Some genetic characteristics of sabin-like poliovirus isolated from acute flaccid paralysis cases in Nigeria

A total of 34 sabin strains of the poliovirus isolated from 22 children with 60-day follow-up residual acute flaccid paralysis (AFP) were genetically characterized and screened for any form of recombination. Sequence analysis of the 906-nucleotide capsid showed that all the isolates were similar to their original sabin serotypes, however two of the viruses had drifted in their 3D noncapsid regions toward a sabin-sabin and sabin-nonpolio entero combination. Routine immunization in Nigeria is low and in spite of the increase in the frequency of supplemental immunizations, a lot of children are still inadequately immunized, which may be the reason for our observation in this study. Although we are not dealing with a case of circulating vaccine derived poliovirus (cVDPV) yet, if the above condition persists, the advent of cVDVP may not be too far. There is therefore the need to maintain a high quality mass immunization and sustained routine immunization. Key words: Poliovirus, sequence, crossover, non polio enterovirus, recombination, genome, Sabin-like, vaccine, Nigeria. African Journal of Biotechnology Vol.2(11) 2003: 460-46

A search-based geographic metadata curation pipeline to refine sequencing institution information and support public health

BackgroundThe National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) has amassed a vast reservoir of genetic data since its inception in 2007. These public data hold immense potential for supporting pathogen surveillance and control. However, the lack of standardized metadata and inconsistent submission practices in SRA may impede the data’s utility in public health.MethodsTo address this issue, we introduce the Search-based Geographic Metadata Curation (SGMC) pipeline. SGMC utilized Python and web scraping to extract geographic data of sequencing institutions from NCBI SRA in the Cloud and its website. It then harnessed ChatGPT to refine the sequencing institution and location assignments. To illustrate the pipeline’s utility, we examined the geographic distribution of the sequencing institutions and their countries relevant to polio eradication and categorized them.ResultsSGMC successfully identified 7,649 sequencing institutions and their global locations from a random selection of 2,321,044 SRA accessions. These institutions were distributed across 97 countries, with strong representation in the United States, the United Kingdom and China. However, there was a lack of data from African, Central Asian, and Central American countries, indicating potential disparities in sequencing capabilities. Comparison with manually curated data for U.S. institutions reveals SGMC’s accuracy rates of 94.8% for institutions, 93.1% for countries, and 74.5% for geographic coordinates.ConclusionSGMC may represent a novel approach using a generative AI model to enhance geographic data (country and institution assignments) for large numbers of samples within SRA datasets. This information can be utilized to bolster public health endeavors

Phylogeny of imported and reestablished wild polioviruses in the Democratic Republic of the Congo from 2006 to 2011

BACKGROUND : The last case of polio associated with wild poliovirus (WPV) indigenous to the Democratic Republic of the Congo (DRC) was reported in 2001, marking a major milestone toward polio eradication in Africa. However, during 2006-2011, outbreaks associated with WPV type 1 (WPV1) were widespread in the DRC, with >250 reported cases. METHODS : WPV1 isolates obtained from patients with acute flaccid paralysis (AFP) were compared by nucleotide sequencing of the VP1 capsid region (906 nucleotides). VP1 sequence relationships among isolates from the DRC and other countries were visualized in phylogenetic trees, and isolates representing distinct lineage groups were mapped. RESULTS : Phylogenetic analysis indicated that WPV1 was imported twice in 2004-2005 and once in approximately 2006 from Uttar Pradesh, India (a major reservoir of endemicity for WPV1 and WPV3 until 2010-2011), into Angola. WPV1 from the first importation spread to the DRC in 2006, sparking a series of outbreaks that continued into 2011. WPV1 from the second importation was widely disseminated in the DRC and spread to the Congo in 2010-2011. VP1 sequence relationships revealed frequent transmission of WPV1 across the borders of Angola, the DRC, and the Congo. Long branches on the phylogenetic tree signaled prolonged gaps in AFP surveillance and a likely underreporting of polio cases. CONCLUSIONS : The reestablishment of widespread and protracted WPV1 transmission in the DRC and Angola following long-range importations highlights the continuing risks of WPV spread until global eradication is achieved, and it further underscores the need for all countries to maintain high levels of poliovirus vaccine coverage and sensitive surveillance to protect their polio-free status.Centers for Disease Control and Preventionhttp://jid.oxfordjournals.org2015-11-30hb201

