bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian Folliculogenesis and Uterine Endometrial Receptivity after Intermittent Vaginal Injection of Recombinant Human Follicle-Stimulating Hormone in Infertile Women Receiving In Vitro Fertilization and in Immature Female Rats
Authors: Hsu Chao-Chin , Hsu Leonard , Hsueh Yuan-Shuo , Lin Chih-Ying , Chang Hui Hua , Hsu Chao-Tien
Published: October 2021

The uterine first-pass effect occurs when drugs are delivered vaginally. However, the effect of vaginally administered recombinant human follicle-stimulating hormone (rhFSH) on ovarian folliculogenesis and endometrial receptivity is not well established. We aimed to compare the efficacy of rhFSH administered vaginally and abdominally in clinical in vitro fertilization (IVF) treatment, pharmacokinetic study, and animal study. In IVF treatment, the number of oocytes retrieved, endometrial thickness and uterine artery blood perfusion were not different between women who received the rhFSH either vaginally or abdominally. For serum pharmacokinetic parameters, significantly lower Tmax, clearance, and higher AUC and T1/2_elimination of rhFSH were observed in women who received rhFSH vaginally, but urine parameters were not different. Immature female rats that received daily abdominal or vaginal injections (1 IU twice daily for 4 days) or intermittent vaginal injections (4 IU every other day for two doses) of rhFSH had more total follicles than the control group. In addition, the serum progesterone and progesterone receptors in the local endometrium were significantly higher in the groups treated with intermittent abdominal or vaginal injection of rhFSH, compared with those who recieved daily injection. In summary, vaginal administration of rhFSH may provide an alternative treatment regimen in women receiving IVF.
Constitutive Photomorphogenic 1 Enhances ER Stress Tolerance in Arabidopsis
Authors: Kang Chang Ho , Lee Eun Seon , Nawkar Ganesh M. , Park Joung Hun , Wi Seong Dong , Bae Su Bin , Chae Ho Byoung , Paeng Seol Ki , Hong Jong Chan , Lee Sang Yeol
Published: October 2021

Interaction between light signaling and stress response has been recently reported in plants. Here, we investigated the role of CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), a key regulator of light signaling, in endoplasmic reticulum (ER) stress response in Arabidopsis. The cop1-4 mutant Arabidopsis plants were highly sensitive to ER stress induced by treatment with tunicarmycin (Tm). Interestingly, the abundance of nuclear-localized COP1 increased under ER stress conditions. Complementation of cop1-4 mutant plants with the wild-type or variant types of COP1 revealed that the nuclear localization and dimerization of COP1 are essential for its function in plant ER stress response. Moreover, the protein amount of ELONGATED HYPOCOTYL 5 (HY5), which inhibits bZIP28 to activate the unfolded protein response (UPR), decreased under ER stress conditions in a COP1-dependent manner. Accordingly, the binding of bZIP28 to the BIP3 promoter was reduced in cop1-4 plants and increased in hy5 plants compared with the wild type. Furthermore, introduction of the hy5 mutant locus into the cop1-4 mutant background rescued its ER stress-sensitive phenotype. Altogether, our results suggest that COP1, a negative regulator of light signaling, positively controls ER stress response by partially degrading HY5 in the nucleus.
Identification and Characterization of a Thermostable GH36 α-Galactosidase from Anoxybacillus vitaminiphilus WMF1 and Its Application in Synthesizing Isofloridoside by Reverse Hydrolysis
Authors: Wang Jialing , Cao Xuefei , Chen Weihao , Xu Jiaxing , Wu Bin
Published: October 2021

An α-galactosidase-producing strain named Anoxybacillus vitaminiphilus WMF1, which catalyzed the reverse hydrolysis of d-galactose and glycerol to produce isofloridoside, was isolated from soil. The α-galactosidase (galV) gene was cloned and expressed in Escherichia coli. The galV was classified into the GH36 family with a molecular mass of 80 kDa. The optimum pH and temperature of galV was pH 7.5 and 60 °C, respectively, and it was highly stable at alkaline pH (6.0–9.0) and temperature below 65 °C. The specificity for p-nitrophenyl α-d-galactopyranoside was 70 U/mg, much higher than that for raffinose and stachyose. Among the metals and reagents tested, galV showed tolerance in the presence of various organic solvents. The kinetic parameters of the enzyme towards p-nitrophenyl α-d-galactopyranoside were obtained as Km (0.12 mM), Vmax (1.10 × 10−3 mM s−1), and Kcat/Km (763.92 mM−1 s−1). During the reaction of reverse hydrolysis, the enzyme exhibited high specificity towards the glycosyl donor galactose and acceptors glycerol, ethanol and ethylene glycol. Finally, the isofloridoside was synthesized using galactose as the donor and glycerol as the acceptor with a 26.6% conversion rate of galactose. This study indicated that galV might provide a potential enzyme source in producing isofloridoside because of its high thermal stability and activity.
Early Changes in Exo- and Endocytosis in the EAE Mouse Model of Multiple Sclerosis Correlate with Decreased Synaptic Ribbon Size and Reduced Ribbon-Associated Vesicle Pools in Rod Photoreceptor Synapses
Authors: Kesharwani Ajay , Schwarz Karin , Dembla Ekta , Dembla Mayur , Schmitz Frank
Published: October 2021

