Investigating the Modulation of Aggregating Amyloid Beta 40

Amyloid beta protein has been linked to the formation of Alzheimer’s disease in patients.¹ Plaques form from amyloid beta fibrils. The formation of these plaques between neural connections in the brain are associated with Alzheimer’s disease.² The reduction of the formation of fibrils can be linked to utilizing protein mimics. The protocols that are used to reproduce the simulation of amyloid beta in the brain can be very important. Also, the structure of the protein mimic that is being used to inhibit the formation of fibrils can determine how the amyloid beta plaques are reduced. The structure of sequence KLLFFLFFLLK peptoid was synthesized to test with amyloid beta. The amyloid beta must first be monomerized to the desired monomer 40 or 42 which are believed to be the main amino acid residues associated with the formation of plaques.³ This was accomplished through both 1,1,1,3,3,3 hexaprop-2-flouro treatment and fast protein liquid chromatography. The peptoid was synthesized by hand, purified by high pressure liquid chromatography, and tested by matrix-assisted laser desorption/ionization

Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity

Virus infection of mammalian cells is sensed by pattern recognition receptors and leads to an innate immune response that restricts virus replication and induces adaptive immunity. In response, viruses have evolved many countermeasures that enable them to replicate and be transmitted to new hosts, despite the host innate immune response. Poxviruses, such as vaccinia virus (VACV), have large DNA genomes and encode many proteins that are dedicated to host immune evasion. Some of these proteins are secreted from the infected cell, where they bind and neutralize complement factors, interferons, cytokines and chemokines. Other VACV proteins function inside cells to inhibit apoptosis or signalling pathways that lead to the production of interferons and pro-inflammatory cytokines and chemokines. In this review, these VACV immunomodulatory proteins are described and the potential to create more immunogenic VACV strains by manipulation of the gene encoding these proteins is discussed

Una figurita de guerrero, con espada al hombro, procedente del castro del Cerro del Berrueco, Salamanca.

62 (3-4) Jul.-Dez. 1952, p. 233-243

Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans with Gulf War Illness.

Gulf War Illness is associated with toxic exposure to cholinergic disruptive chemicals. The cholinergic system has been shown to mediate the central executive of working memory (WM). The current work proposes that impairment of the cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and neural deficits of the central executive of WM. A large sample of GWIPs and matched controls (MCs) underwent functional magnetic resonance imaging during a varied-load working memory task. Compared to MCs, GWIPs showed a greater decline in performance as WM-demand increased. Functional imaging suggested that GWIPs evinced separate processing strategies, deferring prefrontal cortex activity from encoding to retrieval for high demand conditions. Greater activity during high-demand encoding predicted greater WM performance. Behavioral data suggest that WM executive strategies are impaired in GWIPs. Functional data further support this hypothesis and suggest that GWIPs utilize less effective strategies during high-demand WM

Fertilizing commercial vegetables

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Influence of voluntary contractions on the basal sEMG activity of the pelvic floor muscles

[EN] Chronic pelvic pain (CPP) is a complex clinical condition that affects many women, being sometimes misdiagnosed or mistreated,which can be treated with the infiltration of botulinum toxin (BoNTA). The pelvic floor musculature (PFM) condition from CPP patients can be assessed by means of surface electromyography (sEMG). The evaluation of the basal activity can help to detect a muscular dysfunction, therefore it is important to ensure that the PFM shows a minimum activation when its sEMG is being analysed. In this study, we recorded the sEMG of 25 women with CPP before and 8, 12 and 24 weeks after their treatment with BoNTA while they performed a protocol of 5 voluntary contractions. The root mean square (RMS) and sample entropy (SampEn) of basal segments pre- (B[PRE]), inter- (B[I]) and post- (B[POST]) contractions of the sEMG were computed and normalized according to the minimum (RMSnorm) and maximum (SampEnorm) of the recording. B(PRE) showed the lowest RMSnorm median both before and after the treatment with BoNTA, which proved that the activity of the PFM is minimum before the first contraction. As for SampEnnorm, although results were not so conclusive, they also indicated that B(PRE) should be taken as a reference to analyse the PFM function at its state of minimum activity. Future works aiming to characterize the effects of BoNTA in PFM by means of sEMG should consider basal segments before contractions to assess basal tone conditions.This study was funded by ISCIII, MCIU, VLC Campus in Convocatoria Ayudas: UPV-La Fe (INBIO): 2016 SPEHG (ID:C18), 2019 sEMG_BONTAv (ID:C06) and with funds from private contracts with Merz Pharma España S.L.Albaladejo-Belmonte, M.; Tarazona-Motes, M.; Nohales-Alfonso, FJ.; Alberola-Rubio, J.; Garcia-Casado, J. (2020). Influence of voluntary contractions on the basal sEMG activity of the pelvic floor muscles. Sociedad Española de Ingeniería Biomédica. 240-243. http://hdl.handle.net/10251/178256S24024

