Rapid microsphere‐assisted peptide screening (MAPS) of promiscuous MHCII‐binding peptides in Zika virus envelope protein

Despite promising developments in computational tools, peptide‐class II MHC (MHCII) binding predictors continue to lag behind their peptide‐class I MHC counterparts. Consequently, peptide–MHCII binding is often evaluated experimentally using competitive binding assays, which tend to sacrifice throughput for quantitative binding detail. Here, we developed a high‐throughput semiquantitative peptide–MHCII screening strategy termed microsphere‐assisted peptide screening (MAPS) that aims to balance the accuracy of competitive binding assays with the throughput of computational tools. Using MAPS, we screened a peptide library from Zika virus envelope (E) protein for binding to four common MHCII alleles (DR1, DR4, DR7, DR15). Interestingly, MAPS revealed a significant overlap between peptides that promiscuously bind multiple MHCII alleles and antibody neutralization sites. This overlap was also observed for rotavirus outer capsid glycoprotein VP7, suggesting a deeper relationship between B cell and CD4+ T cell specificity which can facilitate the design of broadly protective vaccines to Zika and other viruses.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154342/1/aic16697.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154342/2/aic16697_am.pd

Optimized machine learning model for air quality index prediction in major cities in India

Industrial advancements and utilization of large amount of fossil fuels, vehicle pollution, and other calamities increases the Air Quality Index (AQI) of major cities in a drastic manner. Major cities AQI analysis is essential so that the government can take proper preventive, proactive measures to reduce air pollution. This research incorporates artificial intelligence in AQI prediction based on air pollution data. An optimized machine learning model which combines Grey Wolf Optimization (GWO) with the Decision Tree (DT) algorithm for accurate prediction of AQI in major cities of India. Air quality data available in the Kaggle repository is used for experimentation, and major cities like Delhi, Hyderabad, Kolkata, Bangalore, Visakhapatnam, and Chennai are considered for analysis. The proposed model performance is experimentally verified through metrics like R-Square, RMSE, MSE, MAE, and accuracy. Existing machine learning models, like k-nearest Neighbor, Random Forest regressor, and Support vector regressor, are compared with the proposed model. The proposed model attains better prediction performance compared to traditional machine learning algorithms with maximum accuracy of 88.98% for New Delhi city, 91.49% for Bangalore city, 94.48% for Kolkata, 97.66% for Hyderabad, 95.22% for Chennai and 97.68% for Visakhapatnam city

Use of endovascular embolization to treat a ruptured arteriovenous malformation in a pregnant woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pregnancy has been linked to increased rates of arteriovenous malformation rupture. This link remains a matter of debate and very few studies have addressed the management of arteriovenous malformation in pregnancy. Unruptured arteriovenous malformations in pregnant woman generally warrant conservative management due to the low rupture risk. When pregnant women present with ruptured arteriovenous malformation, however, surgery is often indicated due to the increased risk of re-rupture and associated mortality. Endovascular embolization is widely accepted as an important component of contemporary, multimodal therapy for arteriovenous malformations. Although rarely curative, embolization can facilitate subsequent surgical resection or radiosurgery. No previous reports have been devoted to the endovascular management of an arteriovenous malformation in a pregnant woman.</p> <p>Case presentation</p> <p>A 23-year-old Caucasian woman presented with headache and visual disturbance after the rupture of a left parieto-occipital arteriovenous malformation in the 22nd week of her pregnancy. After involving high-risk obstetric consultants and taking precautions to shield the fetus from ionizing radiation, we proceeded with a single stage of endovascular embolization followed soon after by open surgical resection of the arteriovenous malformation. There were several goals for the angiography in this patient: to better understand the anatomy of the arteriovenous malformation, including the number and orientation of feeding arteries and draining veins; to look for associated pre-nidal or intra-nidal aneurysms; and to partially embolize the arteriovenous malformation via safely-accessible feeders to facilitate surgical resection and minimize blood loss and operative morbidity.</p> <p>Conclusion</p> <p>From our experience and review of the literature, we maintain that ruptured arteriovenous malformations in pregnancy may be managed in a similar manner to those in non-gravid women. Precautions should be taken to reduce the operative time and exposure of the fetus to ionizing radiation and contrast agents.</p

Bactericidal activity of biosynthesized silver nanoparticles against human pathogenic bacteria