Endothelial Domes Encapsulate Adherent Neutrophils and Minimize Increases in Vascular Permeability in Paracellular and Transcellular Emigration

Local edema, a cardinal sign of inflammation associates closely with neutrophil emigration. Neutrophil emigration has been described to occur primarily through endothelial junctions (paracellular) and more rarely directly through endothelial cells (transcellular). Recently, we reported that unlike in wild-type (wt) mice, Mac-1-/- (CD11b) neutrophils predominantly emigrated transcellularly and was significantly delayed taking 20–30 min longer than the paracellular emigration (wt). In the present study we noted significant anatomical disruption of the endothelium and hypothesized that transcellular emigration would greatly increase vascular permeability. Surprisingly, despite profound disruption of the endothelial barrier as the neutrophils moved through the cells, the changes in vascular permeability during transcellular emigration (Mac-1-/-) were not increased more than in wt mice. Instead increased vascular permeability completely tracked the number of emigrated cells and as such, permeability changes were delayed in Mac-1-/- mice. However, by 60 min neutrophils from both sets of mice were emigrating in large numbers. Electron-microscopy and spinning disk multichannel fluorescence confocal microscopy revealed endothelial docking structures that progressed to dome-like structures completely covering wt and Mac-1-/- neutrophils. These domes completely enveloped the emigrating neutrophils in both wt and Mac-1-/- mice making the mode of emigration underneath these structures extraneous to barrier function. In conclusion, predominantly paracellular versus predominantly transcellular emigration does not affect vascular barrier integrity as endothelial dome-like structures retain barrier function

An Analysis of the Abstracts Presented at the Annual Meetings of the Society for Neuroscience from 2001 to 2006

Annual meeting abstracts published by scientific societies often contain rich arrays of information that can be computationally mined and distilled to elucidate the state and dynamics of the subject field. We extracted and processed abstract data from the Society for Neuroscience (SFN) annual meeting abstracts during the period 2001–2006 in order to gain an objective view of contemporary neuroscience. An important first step in the process was the application of data cleaning and disambiguation methods to construct a unified database, since the data were too noisy to be of full utility in the raw form initially available. Using natural language processing, text mining, and other data analysis techniques, we then examined the demographics and structure of the scientific collaboration network, the dynamics of the field over time, major research trends, and the structure of the sources of research funding. Some interesting findings include a high geographical concentration of neuroscience research in the north eastern United States, a surprisingly large transient population (66% of the authors appear in only one out of the six studied years), the central role played by the study of neurodegenerative disorders in the neuroscience community, and an apparent growth of behavioral/systems neuroscience with a corresponding shrinkage of cellular/molecular neuroscience over the six year period. The results from this work will prove useful for scientists, policy makers, and funding agencies seeking to gain a complete and unbiased picture of the community structure and body of knowledge encapsulated by a specific scientific domain

The Brain Atlas Concordance Problem: Quantitative Comparison of Anatomical Parcellations

