Blood collections from organizations in north central Nigeria: a ten year review

Introduction: Voluntary blood donors in most developing sub Saharan countries are scarcely available with little or no safe donor retention strategies despite the rampant disease and man-made causes of anaemia frequently needing transfusion. The exploration of blood donor sourcing through effective collaboration with organised settings may create a break through.Aims: The study sought to determine the organisations and their contribution to blood collections at the blood service in North central Nigeria.Methods: The records of blood collections in organizations within the North Central Nigeria from 2007 to 2017 were studied. The records of the blood donation clinics and units of blood collected in the organizations were collated. Data was analysed using epi info 2010 version.Results: A total of 52,664 units were collected from volunteer donors at 756 blood donation clinics in three categories of organisations in North Central Nigeria from 2007 to 2017 with a ratio of 70 donations per clinic. 32,228 (61.20%) were from faith base organisations, 17,795 (33.79%) from educational institutions and 2,641 (5.01%) from work places. There were 478 (63.23%), 219 (28.97%) and 59 (7.80%) blood drive clinics with the mean donations rate of 67, 81 and 45 per clinics for the respective organisations.Conclusion: Organizations in North Central Nigeria have contributed to voluntary blood donation. Collaboration between organizations and the blood service could lead to the attainment of national blood security.Keywords: Organizations, North Central Nigeria, Blood, Collectio

Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis

AbstractEbola virus (EBOV) is an enveloped negative-sense RNA virus that causes sporadic outbreaks with high case fatality rates. Ebola viral protein 30 (eVP30) plays a critical role in EBOV transcription initiation at the nucleoprotein (eNP) gene, with additional roles in the replication cycle such as viral assembly. However, the mechanistic basis for how eVP30 functions during the virus replication cycle is currently unclear. Here we define a key interaction between eVP30 and a peptide derived from eNP that is important to facilitate interactions leading to the recognition of the RNA template. We present crystal structures of the eVP30 C-terminus in complex with this eNP peptide. Functional analyses of the eVP30–eNP interface identify residues that are critical for viral RNA synthesis. Altogether, these results support a model where the eVP30–eNP interaction plays a critical role in transcription initiation and provides a novel target for the development of antiviral therapy.</jats:p

VP24-Karyopherin alpha binding affinities differ between Ebolavirus species, nfluencing interferon inhibition and VP24 stability

Zaire ebolavirus (EBOV), Bundibugyo ebolavirus (BDBV), and Reston ebolavirus (RESTV) belong to the same genus but exhibit different virulence properties. VP24 protein, a structural protein present in all family members, blocks interferon (IFN) signaling and likely contributes to virulence. Inhibition of IFN signaling by EBOV VP24 (eVP24) involves its interaction with the NPI-1 subfamily of karyopherin alpha (KPNA) nuclear transporters. Here, we evaluated eVP24, BDBV VP24 (bVP24), and RESTV VP24 (rVP24) interactions with three NPI-1 subfamily KPNAs (KPNA1, KPNA5, and KPNA6). Using purified proteins, we demonstrated that each VP24 binds to each of the three NPI-1 KPNAs. bVP24, however, exhibited approximately 10-fold-lower KPNA binding affinity than either eVP24 or rVP24. Cell-based assays also indicate that bVP24 exhibits decreased KPNA interaction, decreased suppression of IFN induced gene expression, and a decreased half-life in transfected cells compared to eVP24 or rVP24. Amino acid sequence alignments between bVP24 and eVP24 also identified residues within and surrounding the previously defined eVP24-KPNA5 binding interface that decrease eVP24-KPNA affinity or bVP24-KPNA affinity. VP24 mutations that lead to reduced KPNA binding affinity also decrease IFN inhibition and shorten VP24 half-lives. These data identify novel functional differences in VP24-KPNA interaction and reveal a novel impact of the VP24-KPNA interaction on VP24 stability. IMPORTANCE The interaction of Ebola virus (EBOV) VP24 protein with host karyopherin alpha (KPNA) proteins blocks type I interferon (IFN) signaling, which is a central component of the host innate immune response to viral infection. Here, we quantitatively compared the interactions of VP24 proteins from EBOV and two members of the Ebolavirus genus, Bundibugyo virus (BDBV) and Reston virus (RESTV). The data reveal lower binding affinity of the BDBV VP24 (bVP24) for KPNAs and demonstrate that the interaction with KPNA modulates inhibition of IFN signaling and VP24 stability. The effect of KPNA interaction on VP24 stability is a novel functional consequence of this virus-host interaction, and the differences identified between viral species may contribute to differences in pathogenesis

Ebola virus VP35 interaction with dynein LC8 regulates viral RNA synthesis

Ebola virus VP35 inhibits alpha/beta interferon production and functions as a viral polymerase cofactor. Previously, the 8-kDa cytoplasmic dynein light chain (LC8) was demonstrated to interact with VP35, but the functional consequences were unclear. Here we demonstrate that the interaction is direct and of high affinity and that binding stabilizes the VP35 N-terminal oligomerization domain and enhances viral RNA synthesis. Mutational analysis demonstrates that VP35 interaction is required for the functional effects of LC8

A 5S Lean Strategy for a Sustainable Welding Process

[EN] The correct performance of the welding processes used to join metal parts or structural elements is considered to be of vital importance to guarantee the reliability of these products during their useful lives. Adequate workstation design ensures a safe environment in which an operator can perform these processes correctly. In order to guarantee the quality of welding seams, which are used to join metal parts and structural elements, a series of standards have been developed; these standards establish requirements to guarantee the correct performance of welding processes, and the inspection of the metal welds obtained. The 5S methodology has proven to be a valid tool for improving workplaces in industrial and service activities; it is a capstone methodology when companies implement lean production approaches. This work presents a framework for applying the 5S methodology in metal welding workplaces. It defines an index to evaluate the degree of implementation of the 5S methodology, and the application of the important performance analysis methodology (IPA). Fuzzy logic is used to treat the uncertainty in evaluating the different evaluation indicators proposed. This framework is applied to a real practical case, to provide an example of its use in establishing good manufacturing practices that guarantee compliance with the requirements of welding standards, and guaranteeing the correct handling and storage of the materials and tools used in welding processes for the manufacture of welded parts and structural elements.This research was funded by the Annual Grants Call of the International Doctorate School of the Spanish National Distance-Learning University (EIDUNED).Manzanares-Cañizares, C.; Sánchez-Lite, A.; Rosales-Prieto, VF.; Fuentes Bargues, JL.; González-Gaya, C. (2022). A 5S Lean Strategy for a Sustainable Welding Process. Sustainability. 14(11):1-17. https://doi.org/10.3390/su14116499117141

Three-dimensional quantitative evaluation method of nonrigid registration algorithms for adaptive radiotherapy

Purpose: Current radiotherapy is progressing to the concept of adaptive radiotherapy, which implies the adaptation of planning along the treatment course. Nonrigid registration is an essential image processing tool for adaptive radiotherapy and image guided radiotherapy, and the three-dimensional (3D) nature of the current radiotherapy techniques requires a 3D quantification of the registration error that existing evaluation methods do not cover appropriately. The authors present a method for 3D evaluation of nonrigid registration algorithms’ performance, based on organ delineations, capable of working with near-spherical volumes even in the presence of concavities. Methods: The evaluation method is composed by a volume shape description stage, developed using a new ad hoc volume reconstruction algorithm proposed by the authors, and an error quantification stage. The evaluation method is applied to the organ delineations of prostate and seminal vesicles, obtained by an automatic segmentation method over images of prostate cancer patients treated with intensity modulated radiation therapy. Results: The volume reconstruction algorithm proposed has been shown to accurately model complex 3D surfaces by the definition of clusters of control points. The quantification method, inspired by the Haussdorf–Chebysev distance, provides a measure of the largest registration error per control direction, defining a valid metric for concave-convex volumes. Summarizing, the proposed evaluation methodology presents accurate results with a high spatial resolution in a negligible computation time in comparison with the nonrigid registration time. Conclusions: Experimental results show that the metric selected for quantifying the registration error is of utmost importance in a quantitative evaluation based on measuring distances between volumes. The accuracy of the volume reconstruction algorithm is not so relevant as long as the reconstruction is tight enough on the actual volume of the organ. The new evaluation method provides a smooth and accurate volume reconstruction for both the reference and the registered organ, and a complete 3D description of nonrigid registration algorithms’ performance, resulting in a useful tool for study and comparison of registration algorithms for adaptive radiotherapy

An upstream open reading frame modulates ebola virus polymerase translation and virus replication

Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5' and 3' untranslated regions (UTRs) present in the seven viral transcriptional units. To date, specific functions have not been assigned to these UTRs. With reporter assays, we demonstrated that the Zaire ebolavirus (EBOV) 5'-UTRs lack internal ribosomal entry site function. However, the 5'-UTRs do differentially regulate cap-dependent translation when placed upstream of a GFP reporter gene. Most dramatically, the 5'-UTR derived from the viral polymerase (L) mRNA strongly suppressed translation of GFP compared to a β-actin 5'-UTR. The L 5'-UTR is one of four viral genes to possess upstream AUGs (uAUGs), and ablation of each uAUG enhanced translation of the primary ORF (pORF), most dramatically in the case of the L 5'-UTR. The L uAUG was sufficient to initiate translation, is surrounded by a "weak" Kozak sequence and suppressed pORF translation in a position-dependent manner. Under conditions where eIF2α was phosphorylated, the presence of the uORF maintained translation of the L pORF, indicating that the uORF modulates L translation in response to cellular stress. To directly address the role of the L uAUG in virus replication, a recombinant EBOV was generated in which the L uAUG was mutated to UCG. Strikingly, mutating two nucleotides outside of previously-defined protein coding and cis-acting regulatory sequences attenuated virus growth to titers 10-100-fold lower than a wild-type virus in Vero and A549 cells. The mutant virus also exhibited decreased viral RNA synthesis as early as 6 hours post-infection and enhanced sensitivity to the stress inducer thapsigargin. Cumulatively, these data identify novel mechanisms by which EBOV regulates its polymerase expression, demonstrate their relevance to virus replication and identify a potential therapeutic target

Mutual Antagonism between the Ebola Virus VP35 Protein and the RIG-I Activator PACT Determines Infection Outcome

SummaryThe cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and induces type I IFN responses to control viral replication. The cellular dsRNA binding protein PACT can also activate RIG-I. To counteract innate antiviral responses, some viruses, including Ebola virus (EBOV), encode proteins that antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT. In addition, PACT-VP35 interaction impairs the association between VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and modulating EBOV replication. PACT-deficient cells are defective in IFN induction and are insensitive to VP35 function. These data support a model in which the VP35-PACT interaction is mutually antagonistic and plays a fundamental role in determining the outcome of EBOV infection