Rice varietal resistance to the vector Sogatella furcifera hinders transmission of Southern rice black-streaked dwarf virus.

BACKGROUND: The Southern rice black-streaked dwarf virus (SRBSDV) transmitted by Sogatella furcifera constitutes a threat to sustainable rice production. However, most rice varieties are highly vulnerable to SRBSDV, whereas the occurrence of the viral disease varies significantly under field conditions. This study aimed to evaluate the potential of rice varietal resistance to S. furcifera in reducing SRBSDV transmission. RESULTS: Among the five rice varieties, Zhongzheyou8 and Deyou108 exhibited high resistance to S. furcifera, Baixiangnuo33 was susceptible, and TN1 and Diantun502 were highly susceptible. The S. furcifera generally showed non-preference for and low feeding on the Zhongzheyou8 and Deyou108 plants, which may explain the resistance of these varieties to S. furcifera. Transmission of SRBSDV by S. furcifera was significantly impaired on the resistant varieties, both inoculation and acquisition rates were much lower on Zhongzheyou8 than on TN1. The short durations of S. furcifera salivation and phloem-related activities and the low S. furcifera feeding amount may explain the reduced SRBSDV inoculation and acquisition rates associated with Zhongzheyou8. Spearman's rank correlation revealed a significant negative correlation between S. furcifera resistance and SRBSDV transmission among the tested varieties. CONCLUSION: The results indicate that rice varietal resistance to the vector S. furcifera hinders SRBSDV transmission, which is largely associated with the host plant selection and feeding behaviors of the vector. The current findings shed light on the management of the SRBSDV viral disease through incorporation of S. furcifera resistant rice varieties in the management protocol. © 2024 Society of Chemical Industry.

Influence of Zr Addition on the Microstructure and Hydrogenation Kinetics of Ti50-xV25Cr25Zrx (x = 0, 5, 7, and 9) Alloys.

Due to the poor activation performance and kinetics of Ti50V25Cr25 alloys, the element Zr was added to improve the phase structure of the alloy and achieve a high-performance hydrogen storage alloy. The Ti50-xV25Cr25Zrx (x = 0, 5, 7, and 9) system alloys were prepared by arc melting. The alloys were analyzed using an X-ray diffractometer (XRD), scanning electron microscope (SEM), and differential scanning calorimeter (DSC). The hydrogen storage capabilities of the alloys were also obtained by the Sievert volumetric method. The results indicated that the alloy with Zr added had a combination of the C15 Laves phase and the BCC phase, whereas the Zr-free alloy had a BCC single phase. The partial replacement of Zr with Ti resulted in an increase in the lattice parameters of the main phase. The hydrogen storage kinetic performance and activation of the alloys both significantly improved with an increasing Zr concentration. The time to reach 90% of the maximum hydrogen storage capacity decreased to 2946 s, 230 s, and 120 s, respectively, with the increases in Zr concentration. The initial hydrogen absorption content of the alloys increased and then decreased after the addition of the element Zr. The second phase expanded with an increasing Zr concentration, which in turn decreased the abundance of the BCC main phase. The Ti43V25Cr25Zr7 alloy showed good cycle stability and hydrogen-desorption performance, and it could absorb 90% of the maximum hydrogen storage capacity in around 230 s. The maximum hydrogen-absorption capacity of the alloy was 2.7 wt%. The diffusion activation energy of hydrogen desorption dropped from 102.67 kJ/mol to 92.62 kJ/mol.

Functional characterization of alkaline phosphatases involved alarm pheromone in the vetch aphid Megoura viciae.

The alkaline phosphatases (ALPs) are highly promiscuous enzymes and have been extensively investigated in mammals for their medical significance, but their functional promiscuity is relatively poorly understood in insects. Here, we first identified four ALP genes (designated as MvALP1-4) in the vetch aphid Megoura viciae that contained one alkaline phosphatase site, three metal-binding sites, and varied other functional sites. Phylogenetic analysis, molecular docking and the spatiotemporal expression profiling of MvALP1-4 were very different, indicating a promiscuous functionality. We also found that MvALP4 involved the biosynthesis of aphid alarm pheromones (EßF) in vitro and in vivo. Finally, transcriptome analysis in the stimulated and unstimulated aphids supported the involvement of MvALPs in the biosynthesis of aphid alarm pheromones. Our study identified a multifunctional ALP involved terpene synthase enzyme activity in the aphid, which contributes to the understanding of the functional plasticity of ALPs in insects.

