Acute respiratory distress after metofluthrin insecticide ingestion in a 19-month-old girl

Metofluthrin is a volatile pyrethroid insecticide. Despite being widely used as a safe household insecticide, it could cause severe systemic symptoms. A 19-month-old girl was taken to the emergency department after ingesting 1 mL of a mosquito repellent containing metofluthrin. After the arrival, the girl developed respiratory distress, which worsened progressively despite the administration of oxygen with nebulized salbutamol and budesonide. Additionally, she underwent application of high-flow nasal cannula, and administration of activated charcoal and systemic steroids. Her dyspnea gradually improved, and she was thus discharged on day 4 with oral prednisolone. All medications were discontinued 10 days after the discharge without any complication. Respiratory distress can develop after the ingestion of even a small amount of metofluthrin. Symptomatic and adjunctive steroid therapies can be effective therapeutic options

Corrigendum: Secretion of Salmonella Pathogenicity Island 1-Encoded Type III Secretion System Effectors by Outer Membrane Vesicles in Salmonella Enterica Serovar Typhimurium

Outer membrane vesicles (OMVs) are spherical membranous structures released by Gram-negative bacteria. Several bacterial pathogens utilize OMVs as vehicles for the delivery of virulence factors into host cells. Results of our previous study on proteomic analysis revealed that OMVs isolated from Salmonellaenterica serovar Typhimurium had virulence effectors that are known to be translocated by Salmonella pathogenicity island 1 (SPI-1)-encoded type III secretion system (T3SS1) into the host cell. In the present study, immunoblot analysis confirmed the secretion of the six T3SS1 effector proteins, namely SipB and SipC (translocators of T3SS1), and SipA, SopA, SopB, and SopE2 (effectors translocated by T3SS1), by OMVs. Results of proteinase K treatment revealed the localization of these T3SS1 effector proteins on the outer surface of OMVs. SipC and SopE2 were secreted by OMVs independent of the three secretion systems T3SS1, T3SS2, and flagella, signifying OMVs to be an alternative delivery system to T3SSs. T3SS1 effectors SipA, SipC, and SopE2 were internalized into the cytoplasm of the host cell by OMVs independent of cellular Salmonella–host cell contact. In epithelial cells, addition of OMVs harboring T3SS1 effectors stimulated the production of F-actin, thereby complementing the attenuated invasion of ΔsopE2 into host cells. These results suggest that S. Typhimurium might exploit OMVs as a long-distance vehicle to deliver T3SS1 effectors into the cytoplasm of the host cell independent of bacteria–host cell interaction

Secretion of Salmonella Pathogenicity Island 1-Encoded Type III Secretion System Effectors by Outer Membrane Vesicles in Salmonella enterica Serovar Typhimurium

Outer membrane vesicles (OMVs) are spherical membranous structures released by Gram-negative bacteria. Several bacterial pathogens utilize OMVs as vehicles for the delivery of virulence factors into host cells. Results of our previous study on proteomic analysis revealed that OMVs isolated from Salmonellaenterica serovar Typhimurium had virulence effectors that are known to be translocated by Salmonella pathogenicity island 1 (SPI-1)-encoded type III secretion system (T3SS1) into the host cell. In the present study, immunoblot analysis confirmed the secretion of the six T3SS1 effector proteins, namely SipB and SipC (translocators of T3SS1), and SipA, SopA, SopB, and SopE2 (effectors translocated by T3SS1), by OMVs. Results of proteinase K treatment revealed the localization of these T3SS1 effector proteins on the outer surface of OMVs. SipC and SopE2 were secreted by OMVs independent of the three secretion systems T3SS1, T3SS2, and flagella, signifying OMVs to be an alternative delivery system to T3SSs. T3SS1 effectors SipA, SipC, and SopE2 were internalized into the cytoplasm of the host cell by OMVs independent of cellular Salmonella–host cell contact. In epithelial cells, addition of OMVs harboring T3SS1 effectors stimulated the production of F-actin, thereby complementing the attenuated invasion of ΔsopE2 into host cells. These results suggest that S. Typhimurium might exploit OMVs as a long-distance vehicle to deliver T3SS1 effectors into the cytoplasm of the host cell independent of bacteria–host cell interaction

Adjacent Segment Pathology after Anterior Cervical Fusion

Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion

Stimulation of the Migration and Expansion of Adult Mouse Neural Stem Cells by the FPR2-Specific Peptide WKYMVm

Neural stem cells (NSCs) are multipotent cells capable of self-renewal and differentiation into different nervous system cells. Mouse NSCs (mNSCs) are useful tools for studying neurogenesis and the therapeutic applications of neurodegenerative diseases in mammals. Formyl peptide receptor 2 (FPR2), expressed in the central nervous system and brain, is involved in the migration and differentiation of murine embryonic-derived NSCs. In this study, we explored the effect of FPR2 activation in adult mNSCs using the synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met-NH2 (WKYMVm), an agonist of FPR2. After isolation of NSCs from the subventricular zone of the adult mouse brain, they were cultured in two culture systems—neurospheres or adherent monolayers—to demonstrate the expression of NSC markers and phenotypes. Under different conditions, mNSCs differentiated into neurons and glial cells such as astrocytes, microglia, and oligodendrocytes. Treatment with WKYMVm stimulated the chemotactic migration of mNSCs. Moreover, WKYMVm-treated mNSCs were found to promote proliferation; this result was confirmed by the expansion of mNSCs in Matrigel and the increase in the number of Ki67-positive cells. Incubation of mNSCs with WKYMVm in a supplement-free medium enhanced the survival rate of the mNSCs. Together, these results suggest that WKYMVm-induced activation of FPR2 stimulates cellular responses in adult NSCs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.1

