Status of DDT and pyrethroid resistance in Indian aedes Albopictus and absence of knockdown resistance (kdr) mutation

Background & objectives: Aedes albopictus is one of the vectors for dengue and chikungunya and emergence of pyrethroid resistance in this species could be of a major concern in controlling the vector. This study reports insecticide susceptibility status of Ae. albopictus to DDT and pyrethroids in some Indian populations and status of presence of knockdown resistance (kdr) mutations. Methods: Three to four day old adult female Ae. albopictus collected from Delhi, Gurgaon (Haryana), Hardwar (Uttarakhand), Guwahati (Assam) and Kottayam (Kerala) were bio-assayed with DDT (4), permethrin (0.75) and deltamethrin (0.05) impregnated papers using WHO standard susceptibility test kit. Mosquitoes were PCRgenotyped for F1534C kdr-mutation in the voltage-gated sodium channel (VGSC) gene. DDT and pyrethroid resistant individuals were sequenced for partial domain II, III and IV of VGSC targeting residues S989, I1011, V1016, F1534 and D1794 where kdr mutations are reported in Ae. aegypti. Results: Adult bioassays revealed varying degree of resistance against DDT among five populations of Ae. albopictus with corrected mortalities ranging between 61 and 92. Kerala and Delhi populations showed incipient resistance against permethrin and deltamethrin respectively. All other populations were susceptible for both the synthetic pyrethroids. None of the kdr mutations was detected in any of DDT, deltamethrin and permethrin resistant individuals. Interpretation & conclusion: Ae. albopictus has developed resistance against DDT and there is emergence of incipient resistance against pyrethroids in some populations. So far, there is no evidence of presence of knockdown resistance (kdr) mutation in Ae. albopictus. © 2015, Malaria Research Center. All right reserved

Excretory/Secretory-Products of Echinococcus multilocularis Larvae Induce Apoptosis and Tolerogenic Properties in Dendritic Cells In Vitro

Parasitic helminths are inducers of chronic diseases and have evolved mechanisms to suppress the host immune response. Mostly from studies on roundworms, a picture is currently emerging that helminths secrete factors (E/S-products) that directly act on sentinels of the immune system, dendritic cells, in order to achieve an expansion of immunosuppressive, regulatory T cells (T-reg). Parasitic helminths are currently also intensely studied as therapeutic agents against autoimmune diseases and allergies, which is directly linked to their immunosuppressive activities. The immunomodulatory products of parasitic helminths are therefore of high interest for understanding immunopathology during infections and for the treatment of allergies. The present work was conducted on larvae of the tapeworm E. multilocularis, which grow like a tumor into surrounding host tissue and thus cause the lethal disease alveolar echinococcosis. The authors found that E/S-products from early infective larvae are strong inducers of tolerogenic DC in vitro and show that E/S-products of larvae of the chronic stage lead to an in vitro expansion of Foxp3+ T cells, suggesting that both the expansion of these T cells and poorly responsive DC are important for the establishment and persistence of E. multilocularis larvae within the host

Ground Water Chemistry Changes before Major Earthquakes and Possible Effects on Animals

Prior to major earthquakes many changes in the environment have been documented. Though often subtle and fleeting, these changes are noticeable at the land surface, in water, in the air, and in the ionosphere. Key to understanding these diverse pre-earthquake phenomena has been the discovery that, when tectonic stresses build up in the Earth’s crust, highly mobile electronic charge carriers are activated. These charge carriers are defect electrons on the oxygen anion sublattice of silicate minerals, known as positive holes, chemically equivalent to O− in a matrix of O2−. They are remarkable inasmuch as they can flow out of the stressed rock volume and spread into the surrounding unstressed rocks. Travelling fast and far the positive holes cause a range of follow-on reactions when they arrive at the Earth’s surface, where they cause air ionization, injecting massive amounts of primarily positive air ions into the lower atmosphere. When they arrive at the rock-water interface, they act as •O radicals, oxidizing water to hydrogen peroxide. Other reactions at the rock-water interface include the oxidation or partial oxidation of dissolved organic compounds, leading to changes of their fluorescence spectra. Some compounds thus formed may be irritants or toxins to certain species of animals. Common toads, Bufo bufo, were observed to exhibit a highly unusual behavior prior to a M6.3 earthquake that hit L’Aquila, Italy, on April 06, 2009: a few days before the seismic event the toads suddenly disappeared from their breeding site in a small lake about 75 km from the epicenter and did not return until after the aftershock series. In this paper we discuss potential changes in groundwater chemistry prior to seismic events and their possible effects on animals

Action potentials in abscisic acid-deficient tomato mutant generated spontaneously and evoked by electrical stimulation

