Seasonality of common respiratory viruses: Analysis of nationwide time-series data.

BACKGROUND AND OBJECTIVE: Understanding the seasonal behaviours of respiratory viruses is crucial for preventing infections. We evaluated the seasonality of respiratory viruses using time-series analyses. METHODS: This study analysed prospectively collected nationwide surveillance data on eight respiratory viruses, gathered from the Korean Influenza and Respiratory Surveillance System. The data were collected on a weekly basis by 52 nationwide primary healthcare institutions between 2015 and 2019. We performed Spearman correlation analyses, similarity analyses via dynamic time warping (DTW) and seasonality analyses using seasonal autoregressive integrated moving average (SARIMA). RESULTS: The prevalence of rhinovirus (RV, 23.6%-31.4%), adenovirus (AdV, 9.2%-16.6%), human coronavirus (HCoV, 3.0%-6.6%), respiratory syncytial virus (RSV, 11.7%-20.1%), influenza virus (IFV, 11.7%-21.5%), parainfluenza virus (PIV, 9.2%-12.6%), human metapneumovirus (HMPV, 5.6%-6.9%) and human bocavirus (HBoV, 5.0%-6.4%) were derived. Most of them exhibited a high positive correlation in Spearman analyses. In DTW analyses, all virus data from 2015 to 2019, except AdV, exhibited good alignments. In SARIMA, AdV and RV did not show seasonality. Other viruses showed 12-month seasonality. We describe the viruses as winter viruses (HCoV, RSV and IFV), spring/summer viruses (PIV, HBoV), a spring virus (HMPV) and all-year viruses with peak incidences during school periods (RV and AdV). CONCLUSION: This is the first study to comprehensively analyse the seasonal behaviours of the eight most common respiratory viruses using nationwide, prospectively collected, sentinel surveillance data.

Prior pneumococcal vaccination improves in-hospital mortality among elderly population hospitalized due to community-acquired pneumonia.

BACKGROUND: Pneumococcal vaccination is a preventive method to reduce pneumonia related mortality. However, real-world data on efficacy of the pneumococcal vaccine in reducing mortality is lacking, especially in elderly patients. This study was conducted to assess the effects of prior pneumococcal vaccination in elderly pneumonia patients. METHODS: The data was procured from the Health Insurance Review and Assessment and Quality Assessment database. Hospitalized patients who met the criteria of community-acquired pneumonia (CAP) were included and they were grouped according to vaccination state. Patients were aged ≥ 65 years and treated with beta-lactam, quinolone, or macrolide. Patients were excluded when treatment outcomes were unknown. RESULTS: A total of 4515 patients were evaluated, and 1609 (35.6%) of them were vaccinated prior to hospitalization. Mean age was 77.0 [71.0;82.0], 54.2% of them were male, and mean Charlson comorbidity index (CCI) was 3.0. The patients in the vaccinated group were younger than those in the unvaccinated group (76.0 vs. 78.0 years; P < 0.001), and showed higher in-hospital improvement (97.6 vs. 95.0%; P < 0.001) and lower 30-day mortality (2.6 vs. 5.3%; P < 0.001). After adjusting confounding factors such as age, gender, CURB score and CCI score, the vaccinated group demonstrated a significant reduction in 30-day mortality (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.41-0.81; P < 0.01) and in-hospital mortality (HR 0.53, 95% CI0.37-0.78; P < 0.001) compared to the unvaccinated group in multivariate analysis. Vaccinated group showed better 30-day survival than those in non-vaccinated group (log-rank test < 0.05). CONCLUSIONS: Among elderly hospitalized CAP patients, prior pneumococcal vaccination was associated with improved in-hospital mortality and 30-day mortality.

ZmCOI2a and ZmCOI2b redundantly regulate anther dehiscence and gametophytic male fertility in maize.

