Major Surface Research Articles

Overcoming the egress block of Plasmodium sporozoites expressing fluorescently tagged circumsporozoite protein.

Plasmodium sporozoites are the highly motile and invasive forms of the malaria parasite transmitted by mosquitoes. Sporozoites form within oocysts at the midgut wall of the mosquito, egress from oocysts and enter salivary glands prior to transmission. The GPI-anchored major surface protein, the circumsporozoite protein (CSP) is important for Plasmodium sporozoite formation, egress, migration and invasion. To visualize CSP, we previously generated full-length versions of CSP internally tagged with the green fluorescent protein, GFP. However, while these allowed for imaging of sporogony in oocysts, sporozoites failed to egress. Here, we explore different strategies to overcome this block in egress and obtain salivary gland resident sporozoites that express CSP-GFP. Replacing the N-terminal and repeat region with GFP did not allow sporozoite formation. Lowering expression of CSP-GFP at the endogenous locus allowed sporozoite formation but did not overcome egress block. Crossing of CSP-GFP expressing parasites that are blocked in egress with wild-type parasites yielded a small fraction of parasites that entered salivary glands and expressed various levels of CSP-GFP. Expressing CSP-GFP constructs from a silent chromosome region from promoters that are active only post salivary gland invasion yielded normal numbers of fluorescent salivary gland sporozoites, albeit with low levels of fluorescence. We also show that lowering CSP expression by 50% allowed egress from oocysts but not salivary gland entry. In conclusion, Plasmodium berghei parasites with normal CSP expression tolerate a certain level of CSP-GFP without disruption of oocyst egress and salivary gland invasion.

Different Methods of Scan Alignment in Erosive Tooth Wear Measurements: An In Vitro Study.

Model alignment in cases of erosive tooth wear can be challenging, and no method has been reported to outweigh the others. Extracted human teeth were mounted on two models and scanned at different times, from 1 h to 2 weeks, with an intraoral scanner (3Shape TRIOS 4) before and after immersion in Monster® energy drink and tap water. The scans were superimposed (3Shape TRIOS Patient Monitoring, Version 2.2.3.3, 3Shape A/S, Copengagen, Denmark). Best fit, best-fit tooth comparison, reference best fit using fillings, and palatal rugae as reference points were used for alignment. Surface profile differences were calculated in a cross-section view. The nonparametric Bland-Altman and Kruskal-Wallis tests were used. First, statistically significant differences were marked after 4 days of immersion. The measurements obtained after 2 weeks of immersion were statistically significantly different from the measurements obtained at the different time points until 1 week. No statistically significant differences (p < 0.05) were observed among the alignment methods at any time. In comparison to the best-fit model, both palatal rugae and fillings can be used. The best-fit tooth comparison method is a reliable option; however, it should be used with caution in cases of major surface loss.

Increased CD44 expression in primary meningioma: its clinical significance and association with peritumoral brain edema.

CD44 is a major cell surface receptor involved in cell adhesion and migration. The overexpression of CD44 is a poor prognostic factor in many neoplasms, including meningiomas. The aim of this study was to investigate the association between CD44 gene expression and clinical signatures of primary meningiomas. CD44 gene expression was quantitatively evaluated by snap freezing tumor tissues obtained from 106 patients with primary meningioma. The relationships between CD44 expression and clinical signatures of meningiomas, including histological malignancy, tumor volume, and peritumoral brain edema (PTBE), were analyzed. PTBE was assessed using the Steinhoff classification (SC) system (from SC 0 to SC III). CD44 gene expression in WHO grade 2 and 3 meningiomas was significantly higher than that in grade 1 meningiomas. In addition, CD44 expression increased with the severity of PTBE. Particularly, among the grade 1 meningiomas or small-sized tumors (maximum tumor diameter < 43 mm), CD44 expression in tumors with severe PTBE (SC II or III) was significantly higher than that in tumors without or with mild PTBE (SC 0 or I). Multivariate logistic regression analysis also revealed that overexpression of CD44 was an independent significant factor of severe PTBE development in primary meningiomas. In addition to tumor cell aggressiveness, CD44 expression promotes the development of PTBE in meningioma. Since PTBE is a strong factor of tumor-related epilepsy or cognitive dysfunction in patients with meningioma, CD44 is thus a potential therapeutic target in meningioma with PTBE.

