Flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV) are spread by mosquitoes and cause human disease and mortality in tropical areas. In contrast, Powassan virus ...(POWV), which causes severe neurologic illness, is a flavivirus transmitted by ticks in temperate regions of the Northern hemisphere. We find serologic neutralizing activity against POWV in individuals living in Mexico and Brazil. Monoclonal antibodies P002 and P003, which were derived from a resident of Mexico (where POWV is not reported), neutralize POWV lineage I by recognizing an epitope on the virus envelope domain III (EDIII) that is shared with a broad range of tick- and mosquito-borne flaviviruses. Our findings raise the possibility that POWV, or a flavivirus closely related to it, infects humans in the tropics.
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•Sera from Mexico and Brazil neutralize POWV and TBEV, which are not known to circulate there•Monoclonal antibody P014 binds to POWV but not to endemic flaviviruses•Monoclonal antibodies P002 and P003 neutralize POWV lineage I•The P003 epitope is shared across 13 flaviviruses from tick and mosquito serocomplexes
Cervantes Rincón et al. describe antibody neutralizing activity against Powassan virus from regions of the Americas where this flavivirus transmitted by ticks is not known to circulate. Two monoclonal antibodies to the EDIII (P002 and P003) are broadly cross-reactive against tick- and mosquito-borne flaviviruses.
Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but ...little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI-EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.
Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or ...prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement (ADE) in vitro and extend their half-lives. Here we report on prophylactic coadministration of the Fc-modified antibodies to pregnant rhesus macaques challenged three times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission, protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV.
Lyme disease (LD) affects ∼476,000 people each year in the United States. Symptoms are variable and include rash and flu-like symptoms. Reasons for the wide variation in disease outcomes are unknown. ...Powassan virus (POWV) is a tick-borne flavivirus that causes disease ranging from asymptomatic infection to encephalitis, neurologic damage, and death. POWV and LD geographic case distributions overlap, with
species ticks as the common vectors. Clinical ramifications of coinfection or sequential infection are unknown.
This study's primary objective was to determine the prevalence of POWV-reactive antibodies in sera samples collected from previously studied cohorts of individuals with self-reported LD history residing in the Northeastern United States. As a secondary objective, we studied clinical differences between people with self-reported LD history and low versus high POWV antibody levels.
We used an enzyme-linked immunosorbent assay (ELISA) to quantify IgG directed at the POWV envelope (E) protein domain III in 538 samples from individuals with self-reported LD history and 16 community controls. The samples were also tested with an ELISA assay to quantify IgG directed at the POWV NS1 protein.
The percentage of individuals with LD history and possible evidence of POWV exposure varied depending on the assay utilized. We found no significant difference in clinical symptoms between those with low or high POWV IgG levels in the in-house assay. Congruence of the EDIII and NS1 assays was low with only 12% of those positive in the in-house EDIII ELISA testing positive in the POWV NS1 ELISA.
The results highlight the difficulty in flavivirus diagnostic testing, particularly in the retrospective detection of flavivirus exposure. The findings suggest that a prospective study with symptomatic patients using approved clinical testing is necessary to address the incidence and clinical implications of LD and POWV co-infection or sequential infection.
The adoption of smart devices, smartphones and IOT (Internet of things) devices, has witnessed a tremendous growth because of the convenience that they bring to users. However, at the same time, it ...makes them the target of malware developers and security attacks. Therefore, in this work, we propose a machine learning based methodology to detect malicious activities in wireless devices using power consumption footprints. The methodology consists of two main steps. First, a set of effective features are extracted from power measurements using both frequency spectral estimation and principal component analysis. Second, malware detection is formulated as a binary classification problem. Three different classifier algorithms are evaluated: support vector machines (SVM), naive Bayes (NB), and decision trees (DT). The SVM classifier shows better performance in terms of classification accuracy. Six different malicious behaviours are considered in the evaluation of the methodology process. The proposed methodology has successfully detected hard to spot malicious behaviours with (96-99)% accuracy.
