bluuebunny/crossref_metadata_2025 huggingface dataset:
G Protein-Coupled Receptors in Taste Physiology and Pharmacology
Authors: Ahmad Raise , Dalziel Julie E.
Published: November 2020

Heterotrimeric G protein-coupled receptors (GPCRs) comprise the largest receptor family in mammals and are responsible for the regulation of most physiological functions. Besides mediating the sensory modalities of olfaction and vision, GPCRs also transduce signals for three basic taste qualities of sweet, umami (savory taste), and bitter, as well as the flavor sensation kokumi. Taste GPCRs reside in specialised taste receptor cells (TRCs) within taste buds. Type I taste GPCRs (TAS1R) form heterodimeric complexes that function as sweet (TAS1R2/TAS1R3) or umami (TAS1R1/TAS1R3) taste receptors, whereas Type II are monomeric bitter taste receptors or kokumi/calcium-sensing receptors. Sweet, umami and kokumi receptors share structural similarities in containing multiple agonist binding sites with pronounced selectivity while most bitter receptors contain a single binding site that is broadly tuned to a diverse array of bitter ligands in a non-selective manner. Tastant binding to the receptor activates downstream secondary messenger pathways leading to depolarization and increased intracellular calcium in TRCs, that in turn innervate the gustatory cortex in the brain. Despite recent advances in our understanding of the relationship between agonist binding and the conformational changes required for receptor activation, several major challenges and questions remain in taste GPCR biology that are discussed in the present review. In recent years, intensive integrative approaches combining heterologous expression, mutagenesis and homology modeling have together provided insight regarding agonist binding site locations and molecular mechanisms of orthosteric and allosteric modulation. In addition, studies based on transgenic mice, utilizing either global or conditional knock out strategies have provided insights to taste receptor signal transduction mechanisms and their roles in physiology. However, the need for more functional studies in a physiological context is apparent and would be enhanced by a crystallized structure of taste receptors for a more complete picture of their pharmacological mechanisms.
Huidouba Improved Podocyte Injury by Down-Regulating Nox4 Expression in Rats With Diabetic Nephropathy
Authors: Yang KunBao , Bai YingHui , Yu Ning , Lu BiNan , Han GuiYan , Yin ChangJiang , Pang ZongRan
Published: November 2020

Diabetic nephropathy (DN), as the most common microvascular complication of diabetes mellitus (DM), has become one of the leading causes of end-stage renal disease (ESRD). Numerous studies have indicated that podocyte loss plays an important role in the development of DN and can even cause proteinuria in the early stage of DN. In the study, we found that Huidouba (HDB) significantly decreased the level of fasting blood glucose (FBG), the ratio of microalbumin to urine creatine (mAlb/Ucr), serum creatine (Scr), serum urea nitrogen (BUN), and malondialdehyde (MDA) in the kidney and downregulated the expression of Nox4 predominantly located in glomerular tissue while upregulating nephrin and WT1 expression in DN rats. In addition, HDB could also reduce podocyte damage and glomerular basement membrane (GBM) pathologic changes, as shown by transmission electron microscopy (TEM). In vitro study showed that HDB could inhibit high glucose (HG)-induced Reactive Oxygen Species (ROS) production and protect against podocyte apoptosis by downregulated Nox4 expression in podocytes. These results may provide a scientific basis for developing HDB as a potential folk medicine for the treatment of DN.
Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model
Authors: Delgado-Roche Livan , González Kethia , Mesta Fernando , Couder Beatriz , Tavarez Zaira , Zavala Ruby , Hernandez Ivones , Garrido Gabino , Rodeiro Idania , Vanden Berghe Wim
Published: November 2020

Marine plants are important sources of pharmacologically active metabolites. The aim of the present work was to evaluate the cytotoxic and antitumor activity of a polyphenolic fraction obtained fromThalassia testudinummarine plant and thalassiolin B in human colorectal cancer cells. Human cancer cell lines, including HCT15, HCT116, SW260, and HT29 were treated with tested products for cytotoxicity evaluation by crystal violet assay. The potential proapoptotic effect of these natural products was assessed by flow cytometry in HCT15 cells at 48 h using Annexin V-FITC/propidium iodide. In addition, reactive oxygen species (ROS) generation was measured by fluorescence using DCFH-DA staining, and sulfhydryl concentration by spectrophotometry. Thein vivoantitumor activity of the polyphenolic fraction (25 mg/kg) was evaluated in a xenograft model in nu/nu mice.In vivoproapoptotic effect was also evaluated by immunohistochemistry using anti-caspase 3 and anti-Bcl-2 antibodies. The results showed that tested products exert colorectal cancer cell cytotoxicity. Besides, the tested products induced a significant increase (p< 0.05) of intracellular ROS generation, and a depletion of sulfhydryl concentration in HCT15 cells. The polyphenolic fraction arrested tumor growth and induced apoptosis in the xenograft mice model. These results demonstrate the cytotoxic activity ofT. testudinummetabolites associated, at least, with ROS overproduction and pro-apoptotic effects. Here we demonstrated for the first time the antitumor activity of aT. testudinumpolar extract in a xenograft mice model. These results suggest the potential use ofT. testudinummarine plant metabolites as adjuvant treatment in cancer therapy.
Overcoming Biological Barriers With Block Copolymers-Based Self-Assembled Nanocarriers. Recent Advances in Delivery of Anticancer Therapeutics
Authors: Torres Jazmin , Dhas Namdev , Longhi Marcela , García Mónica C.
Published: November 2020

Cancer is one of the most common life-threatening illness and it is the world’s second largest cause of death. Chemotherapeutic anticancer drugs have many disadvantages, which led to the need to develop novel strategies to overcome these shortcomings. Moreover, tumors are heterogenous in nature and there are various biological barriers that assist in treatment reisistance. In this sense, nanotechnology has provided new strategies for delivery of anticancer therapeutics. Recently, delivery platforms for overcoming biological barriers raised by tumor cells and tumor-bearing hosts have been reported. Among them, amphiphilic block copolymers (ABC)-based self-assembled nanocarriers have attracted researchers worldwide owing to their unique properties. In this work, we addressed different biological barriers for effective cancer treatment along with several strategies to overcome them by using ABC‐based self-assembled nanostructures, with special emphasis in those that have the ability to act as responsive nanocarriers to internal or external environmental clues to trigger release of the payload. These nanocarriers have shown promising properties to revolutionize cancer treatment and diagnosis, but there are still challenges for their successful translation to clinical applications.
Pharmacological Programming of Endosomal Signaling Activated by Small Molecule Ligands of the Follicle Stimulating Hormone Receptor
Authors: Sposini Silvia , De Pascali Francesco , Richardson Rachel , Sayers Niamh S. , Perrais David , Yu Henry N. , Palmer Stephen , Nataraja Selva , Reiter Eric , Hanyaloglu Aylin C.
Published: November 2020

Follicle-stimulating hormone receptor (FSHR) is a G protein-coupled receptor (GPCR) with pivotal roles in reproduction. One key mechanism dictating the signal activity of GPCRs is membrane trafficking. After binding its hormone FSH, FSHR undergoes internalization to very early endosomes (VEEs) for its acute signaling and sorting to a rapid recycling pathway. The VEE is a heterogeneous compartment containing the Adaptor Protein Phosphotyrosine Interacting with Pleckstrin homology Domain and Leucine Zipper 1 (APPL1) with distinct functions in regulating endosomal Gαs/cAMP signaling and rapid recycling. Low molecular weight (LMW) allosteric FSHR ligands were developed for use in assisted reproductive technology yet could also provide novel pharmacological tools to study FSHR. Given the critical nature of receptor internalization and endosomal signaling for FSHR activity, we assessed whether these compounds exhibit differential abilities to alter receptor endosomal trafficking and signaling within the VEE. Two chemically distinct LMW agonists (benzamide, termed B3 and thiazolidinone, termed T1) were employed. T1 was able to induce a greater level of cAMP than FSH and B3. As cAMP signaling drives gonadotrophin hormone receptor recycling, rapid exocytic events were evaluated at single event resolution. Strikingly, T1 was able to induce a 3-fold increase in recycling events compared to FSH and two-fold more compared to B3. As T1-induced internalization was only marginally greater, the dramatic increase in recycling and cAMP signaling may be due to additional mechanisms. All compounds exhibited a similar requirement for receptor internalization to increase cAMP and proportion of FSHR endosomes with active Gαs, suggesting regulation of cAMP signaling induced by T1 may be altered. APPL1 plays a central role for GPCRs targeted to the VEE, and indeed, loss of APPL1 inhibited FSH-induced recycling and increased endosomal cAMP signaling. While T1-induced FSHR recycling was APPL1-dependent, its elevated cAMP signaling was only partially increased following APPL1 knockdown. Unexpectedly, B3 altered the dependence of FSHR to APPL1 in an opposing manner, whereby its endosomal signaling was negatively regulated by APPL1, while B3-induced FSHR recycling was APPL1-independent. Overall, FSHR allosteric compounds have the potential to re-program FSHR activity via altering engagement with VEE machinery and also suggests that these two distinct functions of APPL1 can potentially be selected pharmacologically.
Linalool Prevents Cisplatin Induced Muscle Atrophy by Regulating IGF-1/Akt/FoxO Pathway
Authors: Zhang Hong , Chi Mengyi , Chen Linlin , Sun Xipeng , Wan Lili , Yang Quanjun , Guo Cheng
Published: November 2020

Skeletal muscle atrophy is an important feature of cancer cachexia, which can be induced by chemotherapy, and affects the survival and quality of life of cancer patients seriously. No specific drugs for cancer cachexia have been applied in clinical practice. This study explored the therapeutic effect of linalool (LIN) on cisplatin (DDP) induced skeletal muscle atrophy. In vivo, LIN can improve skeletal muscle weight loss, anorexia, muscle strength decline and other cachexia symptoms caused by cisplatin treatment in a Lewis lung cancer tumor bearing mouse model, and cause no adverse effects on the anti-tumour effect. LIN treatment decreased the expression of muscle RING-finger protein-1 (MuRF1) and Atrogin1(MAFbx) in muscle, and the activation of insulin-like growth factor-1 (IGF-1)/protein kinase B (Akt)/forkhead box O (FoxO) pathway was observed. In vitro, LIN alleviated DDP induced C2C12 myotube atrophy, and IGF-1 receptor inhibitor Picropodophyllin (PIC), which had no adverse effect on C2C12 myotube cells, could reverse the protective effect of LIN. These results indicate that LIN down-regulates the expression of Atrogin1 and MuRF1 through the IGF-1/Akt/FoxO pathway, alleviating DDP-induced muscle atrophy and improving cachexia symptoms. LIN has the potential to be developed as a drug against cancer cachexia.
Are Further Cross Section Measurements Necessary for Space Radiation Protection or Ion Therapy Applications? Helium Projectiles
Authors: Norbury John W. , Battistoni Giuseppe , Besuglow Judith , Bocchini Luca , Boscolo Daria , Botvina Alexander , Clowdsley Martha , de Wet Wouter , Durante Marco , Giraudo Martina , Haberer Thomas , Heilbronn Lawrence , Horst Felix , Krämer Michael , La Tessa Chiara , Luoni Francesca , Mairani Andrea , Muraro Silvia , Norman Ryan B. , Patera Vincenzo , Santin Giovanni , Schuy Christoph , Sihver Lembit , Slaba Tony C. , Sobolevsky Nikolai , Topi Albana , Weber Uli , Werneth Charles M. , Zeitlin Cary
Published: November 2020

