Susceptibility of \u3ci\u3eAedes aegypti, Culex quinquefasciatus\u3c/i\u3e Say, and \u3ci\u3eAnopheles quadrimaculatus\u3c/i\u3e Say to 19 Pesticides with Different Modes of Action

To access the relative potency of pesticides to control adult mosquitoes, 19 pesticides with various modes of action were evaluated against Aedes aegypti, Culex quinquefasciatus Say, and Anopheles quadrimaculatus Say. On the basis of 24-h LD50 values after topical application, the only pesticide that had higher activity than permethrin was fipronil, with LD50 values lower than permethrin for 107-, 4,849-, and 2-fold against Ae. aegypti, Cx. quinquefasciatus Say, and An. quadrimaculatus Say, respectively. Abamectin, imidacloprid, spinosad, diazinon, and carbaryl showed slightly lower activity than permethrin (\u3c20-fold). However, bifenazate showed very low activity against the three mosquito species tested, with LD50 values higher than permthrin for \u3e1000-fold. On the basis of 24-h LD50 values, Cx. quinquefasciatus was the least susceptible species to nine pesticides tested (DNOC, azocyclotin, chlorfenapyr, carbaryl, spinosad, imidaclorid, diazinon, abamectin, and permethrin), whereas Ae. aegypti was the least susceptible species to six pesticides tested (dicofol, amitraz, propargite, hydramethylnon, cyhexatin, and diafenthiuron), and An. quadrimaculatus was the least susceptible species to four pesticides tested (bifenazate, pyridaben, indoxacarb, and fipronil). Our results revealed that different species of mosquitoes had different susceptibility to pesticides, showing the need to select the most efficacious compounds for the least susceptible mosquito species to achieve successful mosquito control

Susceptibility of \u3ci\u3eAedes aegypti, Culex quinquefasciatus\u3c/i\u3e Say, and \u3ci\u3eAnopheles quadrimaculatus\u3c/i\u3e Say to 19 Pesticides with Different Modes of Action

To access the relative potency of pesticides to control adult mosquitoes, 19 pesticides with various modes of action were evaluated against Aedes aegypti, Culex quinquefasciatus Say, and Anopheles quadrimaculatus Say. On the basis of 24-h LD50 values after topical application, the only pesticide that had higher activity than permethrin was fipronil, with LD50 values lower than permethrin for 107-, 4,849-, and 2-fold against Ae. aegypti, Cx. quinquefasciatus Say, and An. quadrimaculatus Say, respectively. Abamectin, imidacloprid, spinosad, diazinon, and carbaryl showed slightly lower activity than permethrin (\u3c20-fold). However, bifenazate showed very low activity against the three mosquito species tested, with LD50 values higher than permthrin for \u3e1000-fold. On the basis of 24-h LD50 values, Cx. quinquefasciatus was the least susceptible species to nine pesticides tested (DNOC, azocyclotin, chlorfenapyr, carbaryl, spinosad, imidaclorid, diazinon, abamectin, and permethrin), whereas Ae. aegypti was the least susceptible species to six pesticides tested (dicofol, amitraz, propargite, hydramethylnon, cyhexatin, and diafenthiuron), and An. quadrimaculatus was the least susceptible species to four pesticides tested (bifenazate, pyridaben, indoxacarb, and fipronil). Our results revealed that different species of mosquitoes had different susceptibility to pesticides, showing the need to select the most efficacious compounds for the least susceptible mosquito species to achieve successful mosquito control

Susceptibility of \u3ci\u3eAedes aegypti, Culex quinquefasciatus\u3c/i\u3e Say, and \u3ci\u3eAnopheles quadrimaculatus\u3c/i\u3e Say to 19 Pesticides with Different Modes of Action

To access the relative potency of pesticides to control adult mosquitoes, 19 pesticides with various modes of action were evaluated against Aedes aegypti, Culex quinquefasciatus Say, and Anopheles quadrimaculatus Say. On the basis of 24-h LD50 values after topical application, the only pesticide that had higher activity than permethrin was fipronil, with LD50 values lower than permethrin for 107-, 4,849-, and 2-fold against Ae. aegypti, Cx. quinquefasciatus Say, and An. quadrimaculatus Say, respectively. Abamectin, imidacloprid, spinosad, diazinon, and carbaryl showed slightly lower activity than permethrin (\u3c20-fold). However, bifenazate showed very low activity against the three mosquito species tested, with LD50 values higher than permthrin for \u3e1000-fold. On the basis of 24-h LD50 values, Cx. quinquefasciatus was the least susceptible species to nine pesticides tested (DNOC, azocyclotin, chlorfenapyr, carbaryl, spinosad, imidaclorid, diazinon, abamectin, and permethrin), whereas Ae. aegypti was the least susceptible species to six pesticides tested (dicofol, amitraz, propargite, hydramethylnon, cyhexatin, and diafenthiuron), and An. quadrimaculatus was the least susceptible species to four pesticides tested (bifenazate, pyridaben, indoxacarb, and fipronil). Our results revealed that different species of mosquitoes had different susceptibility to pesticides, showing the need to select the most efficacious compounds for the least susceptible mosquito species to achieve successful mosquito control

