Interferon-ß deficiency alters brain response to chronic HIV-1 envelope protein exposure in a transgenic model of NeuroHIV.

Human immunodeficiency virus-1 (HIV-1) infects the central nervous system (CNS) and causes HIV-associated neurocognitive disorders (HAND) in about half of the population living with the virus despite combination anti-retroviral therapy (cART). HIV-1 activates the innate immune system, including the production of type 1 interferons (IFNs) α and ß. Transgenic mice expressing HIV-1 envelope glycoprotein gp120 (HIVgp120tg) in the CNS develop memory impairment and share key neuropathological features and differential CNS gene expression with HIV patients, including the induction of IFN-stimulated genes (ISG). Here we show that knocking out IFNß (IFNßKO) in HIVgp120tg and non-tg control mice impairs recognition and spatial memory, but does not affect anxiety-like behavior, locomotion, or vision. The neuropathology of HIVgp120tg mice is only moderately affected by the KO of IFNß but in a sex-dependent fashion. Notably, in cerebral cortex of IFNßKO animals presynaptic terminals are reduced in males while neuronal dendrites are reduced in females. The IFNßKO results in the hippocampal CA1 region of both male and female HIVgp120tg mice in an ameliorated loss of neuronal presynaptic terminals but no protection of neuronal dendrites. Only female IFNß-deficient HIVgp120tg mice display diminished microglial activation in cortex and hippocampus and increased astrocytosis in hippocampus compared to their IFNß-expressing counterparts. RNA expression for some immune genes and ISGs is also affected in a sex-dependent way. The IFNßKO abrogates or diminishes the induction of MX1, DDX58, IRF7 and IRF9 in HIVgp120tg brains of both sexes. Expression analysis of neurotransmission related genes reveals an influence of IFNß on multiple components with more pronounced changes in IFNßKO females. In contrast, the effects of IFNßKO on MAPK activities are independent of sex with pronounced reduction of active ERK1/2 but also of active p38 in the HIVgp120tg brain. In summary, our findings show that the absence of IFNß impairs memory dependent behavior and modulates neuropathology in HIVgp120tg brains, indicating that its absence may facilitate development of HAND. Moreover, our data suggests that endogenous IFNß plays a vital role in maintaining neuronal homeostasis and memory function.

ACCT is a fast and accessible automatic cell counting tool using machine learning for 2D image segmentation.

Counting cells is a cornerstone of tracking disease progression in neuroscience. A common approach for this process is having trained researchers individually select and count cells within an image, which is not only difficult to standardize but also very time-consuming. While tools exist to automatically count cells in images, the accuracy and accessibility of such tools can be improved. Thus, we introduce a novel tool ACCT: Automatic Cell Counting with Trainable Weka Segmentation which allows for flexible automatic cell counting via object segmentation after user-driven training. ACCT is demonstrated with a comparative analysis of publicly available images of neurons and an in-house dataset of immunofluorescence-stained microglia cells. For comparison, both datasets were manually counted to demonstrate the applicability of ACCT as an accessible means to automatically quantify cells in a precise manner without the need for computing clusters or advanced data preparation.

Macrophage: A Cell With Many Faces and Functions in Tuberculosis.

Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) which primarily infects the macrophages. Nearly a quarter of the world's population is infected latently by Mtb. Only around 5%-10% of those infected develop active TB disease, particularly during suppressed host immune conditions or comorbidity such as HIV, hinting toward the heterogeneity of Mtb infection. The aerosolized Mtb first reaches the lungs, and the resident alveolar macrophages (AMs) are among the first cells to encounter the Mtb infection. Evidence suggests that early clearance of Mtb infection is associated with robust innate immune responses in resident macrophages. In addition to lung-resident macrophage subsets, the recruited monocytes and monocyte-derived macrophages (MDMs) have been suggested to have a protective role during Mtb infection. Mtb, by virtue of its unique cell surface lipids and secreted protein effectors, can evade killing by the innate immune cells and preferentially establish a niche within the AMs. Continuous efforts to delineate the determinants of host defense mechanisms have brought to the center stage the crucial role of macrophage phenotypical variations for functional adaptations in TB. The morphological and functional heterogeneity and plasticity of the macrophages aid in confining the dissemination of Mtb. However, during a suppressed or hyperactivated immune state, the Mtb virulence factors can affect macrophage homeostasis which may skew to favor pathogen growth, causing active TB. This mini-review is aimed at summarizing the interplay of Mtb pathomechanisms in the macrophages and the implications of macrophage heterogeneity and plasticity during Mtb infection.