The helium (4He) component of the primary particles in the galactic cosmic ray spectrum makes significant contributions to the total astronaut radiation exposure. 4He ions are also desirable for direct applications in ion therapy. They contribute smaller projectile fragmentation than carbon (12C) ions and smaller lateral beam spreading than protons. Space radiation protection and ion therapy applications need reliable nuclear reaction models and transport codes for energetic particles in matter. Neutrons and light ions (1H, 2H, 3H, 3He, and 4He) are the most important secondary particles produced in space radiation and ion therapy nuclear reactions; these particles penetrate deeply and make large contributions to dose equivalent. Since neutrons and light ions may scatter at large angles, double differential cross sections are required by transport codes that propagate radiation fields through radiation shielding and human tissue. This work will review the importance of 4He projectiles to space radiation and ion therapy, and outline the present status of neutron and light ion production cross section measurements and modeling, with recommendations for future needs.
Mechanistic Model of Signaling Dynamics Across an Epithelial Mesenchymal Transition
Authors: Wade James D. , Lun Xiao-Kang , Zivanovic Nevena , Voit Eberhard O. , Bodenmiller Bernd
Published: November 2020

Intracellular signaling pathways are at the core of cellular information processing. The states of these pathways and their inputs determine signaling dynamics and drive cell function. Within a cancerous tumor, many combinations of cell states and microenvironments can lead to dramatic variations in responses to treatment. Network rewiring has been thought to underlie these context-dependent differences in signaling; however, from a biochemical standpoint, rewiring of signaling networks should not be a prerequisite for heterogeneity in responses to stimuli. Here we address this conundrum by analyzing an in vitro model of the epithelial mesenchymal transition (EMT), a biological program implicated in increased tumor invasiveness, heterogeneity, and drug resistance. We used mass cytometry to measure EGF signaling dynamics in the ERK and AKT signaling pathways before and after induction of EMT in Py2T murine breast cancer cells. Analysis of the data with standard network inference methods suggested EMT-dependent network rewiring. In contrast, use of a modeling approach that adequately accounts for single-cell variation demonstrated that a single reaction-based pathway model with constant structure and near-constant parameters is sufficient to represent differences in EGF signaling across EMT. This result indicates that rewiring of the signaling network is not necessary for heterogeneous responses to a signal and that unifying reaction-based models should be employed for characterization of signaling in heterogeneous environments, such as cancer.
A P3A-Type ATPase and an R2R3-MYB Transcription Factor Are Involved in Vacuolar Acidification and Flower Coloration in Soybean
Authors: Sundaramoorthy Jagadeesh , Park Gyu Tae , Lee Jeong-Dong , Kim Jeong Hoe , Seo Hak Soo , Song Jong Tae
Published: November 2020

The determination of flower color mainly depends on the anthocyanin biosynthesis pathway and vacuolar pH; however, unlike the former, the mechanism of vacuolar acidification in soybean remains uncharacterized at the molecular level. To investigate this mechanism, we isolated four recessive purple–blue EMS-induced flower mutants from the purple flower soybean cultivar, Pungsannamul. The petals of all the mutants had increased pH compared with those of wild Pungsannamul. One of the mutants had a single nucleotide substitution in GmPH4, a regulator gene encoding an MYB transcription factor, and the substitution resulted in a premature stop codon in its first exon. The other three mutants had nucleotide substitutions in GmPH5, a single new gene that we identified by physical mapping. It corresponds to Glyma.03G262600 in chromosome 3 and encodes a proton pump that belongs to the P3A-ATPase family. The substitutions resulted in a premature stop codon, which may be a defect in the ATP-binding capacity of GmPH5 and possibly a catalytic inefficiency of GmPH5. The result is consistent with their genetic recessiveness as well as the high pH of mutant petals, suggesting that GmPH5 is directly involved in vacuolar acidification. We also found that the expression of GmPH5 and several putative “acidifying” genes in the gmph4 mutant was remarkably reduced, indicating that GmPH4 may regulate the genes involved in determining the vacuolar pH of soybean petals.
Analysis of Cognitive Skills in History Textbook (Spain-England-Portugal)
Authors: Gómez Cosme J. , Solé Glória , Miralles Pedro , Sánchez Raquel
Published: November 2020