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that finally leads to demyelination. Demyelinating optic neuritis is a frequent symptom in MS. Recent studies also revealed synapse dysfunctions in MS patients and MS mouse models. We previously reported alterations of photoreceptor ribbon synapses in the experimental auto-immune encephalomyelitis (EAE) mouse model of MS. In the present study, we found that the previously observed decreased imunosignals of photoreceptor ribbons in early EAE resulted from a decrease in synaptic ribbon size, whereas the number/density of ribbons in photoreceptor synapses remained unchanged. Smaller photoreceptor ribbons are associated with fewer docked and ribbon-associated vesicles. At a functional level, depolarization-evoked exocytosis as monitored by optical recording was diminished even as early as on day 7 after EAE induction. Moreover compensatory, post-depolarization endocytosis was decreased. Decreased post-depolarization endocytosis in early EAE correlated with diminished synaptic enrichment of dynamin3. In contrast, basal endocytosis in photoreceptor synapses of resting non-depolarized retinal slices was increased in early EAE. Increased basal endocytosis correlated with increased de-phosphorylation of dynamin1. Thus, multiple endocytic pathways in photoreceptor synapse are differentially affected in early EAE and likely contribute to the observed synapse pathology in early EAE.
Inhibition of Mitochondrial Metabolism Leads to Selective Eradication of Cells Adapted to Acidic Microenvironment
Authors: Koncošová Martina , Vrzáčková Nikola , Křížová Ivana , Tomášová Petra , Rimpelová Silvie , Dvořák Aleš , Vítek Libor , Rumlová Michaela , Ruml Tomáš , Zelenka Jaroslav
Published: October 2021

Metabolic transformation of cancer cells leads to the accumulation of lactate and significant acidification in the tumor microenvironment. Both lactate and acidosis have a well-documented impact on cancer progression and negative patient prognosis. Here, we report that cancer cells adapted to acidosis are significantly more sensitive to oxidative damage induced by hydrogen peroxide, high-dose ascorbate, and photodynamic therapy. Higher lactate concentrations abrogate the sensitization. Mechanistically, acidosis leads to a drop in antioxidant capacity caused by a compromised supply of nicotinamide adenine dinucleotide phosphate (NADPH) derived from glucose metabolism. However, lactate metabolism in the Krebs cycle restores NADPH supply and antioxidant capacity. CPI-613 (devimistat), an anticancer drug candidate, selectively eradicates the cells adapted to acidosis through inhibition of the Krebs cycle and induction of oxidative stress while completely abrogating the protective effect of lactate. Simultaneous cell treatment with tetracycline, an inhibitor of the mitochondrial proteosynthesis, further enhances the cytotoxic effect of CPI-613 under acidosis and in tumor spheroids. While there have been numerous attempts to treat cancer by neutralizing the pH of the tumor microenvironment, we alternatively suggest considering tumor acidosis as the Achilles’ heel of cancer as it enables selective therapeutic induction of lethal oxidative stress.
The Role of Peritoneal Macrophages in Endometriosis
Authors: Ramírez-Pavez Tamara N. , Martínez-Esparza María , Ruiz-Alcaraz Antonio J. , Marín-Sánchez Pilar , Machado-Linde Francisco , García-Peñarrubia Pilar
Published: October 2021

Endometriosis is an estrogen-dependent gynecological disorder, defined as the growth of endometrial stromal cells and glands at extrauterine sites. Endometriotic lesions are more frequently located into the abdominal cavity, although they can also be implanted in distant places. Among its etiological factors, the presence of immune dysregulation occupies a prominent place, pointing out the beneficial and harmful outcomes of macrophages in the pathogenesis of this disease. Macrophages are tissue-resident cells that connect innate and adaptive immunity, playing a key role in maintaining local homeostasis in healthy conditions and being critical in the development and sustainment of many inflammatory diseases. Macrophages accumulate in the peritoneal cavity of women with endometriosis, but their ability to clear migrated endometrial fragments seems to be inefficient. Hence, the characteristics of the peritoneal immune system in endometriosis must be further studied to facilitate the search for new diagnostic and therapeutic tools. In this review, we summarize recent relevant advances obtained in both mouse, as the main animal model used to study endometriosis, and human, focusing on peritoneal macrophages obtained from endometriotic patients and healthy donors, under the perspective of its future clinical translation to the role that these cells play on this pathology.
Lecithin Inclusion by α-Cyclodextrin Activates SREBP2 Signaling in the Gut and Ameliorates Postprandial Hyperglycemia
Authors: Lee Eunyoung , Zhang Xilin , Noda Tomoe , Miyamoto Junki , Kimura Ikuo , Tanaka Tomoaki , Sakurai Kenichi , Hatano Ryo , Miki Takashi
Published: October 2021

Background: α-cyclodextrin (α-CD) is one of the dietary fibers that may have a beneficial effect on cholesterol and/or glucose metabolism, but its efficacy and mode of action remain unclear. Methods: In the present study, we examined the anti-hyperglycemic effect of α-CD after oral loading of glucose and liquid meal in mice. Results: Administration of 2 g/kg α-CD suppressed hyperglycemia after glucose loading, which was associated with increased glucagon-like peptide 1 (GLP-1) secretion and enhanced hepatic glucose sequestration. By contrast, 1 g/kg α-CD similarly suppressed hyperglycemia, but without increasing secretions of GLP-1 and insulin. Furthermore, oral α-CD administration disrupts lipid micelle formation through its inclusion of lecithin in the gut luminal fluid. Importantly, prior inclusion of α-CD with lecithin in vitro nullified the anti-hyperglycemic effect of α-CD in vivo, which was associated with increased intestinal mRNA expressions of SREBP2-target genes (Ldlr, Hmgcr, Pcsk9, and Srebp2). Conclusions: α-CD elicits its anti-hyperglycemic effect after glucose loading by inducing lecithin inclusion in the gut lumen and activating SREBP2, which is known to induce cholecystokinin secretion to suppress hepatic glucose production via a gut/brain/liver axis.
Oligomeric Structural Transition of HspB1 from Chinese Hamster
Authors: Kurokawa Nina , Midorikawa Rio , Nakamura Manami , Noguchi Keiichi , Morishima Ken , Inoue Rintaro , Sugiyama Masaaki , Yohda Masafumi
Published: October 2021