In higher plants, the generation and release of viable pollen from anthers is vital for double fertilization and the initiation of seed development. Thus, the characterization of genes related to pollen development and anther dehiscence in plants is of great significance. The F-box protein COI1 plays a crucial role in the jasmonate (JA) signaling pathway and interacts with many JAZ family proteins in the presence of jasmonoyl-isoleucine (JA-Ile) or coronatine (COR). The mutation of AtCOI1 in Arabidopsis leads to defective anther dehiscence and male sterility (MS), although COI has not been shown to affect fertility in Zea mays (maize). Here we identified two genes, ZmCOI2a and ZmCOI2b, that redundantly regulate gametophytic male fertility. Both ZmCOI2a and ZmCOI2b are highly homologous and constitutively expressed in all tissues tested. Subcellular localization revealed that ZmCOI2a and ZmCOI2b were located in the nucleus. The coi2a coi2b double mutant, generated by CRISPR/Cas9, had non-dehiscent anthers, delayed anther development and MS. In addition, coi2a coi2b male gametes could not be transmitted to the next generation because of severe defects in pollen germination. The JA content of coi2a coi2b anthers was unaltered compared with those of the wild type, and the exogenous application of JA could not rescue the fertility defects of coi2a coi2b. Transcriptome analysis showed that the expression of genes involving the JA signaling transduction pathway, including ZmJAZ3, ZmJAZ4, ZmJAZ5 and ZmJAZ15, was affected in coi2a coi2b. However, yeast two-hybrid assays showed that ZmJAZs interacted with ZmCOI1s, but not with ZmCOI2s. In conclusion, ZmCOI2a and ZmCOI2b redundantly regulate anther dehiscence and gametophytic male fertility in maize.

Effect of Broncho-Vaxom (OM-85) on the frequency of chronic obstructive pulmonary disease (COPD) exacerbations.

BACKGROUND: Efforts have been made to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations using a variety of measures. Broncho-Vaxom (BV) is an immunomodulating agent that has shown potential benefit by balancing between immune stimulation and regulation in patients with COPD. In this study, we evaluated the clinical efficacy of BV for reducing the risk of COPD exacerbations. METHODS: This study was based on the Korean National Health Insurance database, which contains reimbursement information for almost the entire population of South Korea. We extracted data from 2016 to 2019 for patients started on BV during 2017-2018. We collected baseline data on demographics, comorbidities, inhaler use, hospital type, and insurance type 1 year before starting BV. We also analyzed exacerbation history, starting from the year before BV initiation. RESULTS: In total, 238 patients were enrolled in this study. Their mean age was 69.2 ± 9.14 years, 79.8% were male, and 45% experienced at least one exacerbation. BV reduced the risk of moderate (odds ratio [OR] = 0.59, 95% confidence interval [CI]: 0.38-0.91) and moderate-to-severe exacerbations compared to pre- and post-BV (OR = 0.571, 95% CI: 0.37-0.89). BV use also reduced the incidence of moderate and moderate-to-severe exacerbations (incidence rate ratio [IRR] = 0.75, p = 0.03; and IRR = 0.77, p = 0.03, respectively). The use of BV was significantly delayed moderate exacerbations (hazard ratio = 0.68, p = 0.02), but not with moderate-to-severe or severe exacerbations. CONCLUSION: The use of BV was associated with fewer moderate and moderate-to-severe exacerbations. Additionally, BV was associated with a delay in moderate COPD exacerbations.

Tiotropium Bromide Improves Neutrophilic Asthma by Recovering Histone Deacetylase 2 Activity.

BACKGROUND: The value of tiotropium bromide (TIO) in neutrophilic asthma was meaningful in previous study. We hypothesized that TIO's mechanism of action is associated with histone deacetylase 2 (HDAC2) activity, which is key for controlling the transcription of inflammatory cytokines and usually downregulated in neutrophilic asthma. METHODS: The effects of TIO and dexamethasone (DEX) on HDAC2 activity, nuclear factor kappa B (NF-κB), and C-X-C motif chemokine ligand 1 (CXCL1) were evaluated in neutrophilic asthma mouse model (C57BL, 6-week-old). An in-vitro study was conducted using primary human bronchial/tracheal epithelial (HBE) cells from asthma patients. Western blot analyses were performed for phospho-phospholipase Cγ-1 (PLCγ-1) and inositol trisphosphate (IP3) receptors (IP3R) with treating lipopolysaccharide (LPS) and TIO. RESULTS: Ovalbumin was used to induce eosinophilic inflammation in this study. After neutrophilic asthma was induced by LPS (O+L group), HDAC2 activity was diminished with increased NF-κB activity and CXCL1 compared to the control group. TIO significantly improved NF-κB activity, CXCL1, and HDAC2 activity compared with the O+L group in in-vivo study (P < 0.05, each). Western blot analyses showed that LPS treated HBE cells from asthma patients increased PLCγ-1 and diminished IP3 receptor levels. After TIO treatment, recovery of IP3R and improved PLCγ-1 levels were observed. CONCLUSION: These results support the hypothesis that TIO modulates inflammation by recovering HDAC2 activity from the acetylcholine-stimulated inflammation cascade in neutrophilic asthma. The detailed inflammation cascade of recovering HDAC2 activity by TIO might be associated with PLCγ-1-IP3-IP3R mediated intracellular calcium ion pathway.