Complete Genome Sequence Data of Pseudomonas bijieensis SP1 Associated with Root Soft Rot of Yam Bean.

Pseudomonas bijieensis is a newly established species with antifungal activity. Here, we report the high-quality and complete genome sequence for P. bijieensis strain SP1, created by hybrid assembly using both short reads and long reads. The length of the circular chromosome is about 6.67 Mb, with a GC content of 60.89%. Bioinformatic analyses revealed gene clusters for the biosynthesis of antimicrobial metabolites 2,4-diacetylphloroglucinol as well as bacterial secretion systems (type I to III and type V to VI). Interestingly, this strain can cause soft rot symptoms in the roots of yam bean, showing the potential to be a plant pathogen. The genomic data will be a valuable resource for exploring the virulence mechanism and antifungal activity of this strain.

Transinfected Wolbachia strains induce a complex of cytoplasmic incompatibility phenotypes: Roles of CI factor genes.

Wolbachia can modulate the reproductive development of their hosts in multiple modes, and cytoplasmic incompatibility (CI) is the most well-studied phenotype. The whitefly Bemisia tabaci is highly receptive to different Wolbachia strains: wCcep strain from the rice moth Corcyra cephalonica and wMel strain from the fruit fly Drosophila melanogaster could successfully establish and induce CI in transinfected whiteflies. Nevertheless, it is unknown what will happen when these two exogenous Wolbachia strains are co-transinfected into a new host. Here, we artificially transinferred wCcep and wMel into the whitefly and established double- and singly-transinfected B. tabaci isofemale lines. Reciprocal crossing experiments showed that wCcep and wMel induced a complex of CI phenotypes in the recipient host, including unidirectional and bidirectional CI. We next sequenced the whole genome of wCcep and performed a comparative analysis of the CI factor genes between wCcep and wMel, indicating that their cif genes were phylogenetically and structurally divergent, which can explain the crossing results. The amino acid sequence identity and structural features of Cif proteins may be useful parameters for predicting their function. Structural comparisons between CifA and CifB provide valuable clues for explaining the induction or rescue of CI observed in crossing experiments between transinfected hosts.

Farnesyl/geranylgeranyl diphosphate synthases regulate the biosynthesis of alarm pheromone in a unique manner in the vetch aphid Megoura viciae.

Farnesyl/geranylgeranyl diphosphate synthases (FPPS/GGPPS) as the short-chain prenyltransferases catalyse the formation of the acyclic precursors (E)-FPP and (E)-GGPP for isoprenoid biosynthesis. Here, we first cloned the cDNAs encoding FPPS and GGPPS in the vetch aphid Megoura viciae (designated as MvFPPS and MvGGPPS). They had an open reading frame of 1185 and 930 bp in length, encoding 395 and 309 amino acids, with a theoretical isoelectric point of 6.52 and 6.21, respectively. Sequence alignment and phylogenetic analysis showed that MvFPPS and MvGGPPS shared the conserved aspartate-rich motifs characterized by all prenyltransferases identified to date and were clustered with their homologues in two large clades. RNA interference (RNAi) combined with gas chromatography/mass spectrometry (GC-MS) analysis showed that both MvFPPS and MvGGPPS were involved in the biosynthesis of alarm pheromone. Spatiotemporal expression profiling showed that the expression of MvFPPS and MvGGPPS was significantly higher in embryos than in other tissues. RNAi and GC-MS performed specifically in embryos corroborated the function of MvFPPS and MvGGPPS. In vitro, enzymatic activity assay and product analysis demonstrated that MvFPPS could catalysed the formation of (E)-FPP using DMAPP or (E)-GPP as the allylic cosubstrates in the presence of IPP, while MvGGPPS could only use (E)-GPP or (E)-FPP as cosubstrates. Functional interaction analysis using RNAi revealed that MvGGPPS exerts unidirectional functional compensation for MvFPPS. Moreover, it can regulate the biosynthesis of alarm pheromone by imposing a negative feedback regulation on MvFPPS. Our study helps to understand the molecular regulatory mechanism of terpenoid biosynthesis in the aphid.

