bluuebunny/crossref_metadata_2025 huggingface dataset:
Jumonji C Demethylases in Cellular Senescence
Authors: Leon Kelly E. , Aird Katherine M.
Published: January 2019

Senescence is a stable cell cycle arrest that is either tumor suppressive or tumor promoting depending on context. Epigenetic changes such as histone methylation are known to affect both the induction and suppression of senescence by altering expression of genes that regulate the cell cycle and the senescence-associated secretory phenotype. A conserved group of proteins containing a Jumonji C (JmjC) domain alter chromatin state, and therefore gene expression, by demethylating histones. Here, we will discuss what is currently known about JmjC demethylases in the induction of senescence, and how these enzymes suppress senescence to contribute to tumorigenesis.
Methods for RNA Modification Mapping Using Deep Sequencing: Established and New Emerging Technologies
Authors: Motorin Yuri , Helm Mark
Published: January 2019

New analytics of post-transcriptional RNA modifications have paved the way for a tremendous upswing of the biological and biomedical research in this field. This especially applies to methods that included RNA-Seq techniques, and which typically result in what is termed global scale modification mapping. In this process, positions inside a cell’s transcriptome are receiving a status of potential modification sites (so called modification calling), typically based on a score of some kind that issues from the particular method applied. The resulting data are thought to represent information that goes beyond what is contained in typical transcriptome data, and hence the field has taken to use the term “epitranscriptome”. Due to the high rate of newly published mapping techniques, a significant number of chemically distinct RNA modifications have become amenable to mapping, albeit with variegated accuracy and precision, depending on the nature of the technique. This review gives a brief overview of known techniques, and how they were applied to modification calling.
Acknowledgement to Reviewers of Geosciences in 2018
Authors:   Geosciences Editorial Office
Published: January 2019

Peer review is an essential part of the publication process, which ensures that Geosciences maintains high quality standards for its published papers [...]
Sour Beer at the Boar’s Head: Salvaging Shakespeare’s Alewife, Mistress Quickly
Authors: Romanelli Christina
Published: January 2019

Using William Shakespeare’s character Mistress Nell Quickly as an example, this article contends that familiarity with both the literary tradition of alewives and the historical conditions in which said literary tradition brewed aids in revising our interpretation of working-class women on the early modern stage. Mistress Quickly, the multi-faceted comic character in three history plays and a city-comedy, resembles closely those women with whom Shakespeare and his contemporaries would have lived and worked in their day-to-day lives. Rather than dismissing her role as minor or merely comic, as previous criticism largely has, scholarship can embrace this character type and her narrative as an example to complicate teleological progressions for women.
Evaluation of Wastewater Treatment by Microcosms of Vertical Subsurface Wetlands in Partially Saturated Conditions Planted with Ornamental Plants and Filled with Mineral and Plastic Substrates
Authors: Sandoval Luis , Marín-Muñiz José Luis , Zamora-Castro Sergio Aurelio , Sandoval-Salas Fabiola , Alvarado-Lassman Alejandro
Published: January 2019

The current knowledge about the role terrestrial ornamental plants play in constructed wetlands (CWs) has scarcely been evaluated. Likewise, little attention has been given towards the use of new support or fill media for subsurface flow CWs, which may result in the reduction of costs when implemented on a large scale. This study evaluated, during nine months, the effect of three terrestrial ornamental plants and two substrates on the elimination of pollutants in wastewaters by using fill-and-drain vertical subsurface flow CWs (FD-CWs). Sixteen microcosms were used, nine filled with polyethylene terephthalate (PET) and nine with porous river stone (PRS). For each type of substrate, duplicates of microcosms were used, utilizing Anthurium sp., Zantedeschia aethiopica, and Spathiphyllum wallisii as vegetation and two other CWs without vegetation as controls. The environmental conditions, number of flowers, and height of the plants were registered. The results revealed that both substrates in the FD-CWs were efficient in removing pollutants. The average removal of pollutants in systems with vegetation revealed a positive effect on the reduction of the biochemical oxygen demand (55–70%), nitrates (28–44%), phosphates (25–45%), and fecal coliforms (52–65%). Meanwhile, in units without vegetation, the reduction of pollutants was nearly 40–50% less than in those with vegetation. The use of PET as a filling substrate in CWs did not affect the growth and/or the flowering of the species; therefore, its use combined with the species studied in CWs may be replicated in villages with similar wastewater problems. This may represent a reduction in implementation costs when utilizing PET recycled wastes and PRS as substrates in these systems in comparison with the typical substrates used in CWs. More studies are needed to better understand the interactions among these novel support media and the commercial terrestrial ornamental plants.
Features of Online Hospital Appointment Systems in Taiwan: A Nationwide Survey
Authors: Yang Po-Chin , Chu Feng-Yuan , Liu Hao-Yen , Shih Mei-Ju , Chen Tzeng-Ji , Chou Li-Fang , Hwang Shinn-Jang
Published: January 2019