FAZ27 cooperates with FLAM3 and ClpGM6 to maintain cell morphology in Trypanosoma brucei.

The human parasite Trypanosoma brucei transitions from the trypomastigote form to the epimastigote form in the insect vector by repositioning its mitochondrial genome and flagellum-associated cytoskeleton. The molecular mechanisms underlying such changes in cell morphology remain elusive, but recent works demonstrated the involvement of three flagellar proteins, FLAM3, ClpGM6 and KIN-E, in this process by controlling the elongation of the flagellum attachment zone (FAZ). In this report, we identified a FAZ flagellum domain-localizing protein named FAZ27 and characterized its role in cell morphogenesis. Depletion of FAZ27 in the trypomastigote form caused major morphological changes and repositioning of the mitochondrial genome and flagellum-associated cytoskeleton, generating epimastigote-like cells. Furthermore, proximity biotinylation and co-immunoprecipitation identified FLAM3 and ClpGM6 as FAZ27-interacting proteins, and analyses of their functional interplay revealed an interdependency for assembly into the FAZ flagellum domain. Finally, we showed that assembly of FAZ27 occurred proximally, identical to the assembly pattern of other FAZ sub-domain proteins. Taken together, these results demonstrate a crucial role for the FAZ flagellum domain in controlling cell morphogenesis and suggest a coordinated assembly of all the FAZ sub-domains at the proximal end of the FAZ.

MitoFlex: an efficient, high-performance toolkit for animal mitogenome assembly, annotation and visualization.

SUMMARY: MitoFlex is a linux-based mitochondrial genome analysis toolkit, which provides a complete workflow of raw data filtering, de novo assembly, mitochondrial genome identification and annotation for animal High Throughput Sequencing data. The overall performance was compared between MitoFlex and its analogue MitoZ, in terms of protein-coding gene recovery, memory consumption and processing speed. AVAILABILITYAND IMPLEMENTATION: MitoFlex is available at https://github.com/Prunoideae/MitoFlex under GPLv3 license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A New Species and New Record of Freshwater Turbellarians of the Genus Gieysztoria (Platyhelminthes: Rhabdocoela) from China.

A new species of Dalyelliidae, Gieysztoria pellucida Wang and You, is described based on material collected in southern China through an integrative approach combining morphological, histological, and molecular (18S and 28S rDNA) data. Gieysztoria pellucida sp. nov. is morphologically characterized by a fan-shaped (about 270° when pressed) stylet, consisting of 13 similar distal spines and a broad girdle without fenestrae region. This stylet is distinct from that of any other similar species in the Aequales group to which this species belongs. In addition, specimens identifiable as Gieysztoria garudae Van Steenkiste, Van Mulken, and Artois, 2012 were discovered from the same location as G. pellucida sp. nov. Gieysztoria garudae has previously been known only from India; the present study thus represents the first record of the species from China.

Combination of Developmental Behaviors and Transcriptome Reveals Differential Response Mechanisms of Phytophthora sojae to Aspartic Acid and Glucose in Seed Exudates.