HspB1 is a mammalian sHsp that is ubiquitously expressed in almost all tissues and involved in regulating many vital functions. Although the recent crystal structure of human HspB1 showed that 24 monomers form the oligomeric complex of human HspB1 in a spherical configuration, the molecular architecture of HspB1 is still controversial. In this study, we examined the oligomeric structural change of CgHspB1 by sedimentation velocity analytical ultracentrifugation. At the low temperature of 4 °C, CgHspB1 exists as an 18-mer, probably a trimeric complex of hexamers. It is relatively unstable and partially dissociates into small oligomers, hexamers, and dodecamers. At elevated temperatures, the 24-mer was more stable than the 18-mer. The 24-mer is also in dynamic equilibrium with the dissociated oligomers in the hexameric unit. The hexamer further dissociates to dimers. The disulfide bond between conserved cysteine residues seems to be partly responsible for the stabilization of hexamers. The N-terminal domain is involved in the assembly of dimers and the interaction between hexamers. It is plausible that CgHspB1 expresses a chaperone function in the 24-mer structure.
An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure
Authors: Boopathi Subramanian , Poma Adolfo B. , Garduño-Juárez Ramón
Published: October 2021

Amyloid beta (Aβ) oligomers are the most neurotoxic aggregates causing neuronal death and cognitive damage. A detailed elucidation of the aggregation pathways from oligomers to fibril formation is crucial to develop therapeutic strategies for Alzheimer’s disease (AD). Although experimental techniques rely on the measure of time- and space-average properties, they face severe difficulties in the investigation of Aβ peptide aggregation due to their intrinsically disorder character. Computer simulation is a tool that allows tracing the molecular motion of molecules; hence it complements Aβ experiments, as it allows to explore the binding mechanism between metal ions and Aβ oligomers close to the cellular membrane at the atomic resolution. In this context, integrated studies of experiments and computer simulations can assist in mapping the complete pathways of aggregation and toxicity of Aβ peptides. Aβ oligomers are disordered proteins, and due to a rapid exploration of their intrinsic conformational space in real-time, they are challenging therapeutic targets. Therefore, no good drug candidate could have been identified for clinical use. Our previous investigations identified two small molecules, M30 (2-Octahydroisoquinolin-2(1H)-ylethanamine) and Gabapentin, capable of Aβ binding and inhibiting molecular aggregation, synaptotoxicity, intracellular calcium signaling, cellular toxicity and memory losses induced by Aβ. Thus, we recommend these molecules as novel candidates to assist anti-AD drug discovery in the near future. This review discusses the most recent research investigations about the Aβ dynamics in water, close contact with cell membranes, and several therapeutic strategies to remove plaque formation.
Culturomics Approaches Expand the Diagnostic Accuracy for Sexually Transmitted Infections
Authors: Wolf Ellinor Anna , Rettig Hannah Clara , Lupatsii Mariia , Schlüter Britta , Schäfer Kathrin , Friedrich Dirk , Graspeuntner Simon , Rupp Jan
Published: October 2021

Sexually transmitted infections (STIs) are a major health concern with clinical manifestations being acknowledged to cause severe reproductive impairment. Research in infectious diseases has been centered around the known major pathogens for decades. However, we have just begun to understand that the microbiota of the female genital tract is of particular importance for disease initiation, infection progression, and pathological outcome. Thus, we are now aware that many poorly described, partially not yet known, or cultured bacteria may pave the way for an infection and/or contribute to disease severity. While sequencing-based methods are an important step in diagnosing STIs, culture-based methods are still the gold-standard method in diagnostic routine, providing the opportunity to distinguish phenotypic traits of bacteria. However, current diagnostic culture routines suffer from several limitations reducing the content of information about vaginal microbiota. A detailed characterization of microbiota-associated factors is needed to assess the impact of single-bacterial isolates from the vaginal community on vaginal health and the containment of STIs. Here we provide current concepts to enable modern culture routines and create new ideas to improve diagnostic approaches with a conjunct usage of bioinformatics. We aim to enable scientists and physicians alike to overcome long-accepted limitations in culturing bacteria of interest to the human health. Eventually, this may improve the quality of culture-based diagnostics, facilitate a research interface, and lead to a broader understanding of the role of vaginal microbiota in reproductive health and STIs.
Amyloid-β Processing in Aged S100B Transgenic Mice Is Sex Dependent
Authors: Wartchow Krista Minéia , Rodrigues Leticia , Swierzy Izabela , Buchfelder Michael , de Souza Diogo Onofre , Gonçalves Carlos-Alberto , Kleindienst Andrea
Published: October 2021