Background: In the Internet era, many web-based appointment systems for hospitals have been established to replace traditional systems. Our study aimed to highlight the features of online appointment systems for hospitals in Taiwan, where patients can visit outpatient departments without a referral. Methods: All hospitals online appointment systems were surveyed in October 2018. Features of first-visit registrations were analyzed and stratified according to the hospitals’ accreditation levels. Results: Of the 417 hospitals, 59.7% (249) had public online appointment systems. For first-visit patients, only 199 hospitals offered the option of making appointments online from 7 to 98 (mean 38.9) days prior to the appointment itself. Before appointments, 68 (34.2%) hospitals recommended specialties for patients to choose according to their symptoms, and only 11 (5.5%) had a function for sending messages to doctors. After appointments, 176 (88.4%) provided links to real-time monitoring of outpatient service progress. Conclusions: More than half of the hospitals in Taiwan have public online appointment systems. However, most of these systems simply fulfill the function of registration, and rarely take the opportunity to improve efficiency by gathering information regarding patients’ medical history or reasons for making the appointment.
Association between Urban Greenness and Depressive Symptoms: Evaluation of Greenness Using Various Indicators
Authors: Song Hyeonjin , Lane Kevin James , Kim Honghyok , Kim Hyomi , Byun Garam , Le Minh , Choi Yongsoo , Park Chan Ryul , Lee Jong-Tae
Published: January 2019

An increasing number of studies have suggested benefits of greenness exposure on mental health. We examined the association between urban greenness and depressive symptoms in adults in the general population living in the seven major cities in Korea (N = 65,128). Using data from the Korean Community Health Survey 2009, depressive symptoms were measured on the Center for Epidemiological Studies Depression Scale (CES-D). Greenness was assessed using Normalized Difference Vegetation Index (NDVI) and land-use data (forest area and forest volume). Logistic regression models were fitted to adjust for potential confounders. Individuals in regions with the highest NDVI (quartile 4) had the lowest odds for depressive symptoms compared to quartile 1, after adjusting for potential confounders (OR = 0.813; 95% CI: 0.747, 0.884). For all greenness indicators except for forest area per district area (%), the highest rate of depressive symptoms was found for the individuals in the lowest quartile of greenness (quartile 1) and the lowest rate of depressive symptoms for those in the highest quartile of greenness (quartile 4). We found an inverse association between urban greenness and depressive symptoms, which was consistent across a variety of greenness indicators. Our study suggests health benefits of greenness and could provide a scientific basis for policy making and urban planning.
Effects of Developmental Arsenic Exposure on the Social Behavior and Related Gene Expression in C3H Adult Male Mice
Authors: Htway Soe-Minn , Sein Mya-Thanda , Nohara Keiko , Win-Shwe Tin-Tin
Published: January 2019

Arsenic is carcinogenic and teratogenic. In addition, it is also a developmental neurotoxicant. Little is known however about the effect of arsenic exposure during brain development on social behavior. This study aimed to detect the effect of developmental arsenic exposure on social behavior and related gene expression in C3H adult male mice. Pregnant C3H mice were exposed to sodium arsenite (NaAsO2, 85 ppm in the drinking water) from gestational day (GD) 8 to 18. The F1 generation male pups from different mothers were taken and social behavior tasks were examined. Social behavioral-related gene expression in the prefrontal cortex was determined by the real-time RT-PCR method. The mice with developmental arsenic exposure showed poor sociability and poor social novelty preference. Glutamate receptor expression (NMDA and AMPA receptor subunits) showed no significant difference, but gene expressions of serotonin receptor 5B (5-HT 5B) and brain-derived neurotrophic factor (BDNF) were significantly decreased (p < 0.05) in the arsenic-exposed group compared to control group. The heme oxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) gene expressions were not significantly different. Our findings indicate that developmental arsenic exposure might affect social behavior by modulating serotonin receptors and reducing BDNF. Some oxidative stress markers and inflammatory markers were not affected.
Risk Taking and Fiscal Smoothing with Sovereign Wealth Funds in Advanced Economies
Authors: Lindset Snorre , Mork Knut Anton
Published: January 2019

In an economy with a sovereign wealth fund (SWF), the government may draw on the fund to supplement other government revenues. If the fund is invested in risky assets, this introduces a new stochastic element into the government’s budget. We analyze the interaction between the draw from and risk taking in the SWF. Using non-expected utility preferences, we distinguish between intended changes and stochastic changes in the SWF draws over time. We show that the desire for smoothness in taxes and public services translates into smoothing of SWF draws and lower risk taking. It can even lead to procyclical rebalancing of the SWF portfolio. Future interest rates are associated with interest-rate risk. We show that this risk may lead to a higher optimal equity share in the SWF portfolio. Policy makers can use the draws from the SWF to smooth over time variation in risk-free rates.
Swim Training Modulates Mouse Skeletal Muscle Energy Metabolism and Ameliorates Reduction in Grip Strength in a Mouse Model of Amyotrophic Lateral Sclerosis
Authors: Flis Damian Jozef , Dzik Katarzyna , Kaczor Jan Jacek , Cieminski Karol , Halon-Golabek Malgorzata , Antosiewicz Jedrzej , Wieckowski Mariusz Roman , Ziolkowski Wieslaw
Published: January 2019