Isoflavones in soybean seed and root exudates are host-specific signal molecules for Phytophthora sojae to recognize host soybean. G protein and calcium signaling pathway are involved in the chemotaxis of zoospores in the recognition of isoflavones. To investigate the role of host nonspecific signaling molecules (sugars and amino acids) in seed and root exudates in zoospore chemotaxis and mycelial growth, the transcriptome of P. sojae responding to aspartic acid (Asp) and glucose (Glc) was analyzed by the RNA-seq method. We found that the relative in situ concentrations of amino acids and sugars significantly promoted zoospore chemotaxis, as do isoflavones. Transcriptomics showed that both similarity and difference existed in response mechanisms of P. sojae to Asp and Glc. Asp and Glc activated mitogen-activated protein kinase signaling pathway and phosphatidylinositol signaling system but not G-protein signaling pathway, which have been reported to be responsible for zoospore chemotaxis. In addition, ubiquitin-mediated proteolysis and ATP binding cassette transporters were also activated by Asp and Glc. Meanwhile, glutathione signaling pathway uniquely participated in the response of P. sojae to Asp but not involved in the response process to Glc, which is waiting for further study. Our results provide new insights into the molecular mechanism of zoospore response to Asp and Glc.

Benzoxazines in the Root Exudates Responsible for Nonhost Disease Resistance of Maize to Phytophthora sojae.

It has been reported that the root exudates of nonhost maize inhibit Phytophthora sojae because of the presence of benzoxazines in maize roots. To understand the concentrations of benzoxazines (Bxs) in maize root exudates and the molecular mechanism of P. sojae being inhibited, the transcriptomes of P. sojae responding to three different Bxs, 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA), 6-methoxy-2-benzoxazolinone (MBOA), and benzoxazolinone (BOA), were analyzed by RNA sequencing method. We detected DIMBOA, MBOA, and BOA with a concentration range of 7 to 126 µg/ml in root exudates of three tested maize cultivars (A6565, Pengyu 1, and Xianyu 696). DIMBOA, MBOA, and BOA inhibited chemotaxis and invasiveness of P. sojae zoospores and mycelial growth. The inhibition was regulated mainly by endocytosis and the calcium signaling pathway, PI3K-Akt signaling pathway, and mTOR signaling pathway; meanwhile, the glutathione signaling pathway was activated to increase the antioxidant capacity and efflux of toxic substances. It was speculated that endocytosis plays an important role in the response of P. sojae to Bxs, and the specific functions of genes in this pathway must be further studied. This result provides new insights into the response mechanisms of P. sojae response to Bxs.

Maize and Common Bean Seed Exudates Mediate Part of Nonhost Resistance to Phytophthora sojae Prior to Infection.

Phytophthora sojae does not infect nonhost maize (Zea mays) but infects nonhost common bean (Phaseolus vulgaris) under inoculation. Soybean seed exudates participate in mediating host resistance to P. sojae before infection. This study aims to elucidate the role of seed exudates in mediating the nonhost resistance of maize and common bean to P. sojae before infection. The behaviors of P. sojae zoospores in response to the seed exudates were determined using an assay chamber and a concave slide. The proteomes of P. sojae zoospores in response to the seed exudates were analyzed with the tandem mass tag method. The key proteins were quantitatively verified by parallel reaction monitoring. Maize seed exudates exerted a repellent effect on zoospores of P. sojae. This result explains why zoospores sense repelling signaling molecules in maize seed exudates that weaken and strongly inhibit chemotaxis signals in the phosphatidylinositol signaling pathway and arachidonic acid metabolism pathway. Common bean seed exudates did not exhibit any attraction to the zoospores because the guanine nucleotide-binding protein signaling pathway, which is responsible for transmitting chemotactic signals, had no significant change. The proteins protecting the cell membrane structure were significantly downregulated, and the early apoptosis signal glutathione was enhanced in zoospores responding to common bean seed exudates, which resulted in dissolution of the cysts. Maize and common bean seed exudates mediate part of the nonhost resistance to P. sojae via different mechanisms before infection. The immunity of maize to P. sojae is caused by the repellent effect of maize seed exudates on zoospores. Common bean seed exudates participate in mediating nonhost resistance by dissolving the cysts.

Synergistic effect of roflumilast with dexamethasone in a neutrophilic asthma mouse model.