(1) Background: Calcium-binding protein S100B is involved in neuroregeneration but has also been associated with neurodegeneration. These contrasting effects may result from concentration or duration of exposure. We investigated the effect of long-term increased S100B levels on amyloid-β processing in one-year-old transgenic (tg) mice with 12 copies of the murine S100B gene with specific consideration of sex and specific brain regions. (2) Methods: S100B and amyloid-β 42 (Aβ42) were quantified in serum, cerebrospinal fluid (CSF), adipose tissue, and different brain regions by ELISA in wild-type (wt) and S100Btg mice (each n = 7 per group). Thioflavin T (ThT) and Aβ immunostaining were performed for visualization of Aβ deposition. (3) Results: S100B in serum, CSF, and brain was significantly increased in S100Btg mice of both sexes. Aβ42 was significantly increased in the hippocampus of male S100Btg mice (p = 0.0075), and the frontal cortex of female S100Btg mice (p = 0.0262). ThT and Aβ immunostaining demonstrated Aβ deposition in different brain regions in S100Btg mice of both sexes and female wt. (4) Conclusion: Our data validate this experimental model for studying the role of S100B in neurodegeneration and indicate that Aβ processing is sex-dependent and brain region-specific, which deserves further investigation of signaling pathways and behavioral responses.
Mulches Used in Highbush Blueberry and Entomopathogenic Nematodes Affect Mortality Rates of Third-Instar Popillia japonica
Authors: Renkema Justin M. , Parent Jean-Philippe
Published: October 2021

Popillia japonica Newman (Japanese beetle) is an invasive, polyphagous pest in North America, as adults feed on plant foliage and larvae on roots. Management in crops relies on foliar and soil applications of insecticides, but entomopathogenic nematodes (EPN) are effective biocontrol agents. In highbush blueberry, mulches (composts, woodshavings, sawdust, bark) are used for weed control and fertility. Therefore, our objective was to determine the effects of Heterorhabditis bacteriophora and Steinernema scarabaei on third-instar P. japonica in substrates commonly used as mulches in blueberry. In containers in the laboratory, larval mortality was 90–100% with H. bacteriophora for all substrates, but rates with S. scarabaei were lower and variable among substrates. A mixture of municipal compost + woodchips/sawdust resulted in 60% larval mortality without adding EPN, but few nematodes were recovered, indicating other causes of death. In a field microplot experiment in October, larval mortality rates were 50% at most for all EPN and substrate type combinations, likely due to lower than optimal soil and substrate temperatures for EPN survival and infectivity. Overall, a compost and woodchip/sawdust mulch should help suppress P. japonica populations in blueberry, and applying H. bacteriophora when temperatures are optimal to mulches can provide excellent larval control.
Preferential Attraction of Oviposition-Ready Oriental Fruit Flies to Host Fruit Odor over Protein Food Odor
Authors: Roh Gwang-Hyun , Kendra Paul E. , Cha Dong H.
Published: October 2021

Olfaction plays a key role in the location of food and oviposition resources by tephritid fruit flies. Adult females, including oriental fruit fly, Bactrocera dorsalis, can sustain egg production throughout their lives provided they obtain sufficient protein. Thus, preferential attraction to food or oviposition sites (host fruit) will depend on a fly’s particular physiological state. In this study, laboratory bioassays were conducted with mature, mated B. dorsalis (provisioned protein and sugar ad libitum) to evaluate attraction to traps baited with torula yeast versus six host fruit sources (guava, guava juice, mango, orange, Surinam cherry, or white sapote). Females that preferred fruit laid a significant number of eggs around the trap entrance (average 405 eggs/fly), while almost no eggs were laid by females that preferred yeast (0.5 and 1.3 eggs/fly on two occasions). Similar results were observed in a bioassay using headspace extracts of guava juice and torula yeast, supporting olfactory-mediated responses. When individual females were allowed to oviposit in guava juice traps 0–24 h after a choice test, 45.8% of females that chose guava juice laid eggs (average 14.7 eggs/fly), compared with 27.5% that chose yeast (average 6.5 eggs/fly). Dissections indicated that females with a preference for guava juice had an egg load 2.4 times greater than females that preferred yeast. These results suggest there is an olfactory-based behavioral switch in preference from protein to host odors when female B. dorsalis are oviposition-ready. We discuss the implications of our findings for practical behavioral management and detection programs for B. dorsalis.
Acorn Ants May Create and Use Two Entrances to the Nest Cavity
Authors: Mitrus Sławomir
Published: October 2021

Many ant species construct large nests that are inhabited by numerous workers, but other species dwell in ready-for-use cavities and live in small colonies. Ants of the genus Temnothorax inhabit small cavities, e.g., in acorns, twigs, and under rocks. Although a preference for nest sites with a narrower entrance is known, recent studies have shown that they also use cavities with wider entrances and may modify the size of such entrances. As good cavities for nest sites are a limited resource, the possibility to modify a potential nest site, including a reduction in the size of the hole, should be a favorable matter for the ants. Through field and laboratory experiments, I studied the acorn ant Temnothorax crassispinus. Observations showed that they readily inhabited imperfect cavities and, if necessary, modified the holes to such cavities. If they had to repair a nest site, they sometimes created a second entrance; there was no difference in the sizes of the entrances. In the field, for entrance modification or blocking an unnecessary hole, the acorn ants used soil, grains of sand, and parts of plants. In the laboratory, the ant colonies showed no preference for nest sites with one entrance vs. a nest cavity with two entrances. The results of this study showed that even such small ant colonies could use nest sites with multiple entrances; however, the effect of the presence of more than one entrance on the behavior of the ants is unknown.
In Vitro Activity and Clinical Outcomes of Clofazimine for Nontuberculous Mycobacteria Pulmonary Disease
Authors: Kim Dae Hun , Kim Bo-Guen , Kim Su-Young , Huh Hee Jae , Lee Nam Yong , Koh Won-Jung , Kim Hojoong , Kwon O Jung , Jhun Byung Woo
Published: October 2021

Limited data are available regarding the in vitro activity of clofazimine against nontuberculous mycobacteria (NTM) or on outcomes of clofazimine-containing regimens in NTM-pulmonary disease (PD). Therefore, we evaluated the in vitro activity of clofazimine and the clinical outcomes of clofazimine-containing regimens. We evaluated clofazimine in vitro activity for 303 NTM isolates from NTM-PD patients. Fifty-seven clarithromycin-resistant and 35 amikacin-resistant isolates were also analyzed. Culture conversion after a 12-month treatment regimen containing clofazimine was evaluated in 58 NTM-PD patients, including 20 patients with drug-resistant isolates. Most of the 303 isolates (238/303) had minimum inhibitory concentrations (MICs) ≤ 0.25 µg/mL for clofazimine (57/63 Mycobacterium avium, 53/57 M. intracellulare, 49/52 M. kansasii, 22/64 M. abscessus, and 57/67 M. massiliense). For the 57 clarithromycin-resistant and 35 amikacin-resistant isolates, most had MICs ≤ 0.25 µg/mL (47/57 and 32/35, respectively). Among the 38 NTM-PD patients without resistance to clarithromycin or amikacin, 47% achieved culture conversion (8/27 M. abscessus, 9/9 M. massiliense, 0/1 M. avium, and 1/1 M. intracellulare). The conversion rate was higher in the MIC ≤ 0.25 µg/mL group than in the MIC = 0.5 µg/mL group (13/18 vs. 5/20, p = 0.004), and an MIC ≤ 0.25 µg/mL remained a significant factor in multivariable analysis. Culture conversion was achieved in 20% of 20 patients with clarithromycin- or amikacin-resistant isolates. However, a clofazimine MIC ≤ 0.25 µg/mL was not significant for culture conversion in the 58 NTM-PD patients, regardless of the drug resistance pattern. Clofazimine was effective in vitro against NTM species. Some patients on clofazimine-containing regimens achieved culture conversion.
An Automated Approach for Electric Network Frequency Estimation in Static and Non-Static Digital Video Recordings
Authors: Karantaidis Georgios , Kotropoulos Constantine
Published: October 2021

Electric Network Frequency (ENF) is embedded in multimedia recordings if the recordings are captured with a device connected to power mains or placed near the power mains. It is exploited as a tool for multimedia authentication. ENF fluctuates stochastically around its nominal frequency at 50/60 Hz. In indoor environments, luminance variations captured by video recordings can also be exploited for ENF estimation. However, the various textures and different levels of shadow and luminance hinder ENF estimation in static and non-static video, making it a non-trivial problem. To address this problem, a novel automated approach is proposed for ENF estimation in static and non-static digital video recordings. The proposed approach is based on the exploitation of areas with similar characteristics in each video frame. These areas, called superpixels, have a mean intensity that exceeds a specific threshold. The performance of the proposed approach is tested on various videos of real-life scenarios that resemble surveillance from security cameras. These videos are of escalating difficulty and span recordings from static ones to recordings, which exhibit continuous motion. The maximum correlation coefficient is employed to measure the accuracy of ENF estimation against the ground truth signal. Experimental results show that the proposed approach improves ENF estimation against the state-of-the-art, yielding statistically significant accuracy improvements.
Novel Texture Feature Descriptors Based on Multi-Fractal Analysis and LBP for Classifying Breast Density in Mammograms
Authors: Li Haipeng , Mukundan Ramakrishnan , Boyd Shelley
Published: October 2021

This paper investigates the usefulness of multi-fractal analysis and local binary patterns (LBP) as texture descriptors for classifying mammogram images into different breast density categories. Multi-fractal analysis is also used in the pre-processing step to segment the region of interest (ROI). We use four multi-fractal measures and the LBP method to extract texture features, and to compare their classification performance in experiments. In addition, a feature descriptor combining multi-fractal features and multi-resolution LBP (MLBP) features is proposed and evaluated in this study to improve classification accuracy. An autoencoder network and principal component analysis (PCA) are used for reducing feature redundancy in the classification model. A full field digital mammogram (FFDM) dataset, INBreast, which contains 409 mammogram images, is used in our experiment. BI-RADS density labels given by radiologists are used as the ground truth to evaluate the classification results using the proposed methods. Experimental results show that the proposed feature descriptor based on multi-fractal features and LBP result in higher classification accuracy than using individual texture feature sets.
Bacterial Quorum-Quenching Lactonase Hydrolyzes Fungal Mycotoxin and Reduces Pathogenicity of Penicillium expansum—Suggesting a Mechanism of Bacterial Antagonism
Authors: Dor Shlomit , Prusky Dov , Afriat-Jurnou Livnat
Published: October 2021

Penicillium expansum is a necrotrophic wound fungal pathogen that secrets virulence factors to kill host cells including cell wall degrading enzymes (CWDEs), proteases, and mycotoxins such as patulin. During the interaction between P. expansum and its fruit host, these virulence factors are strictly modulated by intrinsic regulators and extrinsic environmental factors. In recent years, there has been a rapid increase in research on the molecular mechanisms of pathogenicity in P. expansum; however, less is known regarding the bacteria–fungal communication in the fruit environment that may affect pathogenicity. Many bacterial species use quorum-sensing (QS), a population density-dependent regulatory mechanism, to modulate the secretion of quorum-sensing signaling molecules (QSMs) as a method to control pathogenicity. N-acyl homoserine lactones (AHLs) are Gram-negative QSMs. Therefore, QS is considered an antivirulence target, and enzymes degrading these QSMs, named quorum-quenching enzymes, have potential antimicrobial properties. Here, we demonstrate that a bacterial AHL lactonase can also efficiently degrade a fungal mycotoxin. The mycotoxin is a lactone, patulin secreted by fungi such as P. expansum. The bacterial lactonase hydrolyzed patulin at high catalytic efficiency, with a kcat value of 0.724 ± 0.077 s−1 and KM value of 116 ± 33.98 μM. The calculated specific activity (kcat/KM) showed a value of 6.21 × 103 s−1M−1. While the incubation of P. expansum spores with the purified lactonase did not inhibit spore germination, it inhibited colonization by the pathogen in apples. Furthermore, adding the purified enzyme to P. expansum culture before infecting apples resulted in reduced expression of genes involved in patulin biosynthesis and fungal cell wall biosynthesis. Some AHL-secreting bacteria also express AHL lactonase. Here, phylogenetic and structural analysis was used to identify putative lactonase in P. expansum. Furthermore, following recombinant expression and purification of the newly identified fungal enzyme, its activity with patulin was verified. These results indicate a possible role for patulin and lactonases in inter-kingdom communication between fungi and bacteria involved in fungal colonization and antagonism and suggest that QQ lactonases can be used as potential antifungal post-harvest treatment.
Bias of the Immune Response to Pneumocystis murina Does Not Alter the Ability of Neonatal Mice to Clear the Infection
Authors: Kurkjian Cathryn , Hollifield Melissa , Feola David J. , Garvy Beth A.
Published: October 2021

Newborn mice are unable to clear Pneumocystis (PC) infection with the same efficiency as adults due, in part, to their inability to develop a robust immune response to infection until three weeks of age. It is known that infants tend develop a Th2 skewed response to antigen so we sought to determine whether a biased cytokine response altered the clearance of PC infection in neonatal mice. P. murina infection in neonatal mice resulted in increased IL-4 expression by CD4 T cells and myeloid cells, augmented IL-13 secretion within the airways and increased arginase activity in the airways, indicative of Th2-type responses. P. murina-infected IL-4Rα−/− neonates had a shift towards Th1 cytokine production and increased numbers of CD4 and CD8 T cells within the lung as well as elevated levels of P. murina-specific IgG. IFNγ−/− and IL-23 p19−/− mice had altered CD4-T cell-dependent cytokine and cell responses. Though we could alter the T helper cell environment in neonatal knockout mice, there was no loss in the ability of these pups to clear infection. It is possible that the Th2 phenotype normally seen in neonatal mice protects the developing lung from pro-inflammatory immune responses without compromising host defense against P. murina.
Unveiling the Role Displayed by Penicillium digitatum PdMut3 Transcription Factor in Pathogen–Fruit Interaction
Authors: de Ramón-Carbonell Marta , Sánchez-Torres Paloma
Published: October 2021

Zn2Cys6 transcription factors are unique to fungi and are involved in different regulatory functions. In this study, we have identified the Penicillium digitatumPdMut3 gene, which encodes a putative Zn (II) 2Cys6 DNA-binding protein. Elimination of PdMut3 in Pd1 strain caused increased virulence during citrus infection. The transcription of the PdMut3 gene showed a higher expression rate during fungal growth and less transcription during fruit infection. Furthermore, the deletion of the gene in the wild-type isolate of P. digitatum did not produce any modification of the sensitivity to different fungicides, indicating that the gene is not associated with resistance to fungicides. In contrast, PdMut3 null mutants showed a reduction in growth in minimal media, which was associated with severe alterations in conidiophore development and morphological alterations of the hyphae. Mutants showed greater sensitivity to compounds that interfere with the cell wall and an invasive growth block. Thus, PdMut3 might have an indirect role in fungi virulence through metabolism and peroxisomes development.
Nep1-like Proteins from Valsa mali Differentially Regulate Pathogen Virulence and Response to Abiotic Stresses
Authors: Liu Jianying , Nie Jiajun , Chang Yali , Huang Lili
Published: October 2021

Necrosis and ethylene-inducing peptide 1(Nep1)-like protein (NLP) is well known for its cytotoxicity and immunogenicity on dicotyledonous, and it has attracted large attention due to its gene expansion and functional diversification in numerous phytopathogens. Here, two NLP family proteins, VmNLP1 and VmNLP2, were identified in the pathogenic fungus Valsa mali. We showed that VmNLP2 but not VmNLP1 induced cell death when transiently expressed in Nicotiana benthamiana. VmNLP2 was also shown to induce cell death in apple leaves via the treatment of the Escherichia coli-produced recombinant protein. VmNLP1 and VmNLP2 transcripts were drastically induced at the early stage of V. mali infection, whereas only VmNLP2 was shown to be essential for pathogen virulence. We also found that VmNLP1 and VmNLP2 are required for maintaining the integrity of cell membranes, and they differentially contribute to V. mali tolerance to salt- and osmo-stresses. Notably, multiple sequence alignment revealed that the second histidine (H) among the conserved heptapeptide (GHRHDWE) of VmNLP2 is mutated to tyrosine (Y). When this tyrosine (Y) was substituted by histidine (H), the variant displayed enhanced cytotoxicity in N. benthamiana, as well as enhanced virulence on apple leaves, suggesting that the virulence role of VmNLP2 probably correlates to its cytotoxicity activity. We further showed that the peptide among VmNLP2, called nlp25 (VmNLP2), triggered strong immune response in Arabidopsis thaliana. This work demonstrates that NLPs from V. mali involve multiple biological roles, and shed new light on how intricately complex the functions of NLP might be.
Genome Analyses of the Less Aggressive Rhizoctonia solani AG1-IB Isolates 1/2/21 and O8/2 Compared to the Reference AG1-IB Isolate 7/3/14
Authors: Wibberg Daniel , Genzel Franziska , Verwaaijen Bart , Blom Jochen , Rupp Oliver , Goesmann Alexander , Zrenner Rita , Grosch Rita , Pühler Alfred , Schlüter Andreas
Published: October 2021

Rhizoctonia solani AG1-IB of the phylum Basidiomycota is known as phytopathogenic fungus affecting various economically important crops, such as bean, rice, soybean, figs, cabbage and lettuce. The isolates 1/2/21 and O8/2 of the anastomosis group AG1-IB originating from lettuce plants with bottom rot symptoms represent two less aggressive R. solani isolates, as confirmed in a pathogenicity test on lettuce. They were deeply sequenced on the Illumina MiSeq system applying the mate-pair and paired-end mode to establish their genome sequences. Assemblies of obtained sequences resulted in 2092 and 1492 scaffolds, respectively, for isolate 1/2/21 and O8/2, amounting to a size of approximately 43 Mb for each isolate. Gene prediction by applying AUGUSTUS (v. 3.2.1.) yielded 12,827 and 12,973 identified genes, respectively. Based on automatic functional annotation, genes potentially encoding cellulases and enzymes involved in secondary metabolite synthesis were identified in the AG1-IB genomes. The annotated genome sequences of the less aggressive AG1-IB isolates were compared with the isolate 7/3/14, which is highly aggressive on lettuce and other vegetable crops such as bean, cabbage and carrot. This analysis revealed the first insights into core genes of AG1-IB isolates and unique determinants of each genome that may explain the different aggressiveness levels of the strains.
Volatile Organic Compounds in the Azteca/Cecropia Ant-Plant Symbiosis and the Role of Black Fungi
Authors: Mayer Veronika E. , de Hoog Sybren , Cristescu Simona M. , Vera Luciano , Prenafeta-Boldú Francesc X.
Published: October 2021

Black fungi of the order Chaetothyriales are grown by many tropical plant-mutualistic ants as small so-called “patches” in their nests, which are located inside hollow structures provided by the host plant (“domatia”). These fungi are introduced and fostered by the ants, indicating that they are important for the colony. As several species of Chaetothyriales tolerate, adsorb, and metabolize toxic volatiles, we investigated the composition of volatile organic compounds (VOCs) of selected domatia in the Azteca/Cecropia ant-plant mutualism. Concentrations of VOCs in ant-inhabited domatia, empty domatia, and background air were compared. In total, 211 compounds belonging to 19 chemical families were identified. Ant-inhabited domatia were dominated by ketones with 2-heptanone, a well-known ant alarm semiochemical, as the most abundant volatile. Empty domatia were characterized by relatively high concentrations of the monoterpenes d-limonene, p-cymene and β-phellandrene, as well as the heterocyclic sulphur-containing compound, benzothiazole. These compounds have biocidal properties and are primarily biosynthesized by plants as a defense mechanism. Interestingly, most of the latter compounds were present at lower concentrations in ant inhabited domatia than in non-colonized ones. We suggest that Chaetothyriales may play a role in reducing the VOCs, underlining that the mutualistic nature of these fungi as VOCs accumulation might be detrimental for the ants, especially the larvae.
Impact of Tacrolimus Daily Dose Limitation in Renal Transplant Recipients Expressing CYP3A5: A Retrospective Study
Authors: Lenain Rémi , Maanaoui Mehdi , Hamroun Aghilès , Larrue Romain , Van Der Hauwaert Cynthia , Gibier Jean-Baptiste , Gnemmi Viviane , Gomis Sébastien , Labalette Myriam , Broly Franck , Hennart Benjamin , Pottier Nicolas , Hazzan Marc , Cauffiez Christelle , Glowacki François
Published: October 2021

The pharmacokinetic variability of tacrolimus can be partly explained by CYP3A5 activity. Our objective was to evaluate a tacrolimus sparing policy on renal graft outcome according to CYP3A5 6986A>G genetic polymorphism. This retrospective study included 1114 recipients with a median follow-up of 6.3 years. Genotyping of the 6986A>G allelic variant corresponding to CYP3A5*3 was systematically performed. One year after transplantation, tacrolimus blood trough concentration (C0) target range was 5–7 ng/mL. However, daily dose was capped to 0.10 mg/kg/day regardless of the CYP3A5 genotype. A total 208 CYP3A5*1/- patients were included. Despite a higher daily dose, CYP3A5*1/- recipients exhibited lower C0 during follow-up (p < 0.01). Multivariate analysis did not show any significant influence of CYP3A5*1/- genotype (HR = 0.70, 0.46–1.07, p = 0.10) on patient-graft survival. Glomerular Filtration Rate (GFR) decline was significantly lower for the CYP3A5*1/- group (p = 0.02). The CYP3A5*1/- genotype did not significantly impact the risk of biopsy-proven acute rejection (BPAR) (HR = 1.01, 0.68–1.49, p = 0.97) despite significantly lower C0. Based on our experience, a strategy of tacrolimus capping is associated with a better GFR evolution in CYP3A5*1/- recipients without any significant increase of BPAR incidence. Our study raised some issues about specific therapeutic tacrolimus C0 targets for CYP3A5*1/- patients and suggests to set up randomized control studies in this specific population.
Thermal, Hyperspectral, and Laser Doppler Imaging: Non-Invasive Tools for Detection of The Deep Inferior Epigastric Artery Perforators—A Prospective Comparison Study
Authors: Nischwitz Sebastian P. , Luze Hanna , Schellnegger Marlies , Gatterer Simon J. , Tuca Alexandru-Cristian , Winter Raimund , Kamolz Lars-Peter
Published: October 2021

Perforator flaps have become one of the leading procedures in microsurgical tissue transfer. Individual defects require a tailored approach to guarantee the most effective treatment. A thorough understanding of the individual vascular anatomy and the location of prominent perforators is of utmost importance and usually requires invasive angiography or at least acoustic Doppler exploration. In this study, we aimed at evaluating different non-invasive imaging modalities as possible alternatives for perforator location detection. After a cooling phase, we performed thermal, hyperspectral and Laser Doppler imaging and visually evaluated a possible detection of the perforator for a period of five minutes with an image taken every minute. We identified the most prominent perforator of the deep inferior epigastric artery by handheld acoustic Doppler in 18 patients. The detected perforator locations were then correlated. Eighteen participants were assessed with six images each per imaging method. We could show a positive match for 94.44%, 38.89%, and 0% of patients and 92.59%, 25.93%, and 0% of images for the methods respectively compared to the handheld acoustic Doppler. Sex, age, abdominal girth, and BMI showed no correlation with a possible visual detection of the perforator in the images. Therefore, thermal imaging can yield valuable supporting data in the individualized procedure planning. Future larger cohort studies are required to better assess the full potential of modern handheld thermal imaging devices.
Cross-Border M&A Motives and Home Country Institutions: Role of Regulatory Quality and Dynamics in the Asia-Pacific Region
Authors: Zámborský Peter , Yan Zheng Joseph , Sbaï Erwann , Larsen Matthew
Published: October 2021

The purpose of this paper is to analyze the relationship between home country institutions and cross-border merger and acquisition (M&A) motives of MNEs from the Asia-Pacific region, with a focus on the role of regulatory quality and dynamics. We empirically examine how M&A motives are affected by elements related to risk of the institutional environment of the acquiring firm’s home country regulatory quality over time. The study is grounded in the general theory of springboard MNEs, and the institutional views of cross-border operations, namely the institutional escapism and institutional fostering perspectives. Using data on over 700 cross-border M&As of European firms by Asia-Pacific MNEs in 2007–2017, we analyze the rationales for these deals and their relationship to the institutional characteristics of the buyers’ home countries including regulatory quality and voice and accountability. We found that the quality of home country regulatory environment is significantly related to domestic firms’ motivation for international M&As. However, the significance and sign of the effects differ for different types of motives and over time. Our findings contribute to the literature on general versus emerging MNE-specific internationalization theories (particularly the theory of springboard MNEs) by expounding on the types and dynamics of cross-border M&A motives.
Failure Prediction in the Condition of Information Asymmetry: Tax Arrears as a Substitute When Financial Ratios Are Outdated
Authors: Lukason Oliver , Valgenberg Germo
Published: October 2021

This paper aims to study the usefulness of applying tax arrears in failure prediction, when annual reports to calculate financial ratios are outdated. Three known classification methods from the failure prediction literature are applied to the whole population dataset from Estonia, incorporating various tax arrears variables and financial ratios. The results indicate that accuracies remarkably exceeding those of models based on financial ratios can be obtained with variables portraying the average, maximum, and duration contexts of tax arrears. The main contribution of the current study is that it provides a proof of concept that accounting for the dynamics of payment defaults can lead to useful prediction models in cases in which up-to-date financial reports are not available.
Mapping and Assessment of Ecosystems Services under the Proposed MAES European Common Framework: Methodological Challenges and Opportunities
Authors: Laporta Lia , Domingos Tiago , Marta-Pedroso Cristina
Published: October 2021

The EU Biodiversity Strategy for 2020 was a driving force behind spatially explicit quantifications of Ecosystem Services (ES) in Europe. In Portugal, the MAES initiative (ptMAES–Mapping and Assessment of Ecosystem and their Services) was conducted in 2014 to address Target 2 (Action 5) of the Strategy, namely mapping and assessing ecosystems, ecosystems’ condition (EC), and ES. In this study covering the NUTS II Alentejo region, EC was assessed and mapped based on four indicators (soil organic matter, plant and bird diversity, and ecological value of plant communities) and five ES were assessed and mapped (soil protection, carbon sequestration, and fiber/crop/livestock production). Assessments were performed under a multi-tiered approach, ranging from spatialization of statistical data to analytical modeling, based on the most detailed land-use/land-cover cartography available. In this paper, we detail the methodological and analytical framework applied in ptMAES and present its main outcomes. Our goal is to (1) discuss the main methodological challenges encountered to inform future MAES initiatives in Portugal and other member states; and (2) further explore the outcomes of ptMAES by looking into spatial relationships between EC and ES supply. We highlight the advantages of the proposed analytical framework and identify constraints that, among others, limited the number of ES and EC indicators analyzed. We also show that MAES can provide useful insights to landscape planning at the regional scale, for instance, red-flagging areas where ES supply may be unsustainable over time.
Human and society. Didactic materials for independent work of 10th grade students of educational institutions
Authors: Dokuchaev I.I.
Published: October 2021

The series of publications was prepared on the basis of a teaching manual addressed to 10th grade schoolchildren of schools studying the integrative course “Social Studies” (section “Man and Society”), and is a set of materials for independent work. The content of the manual fully meets the requirements of the Federal State Educational Standards of Basic General Education and work programs for secondary (complete) education in social studies. The presented theoretical and practical material reveals the main aspects of social life: the essence and functional characteristics of consciousness and activity, ideas about society and social institutions as a system, types of societies, views on culture as a cumulative spiritual experience and “collective memory”, its main institutions — science, religion, morality, education, art. Particular attention is paid to the definition of social progress and global problems of mankind.