Enhancing cadmium immobilization on halloysite through varied dissolved organic matter: Exploring the role of halloysite aggregation

This research is focused on studying the effects of different dissolved organic matter (DOM) and electrolyte concentration on the Cd(II) adsorption on halloysite (HNT) surfaces. The DOM significantly decreased the Cd(II) adsorption by more than 25 %. Soil derived dissolved organic matter (SDT) showed the greatest negative impact, followed by humic acid (HA) and Fulvic acid (FA). The effects of background electrolytes NaCl and NH4Cl showed that both salts can undergo complexation with metals. Furthermore, the DOM (SDT/FA/HA) can cover the major HNT surface and the Cd(II) adsorption may occur due to outer-sphere complexation and ion exchange. Additionally, the influence of 100 mML−1 of NaCl on the aggregation tendencies of HNT has demonstrated that the presence of DOM amplifies the aggregation behavior of these nanotubes. The interaction energy barrier between HNT particles is dependent on physicochemical characteristics of DOM that inhibits Cd(II) sorption. These findings suggested that the HNT reduction, electrostatic repulsion and site-competition are the prominent mechanisms to decrease the Cd(II) immobilization on the HNT. The extent of Cd(II) adsorption/desorption on HNT surface followed the order of FA > HA > SDT/ HA > SDT > FA.

Unwrap RAP1's Mystery at Kinetoplastid Telomeres.

Although located at the chromosome end, telomeres are an essential chromosome component that helps maintain genome integrity and chromosome stability from protozoa to mammals. The role of telomere proteins in chromosome end protection is conserved, where they suppress various DNA damage response machineries and block nucleolytic degradation of the natural chromosome ends, although the detailed underlying mechanisms are not identical. In addition, the specialized telomere structure exerts a repressive epigenetic effect on expression of genes located at subtelomeres in a number of eukaryotic organisms. This so-called telomeric silencing also affects virulence of a number of microbial pathogens that undergo antigenic variation/phenotypic switching. Telomere proteins, particularly the RAP1 homologs, have been shown to be a key player for telomeric silencing. RAP1 homologs also suppress the expression of Telomere Repeat-containing RNA (TERRA), which is linked to their roles in telomere stability maintenance. The functions of RAP1s in suppressing telomere recombination are largely conserved from kinetoplastids to mammals. However, the underlying mechanisms of RAP1-mediated telomeric silencing have many species-specific features. In this review, I will focus on Trypanosoma brucei RAP1's functions in suppressing telomeric/subtelomeric DNA recombination and in the regulation of monoallelic expression of subtelomere-located major surface antigen genes. Common and unique mechanisms will be compared among RAP1 homologs, and their implications will be discussed.

Damage Proxy Mapping with SAR interferometric coherence change

Synthetic aperture radar (SAR) can be combined interferometrically to estimate the coherence of the SAR phase. The coherence of the phase over time depends on the stability of the major objects and surface that are reflecting the SAR signal, at spatial scales near the radar wavelength and larger. When there are major changes in the radar reflection, it causes a loss of interferometric coherence, so we use methods of detecting coherence change as a proxy for damage or other sudden change to buildings, other structures, or the land surface, which we call a damage proxy map (DPM). The most common method for estimating the interferometric coherence is with spatial phase correlation measures over small areas. The simplest damage proxy map method is to calculate the coherence of an interferometric SAR (InSAR) pair before the event and another pair that spans the event and take the difference of the coherence to measure the change likely due to the event. This method can be effective for areas where the InSAR coherence is normally very high at the radar wavelength used. SAR at L-band (24 cm) wavelength has high coherence in a wider variety of environments than the shorter wavelengths. A more advanced, but requiring more computational resources, damage proxy map method involves calculating the coherence of all possible InSAR pairs for an interval of some months or years before the event to develop statistics about the coherence of each ground location as a function of InSAR pair interval and other parameters such as interferometric spatial baseline. Then InSAR pairs that span the event are compared to the pre-event statistics to estimate the likelihood that the co-event coherence has been reduced by damage or other surface changes. We have found that damage proxy maps are useful for detecting likely damage from many different types of events, including earthquakes, hurricanes, tornados, tsunami inundation, large landslides, or other causes.

Genetic investigation of glycosylphosphatidylinositol (GPI) anchored Bd37 orthologs in Babesia divergens group and potential use of recombinant protein for ecological survey in deer.

The Babesia divergens/B. capreoli group includes parasites with confirmed or possible zoonotic potential to cause human babesiosis. Currently, diagnostic antigen of the group has not been established. In this study, we investigated the ortholog of Bd37, a (GPI)-anchored major merozoite surface protein of B. divergens sensu stricto, in the Asia lineage of the group. From two genomic isolates from sporozoites/sporoblasts stage, three Bd37 gene variants, namely Bd37 JP-A, JP-B, and JP-C, were isolated with 62.3-64.1% amino acid sequences identity. Discriminative blood direct PCR revealed that Bd37 JP-A was encoded in all parasites infecting wild sika deer examined (n=22). While Bd37 JP-B and JP-C genes were randomly detected in 12 and 11 specimens, respectively. Sequencing of all JP-A variants revealed that the gene was polymorphic with low ratio of non-synonymous to synonymous substitutions (dN/dS) and that a highly polymorphic region was not related to predicted B-cell epitopes. A recombinant JP-A-based ELISA showed an overall positive rate of 13.9% in sika deer in Japan from north (Hokkaido) to south (Kyushu island) across 24 prefectures (n=360). This positive rate was twice as high as that examined by 18S rRNA-based PCR (6.8%). The geographical trends in infection rates were consistent. This study demonstrated that direct examination was informative for revealing genetic background and selecting antigen candidates. Bd37 orthologs may serve diagnostic purposes in combination with indirect fluorescence assay, which requires biological isolates.

X-ray dot map of major surface elements in three common Indian butterflies

X-ray dot map of major surface elements in three common Indian butterflies

Surface-gas chemistry coupling and stability limits of hydrogen/air combustion in catalytic microchannels

The catalytic (heterogeneous) and coupled catalytic-gaseous (hetero-/homogeneous) combustion of fuel-lean hydrogen/air mixtures (equivalence ratio φ = 0.4) in palladium- and rhodium-coated catalytic microchannels was numerically investigated in planar microchannels having a canonical geometry of 10 mm length and 1 mm height. Steady, extinction-induced combustion stability limits were demarcated as a function of inlet velocity and external heat loss at pressures of 1 and 5 bar, with wall thermal conductivities of 1 and 16 W/mK. In each case, interplays between the catalytic and gas-phase chemical reaction pathways, and their impact on the stability limits were identified. The stability results were further compared with literature data for platinum. The simulations indicated that Pd was more resilient against extinction than Rh and had a stronger surface reactivity when competing with gas-phase chemistry in the channel. Similar to Pt, the strong H2 surface reactivity on Pd resulted in wide stability limits purely determined by surface reactions and independent of gas-phase chemistry. In stark contrast, the presence of gas-phase combustion significantly expanded the stability limits of the Rh channel. The stability limits of Rh at 5 bar were consistently broader than those at 1 bar under all investigated conditions, which was also a behavior different to that of Pd and Pt channels, whose stability limit curves had crossover points between the two pressures. Additional simulations were performed in a Surface Perfectly Stirred Reactor (SPSR), providing comprehensive chemistry information, including sensitivity analyses of key reactions and surface coverages. When approaching extinction, OH(s) was a major surface species on Pd, while the Rh surface was primarily blocked by O(s).

A Comprehensive Review of Tick-Born Blood Protozoan Disease in Cattle: Babesiosis and Vaccination

Babesiosis is a tick-borne blood protozoan cattle disease caused by the genus Babesia worldwide and in tropical and subtropical regions. It is mainly caused by Babesia bovis and Babesia bigemina in cattle. When merozoites enter the erythrocyte, the surface coat of B. bigemina produces many merozoite surface antigens. This study is a comprehensive review of the "Tick-Borne Blood Protozoan Cattle Disease: Babesiosis and Vaccination" survey. There is a need to develop effective vaccines to control bovine babesiosis (BB) under field conditions because of the development of drug resistance against it. B. bigemina live-attenuated vaccine is available in the form of infected red blood cells (RBCs) in Australia and Israel, which has the danger of disseminating exotic DNA to other countries. A recombinant protein-based vaccine is a good choice to be developed, but very few immunogens have been explored yet to launch vaccination against B. bigemina. It is concluded from this study that secretory proteins were characterized, and the 65 kDa protein was found to be immunogenic. Major surface protein (gp45) was found to be antigenic and immunogenic when sera samples of infected and vaccinated calves were screened. The multiepitope-based protein rec-gpME was expressed, and the calves were vaccinated. The vaccinated calves had higher humoral and CTL responses. This rec-gpME could be a potential vaccine candidate against the B. bigemina infection. This rec-gpME would be tested on cattle under field conditions in Pakistan in the future.