Kairomonal Effect of Aphid Alarm Pheromones and Analogs on the Parasitoid Diaeretiella rapae.

Aphid alarm pheromones, as important semiochemicals, not only mediate behavioral response of aphids, but can also act as kairomones to attract their natural enemies. The sesquiterpene (E)-ß-farnesene (EßF), the major alarm pheromone component of most aphid species, has been shown to have a kairomonal effect on the predators of aphids, but other alarm pheromone components, especially the monoterpenes and analogs, are rarely investigated. Here, two EßF analogs were successfully synthesized via the nucleophilic substitution reaction, and we then examined the kairomonal effects of four alarm pheromone components and two EßF analogs on the aphid parasitoid, Diaeretiella rapae. In olfactory bioassays, D. rapae females generally showed no significant behavioral response to these alarm pheromone components and analogs under low concentrations (0.1 µg/µL). Nevertheless, their olfactory response to these compounds gradually enhanced with increasing concentrations. Among the four pheromone components, EßF showed the highest attractive activity, but the parasitoid preferred blends over single compounds. Moreover, the response time decreased as the concentration increased. We confirmed the kairomonal effect of monoterpene alarm pheromone components and their blends, in addition to EßF, on the natural enemies of aphids. This is the first report that the blend of alarm pheromone components and their analogs has a stronger kairomonal effect than do the single components on the natural enemies of aphids. This study contributes to our understanding of the mechanisms involved in the regulation of parasitoid behaviors by kairomones and provides a promising opportunity for designing kairomones for the aphid parasitoid to mediate aphid populations in the field.

Improving correlation of wastewater SARS-CoV-2 gene copy numbers with COVID-19 public health cases using readily available biomarkers.

The COVID-19 pandemic has highlighted the potential role that wastewater-based epidemiology can play in assessing aggregate community health. However, efforts to translate SARS-CoV-2 gene copy numbers obtained from wastewater samples into meaningful community health indicators are nascent. In this study, SARS-CoV-2 nucleocapsid (N) genes (N1 and N2) were quantified weekly using reverse transcriptase droplet digital PCR from two municipal wastewater treatment plants for seven months. Four biomarkers (ammonium, biological oxygen demand (BOD), creatinine, and human mitochondrial gene NADH dehydrogenase subunit 5) were quantified and used to normalize SARS-CoV-2 gene copy numbers. These were correlated to daily new case data and one-, two-, and three-week cumulative case data. Over the course of the study, the strongest correlations were observed with a one-day case data lag. However, early measurements were strongly correlated with a five-day case data lag. This indicates that in the early stages of the pandemic, the wastewater samples may have indicated active COVID-19 cases before clinical indications. Mitochondrial and creatinine normalization methods showed the strongest correlations throughout the study, indicating that human-specific biomarkers were better at normalizing wastewater data than ammonium or BOD. Granger causality tests supported this observation and showed that gene copies in wastewater could be predictive of new cases in a sewershed.

Silencing the Autophagy-Related Genes ATG3 and ATG9 Promotes SRBSDV Propagation and Transmission in Sogatella furcifera.

Autophagy plays diverse roles in the interaction among pathogen, vector, and host. In the plant virus and insect vector system, autophagy can be an antiviral/pro-viral factor to suppress/promote virus propagation and transmission. Here, we report the antiviral role of autophagy-related genes ATG3 and ATG9 in the white-backed planthopper (Sogatella furcifera) during the process of transmitting the southern rice black-streaked dwarf virus (SRBSDV). In this study, we annotated two autophagy-related genes, SfATG3 and SfATG9, from the female S. furcifera transcriptome. The cDNA of SfATG3 and SfATG9 comprised an open reading frame (ORF) of 999 bp and 2295 bp that encodes a protein of 332 and 764 amino acid residues, respectively. SfATG3 has two conserved domains and SfATG9 has one conserved domain. In S. furcifera females exposed to SRBSDV, expression of autophagy-related genes was significantly activated and shared similar temporal patterns to those of SRBSDV S9-1 and S10, all peaking at 4 d post viral exposure. Silencing the expression of SfATG3 and SfATG9 promoted SRBSDV propagation and transmission. This study provides evidence for the first time that S. furcifera autophagy-related genes ATG3 and ATG9 play an antiviral role to suppress SRBSDV propagation and transmission.