Many neuroscientific reports reference discrete macro-anatomical regions of the brain which were delineated according to a brain atlas or parcellation protocol. Currently, however, no widely accepted standards exist for partitioning the cortex and subcortical structures, or for assigning labels to the resulting regions, and many procedures are being actively used. Previous attempts to reconcile neuroanatomical nomenclatures have been largely qualitative, focusing on the development of thesauri or simple semantic mappings between terms. Here we take a fundamentally different approach, discounting the names of regions and instead comparing their definitions as spatial entities in an effort to provide more precise quantitative mappings between anatomical entities as defined by different atlases. We develop an analytical framework for studying this brain atlas concordance problem, and apply these methods in a comparison of eight diverse labeling methods used by the neuroimaging community. These analyses result in conditional probabilities that enable mapping between regions across atlases, which also form the input to graph-based methods for extracting higher-order relationships between sets of regions and to procedures for assessing the global similarity between different parcellations of the same brain. At a global scale, the overall results demonstrate a considerable lack of concordance between available parcellation schemes, falling within chance levels for some atlas pairs. At a finer level, this study reveals spatial relationships between sets of defined regions that are not obviously apparent; these are of high potential interest to researchers faced with the challenge of comparing results that were based on these different anatomical models, particularly when coordinate-based data are not available. The complexity of the spatial overlap patterns revealed points to problems for attempts to reconcile anatomical parcellations and nomenclatures using strictly qualitative and/or categorical methods. Detailed results from this study are made available via an interactive web site at http://obart.info

Nuclear Translocation of β-Catenin during Mesenchymal Stem Cells Differentiation into Hepatocytes Is Associated with a Tumoral Phenotype

Wnt/β-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of this pathway has been associated with tumors as hepatocellular carcinoma or hepatoblastoma. The present study evaluated the role of Wnt/β-catenin activation during human mesenchymal stem cells differentiation into hepatocytes. The differentiation to hepatocytes was achieved by the addition of two different conditioned media. In one of them, β-catenin nuclear translocation, up-regulation of genes related to the Wnt/β-catenin pathway, such as Lrp5 and Fzd3, as well as the oncogenes c-myc and p53 were observed. While in the other protocol there was a Wnt/β-catenin inactivation. Hepatocytes with nuclear translocation of β-catenin also had abnormal cellular proliferation, and expressed membrane proteins involved in hepatocellular carcinoma, metastatic behavior and cancer stem cells. Further, these cells had also increased auto-renewal capability as shown in spheroids formation assay. Comparison of both differentiation protocols by 2D-DIGE proteomic analysis revealed differential expression of 11 proteins with altered expression in hepatocellular carcinoma. Cathepsin B and D, adenine phosphoribosyltransferase, triosephosphate isomerase, inorganic pyrophosphatase, peptidyl-prolyl cis-trans isomerase A or lactate dehydrogenase β-chain were up-regulated only with the protocol associated with Wnt signaling activation while other proteins involved in tumor suppression, such as transgelin or tropomyosin β-chain were down-regulated in this protocol. In conclusion, our results suggest that activation of the Wnt/β-catenin pathway during human mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype

Outbreak of Type 2 Vaccine-Derived Poliovirus in Nigeria: Emergence and Widespread Circulation in an Underimmunized Population

Wild poliovirus has remained endemic in northern Nigeria because of low coverage achieved in the routine immunization program and in supplementary immunization activities (SIAs). An outbreak of infection involving 315 cases of type 2 circulating vaccine-derived poliovirus (cVDPV2; >1% divergent from Sabin 2) occurred during July 2005–June 2010, a period when 23 of 34 SIAs used monovalent or bivalent oral poliovirus vaccine (OPV) lacking Sabin 2. In addition, 21 “pre-VDPV2” (0.5%–1.0% divergent) cases occurred during this period. Both cVDPV and pre-VDPV cases were clinically indistinguishable from cases due to wild poliovirus. The monthly incidence of cases increased sharply in early 2009, as more children aged without trivalent OPV SIAs. Cumulative state incidence of pre-VDPV2/cVDPV2 was correlated with low childhood immunization against poliovirus type 2 assessed by various means. Strengthened routine immunization programs in countries with suboptimal coverage and balanced use of OPV formulations in SIAs are necessary to minimize risks of VDPV emergence and circulation

Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry

Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72%) cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4) and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed