Expression and distribution of PPP2R5C gene in leukemia

<p>Abstract</p> <p>Background</p> <p>Recently, we clarified at the molecular level novel chromosomal translocation t(14;14)(q11;q32) in a case of Sézary syndrome, which caused a rearrangement from TRAJ7 to the <it>PPP2R5C </it>gene. <it>PPP2R5C </it>is one of the regulatory B subunits of protein phosphatase 2A (PP2A). It plays a crucial role in cell proliferation, differentiation, and transformation. To characterize the expression and distribution of five different transcript variants of the <it>PPP2R5C </it>gene in leukemia, we analyzed the expression level of <it>PPP2R5C </it>in peripheral blood mononuclear cells from 77 patients with <it>de novo </it>leukemia, 26 patients with leukemia in complete remission (CR), and 20 healthy individuals by real-time PCR and identified the different variants of <it>PPP2R5C </it>by RT-PCR.</p> <p>Findings</p> <p>Significantly higher expression of <it>PPP2R5C </it>was found in AML, CML, T-ALL, and B-CLL groups in comparison with healthy controls. High expression of <it>PPP2R5C </it>was detected in the B-ALL group; however, no significant difference was found compared with the healthy group. The expression level of <it>PPP2R5C </it>in the CML-CR group decreased significantly compared with that in the <it>de novo </it>CML group and was not significantly different from the level in the healthy group. By using different primer pairs that covered different exons, five transcript variants of <it>PPP2R5C </it>could be identified. All variants could be detected in healthy samples as well as in all the leukemia samples, and similar frequencies and distributions of <it>PPP2R5C </it>were indicated.</p> <p>Conclusions</p> <p>Overexpression of <it>PPP2R5C </it>in T-cell malignancy as well as in myeloid leukemia cells might relate to its proliferation and differentiation. Investigation of the effect of target inhibition of this gene might be beneficial to further characterization of molecular mechanisms and targeted therapy in leukemia.</p

A Mutation in the Intracellular Loop III/IV of Mosquito Sodium Channel Synergizes the Effect of Mutations in Helix IIS6 on Pyrethroid Resistance s

ABSTRACT Activation and inactivation of voltage-gated sodium channels are critical for proper electrical signaling in excitable cells

A dual-target molecular mechanism of pyrethrum repellency against mosquitoes

Pyrethrum extracts from flower heads of Chrysanthemum spp. have been used worldwide in insecticides and repellents. While the molecular mechanisms of its insecticidal action are known, the molecular basis of pyrethrum repellency remains a mystery. In this study, we find that the principal components of pyrethrum, pyrethrins, and a minor component, (E)-β-farnesene (EBF), each activate a specific type of olfactory receptor neurons in Aedes aegypti mosquitoes. We identify Ae. aegypti odorant receptor 31 (AaOr31) as a cognate Or for EBF and find that Or31-mediated repellency is significantly synergized by pyrethrin-induced activation of voltage-gated sodium channels. Thus, pyrethrum exerts spatial repellency through a novel, dual-target mechanism. Elucidation of this two-target mechanism may have potential implications in the design and development of a new generation of synthetic repellents against major mosquito vectors of infectious diseases

The efficacy and neural mechanism of acupuncture therapy in the treatment of visceral hypersensitivity in irritable bowel syndrome

Irritable Bowel Syndrome (IBS) is a complex functional gastrointestinal disorder primarily characterized by chronic abdominal pain, bloating, and altered bowel habits. Chronic abdominal pain caused by visceral Hypersensitivity (VH) is the main reason why patients with IBS seek medication. Significant research effort has been devoted to the efficacy of acupuncture as a non-drug alternative therapy for visceral-hyperalgesia-induced IBS. Herein, we examined the central and peripheral analgesic mechanisms of acupuncture in IBS treatment. Acupuncture can improve inflammation and relieve pain by reducing 5-hydroxytryptamine and 5-HT3A receptor expression and increasing 5-HT4 receptor expression in peripheral intestinal sensory endings. Moreover, acupuncture can also activate the transient receptor potential vanillin 1 channel, block the activity of intestinal glial cells, and reduce the secretion of local pain-related neurotransmitters, thereby weakening peripheral sensitization. Moreover, by inhibiting the activation of N-methyl-D-aspartate receptor ion channels in the dorsal horn of the spinal cord and anterior cingulate cortex or releasing opioids, acupuncture can block excessive stimulation of abnormal pain signals in the brain and spinal cord. It can also stimulate glial cells (through the P2X7 and prokinetic protein pathways) to block VH pain perception and cognition. Furthermore, acupuncture can regulate the emotional components of IBS by targeting hypothalamic-pituitary-adrenal axis-related hormones and neurotransmitters via relevant brain nuclei, hence improving the IBS-induced VH response. These findings provide a scientific basis for acupuncture as an effective clinical adjuvant therapy for IBS pain