Functional characterization of two different decaprenyl diphosphate synthases in the vetch aphid Megoura viciae.

Long-chain polyprenyl diphosphate synthases play a critical role in the formation of the prenyl side-chain of ubiquinones, but up to date, their functions have scarcely been characterized in insects. Here, we first cloned the complementary DNAs encoding the subunits of decaprenyl diphosphate synthase (DPPS) in the vetch aphid Megoura viciae, an important agricultural pest insect. The results showed that there existed three DPPS subunits, designated as MvDPPS1, MvDPPS2a, and MvDPPS2b, with an open reading frame of 1218, 1275, and 1290 bp, and a theoretical isoelectric point of 7.91, 6.63, and 9.62, respectively. The sequences of MvDPPS1s from different aphid species were nearly identical, while the sequences of MvDPPS2a and MvDPPS2b shared only moderate sequence similarity. Phylogenetic analysis clearly separated MvDPPS2a and MvDPPS2b, indicating a functional differentiation between them. Functional coexpression analysis in Escherichia coli showed that MvDPPS1 plus MvDPPS2a and MvDPPS1 plus MvDPPS2b, respectively, catalyzed the formation of the prenyl side-chain of the ubiquinone coenzyme Q10 (CoQ10). Interestingly, MvDPPS1 plus MvDPPS2b catalyzed the formation of the prenyl side-chain of a ubiquinone other than CoQ10. RNA interference-mediated knockdown of MvDPPS2a imposed no significant effect on MvDPPS2b, and vice versa, suggesting no compensatory action between them. In the end, we detected the product CoQ10 in the aphid, the first identification of CoQ10 in an insect species. Taken together, we characterized two functional DPPSs in M. viciae, one of which might be multifunctional. Our study helps to understand the functional plasticity of the terpenoid backbone biosynthesis pathway in insects.

Comparison of Transcriptome Responses between Sogatella furcifera Females That Acquired Southern Rice Black-Streaked Dwarf Virus and Not.

The southern rice black-streaked dwarf virus (SRBSDV) is transmitted horizontally by Sogatella furcifera in a persistent, propagative manner. Exposure of S. furcifera females to SRBSDV-infected rice plants may trigger transcriptomic changes in the insects, the transcriptomes of females that acquired SRBSDV and those that failed to, as well as females fed on healthy rice plants as control, were sequenced and compared. Nine transcriptomic libraries were constructed, from which a total of 53,084 genes were assembled. Among the genes, 1043 and 2932 were differentially expressed genes (DEGs) in S. furcifera females that acquired SRBSDV and that failed to, in comparison with the control, respectively. Functional enrichment analysis showed that DEGs identified in S. furcifera females exposed to SRBSDV are primarily involved in diverse signaling pathways related to primary metabolism and innate immunity. The DEGs in the S. furcifera females that failed to acquire the virus significantly outnumbered that in the insects that acquired the virus, and the virus exposure activated the humoral and cellular immune responses of the vectors, especially the apoptosis. The key gene in apoptosis encoding caspase 1 was upregulated by SRBSDV exposure, especially in S. furcifera females that failed to acquire the virus. Analysis of caspase 1 activity validated that SRBSDV exposure induced caspase 1 accumulation. Surprisingly, the expression of six female-specific genes was also upregulated by SRBSDV exposure, which was confirmed by RT-qPCR analysis. This study provides evidence to explain the differential virus acquisition at the transcriptome level.

Identification and Behavioral Assays of Alarm Pheromone in the Vetch Aphid Megoura viciae.

