In the present work, a comparative efficiency of photo-Fenton (PF) treatment process and its combined process with activated carbon (AC) and titanium dioxide (TiO
2
) have been investigated using ...reactive yellow 145 as a model compound. These processes are based on in situ production of hydroxyl radical, a highly strong oxidant, which allows the degradation of organic dye until their mineralization into CO
2
and H
2
O. The effect of different process parameters, such as initial dye concentration, pH of the solution, Fe
2+
concentration, catalyst and adsorbent loadings, and effect of various systems and irradiation times have been studied. The degradation of the dye was monitored by decolorization and COD analysis and then analyzed by high-performance liquid chromatography and IR analysis. Obtained results showed that PF combined with titanium dioxide (PF-TiO
2
) for removal of TOC was more efficient than PF or combination with AC. About 73.7% of TOC removal was obtained after 240 min of UV–F–TiO
2
process, whereas the PF and UV–F–AC process yielded TOC reduction of 61.5% and 54.8% after 240 min. Mineralization studied reveals that effectiveness of treatment processes for RY145 is UV–F–TiO
2
> PF > UV–F–AC > F–AC > F–TiO
2
.
Invasion of human erythrocytes by the malaria parasite
Plasmodium falciparum
is a multi-step process. Previously, a forward genetic screen for
P. falciparum
host factors identified erythrocyte CD55 ...as essential for invasion, but its specific role and how it interfaces with the other factors that mediate this complex process are unknown. Using CRISPR-Cas9 editing, antibody-based inhibition, and live cell imaging, here we show that CD55 is specifically required for parasite internalization. Pre-invasion kinetics, erythrocyte deformability, and echinocytosis were not influenced by CD55, but entry was inhibited when CD55 was blocked or absent. Visualization of parasites attached to CD55-null erythrocytes points to a role for CD55 in stability and/or progression of the moving junction. Our findings demonstrate that CD55 acts after discharge of the parasite’s rhoptry organelles, and plays a unique role relative to all other invasion receptors. As the requirement for CD55 is strain-transcendent, these results suggest that CD55 or its interacting partners may hold potential as therapeutic targets for malaria.
Pyrimidine is the most common in nature, such as in the bases of thymine, cytosine, and uracil. Additionally, a cell's genetic material contains it and is of utmost importance due to carefully chosen ...pharmacological quantities. Most of the marketed drugs contain Pyrimidine scaffold. It was, therefore, the objective of this review to congregate and evaluate the synthetic approach of various substituted non-fused pyrimidines via one-pot MCR, Microwave irradiation, green approach, and many more. The modification in the structure of pyrimidine on carbon or nitrogen atom can increase or decrease its activity. The use of several catalysts, variation of substrates, reduction in reaction time, and site selectivity are also highlighted in this review. We also demonstrated the latest progress in the synthetic approach of non-fused pyrimidine derivatives as the starting point for the pharmacological compound. The review's objective is to provide an overview of methodologies showing the chemistry of synthesis of non-fused pyrimidines.
Binding between DIP and Dpr neuronal recognition proteins has been proposed to regulate synaptic connections between lamina and medulla neurons in the Drosophila visual system. Each lamina neuron was ...previously shown to express many Dprs. Here, we demonstrate, by contrast, that their synaptic partners typically express one or two DIPs, with binding specificities matched to the lamina neuron-expressed Dprs. A deeper understanding of the molecular logic of DIP/Dpr interaction requires quantitative studies on the properties of these proteins. We thus generated a quantitative affinity-based DIP/Dpr interactome for all DIP/Dpr protein family members. This revealed a broad range of affinities and identified homophilic binding for some DIPs and some Dprs. These data, along with full-length ectodomain DIP/Dpr and DIP/DIP crystal structures, led to the identification of molecular determinants of DIP/Dpr specificity. This structural knowledge, along with a comprehensive set of quantitative binding affinities, provides new tools for functional studies in vivo.
•Most neurons in the Drosophila medulla express a single DIP•Some DIPs and some Dprs form homodimers•Quantified binding affinities for all DIP/Dpr interactions•Full-ectodomain crystal structures of DIP/Dpr and DIP/DIP complexes
DIP/Dpr interactions help to pattern the Drosophila nervous system. Cosmanescu et al. quantify their interactions and map DIP expression in medulla neurons. Structural studies identify specificity determinants of DIP/Dpr interactions and reveal a conserved architecture for DIP/DIP homodimers.