Sequencing p72 gene of field strain of African swine fever virus (ASFV) in Vietnam and generation of enhanced immunogenic fusion protein G-p72 potentially expressed as a recombinant antigen in ASFV subunit vaccine

Protein p72 is the major surface protein of African swine fever virus (ASFV), which is immunogenic and can prime the host to elicit a protective immune response, while G protein is the surface glycoprotein of vesicular stomatitis virus (VSV), which is well-known to be a strong antigen to stimulate an effective humoral immunity. The aim of this study was to sequence full length p72 gene of a field strain of ASFV causing typical ASF in Dong Nai province in 2020 and fuse this p72 gene with VSV G gene to generate a recombinant fusion gene G-p72 that could simultaneously express both proteins and stimulate a better host immune response than p72 expression alone. The sequence of the gene showed 99.59% nucleotide sequence similarity to an ASFV isolate from China. The PCR was employed to produce the recombinant G-p72 gene, which was cloned into plasmid pET28a, followed by transformation into E. coli BL21 (DE3) for protein expression. The G-p72 expression was induced at 37°C and 28°C for 6 and 16 h, respectively. The expression showed that G-p72 was observed at 28°C for 16 h. In summary, the full length p72 gene of a field strain of ASFV was successfully sequenced and expressed as the recombinant G-p72 protein in E. coli BL21 (DE3). The expression level of the G-p72 fusion should be optimized and the immunogenicity of the recombinant protein should be examined in futher studies.

Gelatin Zymography of Major Proteases in Exosomes of Leishmania major Promastigotes.

Enzymatic digestion of extra cellular matrix proteins by proteinases of Leishmania promastigotes is a complex process. Hence, studies on functional proteomics of these enzymes can help select these enzymes as possible vaccine candidates or selecting candidates for chemotherapy and immunotherapy. Several proteolytic enzymes are involved in virulence of Leishmania spp. These enzymes are mostly serine, cysteine and metalloproteases. We aimed to detect proteases in Leishmania promastigote exosomes. Serine, cysteine and metalloproteases were investigated in exosomes and lysate of L. major promastigote using gelatin zymography. The study was carried out in the Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran, in 2021. Zymography findings of metalloproteinases showed transparent bands, including a 63-kDa glycoprotein (GP63). This glycoprotein is a major surface metalloproteinase. In addition, transparent bands belonged to serin proteases and cathepsin were demonstrated in gels associated to Leishmania promastigote lysate and exosomes. Several metalloproteases, serin proteases and cathepsins were shown in promastigote lysate and exosomes of L. major, which could purified and used as fractions for immunodiagnostic.

Investigation of structural, optical, and electrical properties of PEDOT:PSS/Au/PEDOT:PSS multilayer films

PEDOT:PSS/Au/PEDOT:PSS multilayer films were successfully prepared and investigated. The PEDOT:PSS and Au layers were prepared using spin coating and DC sputtering, respectively. The thickness of the Au layer was varied within the range of 2–10 nm to investigate its impact on the resulting multilayer films. The amorphous nature of the multilayer films was interpreted from X-ray diffraction analysis. Fourier-transform infrared spectroscopy identified that the multilayer films were the major surface chemical structure of PEDOT:PSS. The optical transmittance and sheet resistance characteristics of the multilayer films exhibited a significant reduction owing to the presence of the Au interlayer. In order to evaluate the optical-electrical properties of the multilayer films, a figure of merit (FOM) was calculated. Remarkably, the multilayer films featuring a thin Au layer of 2 nm yielded the highest FOM value. Therefore, it can be demonstrated that multilayer films of PEDOT:PSS/Au/PEDOT:PSS fabricated with a thin Au layer can be applicable for utilization in optoelectronic devices.