Asthma is a chronic airway inflammatory disease with heterogeneous features. Most cases of asthma are steroid sensitive, but 5%-10% are unresponsive to steroids, leading to challenges in treatment. Neutrophilic asthma is steroid-resistant and characterized by the absence or suppression of the T-helper type II (TH 2) process and an increase in the TH 1 and/or TH 17 process. Roflumilast (ROF) has anti-inflammatory effects and has been used to treat chronic inflammatory airway diseases, such as chronic pulmonary obstructive disease. It is unclear whether ROF may have a therapeutic role in neutrophilic asthma. In this study, we investigated the synergistic effect of ROF with dexamethasone (DEX) in a neutrophilic asthma mouse model. C57BL/6 female mice sensitized to ovalbumin (OVA) were exposed to five intranasal OVA treatments and three intranasal lipopolysaccharide (LPS) treatments for an additional 10 days. During the intranasal OVA challenge, ROF was administrated orally, and DEX was injected intraperitoneally. Protein, pro-inflammatory cytokines, inflammatory cytokines and other suspected markers were identified by enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and western blot. Following exposure to LPS in OVA-induced asthmatic mice, neutrophil predominant airway inflammation rather than eosinophil predominant inflammation was observed, with increases in airway hyperresponsiveness (AHR). The lungs of animals treated with ROF exhibited less airway inflammation and hyperresponsiveness. To investigate the mechanism underlying this effect, we examined the expression of proinflammatory cytokines suspected to be involved in inflammatory cytokines and proteins. Roflumilast reduced total protein in bronchioalveolar lavage fluid; levels of interleukin (IL)-17A, IL-1ß messenger RNA, interferon γ and tumour necrosis factor α; and recovered histone deacetylase-2 (HDAC2) activity. Combination therapy with ROF and DEX further reduced the levels of IL-17, IL-22 and IL-1ß mRNA and proinflammatory cytokines. The combination of ROF and DEX reduced lung inflammation and AHR much more than one of them alone. Roflumilast reduces AHR and lung inflammation in the neutrophilic asthma mouse model. Furthermore, additive effects were observed when DEX was added to ROF treatment, possibly because of recovery of HDAC2/ß-actin activity. This study demonstrates the anti-inflammatory properties of ROF in a neutrophilic asthma mouse model.

Structure of the heterophilic interaction between the nectin-like 4 and nectin-like 1 molecules.

Nectin-like (Necl) molecules are Ca2+-independent Ig-like transmembrane cell adhesion molecules that participate in junctions between different cell types. The specific cell-cell adhesions mediated by Necl proteins are important in neural development and have been implicated in neurodegenerative diseases. Here, we present the crystal structure of the mouse Necl-4 full ectodomain and the structure of the heterophilic Necl ectodomain complex formed by the mNecl-4 and mNecl-1 ectodomains. We demonstrate that, while the ectodomain of mNecl-4 is monomeric, it forms a stable heterodimer with Ig1 of mNecl-1, with an affinity significantly higher than that observed for self-dimerization of the mNecl-1 ectodomain. We validated our structural characterizations by performing a surface plasmon resonance assay and an Fc fusion protein binding assay in mouse primary dorsal root ganglia neurites and Schwann cells and identified a selection of residues important for heterophilic interactions. Finally, we proposed a model of Necl binding specificity that involves an induced-fit conformational change at the dimerization interface.

Continuing Quality Assessment Program Improves Clinical Outcomes of Hospitalized Community-Acquired Pneumonia: A Nationwide Cross-Sectional Study in Korea.

BACKGROUND: Pneumonia, which is the third leading cause of death in South Korea, is continuously increasing with the aging society. The Health Insurance Review and Assessment of South Korea conducted a quality assessment (QA) for improving the outcome of community-acquired pneumonia (CAP). METHODS: We conducted a nationwide cross-sectional study of hospitalized CAP in South Korea. First to third QA data were gathered into a single database. The national health insurance database was merged with the QA database for analyzing the medical claims data. Comorbidities, pneumonia severity, and pneumonia care appropriateness were calculated using Charlson comorbidity index (CCI), CURB-65, and core assessment of CAP scores (CAP scores), respectively. RESULTS: Overall, 54,307 patients were enrolled. The CAP scores significantly improved on QA program implementation (P < 0.001). All the variables demonstrated an association with in-hospital mortality, hospital length of stay (LOS), and 30-day mortality in the univariate analyses. Following the adjustments, higher CCI and CURB-65 scores were associated with higher in-hospital mortality, longer hospital LOS, and higher 30-day mortality. Male sex was associated with higher in-hospital/30-day mortality and shorter hospital LOS. Higher CAP scores were associated with shorter hospital LOS (P < 0.001). Upon QA program implementation, in-hospital mortality (P < 0.001), hospital LOS (P < 0.001), and 30-day mortality (P < 0.001) improved. CONCLUSION: Continuing QA program is effective in improving the clinical outcomes of hospitalized CAP.