Since the discovery of Helicobacter pylori(H. pylori) in 1983, numerous detection methods for the presence of the bacterium have been developed. Each one of them has been associated with advantages ...and disadvantages. Noninvasive tests such as serology, 13 C urea breath test(UBT) and stool antigen tests are usually preferred by the clinicians. Serology has its own limitation especially in endemic areas while 13 C UBT is technically very demanding. The stool antigen detection method, although specific, is usually associated with poor sensitivity. The 13 C UBT is believed to be specific, but with present revelation of the fact that stomach is colonized by many other urease producing bacteria makes it questionable. Histology, culture, rapid urease test and polymerase chain reaction(PCR) are the tests which are carried out on antral biopsies collected by invasive means. Histology has been proposed to be very sensitive and specific but the question is how by simply looking the morphology of the bacteria in the microscope, one can claim that the curved bacterium is exclusively H. pylori. Rapid urease test(RUT), the doctor’s test, is also challenged because the presence of other urease producing bacteria in the stomach cannot be denied. Moreover, RUT has been reported with poor sensitivity specially, when density of the bacterium is low. Isolation of H. pylori is essential to investigate its growth requirements, antibiotic susceptibility testing, studying virulence factor to develop vaccine and many more explorations. It has also got several disadvantages i.e., special condition for transporting, media, incubation and few days waiting for the colonies to appear, apart from the speed essentially needed to process the specimens. Till date, majority of the microbiological laboratories in the world are not equipped and trained to isolate such fastidious bacterium. The option left is PCR methods to detect H. pylori ’s DNA in gastric mucosa, gastric juice, saliva, dental plaques and environmental specimens. There are speculations for false positivity due to detection of non-pylori Helicobacters due to genetic sharing; and false negativity due to low bacterial counts and presence of PCR inhibitors. However, specimen collection, transportation and processing do not require speed and special conditions. PCR based diagnosis may be considered as gold standard by designing primers extremely specific to H. pylori and targeting at least more than one conserved genes. Similarly specificity of PCR may be improved by use of internal Primers. Further, nested PCR will take care of false negatives by countering the effect of PCR inhibitors and low bacterial counts. Therefore, nested PCR based methods if performed properly, may be proposed as gold standard test.
Introduction: Mortality due to sepsis is increasing in the PICUs of India. This study was conducted with the aim to investigate the prognostic value of lactate level at the time of admission and ...lactate clearance for mortality in sepsis and estimate its cut-off value of predicting mortality. This study also aimed to estimate the correlation between lactate clearance with PRISM III score (Pediatric Risk of Mortality score) and duration of stay. Materials and Methods: This was a prospective study on 150 patients admitted with severe inflammatory response syndrome with a probable infection in the paediatric intensive care unit with an estimation of serial lactate levels in the blood at 0-3 h, 24 h and 48 h of admission. Lactate clearance was calculated, and patients were followed up till discharge/death. Results: Out of 150 patients, there were 94 survivors and 56 non-survivors; the mean lactate clearance at 24 h was 6.16% in non-survivors, which was lower than survivors at 28.41%. The cut-off value of lactate clearance for predicting mortality was estimated to be 17.6%. PRISM III score and lactate clearance were inversely related. The duration of intensive care unit stay was more in non-survivors with low lactate clearance. Conclusion: Lactate clearance can be used as a prognostic measure for mortality in patients with sepsis and can be used as a guide for treatment.
The clinical significance of pyran and pyrimidine condensed systems and the raise in problem of multidrug resistant bacterial pathogens has directed us to synthesize pyranopyrimidine derivatives via ...the reactions of the versatile, 2-amino-4-(4-methoxyphenyl)-4
H-substitutedchromene-3-carbonitrile with the appropriate reagents. The newly synthesized compounds were characterized by IR,
1H NMR,
13C NMR, Mass spectra and Elemental analysis. The compounds were evaluated for their
in vitro antitubercular activity against
Mycobacterium tuberculosis H
37
Rv ATCC-27294 and antibacterial activity against
Staphylococcus aureus ATCC-25923 and
Streptococcus pyogenes MTCC-443 as Gram-positive,
Escherichia coli ATCC-25922 and
Pseudomonas aeruginosa MTCC-441 as Gram-negative bacterial strains and antifungal activity against
Aspergillus niger MTCC-282. Several derivatives exhibited pronounced antitubercular and antimicrobial activities.