KVFL: Key-Value-Based Persistent Fuzzing for IoT Web Servers

Abstract As the number of Internet of Thing (IoT) devices increases, attacks against their vulnerabilities have become a serious threat. The web servers (WSs) in IoT devices provide management services for end-users, which are currently the major attack surface. Several fuzzing solutions for identifying vulnerabilities in IoT devices have been proposed, but there is currently no grey-box fuzzer specifically designed for the unique features of WSs in IoT to effectively detect memory corruption vulnerabilities. We design and implement KVFL, an efficient grey-box fuzzer, to address the issues of low throughput and slow exploration of deep code when fuzzing for IoT WSs. Firstly, KVFL employs a delicate hooking technology that heuristically hijacks and emulates hardware-dependent functions, ensuring WSs can be accurately and efficiently emulated in user-mode. On this basis, KVFL fully utilizes the loop parsing HTTP requests feature of WSs through a redesigned fork-server, to minimize nonessential rebooting losses of the target, thereby significantly improving fuzzing throughput. Secondly, KVFL leverages code coverage feedback to automatically infer a set of valid Keys and derive a Key-Value mutation. This enables the generation of high-quality test cases that can facilitate deeper code exploration of WSs. The evaluation results show that compared to the state-of-the-art IoT grey-box fuzzer FIRM-AFL, KVFL improves the throughput by over 2× and explores 4.5× more edges. Additionally, it identifies all 1-day vulnerabilities with over 7× faster speed than the baseline and detects three previously unknown 0-day vulnerabilities. These all indicate that KVFL is effective and efficient at fuzzing IoT WSs.

Immune Landscape Associated with Response to Brentuximab Vedotin with Ipilimumab and/or Nivolumab in Relapsed/Refractory Hodgkin Lymphoma (E4412 Phase 1)

Background: We previously reported that treatment with the anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) in combination with the checkpoint inhibitors targeting CTLA-4 and/or PD-1 (ipilimumab (I) and nivolumab (N)) led to high overall response rates (ORR) and complete response (CR) rates in relapsed/refractory (R/R) Hodgkin's lymphoma patients in a Phase 1 ECOG-ACRIN sponsored clinical trial. As previously presented in the Phase 1 component of NCT01896999 (E4412), the ORR for the treatment arms were: BV+I 76%, BV+N 89%, and BV+I+N 82%, with CR rates of 57%, 61%, and 73% across the groups, respectively. This suggested that not all patients who responded derived equal benefit. Moreover, with a median follow-up of 2.24 years, the PFS of 1.1 year, NR, and 2.49 years across the groups suggest that even some patients who achieved CR progressed on or subsequent to treatment. Currently biomarkers have no ability to predict which patients will maximally benefit from these therapies. We investigated blood-based immune biomarkers mechanistically across all cohorts which may explain differential responses and guide future treatment decisions for R/R HL patients. Methods: Peripheral blood plasma for 54 of 61 (89%) patients evaluable for response was collected at up to 4 time points and tested for 92 immuno-oncology soluble analytes with Olink proximity extension assay and for antibody titers to 20 known tumor antigens by ELISA. Matching peripheral blood mononuclear cells (PBMC) were analyzed by CyTOF mass cytometry for major immune cell subsets and marker surface expression, and for T cell receptor diversity by Immunoseq®. Mixed effect linear models were used to identify significantly associated changes (P&amp;lt;0.05) related to treatment longitudinally within groups and to ORR between groups. Results: Analysis of plasma demonstrated durable increase in soluble plasma PD-1 and decreases in CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens, and higher GZMA and CAIX in BV+I (P&amp;lt;0.05). Despite baseline heterogeneity in PBMC composition, we found durable increases in plasmacytoid dendritic cells (pDC) after N-containing treatments, and transient increases in plasmablasts and memory B cells, as well as early decreases in naïve CD4+ T cells and neutrophils across treatments. Treatment with BV+I+N demonstrated late increases in neutrophils, and changes in memory B cell markers. Clinical benefit analyses revealed that elevated soluble CD5, ADA, CXCL13, and CCL17 at baseline or after two treatment cycles were associated with worse ORR (P&amp;lt;0.05), and that a module of co-regulated soluble analytes at baseline, including MUC16, was associated with worse progression free survival (PFS) (P&amp;lt;0.05). NY-ESO-1 autoantibodies were more frequent in non-responders, and the top 10% of expanded TCR clonotypes were increased in responders after one treatment cycle (P&amp;lt;0.05). Conclusion: This data reveals differential immune activation based on treatment modality for patients with R/R HL receiving checkpoint-based regimens in combination with an ADC. Our data highlights potential tumor- and immune-derived predictive and pharmacodynamic biomarker candidates of response and resistance. These novel findings have relevance for R/R HL patients receiving immunotherapy and other immunotherapy combinations such as immuno-chemotherapy platforms. Prospective evaluation of these biomarkers in the Phase II component of this study, a randomized comparison of BV+N vs. BV+N+I which has completed adult accrual, is planned. Figure Legend Clinical responders and non-responder patient samples were analyzed using ELISA (auto antibodies), CyTOF (Cell populations), TCRseq (T cell clonality) and Olink (proteomics). The results showed that pDCs, Neutrophils and B-Plasmablasts increased with specific drug combinations independently of clinical response. While T Cell expansion was associated with clinical response, the increase of auto antibodies against NY-ESO-1 and circulating proteins CD5, ADA, MUC16, CXCL13, CXCL9 and CCL17 were associated with worse prognosis