Trigeminal neuropathy presenting secondary to SARS-CoV-2 infection

Introduction: A 58-year-old woman presented to a multidisciplinary facial pain clinic in October 2021 complaining of a constant pain in the right side of her face since contracting coronavirus SARS-CoV-2 18 months earlier. The pain extending from the right temple down to her right cheek extraorally and including the maxillary teeth and right side of tongue intraorally. This was accompanied by anosmia, diplopia on lateral gaze, and dizziness. Methods: Clinical examination was supplemented with several neurophysiological tests to confirm the diagnosis including an MRI brain scan, quantitative sensory testing, electrophysiological blink reflex testing, corneal confocal microscopy, and pain and short-form anxiety and depression questionnaires. Results: Quantitative sensory testing showed unilateral loss of perception in thermal and mechanical sensibility and bilateral hyperalgesia indicating central sensitization. Bilateral corneal confocal microscopy showed an abnormally reduced corneal nerve fibre length on the right side. MRI, blink reflex, and masseter inhibitory testing findings were normal. Conclusion: This case study is the first case of trigeminal neuropathy related to SARS-CoV-2 infection reported in the literature. It also discusses the successful management of the patient's trigeminal neuropathic pain

Thiothymidine combined with UVA as a potential novel therapy for bladder cancer

BACKGROUND: Thiothymidine (S4TdR) can be incorporated into DNA and sensitise cells to DNA damage and cell death following exposure to UVA light. Studies were performed to determine if the combination of S4TdR and UVA could be an effective treatmentfor bladder cancer. METHODS: Uptake and incorporation of S4TdR was determined in rat and human bladder tumour cell lines. Measures of DNA crosslinking and apoptosis were also performed. In vivo activity of the combination of S4TdR and UVA was investigated in an orthotopic model of bladder cancer in rats. RESULTS: Thiothymidine (200 uM) replaced up to 0.63% of thymidine in rat and tumour bladder cancer cells. The combination of S4TdR (10–200 uM) and UVA (1–5 kJm-2) caused apoptosis and cell death at doses that were not toxic alone. Addition of raltitrexed (Astra Zeneca, Alderley Edge, Cheshire, UK) increased the incorporation of S4TdR into DNA (up to 20-fold at IC5) and further sensitised cells to UVA. Cytotoxic effect was associated with crosslinking of DNA, at least partially to protein. Intravenous administration of S4TdR, in combination with UVA delivered directly to the bladder, resulted in an antitumour effect in three of five animals treated. CONCLUSION: These data indicate that the combination of S4TdR and UVA has potential as a treatment for bladder cancer, and give some insight into the mechanism of action. Further work is necessary to optimise the delivery of the two components

Structural determinants of PINK1 topology and dual subcellular distribution

<p>Abstract</p> <p>Background</p> <p>PINK1 is a mitochondria-targeted kinase that constitutively localizes to both the mitochondria and the cytosol. The mechanism of how PINK1 achieves cytosolic localization following mitochondrial processing remains unknown. Understanding PINK1 subcellular localization will give us insights into PINK1 functions and how mutations in PINK1 lead to Parkinson's disease. We asked how the mitochondrial localization signal, the transmembrane domain, and the kinase domain participate in PINK1 localization.</p> <p>Results</p> <p>We confirmed that PINK1 mitochondrial targeting signal is responsible for mitochondrial localization. Once inside the mitochondria, we found that both PINK1 transmembrane and kinase domain are important for membrane tethering and cytosolic-facing topology. We also showed that PINK1 dual subcellular distribution requires both Hsp90 interaction with the kinase domain and the proteolysis at a cleavage site downstream of the transmembrane domain because removal of this cleavage site completely abolished cytosolic PINK1. In addition, the disruption of the Hsp90-PINK1 interaction increased mitochondrial PINK1 level.</p> <p>Conclusion</p> <p>Together, we believe that once PINK1 enters the mitochondria, PINK1 adopts a tethered topology because the transmembrane domain and the kinase domain prevent PINK1 forward movement into the mitochondria. Subsequent proteolysis downstream of the transmembrane domain then releases PINK1 for retrograde movement while PINK1 kinase domain interacts with Hsp90 chaperone. The significance of this dual localization could mean that PINK1 has compartmental-specific functions.</p