Inhaled corticosteroid is not associated with a poor prognosis in COVID-19.

Inhaled corticosteroid is not associated with a poor prognosis in COVID-19.

The effect and associated mechanism of action of phosphodiesterase 4 (PDE4) inhibitor on CD4+ lymphocyte proliferation.

PDE4 inhibitors are involved in anti-inflammatory and immunomodulatory responses. Recently, they have been getting attention as a new class of drugs treating inflammatory airway diseases. The T lymphocyte is a major cell type present in the inflammatory infiltrate in the airway wall in patients with chronic obstructive pulmonary disease (COPD), and a previous study found that treatment with a PDE4 inhibitor significantly suppressed T cell proliferation. However, the mechanism of action of PDE4 inhibitors has not been elucidated. The present study aimed to investigate major signal transduction pathways of T lymphocyte and identify the phase, during which PDE4 inhibitors affect T cell proliferation. Isolated splenic CD4+ T cells were grown under stimulation with an anti-CD3/CD28 antibody, and/or treated with roflumilast-n-oxide (RNO). A western blot assay was performed using major antibodies including anti-p-38, anti-p-PI3K, anti-p-JNK, anti-p-ERK 1/2, anti-NFAT1 (NFATc2), and anti-NF-kB antibodies. Additional experiments conducted on the pathway showed significant change following RNO treatment, thus providing further evidence for signal transduction pathway concerning PDE4 inhibitors. T cell proliferation was suppressed by RNO treatment. In the pathways involved in T cell proliferation, only expression of anti-NFAT1 antibody was suppressed by RNO treatment. In additional experiments on the NFAT pathway, the very first phase (TCR signalling) remained unchanged on treatment with RNO, but RNO treatment increased IP3R expression and suppressed calcineurin activity. Calcineurin activity, reduced by RNO, increased on treatment with an IP3 receptor agonist. PED4 inhibitor, roflumilast is speculated to suppress T cell proliferation by interfering with IP3-IP3R binding to inhibit calcium emission, blocking pathway activation from this phase onward, eventually decreasing the level of a growth factor for T cell proliferation, IL-2.

The Influence of Lower Temperature Induction of Valsa mali on the Infection of Apple Trees.

Apple valsa canker (AVC), caused by Valsa mali, is one of the most important diseases of apple trees in China. AVC occurred severely along with cold winter or cold spring. However, the effect of lower temperature on V. mali is poorly understood. This study evaluated the influence of lower temperature pretreatment of V. mali on the infection of apple twigs and leaves. The results showed that exposing V. mali to lower temperatures (between -10°C and 10°C) for more than 18 h significantly increased the disease severity of apple leaves and twigs, with a higher lesion area ratio (LAR), lesion length, and disease incidence (DI) than that at 25°C. In addition, cold treatment ranging from -5°C to 10°C promoted colony growth. Meanwhile, the relative expression of four cell wall degrading enzyme (CWDE)-related genes pretreated at -5°C and 5°C were significantly higher than that at 25°C. The results indicated that the virulence of V. mali mycelium is sensitive to lower temperatures. After sensing lower temperature changes, V. mali can adjust its infection of apple trees by regulating the expression of pathogenicity gene and growth rate. Spring has very frequent temperature changes, and V. mali is highly invasive in this season. Therefore, more attention should be paid in spring to protecting apple trees from infection of V. mali, by reducing pruning wound formation in spring and applying protective agents to pruning wounds in time.

The trypanosome-specific proteins FPRC and CIF4 regulate cytokinesis initiation by recruiting CIF1 to the cytokinesis initiation site.