Plasmodium falciparum Cysteine-Rich Protective Antigen (CyRPA) Elicits Detectable Levels of Invasion-Inhibitory Antibodies during Natural Infection in Humans.

Plasmodium falciparum cysteine-rich protective antigen (CyRPA) is a conserved component of an essential erythrocyte invasion complex (RH5/Ripr/CyRPA) and a target of potent cross-strain parasite-neutralizing antibodies. While naturally acquired human RH5 antibodies have been functionally characterized, there are no similar reports on CyRPA. Thus, we analyzed the parasite-neutralizing activity of naturally acquired human CyRPA antibodies. In this regard, CyRPA human antibodies were measured and purified from malaria-infected plasma obtained from patients in central India and analyzed for their parasite neutralizing activity via in vitro growth inhibition assays (GIA). We report that, despite being susceptible to antibodies, CyRPA is a highly conserved antigen that does not appear to be under substantial immune selection pressure, as a very low acquisition rate for anti-CyRPA antibodies was reported in malaria-exposed Indians. We demonstrate for the first time that the small amounts of natural CyRPA antibodies exhibited functional parasite-neutralizing activity and that a CyRPA-based vaccine formulation induces highly potent antibodies in rabbits. Importantly, the vaccine-induced CyRPA antibodies exhibited a robust 50% inhibitory concentration (IC50) of 21.96 µg/ml, which is comparable to the IC50 of antibodies against the leading blood-stage vaccine candidate, reticulocyte-binding-like homologous protein 5 (RH5). Our data support CyRPA as a unique vaccine target that is highly susceptible to immune attack but is highly conserved compared to other leading candidates such as MSP-1 and AMA-1, further substantiating its promise as a leading blood-stage vaccine candidate.

Innate Immune Sensing of Viruses and Its Consequences for the Central Nervous System.

Viral infections remain a global public health concern and cause a severe societal and economic burden. At the organismal level, the innate immune system is essential for the detection of viruses and constitutes the first line of defense. Viral components are sensed by host pattern recognition receptors (PRRs). PRRs can be further classified based on their localization into Toll-like receptors (TLRs), C-type lectin receptors (CLR), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), NOD-like receptors (NLRs) and cytosolic DNA sensors (CDS). TLR and RLR signaling results in production of type I interferons (IFNα and -ß) and pro-inflammatory cytokines in a cell-specific manner, whereas NLR signaling leads to the production of interleukin-1 family proteins. On the other hand, CLRs are capable of sensing glycans present in viral pathogens, which can induce phagocytic, endocytic, antimicrobial, and pro- inflammatory responses. Peripheral immune sensing of viruses and the ensuing cytokine response can significantly affect the central nervous system (CNS). But viruses can also directly enter the CNS via a multitude of routes, such as the nasal epithelium, along nerve fibers connecting to the periphery and as cargo of infiltrating infected cells passing through the blood brain barrier, triggering innate immune sensing and cytokine responses directly in the CNS. Here, we review mechanisms of viral immune sensing and currently recognized consequences for the CNS of innate immune responses to viruses.

Antibody Combinations Targeting the Essential Antigens CyRPA, RH5, and MSP-119 Potently Neutralize Plasmodium falciparum Clinical Isolates From India and Africa.

BACKGROUND: Targeting multiple key antigens that mediate distinct Plasmodium falciparum erythrocyte invasion pathways is an attractive approach for the development of blood-stage malaria vaccines. However, the challenge is to identify antigen cocktails that elicit potent strain-transcending parasite-neutralizing antibodies efficacious at low immunoglobulin G concentrations feasible to achieve through vaccination. Previous reports have screened inhibitory antibodies primarily against well adapted laboratory parasite clones. However, validation of the parasite-neutralizing efficacy against clinical isolates with minimal in vitro cultivation is equally significant to better ascertain their prospective in vivo potency. METHODS: We evaluated the parasite-neutralizing activity of different antibodies individually and in combinations against laboratory adapted clones and clinical isolates. Clinical isolates were collected from Central India and Mozambique, Africa, and characterized for their invasion properties and genetic diversity of invasion ligands. RESULTS: In our portfolio, we evaluated 25 triple antibody combinations and identified the MSP-Fu+CyRPA+RH5 antibody combination to elicit maximal parasite neutralization against P. falciparum clinical isolates with variable properties that underwent minimal in vitro cultivation. CONCLUSIONS: The MSP-Fu+CyRPA+RH5 combination exhibited highly robust parasite neutralization against P. falciparum clones and clinical isolates, thus substantiating them as promising candidate antigens and establishing a proof of principle for the development of a combinatorial P. falciparum blood-stage malaria vaccine.

A pivotal role for Interferon-α receptor-1 in neuronal injury induced by HIV-1.

BACKGROUND: HIV-1 infection remains a major public health concern despite effective combination antiretroviral therapy (cART). The virus enters the central nervous system (CNS) early in infection and continues to cause HIV-associated neurocognitive disorders (HAND). The pathogenic mechanisms of HIV-associated brain injury remain incompletely understood. Since HIV-1 activates the type I interferon system, which signals via interferon-α receptor (IFNAR) 1 and 2, this study investigated the potential role of IFNAR1 in HIV-induced neurotoxicity. METHODS: We cross-bred HIVgp120-transgenic (tg) and IFNAR1 knockout (IFNAR1KO) mice. At 11-14 months of age, we performed a behavioral assessment and subsequently analyzed neuropathological alterations using deconvolution and quantitative immunofluorescence microscopy, quantitative RT-PCR, and bioinformatics. Western blotting of brain lysates and an in vitro neurotoxicity assay were employed for analysis of cellular signaling pathways. RESULTS: We show that IFNAR1KO results in partial, sex-dependent protection from neuronal injury and behavioral deficits in a transgenic model of HIV-induced brain injury. The IFNAR1KO rescues spatial memory and ameliorates loss of presynaptic terminals preferentially in female HIVgp120tg mice. Similarly, expression of genes involved in neurotransmission reveals sex-dependent effects of IFNAR1KO and HIVgp120. In contrast, IFNAR1-deficiency, independent of sex, limits damage to neuronal dendrites, microgliosis, and activation of p38 MAPK and restores ERK activity in the HIVgp120tg brain. In vitro, inhibition of p38 MAPK abrogates neurotoxicity caused similarly by blockade of ERK kinase and HIVgp120. CONCLUSION: Our findings indicate that IFNAR1 plays a pivotal role in both sex-dependent and independent processes of neuronal injury and behavioral impairment triggered by HIV-1.

Emerging genetic diversity among clinical isolates of SARS-CoV-2: Lessons for today.

Considering the current pandemic of COVID-19, it is imperative to gauge the role of molecular divergence in SARS-CoV-2 with time, due to clinical and epidemiological concerns. Our analyses involving molecular phylogenetics is a step toward understanding the transmission clusters that can be correlated to pathophysiology of the disease to gain insight into virulence mechanism. As the infections are increasing rapidly, more divergence is expected followed possibly by viral adaptation. We could identify mutational hotspots which appear to be major drivers of diversity among strains, with RBD of spike protein emerging as the key region involved in interaction with ACE2 and consequently a major determinant of infection outcome. We believe that such molecular analyses correlated with clinical characteristics and host predisposition need to be evaluated at the earliest to understand viral adaptability, disease prognosis, and transmission dynamics.

Long-range replica exchange molecular dynamics guided drug repurposing against tyrosine kinase PtkA of Mycobacterium tuberculosis.