Metabolic reprogramming in skeletal muscles in the human and animal models of amyotrophic lateral sclerosis (ALS) may be an important factor in the diseases progression. We hypothesized that swim training, a modulator of cellular metabolism via changes in muscle bioenergetics and oxidative stress, ameliorates the reduction in muscle strength in ALS mice. In this study, we used transgenic male mice with the G93A human SOD1 mutation B6SJL-Tg (SOD1G93A) 1Gur/J and wild type B6SJL (WT) mice. Mice were subjected to a grip strength test and isolated skeletal muscle mitochondria were used to perform high-resolution respirometry. Moreover, the activities of enzymes involved in the oxidative energy metabolism and total sulfhydryl groups (as an oxidative stress marker) were evaluated in skeletal muscle. ALS reduces muscle strength (−70% between 11 and 15 weeks, p < 0.05), modulates muscle metabolism through lowering citrate synthase (CS) (−30% vs. WT, p = 0.0007) and increasing cytochrome c oxidase and malate dehydrogenase activities, and elevates oxidative stress markers in skeletal muscle. Swim training slows the reduction in muscle strength (−5% between 11 and 15 weeks) and increases CS activity (+26% vs. ALS I, p = 0.0048). Our findings indicate that swim training is a modulator of skeletal muscle energy metabolism with concomitant improvement of skeletal muscle function in ALS mice.
Silencing of Transcription Factor Sp1 Promotes SN1 Transporter Regulation by Ammonia in Mouse Cortical Astrocytes
Authors: Dąbrowska Katarzyna , Zielińska Magdalena
Published: January 2019

The involvement of the astrocytic SN1 (SNAT3) transporter in ammonia-induced l-glutamine retention was recently documented in mouse-cultured astrocytes. Here we investigated the involvement of specificity protein 1 (Sp1) transcription factor in SN1 regulation in ammonium chloride (“ammonia”)-treated astrocytes. Sp1 expression and its cellular localization were determined using real-time qPCR, Western blot, and confocal microscopy. Sp1 binding to Snat3 promoter was analyzed by chromatin immunoprecipitation. The role of Sp1 in SN1 expression and SN1-mediated [3H]glutamine uptake in ammonia-treated astrocytes was verified using siRNA and mithramycin A. The involvement of protein kinase C (PKC) isoforms in Sp1 level/phosphorylation status was verified using siRNA technology. Sp1 translocation to the nuclei and its enhanced binding to the Snat3 promoter, along with Sp1 dependence of system N-mediated [3H]glutamine uptake, were observed in astrocytes upon ammonia exposure. Ammonia decreased the level of phosphorylated Sp1, and the effect was reinforced by long-term incubation with PKC modulator, phorbol 12-myristate 13-acetate, which is a treatment likely to dephosphorylate Sp1. Furthermore, silencing of the PKCδ isoform appears to enhance the ammonia effect on the Sp1 level. Collectively, the results demonstrate the regulatory role of Sp1 in regulation of SN1 expression and activity in ammonia-treated astrocytes and implicate altered Sp1 phosphorylation status in this capacity.
Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling
Authors: Sato Teruki , Kadowaki Ayumi , Suzuki Takashi , Ito Hiroshi , Watanabe Hiroyuki , Imai Yumiko , Kuba Keiji
Published: January 2019

Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an angiotensin 1–7-dependent manner. Whether apelin antagonizes the over-activation of the renin–angiotensin system in the heart remains elusive. In this study we show that the detrimental effects of angiotensin II (Ang II) were exacerbated in the hearts of aged apelin-gene-deficient mice. Ang II-mediated cardiac dysfunction and hypertrophy were augmented in apelin knockout mice. The loss of apelin increased the ratio of angiotensin-converting enzyme (ACE) to ACE2 expression in the Ang II-stressed hearts, and Ang II-induced cardiac fibrosis was markedly enhanced in apelin knockout mice. mRNA expression of pro-fibrotic genes, such as transforming growth-factor beta (TGF-β) signaling, were significantly upregulated in apelin knockout hearts. Consistently, treatment with the ACE-inhibitor Captopril decreased cardiac contractility in apelin knockout mice. In vitro, apelin ameliorated Ang II-induced TGF-β expression in primary cardiomyocytes, accompanied with reduced hypertrophy. These results provide direct evidence that endogenous apelin plays a crucial role in suppressing Ang II-induced cardiac dysfunction and pathological remodeling.
YC-1 Prevents Tumor-Associated Tissue Factor Expression and Procoagulant Activity in Hypoxic Conditions by Inhibiting p38/NF-κB Signaling Pathway
Authors: Hsieh Kan-Yen , Wei Chien-Kei , Wu Chin-Chung
Published: January 2019

Tissue factor (TF) expressed in cancer cells has been linked to tumor-associated thrombosis, a major cause of mortality in malignancy. Hypoxia is a common feature of solid tumors and can upregulate TF. In this study, the effect of YC-1, a putative inhibitor of hypoxia-inducible factor-1α (HIF-1α), on hypoxia-induced TF expression was investigated in human lung cancer A549 cells. YC-1 selectively prevented hypoxia-induced TF expression and procoagulant activity without affecting the basal TF levels. Surprisingly, knockdown or pharmacological inhibition of HIF-1α failed to mimic YC-1′s effect on TF expression, suggesting other mechanisms are involved. NF-κB, a transcription factor for TF, and its upstream regulator p38, were activated by hypoxia exposure. Treatment of hypoxic A549 cells with YC-1 prevented the activation of both NF-κB and p38. Inhibition of p38 suppressed hypoxia-activated NF-κB, and inhibited TF expression and activity to similar levels as treatment with an NF-κB inhibitor. Furthermore, stimulation of p38 by anisomycin reversed the effects of YC-1. Taken together, our results suggest that YC-1 prevents hypoxia-induced TF in cancer cells by inhibiting the p38/NF-κB pathway, this is distinct from the conventional anticoagulants that systemically inhibit blood coagulation and may shed new light on approaches to treat tumor-associated thrombosis.
PCSK9 is Expressed in Human Visceral Adipose Tissue and Regulated by Insulin and Cardiac Natriuretic Peptides
Authors: Bordicchia Marica , Spannella Francesco , Ferretti Gianna , Bacchetti Tiziana , Vignini Arianna , Di Pentima Chiara , Mazzanti Laura , Sarzani Riccardo
Published: January 2019

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to and degrades the low-density lipoprotein receptor (LDLR), contributing to hypercholesterolemia. Adipose tissue plays a role in lipoprotein metabolism, but there are almost no data about PCSK9 and LDLR regulation in human adipocytes. We studied PCSK9 and LDLR regulation by insulin, atrial natriuretic peptide (ANP, a potent lipolytic agonist that antagonizes insulin), and LDL in visceral adipose tissue (VAT) and in human cultured adipocytes. PCSK9 was expressed in VAT and its expression was positively correlated with body mass index (BMI). Both intracellular mature and secreted PCSK9 were abundant in cultured human adipocytes. Insulin induced PCSK9, LDLR, and sterol-regulatory element-binding protein-1c (SREBP-1c) and -2 expression (SREBP-2). ANP reduced insulin-induced PCSK9, especially in the context of a medium simulating hyperglycemia. Human LDL induced both mature and secreted PCSK9 and reduced LDLR. ANP indirectly blocked the LDLR degradation, reducing the positive effect of LDL on PCSK9. In conclusion, PCSK9 is expressed in human adipocytes. When the expression of PCSK9 is induced, LDLR is reduced through the PCSK9-mediated degradation. On the contrary, when the induction of PCSK9 by insulin and LDL is partially blocked by ANP, the LDLR degradation is reduced. This suggests that NPs could be able to control LDLR levels, preventing PCSK9 overexpression.
Expression, Cellular and Subcellular Localisation of Kv4.2 and Kv4.3 Channels in the Rodent Hippocampus
Authors: Alfaro-Ruíz Rocío , Aguado Carolina , Martín-Belmonte Alejandro , Moreno-Martínez Ana Esther , Luján Rafael
Published: January 2019

The Kv4 family of voltage-gated K+ channels underlie the fast transient (A-type) outward K+ current. Although A-type currents are critical to determine somato-dendritic integration in central neurons, relatively little is known about the precise subcellular localisation of the underlying channels in hippocampal circuits. Using histoblot and immunoelectron microscopic techniques, we investigated the expression, regional distribution and subcellular localisation of Kv4.2 and Kv4.3 in the adult brain, as well as the ontogeny of their expression during postnatal development. Histoblot demonstrated that Kv4.2 and Kv4.3 proteins were widely expressed in the brain, with mostly non-overlapping patterns. During development, levels of Kv4.2 and Kv4.3 increased with age but showed marked region- and developmental stage-specific differences. Immunoelectron microscopy showed that labelling for Kv4.2 and Kv4.3 was differentially present in somato-dendritic domains of hippocampal principal cells and interneurons, including the synaptic specialisation. Quantitative analyses indicated that most immunoparticles for Kv4.2 and Kv4.3 were associated with the plasma membrane in dendritic spines and shafts, and that the two channels showed very similar distribution patterns in spines of principal cells and along the surface of granule cells. Our data shed new light on the subcellular localisation of Kv4 channels and provide evidence for their non-uniform distribution over the plasma membrane of hippocampal neurons.
No More Privacy Any More?
Authors: Grout Vic
Published: January 2019

The embodiment of the potential loss of privacy through a combination of artificial intelligence algorithms, big data analytics and Internet of Things technology might be something as simple, yet potentially terrifying, as an integrated app capable of recognising anyone, anytime, anywhere: effectively a global ‘Shazam for People’; but one additionally capable of returning extremely personal material about the individual. How credible is such a system? How many years away? And what might stop it?
Synthesis, Characterization, and Biological Evaluation of Red-Absorbing Fe(II) Polypyridine Complexes
Authors: Karges Johannes , Goldner Philippe , Gasser Gilles
Published: January 2019

Cancer is known to be one of the major causes of death nowadays. Among others, chemotherapy with cisplatin is a commonly used treatment. Although widely employed, cisplatin is known to cause severe side effects, such as nerve and kidney damage, nausea, vomiting, and bone marrow suppression. Most importantly, a number of cancer tumors are acquiring resistance to cisplatin, limiting its clinical use. There is therefore a need for the discovery of novel anticancer agents. Complementary to chemotherapy, Photodynamic Therapy (PDT) has expanded the range of treatment opportunities of numerous kinds of cancer. Nonetheless, the currently approved PDT photosensitizers (PSs) suffer from major drawbacks, which include poor water solubility or photobleaching, in addition to a slow clearance from the body that causes photosensitivity. Due to these limitations, there is a need for the development of new PDT PSs. To overcome these problems, a lot of research groups around the world are currently focusing their attention towards the development of new metal complexes as PDT PSs. However, most synthesized compounds reported so far show limited use due to their poor absorption in the phototherapeutic window. Herein, we report on the preparation and characterization of three Fe(II) polypyridine complexes (4–6) and evaluate their potential as both anticancer agents and PDT PSs. Very importantly, these compounds are stable in human plasma, photostable upon continuous LED irradiation, and absorb in the red region of the spectrum. We could demonstrate that through additional sulfonic acid groups on the polypyridine ligand being used (bphen: 4,7-diphenyl-1,10-phenanthroline), the water solubility of the complexes could be highly improved, whereas the photophysical properties did not significantly change. One of these complexes (4) shows interesting toxicity, with IC50 values in the low micromolar range in the dark as well as some phototoxicity upon irradiation at 480 and 540 nm against RPE-1 and HeLa cells.
Recruiting on the Spot: A Biodegradable Formulation for Lacewings to Trigger Biological Control of Aphids
Authors: Pålsson Joakim , Thöming Gunda , Silva Rodrigo , Porcel Mario , Dekker Teun , Tasin Marco
Published: January 2019

Upon herbivory, plants release herbivore-induced plant volatiles (HIPVs), which induce chemical defenses in the plant as well as recruit natural enemies. However, whether synthetic HIPVs can be employed to enhance biological control in a cultivated crop in the field is yet to be explored. Here we show that a biodegradable formulation loaded with induced and food-signaling volatiles can selectively recruit the common green lacewing, Chrysoperla carnea, and reduce pest population under field conditions. In apple orchards, the new formulation attracted lacewing adults over a 4-week period, which correlated well with independent assessments of the longevity of the slow-release matrix measured through chemical analyses. In barley, lacewing eggs and larvae were significantly more abundant in treated plots, whereas a significant reduction of two aphid species was measured (98.9% and 93.6% of population reduction, for Sitobion avenae and Rhopalosiphum padi, respectively). Results show the potential for semiochemical-based targeted recruitment of lacewings to enhance biological control of aphids in a field setting. Further research should enhance selective recruitment by rewarding attracted natural enemies and by optimizing the application technique.
Putative Drone Copulation Factors Regulating Honey Bee (Apis mellifera) Queen Reproduction and Health: A Review
Authors: Brutscher Laura M. , Baer Boris , Niño Elina L.
Published: January 2019

Honey bees are major pollinators of agricultural and non-agricultural landscapes. In recent years, honey bee colonies have exhibited high annual losses and commercial beekeepers frequently report poor queen quality and queen failure as the primary causes. Honey bee colonies are highly vulnerable to compromised queen fertility, as each hive is headed by one reproductive queen. Queens mate with multiple drones (male bees) during a single mating period early in life in which they obtain enough spermatozoa to fertilize their eggs for the rest of their reproductive life span. The process of mating initiates numerous behavioral, physiological, and molecular changes that shape the fertility of the queen and her influence on the colony. For example, receipt of drone semen can modulate queen ovary activation, pheromone production, and subsequent worker retinue behavior. In addition, seminal fluid is a major component of semen that is primarily derived from drone accessory glands. It also contains a complex mixture of proteins such as proteases, antioxidants, and antimicrobial proteins. Seminal fluid proteins are essential for inducing post-mating changes in other insects such as Drosophila and thus they may also impact honey bee queen fertility and health. However, the specific molecules in semen and seminal fluid that initiate post-mating changes in queens are still unidentified. Herein, we summarize the mating biology of honey bees, the changes queens undergo during and after copulation, and the role of drone semen and seminal fluid in post-mating changes in queens. We then review the effects of seminal fluid proteins in insect reproduction and potential roles for honey bee drone seminal fluid proteins in queen reproduction and health. We finish by proposing future avenues of research. Further elucidating the role of drone fertility in queen reproductive health may contribute towards reducing colony losses and advancing honey bee stock development.
Is the Brood Pattern within a Honey Bee Colony a Reliable Indicator of Queen Quality?
Authors: Lee Kathleen V. , Goblirsch Michael , McDermott Erin , Tarpy David R. , Spivak Marla
Published: January 2019

Failure of the queen is often identified as a leading cause of honey bee colony mortality. However, the factors that can contribute to “queen failure” are poorly defined and often misunderstood. We studied one specific sign attributed to queen failure: poor brood pattern. In 2016 and 2017, we identified pairs of colonies with “good” and “poor” brood patterns in commercial beekeeping operations and used standard metrics to assess queen and colony health. We found no queen quality measures reliably associated with poor-brood colonies. In the second year (2017), we exchanged queens between colony pairs (n = 21): a queen from a poor-brood colony was introduced into a good-brood colony and vice versa. We observed that brood patterns of queens originally from poor-brood colonies significantly improved after placement into a good-brood colony after 21 days, suggesting factors other than the queen contributed to brood pattern. Our study challenges the notion that brood pattern alone is sufficient to judge queen quality. Our results emphasize the challenges in determining the root source for problems related to the queen when assessing honey bee colony health.
Honey Bee Exposure to Pesticides: A Four-Year Nationwide Study
Authors: Ostiguy Nancy , Drummond Frank A. , Aronstein Kate , Eitzer Brian , Ellis James D. , Spivak Marla , Sheppard Walter S.
Published: January 2019

Pollinators, including honey bees, are responsible for the successful reproduction of more than 87% of flowering plant species: they are thus vital to ecosystem health and agricultural services world-wide. To investigate honey bee exposure to pesticides, 168 pollen samples and 142 wax comb samples were collected from colonies within six stationary apiaries in six U.S. states. These samples were analyzed for evidence of pesticides. Samples were taken bi-weekly when each colony was active. Each apiary included thirty colonies, of which five randomly chosen colonies in each apiary were sampled for pollen. The pollen samples were separately pooled by apiary. There were a total of 714 detections in the collected pollen and 1008 detections in collected wax. A total of 91 different compounds were detected: of these, 79 different pesticides and metabolites were observed in the pollen and 56 were observed in the wax. In all years, insecticides were detected more frequently than were fungicides or herbicides: one third of the detected pesticides were found only in pollen. The mean (standard deviation (SD)) number of detections per pooled pollen sample varied by location from 1.1 (1.1) to 8.7 (2.1). Ten different modes of action were found across all four years and nine additional modes of action occurred in only one year. If synergy in toxicological response is a function of simultaneous occurrence of multiple distinct modes of action, then a high frequency of potential synergies was found in pollen and wax-comb samples. Because only pooled pollen samples were obtained from each apiary, and these from only five colonies per apiary per year, more data are needed to adequately evaluate the differences in pesticide exposure risk to honey bees among colonies in the same apiary and by year and location.
Comb Irradiation Has Limited, Interactive Effects on Colony Performance or Pathogens in Bees, Varroa destructor and Wax Based on Two Honey Bee Stocks
Authors: De Guzman Lilia I. , Simone-Finstrom Michael , Frake Amanda M. , Tokarz Philip
Published: January 2019

Parasitic mites and pathogens compromise honey bee health. Development of sustainable and integrative methods of managing these problems will minimize their detrimental impact on honey bees. Here, we aimed to determine if the combination of using mite-resistant stocks along with gamma-irradiated combs influences colony health and productivity. The major finding concerned honey bee genotype confirming that Russian honey bees are more resistant to Varroa destructor than Italian honey bees. The effect of comb irradiation was inconsistent showing a significant increase in adult bee population and amount of stored pollen in 2015, but not in 2016. The increased amount of stored pollen was probably associated with larger adult population in colonies with irradiated combs in September 2015 regardless of honey bee stock. Nevertheless, the ability of bees to collect and store more pollen in the irradiated group does not appear to compensate the negative impacts of mite parasitism on honey bees especially in the Italian bees, which consistently suffered significant colony losses during both years. Results of viral analyses of wax, newly emerged bees, and Varroa and their pupal hosts showed common detections of Deformed wing virus (DWV), Varroa destructor virus (VDV-1), Chronic bee paralysis virus (CBPV), and Black queen cell virus (BQCV). Wax samples had on average ~4 viruses or pathogens detected in both irradiated and non-irradiated combs. Although pathogen levels varied by month, some interesting effects of honey bee stock and irradiation treatment were notable, indicating how traits of mite resistance and alternative treatments may have additive effects. Further, this study indicates that wax may be a transmission route of viral infection. In addition, pupae and their infesting mites from Italian colonies exhibited higher levels of DWV than those from Russian colonies suggesting potential DWV resistance by Russian honey bees. CBPV levels were also reduced in mites from Russian colonies in general and in mites, mite-infested pupae, and newly emerged bees that were collected from irradiated combs. However, BQCV levels were not reduced by comb irradiation. Overall, the contribution of irradiating comb in improving honey bee health and colony survival appears to be subtle, but may be useful as part of an integrated pest management strategy with the addition of using mite-resistant stocks.
The Dynamics of Deformed Wing Virus Concentration and Host Defensive Gene Expression after Varroa Mite Parasitism in Honey Bees, Apis mellifera
Authors: Zhao Yazhou , Heerman Matthew , Peng Wenjun , Evans Jay D. , Rose Robyn , DeGrandi-Hoffman Gloria , Simone-Finstrom Michael , Li Jianghong , Li Zhiguo , Cook Steven C. , Su Songkun , Rodríguez-García Cristina , Banmeke Olubukola , Hamilton Michele , Chen Yanping
Published: January 2019

The synergistic interactions between the ectoparasitic mite Varroa destructor and Deformed wing virus (DWV) lead to the reduction in lifespan of the European honey bee Apis mellifera and often have been implicated in colony losses worldwide. However, to date, the underlying processes and mechanisms that form the multipartite interaction between the bee, mite, and virus have not been fully explained. To gain a better understanding of honey bees’ defense response to Varroa mite infestation and DWV infection, the DWV titers and transcription profiles of genes originating from RNAi, immunity, wound response, and homeostatic signaling pathways were monitored over a period of eight days. With respect to DWV, we observed low viral titers at early timepoints that coincided with high levels of Toll pathway transcription factor Dorsal, and its downstream immune effector molecules Hymenoptaecin, Apidaecin, Abaecin, and Defensin 1. However, we observed a striking increase in viral titers beginning after two days that coincided with a decrease in Dorsal levels and its corresponding immune effector molecules, and the small ubiquitin-like modifier (SUMO) ligase repressor of Dorsal, PIAS3. We observed a similar expression pattern for genes expressing transcripts for the RNA interference (Dicer/Argonaute), wound/homeostatic (Janus Kinase), and tissue growth (Map kinase/Wnt) pathways. Our results demonstrate that on a whole, honey bees are able to mount an immediate, albeit, temporally limited, immune and homeostatic response to Varroa and DWV infections, after which downregulation of these pathways leaves the bee vulnerable to expansive viral replication. The critical insights into the defense response upon Varroa and DWV challenges generated in this study may serve as a solid base for future research on the development of effective and efficient disease management strategies in honey bees.
Compound and Dose-Dependent Effects of Two Neonicotinoid Pesticides on Honey Bee (Apis mellifera) Metabolic Physiology
Authors: Cook Steven C.
Published: January 2019