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Clinical malaria is associated with the proliferation of Plasmodium parasites in human erythrocytes. The coordinated processes of parasite egress from and invasion into erythrocytes are rapid and ...tightly regulated. We have found that the plant-like calcium-dependent protein kinase PfCDPK5, which is expressed in invasive merozoite forms of Plasmodium falciparum, was critical for egress. Parasites deficient in PfCDPK5 arrested as mature schizonts with intact membranes, despite normal maturation of egress proteases and invasion ligands. Merozoites physically released from stalled schizonts were capable of invading new erythrocytes, separating the pathways of egress and invasion. The arrest was downstream of cyclic guanosine monophosphate-dependent protein kinase (PfPKG) function and independent of protease processing. Thus, PfCDPK5 plays an essential role during the blood stage of malaria replication.
Plasmodium knowlesi is a zoonotic parasite transmitted from macaques causing malaria in humans in Southeast Asia. Plasmodium parasites bind to red blood cell (RBC) surface receptors, many of which ...are sialylated. While macaques synthesize the sialic acid variant N-glycolylneuraminic acid (Neu5Gc), humans cannot because of a mutation in the enzyme CMAH that converts N-acetylneuraminic acid (Neu5Ac) to Neu5Gc. Here we reconstitute CMAH in human RBCs for the reintroduction of Neu5Gc, which results in enhancement of P. knowlesi invasion. We show that two P. knowlesi invasion ligands, PkDBPβ and PkDBPγ, bind specifically to Neu5Gc-containing receptors. A human-adapted P. knowlesi line invades human RBCs independently of Neu5Gc, with duplication of the sialic acid-independent invasion ligand, PkDBPα and loss of PkDBPγ. Our results suggest that absence of Neu5Gc on human RBCs limits P. knowlesi invasion, but that parasites may evolve to invade human RBCs through the use of sialic acid-independent pathways.
The recent stall in the global reduction of malaria deaths has made the development of a highly effective vaccine essential. A major challenge to developing an efficacious vaccine is the extensive ...diversity of Plasmodium falciparum antigens. While genetic diversity plays a major role in immune evasion and is a barrier to the development of both natural and vaccine-induced protective immunity, it has been under-prioritized in the evaluation of malaria vaccine candidates. This study uses genomic approaches to evaluate genetic diversity in next generation malaria vaccine candidate PfRh5. We used targeted deep amplicon sequencing to identify non-synonymous Single Nucleotide Polymorphisms (SNPs) in PfRh5 (Reticulocyte-Binding Protein Homologue 5) in 189 P. falciparum positive samples from Southern Senegal and identified 74 novel SNPs. We evaluated the population prevalence of these SNPs as well as the frequency in individual samples and found that only a single SNP, C203Y, was present at every site. Many SNPs were unique to the individual sampled, with over 90% of SNPs being found in just one infected individual. In addition to population prevalence, we assessed individual level SNP frequencies which revealed that some SNPs were dominant (frequency of greater than 25% in a polygenomic sample) whereas most were rare, present at 2% or less of total reads mapped to the reference at the given position. Structural modeling uncovered 3 novel SNPs occurring under epitopes bound by inhibitory monoclonal antibodies, potentially impacting immune evasion, while other SNPs were predicted to impact PfRh5 structure or interactions with the receptor or binding partners. Our data demonstrate that PfRh5 exhibits greater genetic diversity than previously described, with the caveat that most of the uncovered SNPs are at a low overall frequency in the individual and prevalence in the population. The structural studies reveal that novel SNPs could have functional implications on PfRh5 receptor binding, complex formation, or immune evasion, supporting continued efforts to validate PfRh5 as an effective malaria vaccine target and development of a PfRh5 vaccine.
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