Tuberculosis (TB) is a leading cause of death worldwide and its impact has intensified due to the emergence of multi drug-resistant (MDR) and extensively drug-resistant (XDR) TB strains. Protein phosphorylation plays a vital role in the virulence of Mycobacterium tuberculosis (M.tb) mediated by protein kinases. Protein tyrosine phosphatase A (MptpA) undergoes phosphorylation by a unique tyrosine-specific kinase, protein tyrosine kinase A (PtkA), identified in the M.tb genome. PtkA phosphorylates PtpA on the tyrosine residues at positions 128 and 129, thereby increasing PtpA activity and promoting pathogenicity of MptpA. In the present study, we performed an extensive investigation of the conformational behavior of the intrinsically disordered domain (IDD) of PtkA using replica exchange molecular dynamics simulations. Long-term molecular dynamics (MD) simulations were performed to elucidate the role of IDD on the catalytic activity of kinase core domain (KCD) of PtkA. This was followed by identification of the probable inhibitors of PtkA using drug repurposing to block the PtpA-PtkA interaction. The inhibitory role of IDD on KCD has already been established; however, various analyses conducted in the present study showed that IDDPtkA had a greater inhibitory effect on the catalytic activity of KCDPtkA in the presence of the drugs esculin and inosine pranobex. The binding of drugs to PtkA resulted in formation of stable complexes, indicating that these two drugs are potentially useful as inhibitors of M.tb.

Extracellular synthesis of silver nanoparticles by Pseudomonas sp. THG-LS1.4 and their antimicrobial application.

Silver nanoparticles (AgNPs) are known to have bacteriostatic and bactericidal effects. The present study highlights the extracellular synthesis of AgNPs and its antibacterial properties. The AgNPs were synthesized using Pseudomonas sp. THG-LS1.4 strain which had been isolated from soil. The AgNPs were characterized by field emission-transmission electron microscopy (FE-TEM), X-ray diffraction (XRD), Fourier transform-infrared (FT-IR) spectroscopy, and particle size distribution (DLS). The AgNPs displayed maximum absorbance at 412 nm and were irregular in shape ranging from 10 to 40 nm. The XRD spectroscopy results demonstrated the crystalline nature of nanoparticles. The AgNPs showed antimicrobial activity against Bacillus cereus, Staphylococcus aureus, Candida tropicalis, Vibrio parahaemolyticus, Escherichia coli and Pseudomonas aeruginosa. Furthermore, the AgNPs were also evaluated for their increased antibacterial activities with various antibiotics against Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica. Additionally, AgNPs showd biofilm inhibition activity. The biosynthesized AgNPs were found to be a potent agent against tested pathogens. More importantly, we highlight the applications of AgNPs as an antimicrobial agent.

Development of superparamagnetic iron oxide nanoparticles via direct conjugation with ginsenosides and its in-vitro study.

The current study focused on direct conjugation of superparamagnetic iron oxide nanoparticles (SPIONs) with ginsenosides CK and Rg3. The direct conjugation approach was low-cost, eco-friendly, simple, fast and high yield. The synthesized conjugates (SPION-CK and SPION-Rg3) were characterized by field emission transmission electron microscopy, dynamic light scattering, zeta potential, X-ray diffractometer, and magnetometer. The characterization results confirmed the formation of SPIONs conjugates. The maximum attaching percentage for ginsenosides to SPIONs was found to be 5%. In vitro cytotoxicity assay in HaCaT keratinocyte cells revealed that the conjugates were non-cytotoxic to normal cells. Moreover, the anti-inflammatory activity of SPION-CK and SPION-Rg3 were investigated. The expression of reactive oxygen species (ROS) in lipopolysaccharide-activated RAW 264.7 (murine macrophage cells) were inhibited by SPIONs conjugates in a dose-dependent manner. In addition, SPION-CK and SPION-Rg3 significantly reduced the production of nitric oxide and inducible nitric oxide synthase (iNOS) in a dose-dependent manner in the lipopolysaccharide-induced RAW 264.7 cells. Overall the results suggested that the SPIONs were conjugated with ginsenosides CK and Rg3 by using direct conjugation approach were non-cytotoxic and can be used as a carrier for intracellular release of ginsenosides in inflammatory diseases.

Ecofriendly synthesis of silver and gold nanoparticles by Euphrasia officinalis leaf extract and its biomedical applications.