Aphids are destructive pests, and alarm pheromones play a key role in their chemical ecology. Here, we conducted a detailed analysis of terpenoids in the vetch aphid, Megoura viciae, and its host plant Pisum sativum using gas chromatography/mass spectrometry. Four major components, (-)-ß-pinene (49.74%), (E)-ß-farnesene (32.64%), (-)-α-pinene (9.42%) and ( +)-limonene (5.24%), along with trace amounts of ( +)-sabinene, camphene and α-terpineol) (3.14%) were found in the aphid. In contrast, few terpenoids were found in the host plant, consisting mainly of squalene (66.13%) and its analog 2,3-epoxysqualene (31.59%). Quantitative analysis of the four major terpenes in different developmental stages of the aphid showed that amounts of the monoterpenes increased with increasing stage, while the sesquiterpene amount peaked in the 3rd instar. (-)-ß-Pinene was the most abundant terpene at all developmental stages. Behavioral assays using a three-compartment olfactometer revealed that the repellency of single compounds varied in a concentration-dependent manner, but two mixtures [(-)-α-pinene: (-)-ß-pinene: (E)-ß-farnesene: ( +)-limonene = 1:44.4:6.5:2.2 or 1:18.4:1.3:0.8], were repellent at all concentrations tested. Our results suggest that (-)-α-pinene and (-)-ß-pinene are the major active components of the alarm pheromone of M. viciae, but that mixtures play a key role in the alarm response. Our study contributes to the understanding of the chemical ecology of aphids and may help design new control strategies against this aphid pest.

Transmission of the wMel Wolbachia strain is modulated by its titre and by immune genes in Drosophila melanogaster (Wolbachia density and transmission).

Wolbachia are common intracellular endosymbionts of arthropods, but the interactions between Wolbachia and arthropods are only partially understood. The fruit fly Drosophila melanogaster is a model insect for understanding Wolbachia-host interactions. Here the native wMel strain of D. melanogaster was isolated and then different initial titres of wMel were artificially transferred back into antibiotics-treated fruit flies. Our purpose was to examine the interactions between the injected wMel in a density gradient and the recipient host during trans-generational transmission. The results showed that the trans-generational transmission rates of wMel and titres of wMel exhibited a fluctuating trend over nine generations, and the titres of wMel displayed a similar fluctuating trans-generational trend. There was a significant positive correlation between the transmission rate and the titre of wMel. Reciprocal crossings between wMel-transinfected and uninfected fruit flies revealed that wMel could induce cytoplasmic incompatibility (CI) at different initial titres, but the intensity of CI was not significantly correlated with the initial titre of wMel. Quantitative PCR analysis showed that the immune genes Drsl5 and Spn38F displayed a significant transcriptional response to wMel transfection, with an obvious negative correlation with the titre of wMel at the 3rd and 4th generations. Furthermore, RNA interference-mediated knockdown of Drsl5 and Spn38F elicited a drastic increase in the titre of wMel. In combination, our study suggests that the trans-generational transmission of wMel is modulated by its density, and the immune genes are involved in the regulation of Wolbachia density.

Biosynthesis of aphid alarm pheromone is modulated in response to starvation stress under regulation by the insulin, glycolysis and isoprenoid pathways.

The mechanism for biosynthesis and molecular regulation of the aphid alarm pheromone (AAP) is still a mystery. Previous studies indicated that the biosynthesis of AAP was directly affected by the terpenoid backbone biosynthesis pathway, and several pathways involved in nutritional metabolism providing the bricks for AAP biosynthesis were up-regulated in response to simulated stimulation. This suggests that AAP biosynthesis might be regulated by complex metabolic pathways. Here the molecular responses of the bird cherry-oat aphid Rhopalosiphum padi to starvation stress were investigated, and the molecular pathways were further analyzed by using RNA interference (RNAi) and protein inhibitor, combined with gas chromatography-mass spectrometry analysis of (E)-ß-farnesene (EßF), the major component of the alarm pheromone in R. padi. The results showed that the nutritional stress significantly reduced the weight of aphid and the quantity of EßF, and meanwhile dramatically up-regulated the insulin receptor genes (InsR1/2) and down-regulated the downstream genes encoding the kinases PI3K and Akt, key enzymes in the glycolysis pathway (HK, A6PFK, PK) and the isoprenoid pathway (ACSS, HMGR, FPPS1, FPPS2, GGPPS, DPPS). PI3K inhibitor LY294002 treatment and RNAi-mediated knockdown of InsR1/2 significantly reduced the expression level of downstream genes and the quantity of EßF. Furthermore, knockdown of PK, the rate-limiting enzyme in the glycolysis pathway, down-regulated the genes in the isoprenoid pathway and the production of EßF; knockdown of the genes encoding isoprenyl diphosphate enzymes revealed that FPPS1 and FPPS2 were both required for EßF biosynthesis. Our data suggested that AAP is synthesized via glycolysis and isoprenoid pathways under regulation by the insulin signaling pathway.