Pattern analysis often requires a pre-processing stage for extracting or selecting features in order to help the classification, prediction, or clustering stage discriminate or represent the data in ...a better way. The reason for this requirement is that the raw data are complex and difficult to process without extracting or selecting appropriate features beforehand. This paper reviews theory and motivation of different common methods of feature selection and extraction and introduces some of their applications. Some numerical implementations are also shown for these methods. Finally, the methods in feature selection and extraction are compared.
Wild pomegranate is a high-value crop for pharmaceutical industries. The lack of genetic and genomic resources in this medicinally important plant requires the development of simple sequence repeat ...(SSR) markers necessary for breeding programmes. In the present study, genomic sequences obtained using the Illumina platform revealed the presence of 8,000 sequences having genomic simple sequence repeats (gSSRs), with dinucleotide repeats being the most abundant (50.96%). A total of 103 marker pairs were randomly designed for the validation of 45 wild pomegranate accessions for diversity analysis. The amplicon size of developed gSSRs ranged between 141 and 297 base pairs. From a total of 57 polymorphic primers, 21 SSR pairs revealed 100% polymorphism. The existence of high genetic diversity (average Na-0.506,
He
-0.395,
Ho
-0.246) indicated the presence of heterozygotes in the wild pomegranate population. The polymorphism information content value ranged from 0.01 to 0.53, with the Shannon index values being between 0.09 and 1.60. Further, the genetic dissimilarity value ranged from 0.05 to 0.45, which grouped the wild pomegranate accessions into three clusters with two out-groups through a neighbour-joining analysis. The analysis of molecular variance indicated 25 and 75% of the total variation between and within the accessions, and population genetic structure research grouped the wild pomegranate accessions into four populations, which were partly bolstered by a principal component analysis and a neighbour-joining tree. Cross-species amplification demonstrated that out of 57 SSRs, 26 SSR loci had the transferability rate in cultivated pomegranate cultivars
Ganesh
and
Dholka
and 18 in
Kandhari
and
Bedana
, whereas the transferability rate was between 13.46 and 26.92% for plants from other families. Unique alleles were observed for both cultivated pomegranates and three cross-species tested in the present investigation. This is the first report where developed genomic SSRs would contribute to the genomic resources that will provide the basis for breeding-aided programmes for wild pomegranates.
Background: World Health Organization (WHO) suggests using symptom- based screening tools to improve early detection of tuberculosis (TB). The WHO recommended 4-symptom screening (W4SS) is one such ...tool. Although, found to be effective in screening TB among HIV patients, its implementation among general patients have not been well-studied. Objectives: To assess the predictive value of W4SS in TB screening among outpatients and inpatients in North India. Methodology: A prospective cohort study starting July 1, 2023 included patients in the outdoor or indoor of any department (except Chest TB). Patients were screened with W4SS (cough > 2 weeks, fever > 2 weeks, significant weight loss, night sweats). A presumptive TB case (presence of any one symptom), was further examined by the Chest TB consultant, completing the diagnostic algorithm as per National Tuberculosis Elimination Program guidelines for final diagnosis. Data were collected using a semi-structured study proforma and analysed using JAMOVI version 2.0, an open-source software for statistical analysis. Results: During 5 months of data collection, 8609 patients were screened for TB using the W4SS. Of these, 201 (2.3%) were W4SS positive, and of W4SS positive, 25 had confirmed diagnosis of TB. The positive predictive value of W4SS was 12.4% (95% confidence interval 10.9% to 14.1%). Among W4SS positive patients, being unmarried (p value < 0.05), uneducated (p value < 0.05), family history of TB (p value < 0.01), fever (p value < 0.01), significant weight loss (p value < 0.01) and night sweats (p value < 0.01) were significantly associated with final diagnosis of TB. Age, gender, employment and presence of cough were not significantly associated with confirmed diagnosis of TB among W4SS positive patients. Conclusion: W4SS in its present form has limited usability in screening general patients for TB. A multi-centric study is required to improve the scale.
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