Biogenic synthesis of silver (AgNPs) and gold nanoparticles (AuNPs) using aqueous extract of Euphrasia officinalis has been reported. Stable AgNPs and AuNPs were formed on adding aqueous solutions of silver nitrate and chloroauric acid with E. officinalis leaf extract, in 19 min and 2 min, respectively. The synthesis method used in present study was simple, reliable, rapid, cost effective and ecofriendly. The synthesized nanoparticles were characterized with field emission transmission electron microscopy (FE-TEM), elemental mapping, selected area diffraction pattern (SAED), energy-dispersive X-ray spectroscopy (EDS), X-ray diffractometer (XRD), particle size distribution, zeta potential and Fourier-transform infrared spectroscopy (FTIR). The UV-Vis spectrum confirmed the synthesis of nanoparticles as the absorption band was observed at 450 nm for AgNPs and at 558 nm for AuNPs. The TEM images revealed quasi-spherical shape of AgNPs and AuNPs. The size of nanoparticles was determined to be 40.37 ± 1.8 nm for AgNPs and 49.72 ± 1.2 nm for AuNPs. The zeta potential value demonstrated the negative surface charge and stable nature of nanoparticles. Crystalline nature of the nanoparticles in the face-centred cubic (fcc) structure was confirmed by the peaks in the XRD pattern and SAED pattern. FTIR results showed the functional groups involved in reduction of silver and gold ions to metal nanoparticles. For biomedical application, the nanoparticles have been explored for anticancer, antibacterial and biofilm inhibition activities. It was observed that AgNPs exert anticancer activity against human lung cancer (A549) and human cervical cancer (HeLa) cell lines. On the other hand, AuNPs were able to inhibit only human cervical cancer cells. Furthermore, the AgNPs were active against clinically isolated human pathogens like Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Vibrio parahaemolyticus. Additionally, AgNPs also showed biofilm inhibition activity against S. aureus and P. aeruginosa.

In vitro anti-inflammatory activity of spherical silver nanoparticles and monodisperse hexagonal gold nanoparticles by fruit extract of Prunus serrulata: a green synthetic approach.

Recently, green metal nanoparticles have received global attention owing to their economical synthesis, biocompatible nature, widespread biomedical and environmental applications. Current study demonstrates a sustainable approach for the green synthesis of silver nanoparticles (P-AgNPs) and gold nanoparticles (P-AuNPs) from P. serrulata fresh fruit extract. The silver and gold nanoparticles were synthesized in a very rapid, efficient and facile manner, within 50 min and 30 s at 80 °C, respectively. The nanoparticles were characterized by using visual observation, UV-Vis, FE-TEM, EDX, elemental mapping, FT-IR, XRD and DLS, which confirmed the formation of monodispersed, crystalline and stable nanoparticles. Further, we explored these nanoparticles for anti-inflammatory activity through inhibition of downstream NF-κB activation in macrophages (RAW264.7). We demonstrated that the nanoparticles reduced expression of inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PEG2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was attenuated in lipopolysaccharide (LPS)-induced RAW264.7 cells. Furthermore, nanoparticles significantly suppressed LPS-induced activation of NF-κB signalling pathway via p38 MAPK in RAW 264.7 cells. To the best of our knowledge, this is the first report on the efficient green synthesis of P-AgNPs and P-AuNPs using P. serrulata fresh fruit extract and its in vitro anti-inflammatory effects. Collectively, our results suggest that P. serrulata fresh fruit extract is a green resource for the eco-friendly synthesis of P-AgNPs and P-AuNPs, which further can be utilized as a novel therapeutic agent for prevention and cure of inflammation due to their biocompatible nature.

Extracellular synthesis of silver nanoparticles by Pseudomonas sp. THG-LS1.4 and their antimicrobial application / 药物分析学报

Silver nanoparticles (AgNPs) are known to have bacteriostatic and bactericidal effects. The present study highlights the extracellular synthesis of AgNPs and its antibacterial properties. The AgNPs were synthesized using Pseudomonas sp. THG-LS1.4 strain which had been isolated from soil. The AgNPs werecharacterized by field emission-transmission electron microscopy (FE-TEM), X-ray diffraction (XRD),Fourier transform-infrared (FT-IR) spectroscopy, and particle size distribution (DLS). The AgNPs displayed maximum absorbance at 412 nm and were irregular in shape ranging from 10 to 40 nm. The XRD spectroscopy results demonstrated the crystalline nature of nanoparticles. The AgNPs showed antimicrobial activity against Bacillus cereus, Staphylococcus aureus, Candida tropicalis, Vibrio parahaemolyticus,Escherichia coli and Pseudomonas aeruginosa. Furthermore, the AgNPs were also evaluated for their increased antibacterial activities with various antibiotics against Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica. Additionally, AgNPs showd biofilm inhibition activity. The biosynthesized AgNPs were found to be a potent agent against tested pathogens. More importantly, we highlight the applications of AgNPs as an antimicrobial agent.