Telomere maintenance in African trypanosomes

Telomere maintenance is essential for genome integrity and chromosome stability in eukaryotic cells harboring linear chromosomes, as telomere forms a specialized structure to mask the natural chromosome ends from DNA damage repair machineries and to prevent nucleolytic degradation of the telomeric DNA. In Trypanosoma brucei and several other microbial pathogens, virulence genes involved in antigenic variation, a key pathogenesis mechanism essential for host immune evasion and long-term infections, are located at subtelomeres, and expression and switching of these major surface antigens are regulated by telomere proteins and the telomere structure. Therefore, understanding telomere maintenance mechanisms and how these pathogens achieve a balance between stability and plasticity at telomere/subtelomere will help develop better means to eradicate human diseases caused by these pathogens. Telomere replication faces several challenges, and the “end replication problem” is a key obstacle that can cause progressive telomere shortening in proliferating cells. To overcome this challenge, most eukaryotes use telomerase to extend the G-rich telomere strand. In addition, a number of telomere proteins use sophisticated mechanisms to coordinate the telomerase-mediated de novo telomere G-strand synthesis and the telomere C-strand fill-in, which has been extensively studied in mammalian cells. However, we recently discovered that trypanosomes lack many telomere proteins identified in its mammalian host that are critical for telomere end processing. Rather, T. brucei uses a unique DNA polymerase, PolIE that belongs to the DNA polymerase A family (E. coli DNA PolI family), to coordinate the telomere G- and C-strand syntheses. In this review, I will first briefly summarize current understanding of telomere end processing in mammals. Subsequently, I will describe PolIE-mediated coordination of telomere G- and C-strand synthesis in T. brucei and implication of this recent discovery.

Mifepristone Modulates the Polarization of Th1/Th2 by Inducing the Mature of Monocyte‐Derived Dendritic Cells

AbstractAs an anti‐implantation contraception medicine, mifepristone can alter the development of the endometrium. In contrast, little research is performed to decipher the effect of mifepristone on Th1/Th2 immune homeostasis in the endometrium. CD14+ monocytes derived from healthy donors are cultured with interleukin (IL)‐4 and granulocyte macrophage‐colony stimulating factor to induce monocyte‐derived dendritic cells (DCs), which are further incubated with mifepristone. Mifepristone incubation could induce up‐regulated CD83 and major histocompatibility complex cell surface receptor staining on monocyte‐derived DCs. Functionally, mifepristone incubation could enhance the allostimulatory capacity of DCs to promote the proliferation of allogeneic T cells with up‐regulated Th1 cell proportion and down‐regulated Th2 cell proportion. On the other side, increased Th1 cytokines release (interferon‐γ, tumor necrosis factor α), inhibited Th2 cytokines release (IL‐10, IL‐4), promoted T‐Box transcription factor 21 transcription, and inhibited GATA binding protein 3 transcription are also identified. Mifepristone‐stimulated DCs could alter the Th1/Th2 transcription balance to favor Th1 skewing inflammatory environment.

Revealing Novel-Strain-Specific and Shared Epitopes of Infectious Bronchitis Virus Spike Glycoprotein Using Chemical Linkage of Peptides onto Scaffolds Precision Epitope Mapping.