The evolutionarily early divergent human parasite Trypanosoma brucei proliferates through binary cell fission in both its tsetse fly vector and mammalian host. The parasite divides unidirectionally along the longitudinal cell axis from the anterior cell tip toward the posterior cell tip through a mechanism distinct from that in the cells of its human host. Initiation of cytokinesis in T. brucei is regulated by two evolutionarily conserved protein kinases, the Polo-like kinase TbPLK and the Aurora B kinase TbAUK1, and a cohort of trypanosome-specific proteins, including the three cytokinesis initiation factors CIF1, CIF2, and CIF3. Here, using RNAi, in situ epitope tagging of proteins, GST pulldown, and coimmunoprecipitation assays, and immunofluorescence and scanning electron microscopy analyses, we report the identification and functional characterization of two trypanosome-specific proteins, flagellum attachment zone tip-localizing protein required for cytokinesis (FPRC) and CIF4. We found that the two proteins colocalize to the distal tips of the new and the old flagellum attachment zones and are required for cytokinesis initiation. Knockdown of FPRC or CIF4 disrupted the localization of CIF1, suggesting that they function upstream of CIF1. Moreover, depletion of CIF4 abolished FPRC localization, indicating that CIF4 acts upstream of FPRC. Together, these results identify two new cytokinesis regulators in T. brucei and integrate them into the CIF1-mediated cytokinesis regulatory pathway. These findings highlight the existence of a cytokinesis pathway in T. brucei that is different from that of its mammalian host and therefore suggest that cytokinesis in T. brucei could potentially be exploited as a new drug target.

An orphan kinesin controls trypanosome morphology transitions by targeting FLAM3 to the flagellum.

Trypanosoma brucei undergoes life cycle form transitions from trypomastigotes to epimastigotes in the insect vector by re-positioning the mitochondrial genome and re-locating the flagellum and flagellum-associated cytoskeletal structures. The mechanism underlying these dramatic morphology transitions remains poorly understood. Here we report the regulatory role of the orphan kinesin KIN-E in controlling trypanosome morphology transitions. KIN-E localizes to the flagellum and is enriched at the flagellar tip, and this localization depends on the C-terminal m-calpain domain III-like domains. Depletion of KIN-E in the trypomastigote form of T. brucei causes major morphology changes and a gradual increase in the level of EP procyclin, generating epimastigote-like cells. Mechanistically, through its C-terminal importin α-like domain, KIN-E targets FLAM3, a flagellar protein involved in morphology transitions, to the flagellum to promote elongation of the flagellum attachment zone and positioning of the flagellum and flagellum-associated cytoskeletal structure, thereby maintaining trypomastigote cell morphology. Our findings suggest that morphology transitions in trypanosomes require KIN-E-mediated transport of FLAM3 to the flagellum.

Periodic trapezoidal VO2-Ge multilayer absorber for dynamic radiative cooling.

Nowadays, the requirement for achieving dynamic radiative cooling is more and more intense, so a cooling system is proposed and developed to meet the demand in this paper. This cooling system is composed of a filter and a periodic trapezoidal VO2-Ge multilayer absorber (VGMA). The filter on the top enables the VGMA to reflect most of the solar irradiation at daytime and the absorptance or emittance of the VGMA is very different in the spectrum band of 8-13 µm for insulating and metallic VO2 due to the phase transition characteristic of VO2. With this cooling system, close-to-zero absorptance in the range of 0.3-2.5 µm and high (low) absorptance from 8 to 13 µm are achieved for metallic (insulating) VO2. Based on changing the temperature and absorptivity or emissivity simultaneously, radiative heat can be transferred dynamically to the outer space. When VO2 is in the insulating phase, the absorption mechanism of the absorber is magnetic resonance and surface plasmon polariton resonance, and broadband high absorptivity is achieved by exciting slowlight waveguide mode at broadband wavelengths when VO2 is in metallic phase. The spectral absorptance characteristics of the absorber in the two phase states are investigated as a function of the layer number and the incident angle of the electromagnetic waves. The results show that the absorber designed is insensitive to the incident angle. Moreover, the net cooling power of the VGMA of metallic VO2 is instantly 4 times more than that of insulating VO2 once the phase change temperature is reached. This work will be beneficial to the advancement of dynamic radiative cooling.