Use of neonicotinoid pesticides is now ubiquitous, and consequently non-targeted arthropods are exposed to their residues at sub-lethal doses. Exposure to these neurotoxins may be a major contributor to poor honey bee colony health. Few studies have explored how sub lethal exposure to neonicotinoids affects honey bee metabolic physiology, including nutritional and energetic homeostasis, both of which are important for maintaining colony health. Reported here are results from a study of chronic oral exposure of honey bees to two sub lethal concentrations of clothianidin and imidacloprid. Neonicotinoids altered important aspects of honey bee nutritional and metabolic physiology in a compound and dose-dependent manner; both compounds at low doses reduced honey bee body weight. Low-dose clothianidin exposure resulted in bees having protein, lipids, carbohydrates, and glycogen levels similar to newly emerged bees. High-dose clothianidin exposure lowered lipids and glycogen content of bees. High-dose imidacloprid exposure resulted in bees having depressed metabolic rate. Low-dose imidacloprid exposure resulted in bees consuming low and high levels of protein and carbohydrate rich foods, respectively. Results suggest neonicotinoids interfere with honey bee endocrine neurophysiological pathways. Compound and dose-dependent effects might represent respective chemical structural differences determining an observed effect, and thresholds of compound effects on honey bee physiology.
Combined Toxicity of Insecticides and Fungicides Applied to California Almond Orchards to Honey Bee Larvae and Adults
Authors: Wade Andrea , Lin Chia-Hua , Kurkul Colin , Regan Erzsébet Ravasz , Johnson Reed M.
Published: January 2019

Beekeepers providing pollination services for California almond orchards have reported observing dead or malformed brood during and immediately after almond bloom—effects that they attribute to pesticide exposure. The objective of this study was to test commonly used insecticides and fungicides during almond bloom on honey bee larval development in a laboratory bioassay. In vitro rearing of worker honey bee larvae was performed to test the effect of three insecticides (chlorantraniliprole, diflubenzuron, and methoxyfenozide) and three fungicides (propiconazole, iprodione, and a mixture of boscalid-pyraclostrobin), applied alone or in insecticide-fungicide combinations, on larval development. Young worker larvae were fed diets contaminated with active ingredients at concentration ratios simulating a tank-mix at the maximum label rate. Overall, larvae receiving insecticide and insecticide-fungicide combinations were less likely to survive to adulthood when compared to the control or fungicide-only treatments. The insecticide chlorantraniliprole increased larval mortality when combined with the fungicides propiconazole or iprodione, but not alone; the chlorantraniliprole-propiconazole combination was also found to be highly toxic to adult workers treated topically. Diflubenzuron generally increased larval mortality, but no synergistic effect was observed when combined with fungicides. Neither methoxyfenozide nor any methoxyfenozide-fungicide combination increased mortality. Exposure to insecticides applied during almond bloom has the potential to harm honey bees and this effect may, in certain instances, be more damaging when insecticides are applied in combination with fungicides.
Special Issue: Honey Bee Research in the US: Current State and Solutions to Beekeeping Problems
Authors: López-Uribe Margarita M. , Simone-Finstrom Michael
Published: January 2019

The European honey bee (Apis mellifera) is the most important managed species for agricultural pollination across the world [...]
Transscleral Fixation of Black Diaphragm Intraocular Lens in Complete Aniridia and Aphakia Due to Posttraumatic Eye Rupture: A Pilot Study
Authors: Chorągiewicz Tomasz , Nowomiejska Katarzyna , Haszcz Dariusz , Nowakowska Dominika , Avitabile Teresio , Reibaldi Michele , Jünemann Anselm , Toro Mario Damiano , Rejdak Robert
Published: January 2019

Introduction: To assess long-term outcomes of implantation of black diaphragm intraocular lens (BD IOL) in post-traumatic aniridia and aphakia due to eye rupture. Methods: This is a retrospective consecutive case series of 14 eyes with post-traumatic complete aniridia and aphakia treated with scleral fixation BD IOL. Measurements included ophthalmological comorbidities, best corrected visual acuity (BCVA), complications, and postoperative interventions. The average postoperative follow-up period was 36 months. Results: BCVA improved in 6 cases, was stable in 6 cases and worsened in 2 cases. The lens was well centered in 13 cases. Glaucoma was diagnosed in six cases developed, and three of them required Ahmed valve implantation. One lens developed opacity. The cornea was decompensated in 6 cases, while two of them required penetrating keratoplasty. Conclusion: Implantation of BD IOL in eyes with severely traumatized eyes enables reconstruction of the anterior segment and some functional restoration, although many complications may arise during the longitudinal follow-up.
Acute Effects of Intermittent Versus Continuous Bilateral Ankle Plantar Flexor Static Stretching on Postural Sway and Plantar Pressures: A Randomized Clinical Trial
Authors: Martínez-Jiménez Eva María , Losa-Iglesias Marta Elena , Díaz-Velázquez Jose Ignacio , Becerro-De-Bengoa-Vallejo Ricardo , Palomo-López Patricia , Calvo-Lobo César , López-López Daniel , Rodríguez-Sanz David
Published: January 2019