The main objective of this article is to analyze the cognitive level of the activities in History textbooks in Spain, England, and Portugal in the transition stage from Primary to Secondary Education (11–13 years), according to the country of origin, typology, and the concepts and disciplinary contents included. The design of this research is quantitative, descriptive, and cross-sectional. The non-probabilistic sample consists of 6,561 activities contained in 27 school textbooks from Spain, England, and Portugal. Descriptive and contrast analyses have been carried out using parametric tests. The results indicate that textbooks from Spain and Portugal mainly include activities situated between a basic and intermediate cognitive level while in England, the cognitive level of activities is medium or high. The ANOVA and TukeyBtests show significant differences between the cognitive level required in the activities and the typology of exercises, the concepts, and historical contents worked on. The activities with higher cognitive level correspond to those of creation and essays, the exercises that work on empathy and historical relevance, and that contain activities of social and economic history. In contrast, the activities with the lowest cognitive level are short questions and objective tests, those that work on first-order concepts (data and concrete facts), and those on the History of Art. The conclusion is that there is a need for a balanced presence of first-order content and historical thinking skills, the application in the classroom of a more active student-centered methodology, and the teachers’ conception of history teaching that prioritizes historical skills.
When Love Hurts – Mental and Physical Health Among Recently Divorced Danes
Authors: Sander Søren , Strizzi Jenna Marie , Øverup Camilla S. , Cipric Ana , Hald Gert Martin
Published: November 2020

The last decades of research have consistently found strong associations between divorce and adverse health outcomes among adults. However, limitations of a majority of this research include (a) lack of “real-time” research, i.e., research employing data collected very shortly after juridical divorce where little or no separation periods have been effectuated, (b) research employing thoroughly validated and population-normed measures against which study results can be compared, and (c) research including a comprehensive array of previously researched sociodemographic- and divorce-related variables. The current cross-sectional study, including 1,856 recently divorced Danes, was designed to bridge these important gaps in the literature. Mental and physical health were measured using the Short Form 36 (SF-36)-2. Analyses included correlational analyses, t-test comparisons, and hierarchical multiple regression analyses. The study found that the health-related quality of life of Danish divorcees was significantly worse than the comparative background population immediately following divorce. Across gender, higher levels of divorce conflict were found to predict worse mental health, and worse physical health for women, even when controlling for other socio-demographic variables and divorce characteristics. Among men, lower age and higher income predicted better physical health, while more children, more previous divorces, participant divorce initiation, new partner status, and lower levels of divorce conflict predicted better mental health. Among women, higher income, fewer previous divorces, new partner status, and lower levels of divorce conflict predicted better physical health while higher income, participant divorce initiation, new partner status, and lower levels of divorce conflict predicted better mental health. The findings underscore the relevance of providing assistance to divorcees who experience higher levels of divorce conflict immediately following divorce, in seeking to reduce potential long-term negative health effects of divorce.
Antecedents of Webrooming in Omnichannel Retailing
Authors: Kleinlercher Kristina , Linzmajer Marc , Verhoef Peter C. , Rudolph Thomas
Published: November 2020

Although webrooming has become common practice in omnichannel consumer behavior, only a few empirical studies have managed to shed light on the phenomenon. With this research work, we aim to investigate important antecedents of webrooming. We base our conceptual framework on anticipated utility theory and expect that customers’ anticipated utility from using the physical store versus the online store for purchase can be predicted by four groups of antecedents: psychographic variables, shopping motivations, channel-related variables, and product-related variables. With the help of a data set from a large cross-national online survey in which 1497 customers reconstruct their last purchase journey, we differentiate webroomers from pure online shoppers. In addition, we disentangle customers who used retailer-owned, competitor-owned, and independent touchpoints along the search and purchase phase of the customer journey in order to characterize webroomers in an omnichannel context and assess their prevalence in different countries and industries. Our insights on the characteristics and antecedents of webrooming help retailers to detect and better understand the psychology behind the webrooming phenomenon from a consumer perspective in an omnichannel retailing environment. In addition, results from our exploratory analysis on the positive association between webrooming and customer spending contribute to research and practice by providing first evidence on the economic value of webrooming.
State-Independent and -Dependent Structural Connectivity Alterations in Depression
Authors: Fan Yiming , Liu Jin , Zeng Ling-Li , Dong Qiangli , Su Jianpo , Peng Limin , Shen Hui , Lu Xiaowen , Sun Jinrong , Zhang Liang , Wang Mi , Raj Jugessur , Liu Bangshan , Hu Dewen , Li Lingjiang
Published: November 2020

Some brain abnormalities persist at the remission phase, that is, the state-independent abnormalities, which may be one of the reasons for the high recurrence of major depressive disorder (MDD). Hence, it is of great significance to identify state-independent abnormalities of MDD through longitudinal investigation. Ninety-nine MDD patients and 118 healthy controls (HCs) received diffusion tensor imaging scanning at baseline. After 6-month antidepressant treatment, 68 patients received a second scan, among which 59 patients achieved full clinical remission. Differences in whole-brain structural connectivity (SC) between patients with MDD at baseline and HCs were estimated by two-sample t-tests. Masked with significantly changed SCs in MDD, two-sample t-tests were conducted between the remitted MDD subgroup at follow-up and HCs, and paired t-tests were implemented to compare the differences of SC in the remitted MDD subgroup before and after treatment. Significantly decreased SC between the right insula and the anterior temporal cortex (ATC), between the right ATC and the posterior temporal cortex (PTC), between the left ATC and the auditory cortex as well as increased connectivity between the right posterior cingulate cortex (PCC) and the left medial parietal cortex (MPC) were observed in the MDD group compared with the HC group at baseline (p < 0.05, FDR corrected). The decreased connectivity between the right insula and the ATC and increased connectivity between the right PCC and the left MPC persisted in the remitted MDD subgroup at follow-up (p < 0.05, FDR corrected). The decreased SC between the right insula and the ATC and increased SC between the right PCC and left MPC showed state-independent characters, which may be implicated in the sustained negative attention bias and motor retardation in MDD. In contrast, the decreased SC between the right ATC and the PTC and between the left ATC and the auditory cortex seemed to be state-dependent.
Novel Pre- and Postoperative Care Using Telemedicine
Authors: Ferrari-Light Dana , Geraci Travis C. , Chang Stephanie H. , Cerfolio Robert J.
Published: November 2020