Enhancement of CD8(+) T-cell memory by removal of a vaccinia virus nuclear factor-κB inhibitor.

Factors influencing T-cell responses are important for vaccine development but are incompletely understood. Here, vaccinia virus (VACV) protein N1 is shown to impair the development of both effector and memory CD8(+) T cells and this correlates with its inhibition of nuclear factor-κB (NF-κB) activation. Infection with VACVs that either have the N1L gene deleted (vΔN1) or contain a I6E mutation (vN1.I6E) that abrogates its inhibition of NF-κB resulted in increased central and memory CD8(+) T-cell populations, increased CD8(+) T-cell cytotoxicity and lower virus titres after challenge. Furthermore, CD8(+) memory T-cell function was increased following infection with vN1.I6E, with more interferon-γ production and greater protection against VACV infection following passive transfer to naive mice, compared with CD8(+) T cells from mice infected with wild-type virus (vN1.WT). This demonstrates the importance of NF-κB activation within infected cells for long-term CD8(+) T-cell memory and vaccine efficacy. Further, it provides a rationale for deleting N1 from VACV vectors to enhance CD8(+) T-cell immunogenicity, while simultaneously reducing virulence to improve vaccine safety.This work was supported by grants from the Wellcome Trust and the Medical Research Council. GLS is a Wellcome Trust Principal Research Fellow.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/imm.1242

Treatment of Dyspareunia with Botulinum Neurotoxin Type A: Clinical Improvement and Influence of Patients' Characteristics

[EN] The treatment of chronic pelvic pain (CPP) with botulinum neurotoxin type A (BoNT/A) has increased lately, but more studies assessing its effect are needed. This study aimed to evaluate the evolution of patients after BoNT/A infiltration and identify potential responders to treatment. Twenty-four women with CPP associated with dyspareunia were treated with 90 units of BoNT/A injected into their pelvic floor muscle (PFM). Clinical status and PFM activity were monitored in a previous visit (PV) and 12 and 24 weeks after the infiltration (W12, W24) by validated clinical questionnaires and surface electromyography (sEMG). The influence of patients' characteristics on the reduction in pain at W12 and W24 was also assessed. After treatment, pain scores and the impact of symptoms on quality of life dropped significantly, sexual function improved and sEMG signal amplitude decreased on both sides of the PFM with no adverse events. Headaches and bilateral pelvic pain were risk factors for a smaller pain improvement at W24, while lower back pain was a protective factor. Apart from reporting a significant clinical improvement of patients with CPP associated with dyspareunia after BoNT/A infiltration, this study shows that clinical characteristics should be analyzed in detail to identify potential responders to treatment.This study was funded by Universitat Politecnica de Valencia in Programa de Ayudas de Investigacion y Desarrollo (PAID-01-20), ISCIII, MCIU, VLC Campus in Convocatoria Ayudas: UPV-La Fe (INBIO): 2016 SPEHG (ID:C18), 2019 sEMG_BONTAv (ID:C06) and funds from private contracts with Merz Pharmaceuticals GmbH S.L.Tarazona-Motes, M.; Albaladejo-Belmonte, M.; Nohales-Alfonso, FJ.; De-Arriba, M.; Garcia-Casado, J.; Alberola-Rubio, J. (2021). Treatment of Dyspareunia with Botulinum Neurotoxin Type A: Clinical Improvement and Influence of Patients' Characteristics. International Journal of Environmental research and Public Health. 18(16):1-12. https://doi.org/10.3390/ijerph18168783S112181