Electrophysiological Responses of Eighteen Species of Insects to Fire Ant Alarm Pheromone

Olfaction plays a dominant role in insect communication. Alarm pheromones, which alert other insects of the same species of impending danger, are a major class of releaser pheromones. The major components of alarm pheromones in red imported fire ants, honeybees and aphids have been identified as 2-ethyl-3,6-dimethylpyrazine (2E-3,6-DP), isopentyl acetate (IPA), and E-&beta;-farnesene (E&beta;F), respectively. In this study, electroantennography (EAG) responses to EDP (a mixture of 2-ethyl-3,6-dimethylpyrazine and 2-ethyl-3,5-dimethylpyrazine), IPA and E&beta;F were investigated in a wide range of insect species. Beside imported fire ants, the EDP (2-ethyl-3,6(5)-dimethylpyrazine) elicited significant EAG response from all other tested insects, including six ant species and one hybrid ant, honeybee, bagrada bug, lady beetle, housefly, small hive beetle, yellow fever mosquito, termite, bedbug, water hyacinth weevil, southern green stink bug and two aphid species. In contrast, IPA elicited significant EAG response only in the honeybee, red imported fire ant, an Aphaenogaster ant, and the water hyacinth weevil. The E&beta;F only elicited EAG responses in two aphids, small hive beetle and housefly. The results clearly indicate that EDP can be detected by widespread insect species that did not coevolve with S. invicta and further suggested alkylpyrazine may activate multiple generally tuned olfactory receptors (ORs) across a wide number of insect species

Sodium Channel Mutations and Pyrethroid Resistance in Aedes aegypti

Pyrethroid insecticides are widely used to control insect pests and human disease vectors. Voltage-gated sodium channels are the primary targets of pyrethroid insecticides. Mutations in the sodium channel have been shown to be responsible for pyrethroid resistance, known as knockdown resistance (kdr), in various insects including mosquitoes. In Aedes aegypti mosquitoes, the principal urban vectors of dengue, zika, and yellow fever viruses, multiple single nucleotide polymorphisms in the sodium channel gene have been found in pyrethroid-resistant populations and some of them have been functionally confirmed to be responsible for kdr in an in vitro expression system, Xenopus oocytes. This mini-review aims to provide an update on the identification and functional characterization of pyrethroid resistance-associated sodium channel mutations from Aedes aegypti. The collection of kdr mutations not only helped us develop molecular markers for resistance monitoring, but also provided valuable information for computational molecular modeling of pyrethroid receptor sites on the sodium channel

The Odorant Binding Protein, SiOBP5, Mediates Alarm Pheromone Olfactory Recognition in the Red Imported Fire Ant, Solenopsis invicta

Olfaction is crucial in mediating various behaviors of social insects such as red imported fire ants, Solenopsis invicta Buren. Olfactory receptor (OR) complexes consist of odor-specific ORs and OR co-receptors (Orco). Orcos are highly conserved across insect taxa and are widely co-expressed with ORs. Odorant binding proteins (OBPs) can transport semiochemicals to ORs as protein carriers and thus constitute the first molecular recognition step in insect olfaction. In this study, three OBP genes highly expressed in S. invicta antenna, OBP1, OBP5, OBP6, and Orco were partially silenced using RNA interference (RNAi). RNAi SiOBP5- and Orco-injected ants showed significantly lower EAG (electroantennography) responses to fire ant alarm pheromones and the alkaloid, 2,4,6-trimethylpyridine than water- or GFP-injected ants 72 h post injection. Subsequent qRT-PCR analysis demonstrated that the transcript level of the OBP1, OBP5, OBP6, and Orco significantly decreased 72 h after ants were injected with dsRNAs; however, there were no transcript level or EAG changes in ants fed dsRNAs. Our results suggest that S. invicta Orco and SiOBP5 are crucial to fire ants for their responses to alarm pheromones. RNAi knocking down SiOBP5 can significantly disrupt alarm pheromone communication, suggesting that disrupting SiOBP5 and Orcos could be potentially useful in the management of red imported fire ants

Insecticidal and Enzyme Inhibitory Activities of Isothiocyanates against Red Imported Fire Ants, Solenopsis invicta

Contact and fumigation toxicity of four isothiocyanates (ITCs), including allyl isothiocyanate (AITC), 3-butenyl isothiocyanate (3BITC), 3-(methylthio) propyl isothiocyanate (3MPITC) and 2-phenylethyl isothiocyanate (2PEITC), were evaluated against the red imported fire ant worker, Solenopsis invicta Buren. 2PEITC and 3MPITC exhibited strong contact toxicity. The median lethal dose (LD50)value of AITC, 2PEITC and 3MPITC were 7.99, 2.36 and 2.09 &micro;g/ant respectively. In addition, AITC and 3MPITC also showed strong fumigation toxicity but not 2PEITC. The median lethal concentration (LC50) values of AITC and 3MPITC were 32.49 and 57.6 &micro;g/L, respectively. In contrast, 3BITC did not exhibit any contact and fumigation toxicity even at 100 &mu;g/&mu;L. Esterase (EST), glutathione S-transferase (GST) and acetylcholinesterase (AChE)-inhibiting activities were assessed for three ITCs in S. invicta workers. All three ITCs inhibited both EST and GST activities but not AChE. The in vitro half maximal inhibitory concentration (IC50)values of AITC, 2PEITC and 3MPITC for GST were 3.32, 0.61 and 0.66 &micro;g/&micro;L, respectively. These results suggested that naturally occurring ITCs might be potentially useful for developing fire ants control products

Toxicity Assessment of Four Formulated Pyrethroid-Containing Binary Insecticides in Two Resistant Adult Tarnished Plant Bug (<i>Lygus lineolaris</i>) Populations

Over the past several decades, the extensive use of pyrethroids has led to the development of resistance in many insect populations, including the economically damaging pest tarnished plant bug (TPB), Lygus lineolaris, on cotton. To manage TPB resistance, several commercially formulated pyrethroid-containing binary mixtures, in combination with neonicotinoids or avermectin are recommended for TPB control and resistance management in the mid-South USA. This study aimed to evaluate the toxicity and resistance risks of four formulated pyrethroid-containing binary mixtures (Endigo, Leverage, Athena, and Hero) on one susceptible and two resistant TPB populations, which were field-collected in July (Field-R1) and October (Field-R2), respectively. Based on LC50 values, both resistant TPB populations displayed variable tolerance to the four binary mixtures, with Hero showing the highest resistance and Athena the lowest. Notably, the Field-R2 exhibited 1.5–3-fold higher resistance compared to the Field-R1 for all four binary insecticides. Moreover, both resistant TPB populations demonstrated significantly higher resistance ratios towards Hero and Leverage compared to their corresponding individual pyrethroid, while Endigo and Athena showed similar or lower resistance. This study also utilized the calculated additive index (AI) and co-toxicity coefficient (CTC) analysis, which revealed that the two individual components in Leverage exhibited antagonist effects against the two resistant TPB populations. In contrast, the two individual components in Endigo, Hero, and Athena displayed synergistic interactions. Considering that Hero is a mixture of two pyrethroids that can enhance the development of TPB resistance, our findings suggest that Endigo and Athena are likely superior products for slowing down resistance development in TPB populations. This study provides valuable insight for selecting the most effective mixtures to achieve better TPB control through synergistic toxicity analysis, while simultaneously reducing economic and environmental risks associated with resistance development in the insect pest