Action potentials generated spontaneously (SAPs) and evoked by electrical stimulation (APs) in tomato plants (Solanum lycopersicum L.) cv. Micro-Tom ABA-deficient mutants (sitiens—MTsit) and its wild type (MTwt) were characterized by continuous monitoring of electrical activity for 66 h and by application of an electrical stimulation supplied extracellularly. MTsit generated SAPs which spread along the stem, including petioles and roots with an amplitude of 44.6 ± 4.4 mV, half-time (t½) of 33.1 ± 2.9 s and velocity of 5.4 ± 1.0 cm min−1. Amplitude and velocity were 43 and 108 % higher in MTsit than in MTwt, respectively. The largest number of SAPs was registered in the early morning in both genotypes. MTsit was less responsive to electrical stimuli. The excitation threshold and the refractory period were greater in MTsit than in MTwt. After current application, APs were generated in the MTwt with 21.2 ± 2.4 mV amplitude and propagated with 5.6 ± 0.5 cm min−1 velocity. Lower intensity stimuli did not trigger APs in these plants. In MTsit APs were measured with amplitude of 26.8 ± 4.8 mV and propagated with velocity of 8.5 ± 0.1 cm min−1

Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling

The Notch pathway controls proliferation during development and in adulthood, and is frequently affected in many disorders. However, the genetic sensitivity and multi-layered transcriptional properties of the Notch pathway has made its molecular decoding challenging. Here, we address the complexity of Notch signaling with respect to proliferation, using the developing Drosophila CNS as model. We find that a Notch/Su(H)/E(spl)-HLH cascade specifically controls daughter, but not progenitor proliferation. Additionally, we find that different E(spl)-HLH genes are required in different neuroblast lineages. The Notch/Su(H)/E(spl)-HLH cascade alters daughter proliferation by regulating four key cell cycle factors: Cyclin E, String/Cdc25, E2f and Dacapo (mammalian p21CIP1/p27KIP1/p57Kip2). ChIP and DamID analysis of Su(H) and E(spl)-HLH indicates direct transcriptional regulation of the cell cycle genes, and of the Notch pathway itself. These results point to a multi-level signaling model and may help shed light on the dichotomous proliferative role of Notch signaling in many other systems

Type I Interferon Drives Dendritic Cell Apoptosis via Multiple BH3-Only Proteins following Activation by PolyIC In Vivo

BACKGROUND: DC are activated by pathogen-associated molecular patterns (PAMPs), and this is pivotal for the induction of adaptive immune responses. Thereafter, the clearance of activated DC is crucial to prevent immune pathology. While PAMPs are of major interest for vaccine science due to their adjuvant potential, it is unclear whether and how PAMPs may affect DC viability. We aimed to elucidate the possible apoptotic mechanisms that control activated DC lifespan in response to PAMPs, particularly in vivo. METHODOLOGY/PRINCIPAL FINDINGS: We report that polyinosinic:polycytidylic acid (PolyIC, synthetic analogue of dsRNA) induces dramatic apoptosis of mouse splenic conventional DC (cDC) in vivo, predominantly affecting the CD8α subset, as shown by flow cytometry-based analysis of splenic DC subsets. Importantly, while Bim deficiency conferred only minor protection, cDC depletion was prevented in mice lacking Bim plus one of three other BH3-only proteins, either Puma, Noxa or Bid. Furthermore, we show that Type I Interferon (IFN) is necessary and sufficient for DC death both in vitro and in vivo, and that TLR3 and MAVS co-operate in IFNß production in vivo to induce DC death in response to PolyIC. CONCLUSIONS/SIGNIFICANCE: These results demonstrate for the first time in vivo that apoptosis restricts DC lifespan following activation by PolyIC, particularly affecting the CD8α cDC subset. Such DC apoptosis is mediated by the overlapping action of pro-apoptotic BH3-only proteins, including but not solely involving Bim, and is driven by Type I IFN. While Type I IFNs are important anti-viral factors, CD8α cDC are major cross-presenting cells and critical inducers of CTL. We discuss such paradoxical finding on DC death with PolyIC/Type I IFN. These results could contribute to understand immunosuppression associated with chronic infection, and to the optimization of DC-based therapies and the clinical use of PAMPs and Type I IFNs

Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells

One of the ultimate goals in transplantation is to develop novel therapeutic methods for induction of donor-specific tolerance to reduce the side effects caused by the generalized immunosuppression associated to the currently used pharmacologic regimens. Interaction or phagocytosis of cells in early apoptosis exerts potent anti-inflammatory and immunosuppressive effects on antigen (Ag)-presenting cells (APC) like dendritic cells (DC) and macrophages. This observation led to the idea that apoptotic cell-based therapies could be employed to deliver donor-Ag in combination with regulatory signals to recipient’s APC as therapeutic approach to restrain the anti-donor response. This review describes the multiple mechanisms by which apoptotic cells down-modulate the immuno-stimulatory and pro-inflammatory functions of DC and macrophages, and the role of the interaction between apoptotic cells and APC in self-tolerance and in apoptotic cell-based therapies to prevent/treat allograft rejection and graft-versus-host disease in murine experimental systems and in humans. It also explores the role that in vivo-generated apoptotic cells could have in the beneficial effects of extracorporeal photopheresis, donor-specific transfusion, and tolerogenic DC-based therapies in transplantation