In situ preparation of water-soluble ginsenoside Rh2-entrapped bovine serum albumin nanoparticles: in vitro cytocompatibility studies.

The present study investigates a simple and convenient one-step procedure for the preparation of bovine serum albumin (BSA)-Rh2 nanoparticles (NPs) at room temperature. In this work, ginsenoside Rh2 was entrapped within the BSA protein to form BSA-Rh2 NPs to enhance the aqueous solubility, stability, and therapeutic efficacy of Rh2. The physiochemical characterization by high-performance liquid chromatography, nuclear magnetic resonance, Fourier transform infrared spectroscopy, field emission transmission electron microscopy, dynamic light scattering, and thermogravimetric analysis confirmed that the prepared BSA-Rh2 NPs were spherical, highly monodispersed, and stable in aqueous systems. In addition, the stability of NPs in terms of different time intervals, pHs, and temperatures (20°C-700°C) was analyzed. The results obtained with different pHs showed that the synthesized BSA-Rh2 NPs were stable in the physiological buffer (pH 7.4) for up to 8 days, but degraded under acidic conditions (pH 5.0) representing the pH inside tumor cells. Furthermore, comparative analysis of the water solubility of BSA-Rh2 NPs and standard Rh2 showed that the BSA nanocarrier enhanced the water solubility of Rh2. Moreover, in vitro cytotoxicity assays including cell viability assays and morphological analyses revealed that Rh2-entrapped BSA NPs, unlike the free Rh2, demonstrated better in vitro cell viability in HaCaT skin cell lines and that BSA enhanced the anticancer effect of Rh2 in A549 lung cell and HT29 colon cancer cell lines. Additionally, anti-inflammatory assay of BSA-Rh2 NPs and standard Rh2 performed using RAW264.7 cells revealed decreased lipopolysaccharide-induced nitric oxide production by BSA-Rh2 NPs. Collectively, the present study suggests that BSA can significantly enhance the therapeutic behavior of Rh2 by improving its solubility and stability in aqueous systems, and hence, BSA-Rh2 NPs may potentially be used as a ginsenoside delivery vehicle in cancer and inflammatory cell lines.

Achromobacter panacis sp. nov., isolated from rhizosphere of Panax ginseng.

A novel strain DCY105T was isolated from soil collected from the rhizosphere of ginseng (Panax ginseng), in Gochang, Republic of Korea. Strain DCY105T is Gram-reaction-negative, white, non-motile, non-flagellate, rod-shaped and aerobic. The bacteria grow optimally at 30°C, pH 6.5-7.0 and in the absence of NaCl. Phylogenetically, strain DCY105T is most closely related to Achromobacter marplatensis LMG 26219T (96.81%). The DNA G+C content of strain DCY105T was 64.4 mol%. Ubiquinone 8 was the major respiratory quinone, and phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol were amongst the major polar lipids. C16:00, C8:03OH and iso-C17:03OH were identified as the major fatty acids present in DCY105T. The results of physiological and biochemical tests allowed strain DCY105T to be differentiated phenotypically from other recognized species belonging to the genus Achromobacter. Therefore, it is suggested that the newly isolated organism represents a novel species, for which the name Achromobacter panacis sp. nov. is proposed with the type strain designated as DCY105T (=CCTCCAB 2015193T =KCTC 42751T).

Naturally Acquired Human Antibodies Against Reticulocyte-Binding Domains of Plasmodium vivax Proteins, PvRBP2c and PvRBP1a, Exhibit Binding-Inhibitory Activity.