The avian coronavirus, infectious bronchitis virus (IBV), is an economically important infectious disease affecting chickens, with a diverse range of serotypes found globally. The major surface protein, spike (S), has high diversity between serotypes, and amino acid differences in the S1 sub-unit are thought to be responsible for poor cross-protection afforded by vaccination. Here, we attempt to address this, by using epitope mapping technology to identify shared and serotype-specific immunogenic epitopes of the S glycoprotein of three major circulating strains of IBV, M41, QX, and 4/91, via CLIPS peptide arrays based on peptides from the S1 sub-units. The arrays were screened with sera from chickens immunised with recombinant IBV, based on Beau-R backbone expressing heterologous S, generated in two independent vaccination/challenge trials. The screening of sera from rIBV vaccination experiments led to the identification of 52 immunogenic epitopes on the S1 of M41, QX, and 4/91. The epitopes were assigned into six overlapping epitope binding regions. Based on accessibility and location in the hypervariable regions of S, three sequences, 25YVYYYQSAFRPPNGWHLQGGAYAVVNSTN54, 67TVGVIKDVYNQSVASI82, and 83AMTVPPAGMSWSVS96, were selected for further investigation, and synthetic peptide mimics were recognised by polyclonal sera. These epitopes may have the potential to contribute towards a broader cross-protective IBV vaccine.

Significant Roles of Surface Hydrides in Enhancing the Performance of Cu/BaTiO2.8H0.2 Catalyst for CO2 Hydrogenation to Methanol

AbstractTuning the anionic site of catalyst supports can impact reaction pathways by creating active sites on the support or influencing metal‐support interactions when using supported metal nanoparticles. This study focuses on CO2 hydrogenation over supported Cu nanoparticles, revealing a 3‐fold increase in methanol yield when replacing oxygen anions with hydrides in the perovskite support (Cu/BaTiO2.8H0.2 yields ~146 mg/h/gCu vs. Cu/BaTiO3 yields ~50 mg/h/gCu). The contrast suggests that significant roles are played by the support hydrides in the reaction. Temperature programmed reaction and isotopic labelling studies indicate that BaTiO2.8H0.2 surface hydride species follow a Mars van Krevelen mechanism in CO2 hydrogenation, promoting methanol production. High‐pressure steady‐state isotopic transient kinetic analysis (SSITKA) studies suggest that Cu/BaTiO2.8H0.2 possesses both a higher density and more active and selective sites for methanol production compared to Cu/BaTiO3. An operando high‐pressure diffuse reflectance infrared spectroscopy (DRIFTS)‐SSITKA study shows that formate species are the major surface intermediates over both catalysts, and the subsequent hydrogenation steps of formate are likely rate‐limiting. However, the catalytic reactivity of Cu/BaTiO2.8H0.2 towards the formate species is much higher than Cu/BaTiO3, likely due to the altered electronic structure of interface Cu sites by the hydrides in the support as validated by density functional theory (DFT) calculations.

Significant Roles of Surface Hydrides in Enhancing the Performance of Cu/BaTiO2.8 H0.2 Catalyst for CO2 Hydrogenation to Methanol.

Tuning the anionic site of catalyst supports can impact reaction pathways by creating active sites on the support or influencing metal-support interactions when using supported metal nanoparticles. This study focuses on CO2 hydrogenation over supported Cu nanoparticles, revealing a 3-fold increase in methanol yield when replacing oxygen anions with hydrides in the perovskite support (Cu/BaTiO2.8 H0.2 yields ~146 mg/h/gCu vs. Cu/BaTiO3 yields ~50 mg/h/gCu). The contrast suggests that significant roles are played by the support hydrides in the reaction. Temperature programmed reaction and isotopic labelling studies indicate that BaTiO2.8 H0.2 surface hydride species follow a Mars van Krevelen mechanism in CO2 hydrogenation, promoting methanol production. High-pressure steady-state isotopic transient kinetic analysis (SSITKA) studies suggest that Cu/BaTiO2.8 H0.2 possesses both a higher density and more active and selective sites for methanol production compared to Cu/BaTiO3 . An operando high-pressure diffuse reflectance infrared spectroscopy (DRIFTS)-SSITKA study shows that formate species are the major surface intermediates over both catalysts, and the subsequent hydrogenation steps of formate are likely rate-limiting. However, the catalytic reactivity of Cu/BaTiO2.8 H0.2 towards the formate species is much higher than Cu/BaTiO3 , likely due to the altered electronic structure of interface Cu sites by the hydrides in the support as validated by density functional theory (DFT) calculations.