose a unified method for extracting, characterizing, and recognizing visual landmarks that are robust to human occlusion in a real environment in which robots coexist with people. Using our method, we conducted an evaluation experiment to recognize scenes divided up to 64 zones with fixed intervals. The experimentally obtained results using the datasets revealed the performance and characteristics of meta-parameter optimization, mapping characteristics to category maps, and recognition accuracy. Moreover, we visualized similarities between scene images using category maps. We also identified cluster boundaries obtained from mapping weights.
Yield of Systematic Longitudinal Screening of Household Contacts of Pre-Extensively Drug Resistant (PreXDR) and Extensively Drug Resistant (XDR) Tuberculosis Patients in Mumbai, India
Authors: Paryani Roma Haresh , Gupta Vivek , Singh Pramila , Verma Madhur , Sheikh Sabira , Yadav Reeta , Mansoor Homa , Kalon Stobdan , Selvaraju Sriram , Das Mrinalini , Laxmeshwar Chinmay , Ferlazzo Gabriella , Isaakidis Petros
Published: May 2020

While risk of tuberculosis (TB) is high among household contacts (HHCs) of pre-extensively drug resistant (pre-XDR) TB and XDR-TB, data on yield of systematic longitudinal screening are lacking. We aim to describe the yield of systematic longitudinal TB contact tracing among HHCs of patients with pre-XDR-TB and XDR-TB. At the Médecins Sans Frontières (MSF) clinic, Mumbai, India a cohort comprising 518 HHCs of 109 pre-XDR and XDR index cases was enrolled between January 2016 and June 2018. Regular HHC follow-ups were done till one year post treatment of index cases. Of 518 HHCs, 23 had TB (21 on TB treatment and two newly diagnosed) at the time of first visit. Of the rest, 19% HHCs had no follow-ups. Fourteen (3.5%) TB cases were identified among 400 HHCs; incidence rate: 2072/100,000 person-years (95% CI: 1227–3499). The overall yield of household contact tracing was 3% (16/518). Of 14 who were diagnosed with TB during follow-up, six had drug susceptible TB (DSTB); six had pre-XDR-TB and one had XDR-TB. Five of fourteen cases had resistance patterns concordant with their index case. In view of the high incidence of TB among HHCs of pre-XDR and XDR-TB cases, follow-up of HHCs for at least the duration of index cases’ treatment should be considered.
Severe Multiorgan Failure Following Yellow Fever Vaccination
Authors: Domingo Cristina , Lamerz Judith , Cadar Daniel , Stojkovic Marija , Eisermann Philip , Merle Uta , Nitsche Andreas , Schnitzler Paul
Published: May 2020

Background: The yellow fever (YF) vaccination is recommended by the WHO for people traveling or living in endemic areas at risk for yellow fever infections in Africa and South America. Although the live attenuated yellow fever vaccine is a safe and efficient vaccine, rare serious adverse events after vaccination have been reported. Case presentation: We present the case of a 74-year-old male with multiorgan failure after yellow fever vaccination for a trip to Brazil. The patient required admission to the intensive care unit with a prolonged stay due to severe organ dysfunction. Five days after the YF vaccination, the patient experienced nausea, vomiting, diarrhea, and general illness. Three days later he sought medical attention and was transferred to the University Hospital Heidelberg with beginning multiorgan failure and severe septic shock, including hypotonia, tachypnea, thrombopenia, and acute renal failure the same day. Within one week after vaccination, antibodies against YF virus were already detectable and progressively increased over the next two weeks. Viral RNA was detected in serum on the day of admission, with a viral load of 1.0 × 105 copies/mL. The YF virus (YFV) RNA was also present in tracheal secretions for several weeks and could be detected in urine samples up to 20 weeks after vaccination, with a peak viral load of 1.3 × 106 copies/mL. After 20 weeks in the ICU with nine weeks of mechanical ventilation, the patient was transferred to another hospital for further recovery. Conclusions: The risk for severe adverse events due to the YF vaccination should be balanced against the risk of acquiring a severe YF infection, especially in elderly travelers.
Cloning and Expression of the Tibetan Pig Interleukin-23 Gene and Its Promotion of Immunity of Pigs to PCV2 Vaccine
Authors: Xiao Yongle , Zhang Huan , Chen Jianlin , Chen Yi , Li Jinghai , Song Tingyu , Zeng Guangzhi , Chen Xiaohui , Lü Xuebin , Fang Pengfei , Gao Rong
Published: May 2020

Vaccines against Porcine circovirus type 2 (PCV2) have been studied intensely and found to be effective in decreasing mortality and improving growth in swine populations. In this study, interleukin-23 (IL-23) gene was cloned from peripheral blood mononuclear cells (PBMCs) of Tibetan pigs and inserted into a eukaryotic VR1020 expression vector-VRIL23. Coated with chitosan (CS), the VRIL23-CS was intramuscularly injected into 3-week-old piglets with PCV2 vaccine. The blood was collected after vaccination at 0, 1, 2, 4, 8, and 12 weeks, respectively, to detect the immunological changes. The IgG2a and specific PCV2 antibodies were detected using ELISA, and blood CD4+ and CD8+ T cells were quantified by flow cytometry. Quantitative fluorescence PCR was used to evaluate the expression of immune genes. The results indicate that leukocytes, erythrocytes, and CD4+ and CD8+ T cells increased significantly in the blood of VRIL23-CS inoculated piglets in comparison with the control (p < 0.05) and so did the IgG2a and PCV2 antibodies. In addition, the expressions of Toll-like receptor (TLR) 2, TLR7, cluster of differentiation (CD) 45, IL-15, IL-12, signal transducer and activator of transcription (STAT)1, STAT2, STAT3, STAT4, and B-cell lymphoma (Bcl)-2 genes were also obviously higher in the VRIL23-CS inoculated pigs at different time points (p < 0.05). Overall, the results demonstrated that VRIL23-CS can enhance the comprehensive immune responses to PCV2 vaccine in vivo and has the promising potential to be developed into a safe and effective adjuvant to promote the immunity of pig against PCV disease.
Effects of Spatial Frequency Filtering Choices on the Perception of Filtered Images
Authors: Perfetto Sabrina , Wilder John , Walther Dirk B.
Published: May 2020

The early visual system is composed of spatial frequency-tuned channels that break an image into its individual frequency components. Therefore, researchers commonly filter images for spatial frequencies to arrive at conclusions about the differential importance of high versus and low spatial frequency image content. Here, we show how simple decisions about the filtering of the images, and how they are displayed on the screen, can result in drastically different behavioral outcomes. We show that jointly normalizing the contrast of the stimuli is critical in order to draw accurate conclusions about the influence of the different spatial frequencies, as images of the real world naturally have higher contrast energy at low than high spatial frequencies. Furthermore, the specific choice of filter shape can result in contradictory results about whether high or low spatial frequencies are more useful for understanding image content. Finally, we show that the manner in which the high spatial frequency content is displayed on the screen influences how recognizable an image is. Previous findings that make claims about the visual system’s use of certain spatial frequency bands should be revisited, especially if their methods sections do not make clear what filtering choices were made.