The Intruding Wolbachia Strain from the Moth Fails to Establish Itself in the Fruit Fly Due to Immune and Exclusion Reactions.

Wolbachia is capable of regulating host reproduction, and thus of great significance in preventing the spread of insect-borne diseases and controlling pest insects. The fruit fly Drosophila melanogaster is an excellent model insect for understanding Wolbachia-host interactions. Here we artificially transferred the wCcep strain from the rice moth Corcyra cephalonica into D. melanogaster by microinjection. Crossing experiments indicated that wCcep could induce a high level of CI in the phylogenetically distant host D. melanogaster and imposed no negative fitness costs on host development and fecundity. Based on quantitative analysis, the titres of wCcep and the native wMel strain were negatively correlated, and wCcep could only be transmitted in the novel host for several generations (G0 to G4) after transinfection. Transcriptome sequencing indicated that the invading wCcep strain induced a significant immune- and stress-related response from the host. An association analysis between the expression of immune genes attacin-D/edin and the titre of Wolbachia by linear regression displayed a negative correlation between them. Our study suggest that the intrusion of wCcep elicited a robust immune response from the host and incurred a competitive exclusion from the native Wolbachia strain, which resulted in the failure of its establishment in D. melanogaster.

Fracture shortly before stroke in mice leads to hippocampus inflammation and long-lasting memory dysfunction.

Cognitive impairment occurs in stroke and hip fracture patients. In mice, bone fracture (BF) exacerbates stroke-related neuronal damage and sensorimotor dysfunction. We hypothesize that BF exacerbates post-stroke cognitive impairment. Adult mice were randomly assigned into BF, stroke, BF+stroke (BF 6 h before stroke), and control (sham operated) groups. Memory function was evaluated weekly for eight weeks by Y maze test and at eight weeks post-surgeries by novel object recognition (NOR) test. The neuronal damage and inflammation in hippocampus were analyzed three days and eight weeks after the surgeries. In Y maze test, BF+stroke mice started making fewer alternations than controls two weeks after the surgeries. Significant difference between BF+stroke and stroke groups started at five weeks post-injury and continued to the end of the experiment. In NOR test, BF+stroke group spent less time on novel objective than that of other groups. Cx3cr1+ cells and CD68+ cells accumulated in the stratum lacunosum moleculare (SLM) on the ipsilateral side of stroke injury in stroke and BF+stroke mice. BF+stroke mice had a higher ratio of ipsilateral/contralateral Cx3cr1+ cell-density than that of stroke mice. Therefore, BF shortly before stroke exacerbates hippocampal inflammation and causes long-lasting memory dysfunction.

Both farnesyl diphosphate synthase genes are involved in the production of alarm pheromone in the green peach aphid Myzus persicae.

Farnesyl diphosphate synthase (FPPS) catalyzes the formation of FPP, providing the precursor for the biosynthesis of (E)-ß-farnesene (EßF) in plants, but it is unknown if FPPS supplies the precursor for the biosynthesis of EßF, the major component of aphid alarm pheromone, though our previous studies support the hypothesis that EßF is synthesized by the aphid itself. Here, we used two cohorts of the green peach aphid Myzus persicae separately, reared on pepper plant and artificial diet to test the correlations among droplet emission, EßF quantity, and FPPS gene expression. It was found that the proportion of aphids emitting cornicle droplets and the quantity of EßF per milligram of aphid were both significantly different between the two cohorts, which were positively correlated with the expression of the two FPPS genes ( MpFPPS1/ 2) in M. persicae. These results were further confirmed by RNAi-mediated knockdown of MpFPPS1/ 2. Specifically, knockdown of MpFPPS1/ 2 imposed no significant cost on the survival of aphid but remarkably increased the number of offspring per aphid; most importantly, knockdown of MpFPPS1/ 2 significantly reduced the proportion of aphids emitting droplets and the quantity of EßF calculated as per the weight of aphid. Our results suggest that both FPPS genes are involved in the production of EßF in M. persicae and cornicle droplet emission is closely associated with the EßF release in the aphid.

Thalidomide Reduces Hemorrhage of Brain Arteriovenous Malformations in a Mouse Model.