The use of telemedicine and telehealth services has grown exponentially over the past decade and has become increasingly relevant and necessary during the coronavirus 2019 (COVID-19) pandemic. There remains ample opportunity to electronically connect cardiothoracic surgeons with their patients during both preoperative and postoperative visits. In this review, we examine the various implementations of telemedicine within thoracic surgery and explore future applications in this quickly developing field.
Supplementing Synbiotic in Sows' Diets Modifies Beneficially Blood Parameters and Colonic Microbiota Composition and Metabolic Activity in Suckling Piglets
Authors: Ma Cui , Gao Qiankun , Zhang Wanghong , Zhu Qian , Tang Wu , Blachier Francois , Ding Hao , Kong Xiangfeng
Published: November 2020

Nutrients in the maternal diet favor the growth and development of suckling piglets and alter their gut microbiota composition and metabolic activity, thus affecting the hosts. The present study analyzed, in suckling piglets from sows receiving antibiotic or synbiotic supplements from pregnancy to lactation, several biochemical parameters, oxidative/anti-oxidative indices, inflammatory cytokines, and ingestion-related factor levels in plasma, as well as colonic microbiota composition and metabolic activity, and mucosal expression of genes related to the intestinal barrier function. Compared with the control group, maternal synbiotic supplementation decreased (P < 0.05) the plasma levels of glucose, AMM, TC, low-density lipoprotein-cholesterol (LDL-C), MDA, H2O2, ghrelin, CCK, PP, IL-1β, IL-2, IL-6, TNF-α, Ala, Cys, Tau, and β-AiBA, the levels of propionate and total short-chain fatty acids (SCFAs) in the colonic luminal content, and colonic abundances of RFN20, Anaerostipes, and Butyricimonas; while increased (P < 0.05) the plasma levels of urea nitrogen (UN), Ile, Leu, α-AAA, α-ABA, and 1-Mehis, as well as colonic abundances of Sphingomonas, Anaerovorax, Sharpea, and Butyricicoccus. Compared with the antibiotic group, maternal synbiotic supplementation decreased (P < 0.05) the plasma levels of glucose, gastrin, and Ala, as well as abundances of Pasteurella and RFN20 and propionate level in the colonic content. Expression of genes coding for E-cadherin, Occludin, ZO-1, ZO-2, IL-10, and interferon-α were down-regulated in the colonic mucosa. The synbiotic supplementation increased (P < 0.05) the plasma levels of UN, Leu, α-ABA, and 1-Mehis, the abundances of Anaerovorax, Sharpea, and Butyricicoccus and expression of genes coding for E-cadherin, Occludin, ZO-1, ZO-2, IL-10, and interferon-α. Spearman correlation analysis showed that there was a positive correlation between colonic Anaerostipes abundance and acetate and SCFAs levels; whereas a negative correlation between Fusobacteria and Fusobacterium abundances and acetate level. These findings suggest that synbiotic supplementation in the maternal diet improved nutrient metabolism and intestinal barrier permeability, reduced oxidative stress, and modified colonic microbiota composition and metabolic activity in suckling piglets.
The Influence of Predictability and Controllability on Stress Responses to the Aversive Component of a Virtual Fence
Authors: Kearton Tellisa , Marini Danila , Cowley Frances , Belson Sue , Keshavarzi Hamideh , Mayes Bonnie , Lee Caroline
Published: November 2020

To ensure animal welfare is not compromised, virtual fencing must be predictable and controllable, and this is achieved through associative learning. To assess the influence of predictability and controllability on physiological and behavioral responses to the aversive component of a virtual fence, two methods of training animals were compared. In the first method, positive punishment training involved sheep learning that after an audio stimulus, an electrical stimulus would follow only when they did not respond by stopping or turning at the virtual fence (predictable controllability). In the second method, classical conditioning was used to associate an audio stimulus with an electrical stimulus on all occasions (predictable uncontrollability). Eighty Merino ewes received one of the following treatments: control (no training and no stimuli in testing); positive punishment training with an audio stimulus in testing (PP); classical conditioning training with only an audio stimulus in testing (CC1); and classical conditioning training with an audio stimulus followed by electrical stimulus in testing (CC2). The stimuli were applied manually with an electronic collar. Training occurred on 4 consecutive days with one session per sheep per day. Sheep were then assessed for stress responses to the cues by measuring plasma cortisol, body temperature and behaviors. Predictable controllability (PP) sheep showed no differences in behavioral and physiological responses compared with the control treatment (P< 0.05). Predictable uncontrollability of receiving the aversive stimulus (CC2) induced a higher cortisol and body temperature response compared to the control but was not different to CC1 and PP treatments. CC2 treatment sheep showed a higher number of turning behaviors (P< 0.001), and more time spent running (P< 0.001) than the control and PP treatment groups, indicating that predictability without controllability was stressful. The behavior results also indicate that predicting the event without receiving it (CC1) was less stressful than predicting the event then receiving it (CC2), suggesting that there is a cost to confirmation of uncontrollability. These results demonstrate that a situation of predictability and controllability such as experienced when an animal successfully learns to avoid the aversive component of a virtual fence, induces a comparatively minimal stress response and does not compromise animal welfare.
Effects of Dietary Supplementation with High Fiber (Stevia Residue) on the Fecal Flora of Pregnant Sows
Authors: Yu Miao , Gao Tie , Liu Zhen , Diao Xinping
Published: November 2020

This study aimed to investigate the effects of different supplementation levels of stevia residues in high-fiber diets on the fecal microorganisms of pregnant sows. Forty-eight first-farrowing Danish Landrace sows with similar weight, age, and due date were randomly divided into four groups. The control group was fed a normal diet (CON; 3.15% crude fiber content), and the treatment groups were supplemented with 20% stevia residue (SRL), 30% stevia residue (SRM), or 40% stevia residue (SRH) stevia residue, with crude fiber content of 7.79%, 9.15%, and 10.68%, respectively. The test period was 135 days, and Illumina Miseq high-throughput sequencing was used to test the fecal bacteria of the pregnant sows on day 56. Compared to the control group, species diversity was greater in the 30% stevia residue group. At the phylum level, Firmicutes and Spirochaetes had the greatest relative abundances; Firmicutes was most abundant in the SRM group, and Spirochaetes was most abundant in the CON group. At the genus level, Lactobacillus, Streptococcus, and Lachnospiraceae_XPB1014_group, and Treponema_2 had the highest relative abundances in the stevia-residue treatments. Among them, Lactobacillus and Treponema_2 were more abundant in SRL, Streptococcus was more abundant in SRH, and Lachnospiraceae_XPB1014_group was more abundant in SRM. Linear discriminant analysis effect size (LEfSe) showed that the bacterial species differed among the stevia residue treatments. SRL mainly included g__Lactobacillus and g__Romboutsi, SRM mainly included g__Lachnospiraceae_XPB1014_group and g__Ruminococcaceae_UCG_014, SRH mainly included g__Streptococcus, and CON mainly included g__Treponema_2, f__Clostridiaceae_1, g__norank_f__Muribaculaceae, and g__norank_f__p_251_o5. Stevia-residue supplementation significantly increased the abundance of beneficial bacteria, such as g__Lachnospiraceae_XPB1014_group, g__Christensenellaceae_R-7_group, and g__Ruminococcaceae_UCG-005 (p < 0.05), and significantly reduced the abundance of harmful bacteria, such as Treponema_2 (p < 0.05). Moreover, compared with the control group, the stevia-residues treatment groups reduced the feed cost 8.33%, 12.50%, and 13.33% per sow per day, respectively. In conclusion, high-fiber diets can improve the intestinal balance and evenness index of the intestinal flora in pregnant sows, promote the relative abundance of beneficial bacteria, reduce the relative abundance of harmful bacteria, and reduce feed cost. The optimal supplementation level of the stevia residue was found to be 30%.
The Energy, Momentum, and Peak Power Radiated by Negative Lightning Return Strokes
Authors: Cooray Vernon , Lobato Andre
Published: November 2020

Electromagnetic radiation fields generated by return strokes transport both energy and momentum from the return stroke to outer space. The momentum transported by the radiation field has only a vertical or z component due to azimuthal symmetry (cylindrical symmetry) associated with a vertical return stroke. In this paper, the energy, momentum, and peak power radiated by return strokes as a function of the return stroke current, return stroke speed, and the zero-crossing time of the radiation fields are studied. The results obtained by numerical simulations for the energy, vertical momentum, and the peak power radiated by lightning return strokes (all parameters normalized by dividing them by the square of the radiation field peak at 100 km) are the following: A typical first return stroke generating a radiation field having a 50 μs zero-crossing time will dissipate field normalized energy of about (1.7–2.5) × 103 J/(V/m)2 and field-normalized vertical momentum of approximately (2.3–3.1) × 10−6 Kg m/s/(V/m)2. A radiation field with a zero-crossing time of 70 μs will dissipate about (2.6–3.4) × 103 J/(V/m)2 in field-normalized energy and (3.2–4.3) × 10−6 Kg m/s/(V/m)2 in field-normalized vertical momentum. The results show that, for a given peak radiation field, the radiated energy and momentum increase with increasing zero-crossing time of the radiation field. The normalized peak power generated by a first return stroke radiation field is about 1.2 × 108 W/(V/m)2 and the peak power is generated within about 5–6 μs from the beginning of the return stroke. Conversely, a typical subsequent return stroke generating a radiation field having a 40 μs zero-crossing time will dissipate field-normalized energy of about (6–9) × 102 J/(V/m)2 and field-normalized vertical momentum of approximately (7.5–11) × 10−7 Kg m/s/(V/m)2. The field-normalized peak power generated by a subsequent return stroke radiation field is about 1.26 × 108 W/(V/m)2 and the peak power is generated within about 0.7–0.8 μs from the beginning of the return stroke. In addition to these parameters, the possible upper bounds for the energy and momentum radiated by return strokes are also presented.
Monitoring Dust Events Using Doppler Lidar and Ceilometer in Iceland
Authors: Yang Shu , Preißler Jana , Wiegner Matthias , von Löwis Sibylle , Petersen Guðrún Nína , Parks Michelle Maree , Finger David Christian
Published: November 2020