Green synthesis is an attractive and eco-friendly approach to generate potent antibacterial silver nanoparticles (Ag-NPs). Such particles have long been used to fight bacteria and represent a promising tool to overcome the emergence of antibiotic-resistant bacteria. In this study, green synthesis of Ag-NPs was attempted using plant extracts of Aloe vera, Portulaca oleracea and Cynodon dactylon. The identity and size of Ag-NPs was characterized by ultraviolet–visible spectrophotometer and scanning electron microscopy. Monodispersed Ag-NPs were produced with a range of different sizes based on the plant extract used. The bactericidal activity of Ag-NPs against a number of human pathogenic bacteria was determined using the disc diffusion method. The results showed that Gram positive bacteria were more susceptible than Gram negative ones to these antibacterial agents. The minimum inhibitory concentration was determined using the 96-well plate method. Finally, the mechanism by which Ag-NPs affect bacteria was investigated by SEM analysis. Bacteria treated with Ag-NPs were seen to undergo shrinkage and to lose their viability. This study provides evidence for a cheap and effective method for synthesizing potent bactericidal Ag-NPs and demonstrates their effectiveness against human pathogenic bacteria

Burden of typhoid and paratyphoid fever in India.

BACKGROUND: In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection. METHODS: From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community. RESULTS: A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. Salmonella enterica serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age. CONCLUSIONS: The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.)

Anchor Side Chains of Short Peptide Fragments Trigger Ligand-Exchange of Class II MHC Molecules

Class II MHC molecules display peptides on the cell surface for the surveillance by CD4+ T cells. To ensure that these ligands accurately reflect the content of the intracellular MHC loading compartment, a complex processing pathway has evolved that delivers only stable peptide/MHC complexes to the surface. As additional safeguard, MHC molecules quickly acquire a ‘non-receptive’ state once they have lost their ligand. Here we show now that amino acid side chains of short peptides can bypass these safety mechanisms by triggering the reversible ligand-exchange. The catalytic activity of dipeptides such as Tyr-Arg was stereo-specific and could be enhanced by modifications addressing the conserved H-bond network near the P1 pocket of the MHC molecule. It affected both antigen-loading and ligand-release and strictly correlated with reported anchor preferences of P1, the specific target site for the catalytic side chain of the dipeptide. The effect was evident also in CD4+ T cell assays, where the allele-selective influence of the dipeptides translated into increased sensitivities of the antigen-specific immune response. Molecular dynamic calculations support the hypothesis that occupation of P1 prevents the ‘closure’ of the empty peptide binding site into the non-receptive state. During antigen-processing and -presentation P1 may therefore function as important “sensor” for peptide-load. While it regulates maturation and trafficking of the complex, on the cell surface, short protein fragments present in blood or lymph could utilize this mechanism to alter the ligand composition on antigen presenting cells in a catalytic way

Mutations in SLC25A22: hyperprolinaemia, vacuolated fibroblasts and presentation with developmental delay

Mutations in SLC25A22 are known to cause neonatal epileptic encephalopathy and migrating partial seizures in infancy. Using whole exome sequencing we identified four novel SLC25A22 mutations in six children from three families. Five patients presented clinical features similar to those in the literature including hypotonia, refractory neonatal‐onset seizures and developmental delay. However, the sixth patients presented atypically with isolated developmental delay, developing late‐onset (absence) seizures only at 7 years of age. Abnormal metabolite levels have not been documented in the nine patients described previously. One patient in our series was referred to the metabolic clinic because of persistent hyperprolinaemia and another three had raised plasma proline when tested. Analysis of the post‐prandial plasma amino acid response in one patient showed abnormally high concentrations of several amino acids. This suggested that, in the fed state, when amino acids are the preferred fuel for the liver, trans‐deamination of amino acids requires transportation of glutamate into liver mitochondria by SLC25A22 for deamination by glutamate dehydrogenase; SLC25A22 is an important mitochondrial glutamate transporter in liver as well as in brain. Electron microscopy of patient fibroblasts demonstrated widespread vacuolation containing neutral and phospho‐lipids as demonstrated by Oil Red O and Sudan Black tinctorial staining; this might be explained by impaired activity of the proline/pyrroline‐5‐carboxylate (P5C) shuttle if SLC25A22 transports pyrroline‐5‐carboxylate/glutamate‐γ‐semialdehyde as well as glutamate

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field