Background: Crucial gaps in our understanding of Plasmodium vivax reticulocyte invasion and protective immunity have hampered development of vivax vaccines. P. vivax exclusively invades reticulocytes that is mediated by the P. vivax reticulocyte-binding proteins (PvRBPs) specifically PvRBP2c and PvRBP1a. Vivax infections in Duffy-null individuals have suggested the evolution of alternate invasion pathways that may be mediated by the PvRBPs. Thus, PvRBPs appear as potential targets for efficacious P. vivax neutralization. However, there are limited data validating their vaccine efficacy. In the absence of vivax invasion assays, binding-inhibitory activity of antibodies has been reported to be associated with protection and a measure of vaccine potential. Methods: -based analysis was performed of the PvRBP reticulocyte-binding properties and binding-inhibitory activity of specific anti-PvRBP2c/PvRBP1a human antibodies. Results: PvRBP2c and PvRBP1a displayed a distinct reticulocyte-binding specificity, and their specific reticulocyte-binding domains were mapped within their N-terminal regions. Importantly, naturally acquired antibodies against the reticulocyte-binding domains efficaciously blocked reticulocyte binding of native PvRBPs, suggesting that the human immune system produced functional binding-inhibitory antibodies through exposure to vivax malaria. Conclusions: Reticulocyte-binding domains of PvRBP2c/PvRBP1a are targets of naturally acquired binding-inhibitory antibodies, substantiating their promise as candidate antigens against which vaccine-inducible immunity could potentially be boosted through natural infections.

Kinneretia THG-SQI4 mediated biosynthesis of silver nanoparticles and its antimicrobial efficacy.

Simple, facile, effective approach for the biosynthesis of silver nanoparticles using Kinneretia species and its antimicrobial activity against human pathogens has been demonstrated in this study. Kinneretia THG-SQI4 has been isolated from soil sample collected from Shangqui, China. The synthesized nanoparticles were characterized by ultraviolet-visible spectrophotometry (UV-vis), field emission transmission electron microscopy (FE-TEM), energy dispersive X-ray spectroscopy (EDX), elemental mapping, selected area diffraction pattern, and X-ray diffraction (XRD). The synthesized silver nanoparticles were characterized by a peak at 425 nm in the UV-vis spectrum. The TEM data reveals that the nanoparticles are monodisperse and spherical in shape having a diameter ranging from 15 to 20 nm. The bright circular spots in SAED pattern confirm the crystalline nature of the nanoparticles. The XRD spectra exhibited the characteristic Bragg peaks of 1 1 1, 2 0 0, 2 2 0, and 3 1 1 facets of the face centered cubic symmetry of nanoparticles. The synthesized silver nanoparticles showed potent antibacterial activity against human pathogens like Candida albicans, Candida tropicalis, Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Salmonella enterica, Pseudomonas aeruginosa, Escherichia coli, and Vibrio parahaemolyticus. Moreover, the silver nanoparticles show enhanced synergistic effects in combination with different standard antibiotics against Gram-negative bacteria. This method for synthesis of silver nanoparticle is valuable and has antimicrobial potential.

Biosynthesis of silver nanoparticles using Aeromonas sp. THG-FG1.2 and its antibacterial activity against pathogenic microbes.

Silver nanoparticles were prepared through green route with the aid of Aeromonas sp. THG-FG1.2 as reductant. Visual observation, ultraviolet-visible spectroscopy, transmission electron microscopy, elemental mapping, energy dispersive X-ray spectroscopy, selected area diffraction pattern (SAED), and X-ray diffraction (XRD) were used to characterize the synthesized silver nanoparticles. UV visible studies indicated the surface plasmon resonance at 400 nm which depicts the formation of silver nanoparticles. The TEM images show spherical silver nanoparticles of 8-16 nm. XRD and SAED fringes revealed the structure of silver nanoparticles as face centered cubic (fcc). These silver nanoparticles also tested for their antimicrobial potential and showed effective antimicrobial activity against tested pathogens and thus applicable as potent antimicrobial agent. Furthermore, the nanoparticles potential has been reconnoitered for their enhanced synergistic effect with antibiotics against multidrug resistant bacteria. Thus, the silver nanoparticles synthesized by Aeromonas sp. THG-FG1.2, were effective in inhibition of pathogenic microbes and also show enhanced antibacterial activity with antibiotics.