Ground-based lidars and ceilometers are widely used for dust and volcanic ash observation around the world. This is particularly interesting in Iceland where high-altitude dust events occur frequently during strong wind conditions and volcanic eruptions. To explore the possible application of such technologies in Iceland for monitoring dust events, we used a combination of Doppler wind lidars with depolarization channels, ceilometers, and other instruments, to monitor two dust events that occurred in Iceland during summer 2019. We applied a verified ceilometer data processing procedure with customized local corrections and developed a new procedure to process Doppler lidar data for aerosols measurements. Both lidar and ceilometer observations can be used to detect the dust layer and reveal the temporal and vertical distribution of dust aerosols in Iceland. The depolarization ratio measurements indicate that the weather conditions, e.g., relative humidity, could have a significant impact on lidar measurements. We conclude that using Doppler wind lidar and ceilometer measurements to monitor volcanic and sedimentary aerosols is possible and may be used to provide important information to the scientific community.
Microbial Ecology of the Planetary Boundary Layer
Authors: Tignat-Perrier Romie , Dommergue Aurélien , Vogel Timothy M. , Larose Catherine
Published: November 2020

Aerobiology is a growing research area that covers the study of aerosols with a biological origin from the air that surrounds us to space through the different atmospheric layers. Bioaerosols have captured a growing importance in atmospheric process-related fields such as meteorology and atmospheric chemistry. The potential dissemination of pathogens and allergens through the air has raised public health concern and has highlighted the need for a better prediction of airborne microbial composition and dynamics. In this review, we focused on the sources and processes that most likely determine microbial community composition and dynamics in the air that directly surrounds us, the planetary boundary layer. Planetary boundary layer microbial communities are a mix of microbial cells that likely originate mainly from local source ecosystems (as opposed to distant sources). The adverse atmospheric conditions (i.e., UV radiation, desiccation, presence of radicals, etc.) might influence microbial survival and lead to the physical selection of the most resistant cells during aerosolization and/or aerial transport. Future work should further investigate how atmospheric chemicals and physics influence microbial survival and adaptation in order to be able to model the composition of planetary boundary layer microbial communities based on the surrounding landscapes and meteorology.
The Effect of Boreal Summer Intraseasonal Oscillation on Evaporation Duct and Electromagnetic Propagation over the South China Sea
Authors: Jia Wentao , Zhang Weimin , Zhu Jiahua , Sun Jilin
Published: November 2020

Intraseasonal oscillation of the evaporation duct, lasting 30–60 days, has been identified over the South China Sea (SCS) summer monsoon region based on multiple reanalyses and observational data. The boreal summer intraseasonal oscillation (BSISO) causes anomalies at the air–sea boundary and thus plays a dominant role in modulating the variation of the evaporation duct. The height and strength of the duct enhance/suppress during the negative/positive phase of the BSISO over the SCS. This results from the fact that active BSISO convection reduces solar radiation reaching the sea surface by increasing cumulus cloud cover, whereupon precipitation and water vapor transported by the enhanced southwest jet increase humidity over the air–sea boundary. Reduced air–sea temperatures and humidity differences lead to a weaker evaporation duct. Usually, the temporal evolution of the evaporation duct lags 2–4 days behind the BSISO, with the center of evaporation duct anomalies farther south than the BSISO. Simulated electromagnetic fields substantively influence the condition of the evaporation duct, with obvious over-the-horizon and radar blind spot effects in the typical negative phase of the BSISO, which is very different from standard atmospheric conditions.
Mindfulness, Interoception, and Olfaction: A Network Approach
Authors: Lefranc Barbara , Martin-Krumm Charles , Aufauvre-Poupon Charlotte , Berthail Benoit , Trousselard Marion
Published: November 2020

The fine-tuned interplay between the brain and the body underlies the adaptive ability to respond appropriately in the changing environment. Mindfulness Disposition (MD) has been associated with efficient emotional functioning because of a better ability to feel engaged by information from the body and to notice subtle changes. This interoceptive ability is considered to shape the ability to respond to external stimuli, especially olfaction. However, few studies have evaluated the relationships between interoception and exteroception according to MD. We conducted an exploratory study among 76 healthy subjects for first investigating whether MD is associated with better exteroception and second for describing the causal interactions network between mindfulness, interoception, emotion, and subjective and objective olfaction assessments. Results found that a high level of MD defined by clustering exhibited best scores in positive emotions, interoception, and extra sensors’ acuity. The causal network approach showed that the interactions between the interoception subscales differed according to the MD profiles. Moreover, interoception awareness is strongly connected with both the MD and the hedonic value of odors. Then, differences according to MD might provide arguments for a more mindful attention style toward interoceptive cues in relation to available exteroceptive information. This interaction might underlie positive health.
Lung Cancer Cell-Derived Secretome Mediates Paraneoplastic Inflammation and Fibrosis in Kidney in Mice
Authors: Hung Chi-Chih , Zhen Yen-Yi , Niu Sheng-Wen , Hsu Jui-Feng , Lee Tai-Huang , Chuang Hsiang-Hao , Wang Pei-Hui , Lee Su-Chu , Lin Pi-Chen , Chiu Yi-Wen , Wu Chien-Hsing , Huang Ming-Shyan , Hsiao Michael , Chen Hung-Chun , Yang Chih-Jen
Published: November 2020

Kidney failure is a possible but rare complication in lung cancer patients that may be caused by massive tumor lysis or a paraneoplastic effect. Clinical case reports have documented pathological characteristics of paraneoplastic syndrome in glomeruli, but are short of molecular details. When Lewis lung carcinoma 1 (LLC1) cells were implanted in mice lungs to establish lung cancer, renal failure was frequently observed two weeks post orthotopic xenograft. The high urinary albumin-to-creatinine ratio (ACR) was diagnosed as paraneoplastic nephrotic syndrome in those lung cancer mice. Profiling the secretome of the lung cancer cells revealed that the secretory proteins were potentially nephrotoxic. The nephrotoxicity of lung cancer-derived secretory proteins was tested by examining the pathogenic effects of 1 × 106, 2 × 106, and 5 × 106 LLC1 cell xenografts on the pathogenic progression in kidneys. Severe albuminuria was present in the mice that received 5 × 106 LLC1 cells implantation, whereas 106 cell and 2 × 106 cell-implanted mice have slightly increased albuminuria. Pathological examinations revealed that the glomeruli had capillary loop collapse, tumor antigen deposition in glomeruli, and renal intratubular casts. Since IL-6 and MCP-1 are pathologic markers of glomerulopathy, their distributions were examined in the kidneys of the lung cancer mice. Moderate to severe inflammation in the kidneys was correlated with increases in the number of cells implanted in the mice, which was reflected by renal IL-6 and MCP-1 levels, and urine ACR. TGF-β signaling-engaged renal fibrosis was validated in the lung cancer mice. These results indicated that lung cancer cells could provoke inflammation and activate renal fibrosis.
Combined CDK2 and CDK4/6 Inhibition Overcomes Palbociclib Resistance in Breast Cancer by Enhancing Senescence
Authors: Pandey Kamal , Park Nahee , Park Kyung-Soon , Hur Jin , Cho Yong Bin , Kang Minsil , An Hee-Jung , Kim Sewha , Hwang Sohyun , Moon Yong Wha
Published: November 2020

Breast cancer represents the number one global cancer burden in women and the hormone receptor (HR)-positive subtype comprises approximately 70% of breast cancers. Unfortunately, acquired resistance ultimately occurs in almost all cases, even though cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a highly effective therapy for HR-positive/human epidermal growth factor receptor 2-negative subtype. Here, we investigated mechanisms of resistance to CDK4/6 inhibitor and potential therapeutic strategies using our palbociclib-resistant preclinical model. We observed that cyclin E was significantly overexpressed in palbociclib-resistant cells, and similar association was also confirmed in pleural effusion samples collected from HR-positive breast cancer patients. After confirmation of cyclin E-CDK2 interaction by co-immunoprecipitation, we demonstrated CDK2 inhibition combined with palbociclib synergistically suppressed proliferation of palbociclib-resistant cells and growth of palbociclib-resistant xenograft in mice. We also proved that enhancing C-MYC-mediated senescence is a novel mechanism behind the synergism created by targeting both CDK2 and CDK4/6. Furthermore, the clinical relevance of cyclin E as a therapeutic target was supported by significant association between CCNE1 overexpression and poor prognosis based on large-scale public gene expression data sets in HR-positive breast cancer patients. Therefore, we propose cyclin E-CDK2 signaling as a promising therapeutic target for overcoming cyclin E-associated resistance to CDK4/6 inhibitor.
Fertility Sparing Treatment of Endometrial Cancer with and without Initial Infiltration of Myometrium: A Single Center Experience
Authors: Casadio Paolo , La Rosa Mariangela , Alletto Andrea , Magnarelli Giulia , Arena Alessandro , Fontana Enrico , Fabbri Matilde , Giovannico Kevin , Virgilio Agnese , Raimondo Diego , Guasina Francesca , Paradisi Roberto , Seracchioli Renato
Published: November 2020

Endometrial cancer (EC) is the fourth largest female cancer in Europe and North America. In 5% of cases, the diagnosis is made in women who wish to become pregnant. In our retrospective study, we reported our experience about fertility sparing treatment of G1 endometrioid endometrial cancer (G1 EEC) or atypical endometrial hyperplasia/endometrial intraepithelial neoplasm (AEH/EIN) in young women desiring pregnancy treated in our Center. Conservative treatment was based on operative hysteroscopy and hormone therapy with megestrol acetate (160 mg/die for 9 months). For the first time we included women with G1 EEC with minimal myometrial infiltration. The minimum follow-up period was two years and consisted of serial outpatient hysteroscopies with endometrial biopsies. Among the 36 women with G1 EEC we observed one case of disease persistence and four recurrences and four recurrences among the 46 women diagnosed with AEH/EIN. To date, 35 live births were obtained in both groups. Our results advance the hypothesis that conservative treatment can represent a safe and feasible alternative to propose to young women with desire for pregnancy. Further randomized and multicentric studies are needed to arrive at unambiguous and standardized guidelines on the surgical and medical treatment of young women with EEC or AEH/EIN.