IL-17RA Is Required for CCL2 Expression, Macrophage Recruitment, and Emphysema in Response to Cigarette Smoke

Chronic Obstructive Pulmonary Disease (COPD) is characterized by airspace enlargement and peribronchial lymphoid follicles; however, the immunological mechanisms leading to these pathologic changes remain undefined. Here we show that cigarette smoke is a selective adjuvant that augments in vitro and in vivo Th17, but not Th1, cell differentiation via the aryl hydrocarbon receptor. Smoke exposed IL-17RA−/− mice failed to induce CCL2 and MMP12 compared to WT mice. Remarkably, in contrast to WT mice, IL-17RA−/− mice failed to develop emphysema after 6 months of cigarette smoke exposure. Taken together, these data demonstrate that cigarette smoke is a potent Th17 adjuvant and that IL-17RA signaling is required for chemokine expression necessary for MMP12 induction and tissue emphysema

Hsp90 Inhibition Decreases Mitochondrial Protein Turnover

Cells treated with hsp90 inhibitors exhibit pleiotropic changes, including an expansion of the mitochondrial compartment, accompanied by mitochondrial fragmentation and condensed mitochondrial morphology, with ultimate compromise of mitochondrial integrity and apoptosis.We identified several mitochondrial oxidative phosphorylation complex subunits, including several encoded by mtDNA, that are upregulated by hsp90 inhibitors, without corresponding changes in mRNA abundance. Post-transcriptional accumulation of mitochondrial proteins observed with hsp90 inhibitors is also seen in cells treated with proteasome inhibitors. Detailed studies of the OSCP subunit of mitochondrial F1F0-ATPase revealed the presence of mono- and polyubiquitinated OSCP in mitochondrial fractions. We demonstrate that processed OSCP undergoes retrotranslocation to a trypsin-sensitive form associated with the outer mitochondrial membrane. Inhibition of proteasome or hsp90 function results in accumulation of both correctly targeted and retrotranslocated mitochondrial OSCP.Cytosolic turnover of mitochondrial proteins demonstrates a novel connection between mitochondrial and cytosolic compartments through the ubiquitin-proteasome system. Analogous to defective protein folding in the endoplasmic reticulum, a mitochondrial unfolded protein response may play a role in the apoptotic effects of hsp90 and proteasome inhibitors

Chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors

<p>Abstract</p> <p>Background</p> <p>Malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. Hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. In the present study, chlorfenapyr was evaluated against <it>Anopheles culicifacies </it>and <it>Anopheles stephensi </it>for its possible use in vector control.</p> <p>Methods</p> <p>Efficacy of chlorfenapyr against <it>An. culicifacies </it>and <it>An. stephensi </it>was assessed using adult bioassay tests. In the laboratory, determination of diagnostic dose, assessment of residual activity on different substrates, cross-resistance pattern with different insecticides and potentiation studies using piperonyl butoxide were undertaken by following standard procedures. Potential cross-resistance patterns were assessed on field populations of <it>An. culicifacies</it>.</p> <p>Results</p> <p>A dose of 5.0% chlorfenapyr was determined as the diagnostic concentration for assessing susceptibility applying the WHO tube test method in anopheline mosquitoes with 2 h exposure and 48 h holding period. The DDT-resistant/malathion-deltamethrin-susceptible strain of <it>An. culicifacies </it>species C showed higher LD50 and LD99 (0.67 and 2.39% respectively) values than the DDT-malathion-deltamethrin susceptible <it>An. culicifacies </it>species A (0.41 and 2.0% respectively) and <it>An. stephensi </it>strains (0.43 and 2.13% respectively) and there was no statistically significant difference in mortalities among the three mosquito species tested (p > 0.05). Residual activity of chlorfenapyr a.i. of 400 mg/m²on five fabricated substrates, namely wood, mud, mud+lime, cement and cement + distemper was found to be effective up to 24 weeks against <it>An. culicifacies </it>and up to 34 weeks against <it>An. stephensi</it>. No cross-resistance to DDT, malathion, bendiocarb and deltamethrin was observed with chlorfenapyr in laboratory-reared strains of <it>An. stephensi </it>and field-caught <it>An. culicifacies. </it>Potentiation studies demonstrated the antagonistic effect of PBO.</p> <p>Conclusion</p> <p>Laboratory studies with susceptible and resistant strains of <it>An. culicifacies </it>and <it>An. stephensi</it>, coupled with limited field studies with multiple insecticide-resistant <it>An. culicifacies </it>have shown that chlorfenapyr can be a suitable insecticide for malaria vector control, in multiple-insecticide-resistant mosquitoes especially in areas with pyrethroid resistant mosquitoes.</p