BACKGROUND AND PURPOSE: Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current treatments for bAVM are all associated with considerable risks. There is no safe method to prevent bAVM hemorrhage. Thalidomide reduces nose bleeding in patients with hereditary hemorrhagic telangiectasia, an inherited disorder characterized by vascular malformations. In this study, we tested whether thalidomide and its less toxic analog, lenalidomide, reduce bAVM hemorrhage using a mouse model. METHODS: bAVMs were induced through induction of brain focal activin-like kinase 1 (Alk1, an AVM causative gene) gene deletion and angiogenesis in adult Alk1-floxed mice. Thalidomide was injected intraperitoneally twice per week for 6 weeks, starting either 2 or 8 weeks after AVM induction. Lenalidomide was injected intraperitoneally daily starting 8 weeks after AVM induction for 6 weeks. Brain samples were collected at the end of the treatments for morphology, mRNA, and protein analyses. The influence of Alk1 downregulation on PDGFB (platelet-derived growth factor B) expression was also studied on cultured human brain microvascular endothelial cells. The effect of PDGFB in mural cell recruitment in bAVM was explored by injection of a PDGFB overexpressing lentiviral vector to the mouse brain. RESULTS: Thalidomide or lenalidomide treatment reduced the number of dysplastic vessels and hemorrhage and increased mural cell (vascular smooth muscle cells and pericytes) coverage in the bAVM lesion. Thalidomide reduced the burden of CD68+ cells and the expression of inflammatory cytokines in the bAVM lesions. PDGFB expression was reduced in ALK1-knockdown human brain microvascular endothelial cells and in mouse bAVM lesion. Thalidomide increased Pdgfb expression in bAVM lesion. Overexpression of PDGFB mimicked the effect of thalidomide. CONCLUSIONS: Thalidomide and lenalidomide improve mural cell coverage of bAVM vessels and reduce bAVM hemorrhage, which is likely through upregulation of Pdgfb expression.

Host plants and obligate endosymbionts are not the sources for biosynthesis of the aphid alarm pheromone.

(E)-ß-farnesene (EßF) is the major component of the alarm pheromone of many aphid species, but where EßF is synthesized in aphids is only partly understood. There are at least three most possible sources for the alarm pheromone: host plants, aphid obligate endosymbiont and aphids themselves. Here we eliminated the possibility of host plants and the obligate endosymbiont Buchnera aphidicola as the sources for EßF released by aphids. We excluded the possible effects of host plants on EßF biosynthesis by rearing aphids on non-plant diets. Both the diet-reared aphids, including the cotton aphid Aphis gossypii and the green peach aphid Myzus persicae, could still release EßF based on solid-phase micro-extraction combined with gas chromatography-mass spectrometer analysis. Meanwhile, we treated host aphids with antibiotics to fully eliminate Buchnera bacteria. Though the treatment seriously affected the development and fecundity of host aphids, the treated aphids could still release EßF, and there was no significant difference in the EßF concentration as per the aphid weight under different rearing conditions. Taken together, our experimental results suggest that host plants and obligate endosymbionts are not the sources for EßF released by aphids, indicating that it is most probably the aphid itself synthesizes the alarm pheromone.

Establishment of the cytoplasmic incompatibility-inducing Wolbachia strain wMel in an important agricultural pest insect.

The wMel Wolbachia strain was known for cytoplasmic incompatibility (CI)-induction and blocking the transmission of dengue. However, it is unknown whether it can establish and induce CI in a non-dipteran host insect. Here we artificially transferred wMel from Drosophila melanogaster into the whitefly Bemisia tabaci. Fluorescence in situ hybridisation demonstrated that wMel had successfully transfected the new host. Reciprocal crossing was conducted with wMel-transfected and wild-type isofemale lines, indicating that wMel could induce a strong CI without imposing significant cost on host fecundity. We then determined the maternal transmission efficiency of wMel in the offspring generations, showing a fluctuating trend over a period of 12 generations. We thus detected the titre of wMel during different developmental stages and in different generations by using real-time quantitative PCR, revealing a similar fluctuating mode, but it was not significantly correlated with the dynamics of transmission efficiency. These results suggest that wMel can be established in B.tabaci, a distantly related pest insect of agricultural importance; moreover, it can induce a strong CI phenotype in the recipient host insect, suggesting a potential for its use in biological control of B. tabaci.