YAF2 promotes TP53-mediated genotoxic stress response via stabilization of PDCD5

AbstractProgrammed cell death 5 (PDCD5) plays a crucial role in TP53-mediated apoptosis, but the regulatory mechanism of PDCD5 itself during apoptosis remains obscure. We identified YY1-associated factor 2 (YAF2) as a novel PDCD5-interacting protein in a yeast two-hybrid screen for PDCD5-interacting proteins. We found that YY1-associated factor 2 (YAF2) binds to and increases PDCD5 stability by inhibiting the ubiquitin-dependent proteosomal degradation pathway. However, knocking-down of YAF2 diminishes the levels of PDCD5 protein but not the levels of PDCD5 mRNA. Upon genotoxic stress response, YAF2 promotes TP53 activation via association with PDCD5. Strikingly, YAF2 failed to promote TP53 activation in the deletion of PDCD5, whereas restoration of wild-type PDCD5WT efficiently reversed the ineffectiveness of YAF2 on TP53 activation. Conversely, PDCD5 efficiently overcame the knockdown effect of YAF2 on ET-induced TP53 activation. Finally, impaired apoptosis upon PDCD5 ablation was substantially rescued by restoration of PDCD5WT but not YAF2-interacting defective PDCD5E4D nor TP53-interacting defective PDCD5E16D mutant. Our findings uncovered an apoptotic signaling cascade linking YAF2, PDCD5, and TP53 during genotoxic stress responses

Enhancing GABA Signaling during Middle Adulthood Prevents Age-Dependent GABAergic Interneuron Decline and Learning and Memory Deficits in ApoE4 Mice

Apolipoprotein E4 (apoE4) is the major genetic risk factor for Alzheimer's disease (AD). However, the underlying mechanisms are still poorly understood. We previously reported that female apoE4 knock-in (KI) mice had an age-dependent decline in hilar GABAergic interneurons that correlated with the extent of learning and memory deficits, as determined by Morris water maze (MWM), in aged mice. Enhancing GABA signaling by treating aged apoE4-KI mice with the GABA(A) receptor potentiator pentobarbital (PB) for 4 weeks before and during MWM rescued the learning and memory deficits. Here, we report that withdrawal of PB treatment for 2 weeks before MWM abolished the rescue in aged apoE4-KI mice, suggesting the importance of continuously enhancing GABA signaling in the rescue. However, treating apoE4-KI mice during middle adulthood (9–11 months of age) with PB for 6 weeks prevented age-dependent hilar GABAergic interneuron decline and learning and memory deficits, when examined at 16 month of age. These data imply that increasing inhibitory tone after substantial GABAergic interneuron loss may be an effective symptomatic, but not a disease-modifying, treatment for AD related to apoE4, whereas a similar intervention before substantial interneuron loss could be a disease-modifying therapeutic. SIGNIFICANCE STATEMENT We previously reported that female apoE4-KI mice had an age-dependent decline in hilar GABAergic interneurons that correlated with the extent of cognitive deficits in aged mice. The current study demonstrates that enhancing GABA signaling by treating aged apoE4-KI mice with a GABA(A) receptor potentiator pentobarbital (PB) before and during behavioral tests rescued the cognitive deficits; but withdrawal of PB treatment for 2 weeks before the tests abolished the rescue, suggesting the importance of continuously enhancing GABA signaling. However, treating apoE4-KI mice during middle adulthood with PB for a short period of time prevented age-dependent hilar GABAergic interneuron decline and cognitive deficits late in life, suggesting early intervention by enhancing GABA signaling as a potential strategy to prevent AD related to apoE4

Genome shotgun sequencing and development of microsatellite markers for gerbera (Gerbera hybrida H.) by 454 GS-FLX

The objective of this research was to develop and characterize microsatellite markers for gerbera. We used shotgun sequencing with Roche 454 GS-FLX Titanium technology to identify microsatellite loci in gerbera genomic DNA (Gerbera hybrida). The total length of non-redundant sequences obtained was 22,527,019 bp, which consisted of 3,085 contigs and 28,249 singletons. We assembled 61,958 reads into 3,085 contigs, of which 114 (3.70%) contained microsatellite repeats. The average G+C content was 39.3%. Functional annotation to known sequences yielded 14.7% unigenes in the ‘Raon’ cultivar. Analysis of the gerbera genome DNA (‘Raon’) general library showed that sequences of (AT), (AG), (AAG) and (AAT) repeats appeared most often, whereas (AC), (AAC) and (ACC) were the least frequent. Primer pairs were designed for 80 loci. Only eight primer pairs produced reproducible polymorphic bands in the 28 gerbera accessions analyzed. A total of 30 alleles were identified from the eight polymorphic SSR loci, with two to eight alleles per locus (average level of 3.75). These markers will be useful for investigating genetic diversity and differentiation in gerbera. Keywords: Genetic diversity, genomics, microsatellite isolation, pyrosequencing, SSRs. African Journal of Biotechnology Vol. 11(29), pp. 7388-7396, 10 April, 201