Background: Postural balance and fall efficacy (self-perceived confidence in performing daily physical activities) have been found to be risk factors associated with falls in older adults. Stretching is one intervention that has been investigated to improve balance and therefore reduce fall risk. Various forms of stretching have been evaluated with different outcomes, but there is a lack of knowledge about the effect of stretching (continuous and intermittent) on plantar pressures and balance. Therefore, the aim of the present study was to analyze the effects of stretching (continuous and intermittent) of the bilateral ankle plantar flexors on plantar pressures and static balance. Methods: A randomized clinical trial was carried out. Forty-eight healthy subjects (42 females and 6 males) were recruited in an outpatient clinic. Subjects were randomly assigned to an intermittent stretching group (five sets of 1 min; 15 s of rest) or a continuous stretching group (2 min of continuous stretching) of the plantar flexors. Plantar pressures and balance using stabilometry were measured before and after stretching. Results: There were significant differences between intermittent and continuous stretching in rearfoot maximum pressure, forefoot surface area, and center of pressure surface area with eyes open. Conclusions: Bilateral intermittent stretching of the ankle plantar flexors was found to be more effective than continuous stretching for the reduction of rearfoot maximum pressure and improved balance.
Usefulness of Eye Fixation Assessment for Identifying Type 2 Diabetic Subjects at Risk of Dementia
Authors: Simó-Servat Olga , Ciudin Andreea , Ortiz-Zúñiga Ángel M. , Hernández Cristina , Simó Rafael
Published: January 2019

Type 2 diabetic (T2D) subjects have a significantly higher risk of developing mild cognitive impairment (MCI) and dementia than age-matched non-diabetic individuals. However, the accurate evaluation of cognitive status is based on complex neuropsychological tests, which makes their incorporation into the current standard of care for the T2D population infeasible. Given that the ability to maintain visual gaze on a single location (fixation) is hampered in Alzheimer’s disease (AD), the aim of the present study was: (1) To assess whether the evaluation of gaze fixation during fundus-driven microperimetry correlated with cognitive status in T2D subjects; (2) to examine whether the addition of fixational parameters to the assessment of retinal sensitivity increased the predictive value of retinal microperimetry in identifying T2D subjects with MCI. For this purpose, fixation parameters and retinal sensitivity were compared in three age-matched groups of T2D subjects: normocognitive (n = 34), MCI (n = 33), and AD (n = 33). Our results showed that fixation is significantly more unstable in MCI subjects than normocognitive subjects, and even more altered in those affected by AD (ANOVA; p < 0.01). Moreover, adding fixation parameters to retinal sensitivity significantly increases the predictive value in identifying those subjects with MCI: ROC (Receiver Operating Characteristic) Area 0.68 with retinal sensitivity alone vs. ROC Area 0.86 when parameters of fixation are added to retinal sensitivity (p < 0.01). In conclusion, our results suggest that fixational eye movement parameters assessed by fundus-microperimetry represent a new tool for identifying T2D subjects at risk of dementia.
Relative Dose Intensity of Induction-Phase Pazopanib Treatment of Soft Tissue Sarcoma: Its Relationship with Prognoses of Pazopanib Responders
Authors: Nakano Kenji , Funauchi Yuki , Hayakawa Keiko , Tanizawa Taisuke , Ae Keisuke , Matsumoto Seiichi , Takahashi Shunji
Published: January 2019

The approved standard dose of pazopanib is 800 mg per day, but the appropriate dose of pazopanib to treat soft tissue sarcoma (STS) patients in real-world practice is controversial. Of 124 STS patients treated with pazopanib, we retrospectively analyzed the cases of STS patients who achieved progression-free survival at 12 weeks by pazopanib treatment as pazopanib responders, and we evaluated their relative dose intensity (RDI) in the initial 12 weeks (12W-RDI). We enrolled 78 STS patients in the analyses as pazopanib responders, and 54 patients of the 78 pazopanib responders (69%) were able to maintain 12W-RDI ≥80%. In landmark analyses, patients with 12W-RDI of 80% ≥80% had significantly longer progression-free survival compared to those with 12W-RDI <80% (30.7 weeks vs. 22.0 weeks, hazard ratio [HR]: 0.56 [95%CI: 0.33–0.94], p = 0.026). The most frequently observed reasons of treatment interruption and/or dose reduction of pazopanib during the initial 12 weeks were anorexia and liver function disorders. Liver toxicity was the adverse event most frequently observed in the 12W-RDI <80% patients throughout the treatment periods. Based on our results, it appears that maintaining as high a dose intensity as possible that is tolerable—at least during the initial 12 weeks—is likely to be the better option in pazopanib treatment for STS patients.