Possible role of metal ionophore against zinc induced cognitive dysfunction in <Emphasis Type="SmallCaps">d-</Emphasis>galactose senescent mice

Metal ionophores are considered as potential anti-dementia agents, and some are currently undergoing clinical trials. Many metals are known to accumulate and distribute abnormally in the aging brain. Alterations in zinc metal homeostasis in the glutaminergic synapse could contribute to ageing and the pathophysiology of Alzheimer’s disease (AD). The present study was designed to investigate the effect of metal ionophores on long term administration of zinc in D-galactose induced senescent mice. The ageing model was established by combined administration of zinc and D-galactose to mice for 6 weeks. A novel metal ionophore, PBT-2 was given daily to zinc-induced d-galactose senescent mice. The cognitive behaviour of mice was monitored using the Morris Water Maze. The anti-oxidant status and amyloidogenic activity in the ageing mouse was measured by determining mito-oxidative parameters and deposition of amyloid β (Aβ) in the brain. Systemic administration of both zinc and D-galactose significantly produced memory deficits, mito-oxidative damage, heightened acetylcholinesterase enzymatic activity and deposition of amyloid-β. Treatment with PBT-2 significantly improved behavioural deficits, biochemical profiles, cellular damage, and curbed the deposition of APP in zinc-induced senescent mice. These findings suggest that PBT-2, acting as a metal protein attenuating compound, may be helpful in the prevention of AD or alleviation of ageing.     

Characterization and partial purification of <Emphasis Type="Italic">Candida albicans</Emphasis> Secretory IL-12 Inhibitory Factor

Background  

We have previously shown that supernatant from Candida albicans (CA) culture contains a Secretory Interleukin (IL)-12 Inhibitory Factor (CA-SIIF), which inhibits IL-12 production by human monocytes. However, the effect of CA-SIIF on secretion of other cytokines by monocytes is unknown, and detailed characterization of this factor has not been performed.     

Morphological and Molecular Identification of Spirometra Tapeworms (Cestoda: Diphyllobothriidae) from Carnivorous Mammals in the Serengeti and Selous Ecosystems of Tanzania

Spirometra tapeworms (Cestoda: Diphyllobothriidae) collected from carnivorous mammals in Tanzania were identified by the DNA sequence analysis of the mitochondrial cytochrome c oxidase subunit 1 (cox1) and internal transcribed spacer 1 (ITS1), and by morphological characteristics. A total of 15 adult worms were collected from stool samples and carcasses of Panthera leo, Panthera pardus, and Crocuta crocuta in the Serengeti and Selous ecosystems of Tanzania. Three Spirometra species: S. theileri, S. ranarum and S. erinaceieuropaei were identified based on morphological features. Partial cox1 sequences (400 bp) of 10 specimens were revealed. Eight specimens showed 99.5% similarity with Spirometra theileri ({"type":"entrez-nucleotide","attrs":{"text":"MK955901","term_id":"1796114604","term_text":"MK955901"}}MK955901), 1 specimen showed 99.5% similarity with the Korean S. erinaceieuropaei and 1 specimen had 99.5% similarity with Myanmar S. ranarum. Sequence homology estimates for the ITS1 region of S. theileri were 89.8% with S. erinaceieuropaei, 82.5% with S. decipiens, and 78.3% with S. ranarum; and 94.4% homology was observed between S. decipiens and S. ranarum. Phylogenetic analyses were performed with 4 species of Spirometra and 2 species of Dibothriocephalus (=Diphyllobothrium). By both ML and BI methods, cox1 and ITS1 gave well supported, congruent trees topology of S. erinaceieuropaei and S. theileri with S. decipiens and S. ranarum forming a clade. The Dibothriocephalus species were sisters of each other and collectively forming successive outgroups. Our findings confirmed that 3 Spirometra species (S. theileri, S. ranarum, and S. erinaceieuropaei) are distributed in the Serengeti and Selous ecosystems of Tanzania.     

Evaluation of two communication tools,slideshow and theater,to improve participants’ understanding of a clinical trial in the informed consent procedure on Pemba Island,Tanzania

BackgroundClinical trial participants are required to sign an informed consent form (ICF). However, information is lacking on the most effective methods to convey trial relevant information prior to inviting participants to sign the ICF, being particularly pertinent in low-income countries. A previous study on Pemba Island, Tanzania, found that a verbal information session (IS) was significantly better than providing an ICF alone. However, knowledge gaps remained. Building on these findings, we investigated the effect of adding a slideshow or a theater to the IS in the informed consent procedure of an anthelminthic clinical trial.Methodology/principal findingsA total of 604 caregivers were randomized into the control group that only received an ICF (n = 150) or an ICF plus one of three intervention strategies: (i) verbal IS (n = 135), (ii) verbal IS with a slideshow (n = 174) or (iii) verbal IS followed by a theater (n = 145). All modes of information covered the same key messages. Participants’ understanding was assessed using a semi-structured questionnaire. The mean score of caregivers in the control group (ICF only) was 4.41 (standard deviation = 1.47). Caregivers attending the IS alone were more knowledgeable than those in the control group (estimated difference in mean scores: 2.40, 95% confidence interval (CI) 1.95 to 2.86, p < 0.01). However, there was no evidence of an improvement compared to the IS only when participants attended a slideshow (0.09, 95% CI -0.53 to 0.35, p = 0.68) or a theater (0.28, 95% CI -0.27 to 0.82, p = 0.32). Three out of 10 key messages remained largely misunderstood, regardless of the mode of information group.Conclusions/significanceOur study confirmed that, in this setting, an ICF alone was not sufficient to convey clinical trial-related information. An IS was beneficial, however, additional theater and slideshows did not further improve understanding. Future research should explore methods to improve communication between study teams and participants for different key messages, study types and settings.     

Intracellular regulation of cell signaling cascades: how location makes a difference

Organelles such as endosomes and the Golgi apparatus play a critical role in regulating signal transmission to the nucleus. Recent experiments have shown that appropriate positioning of these organelles within the intracellular space is critical for effective signal regulation. To understand the mechanism behind this observation, we consider a reaction-diffusion model of an intracellular signaling cascade and investigate the effect on the signaling of intracellular regulation in the form of a small release of phosphorylated signaling protein, kinase, and/or phosphatase. Variational analysis is applied to characterize the most effective regions for the localization of this intracellular regulation. The results demonstrate that signals reaching the nucleus are most effectively regulated by localizing the release of phosphorylated substrate protein and kinase near the nucleus. Phosphatase release, on the other hand, is nearly equally effective throughout the intracellular space. The effectiveness of the intracellular regulation is affected strongly by the characteristics of signal propagation through the cascade. For signals that are amplified as they propagate through the cascade, reactions in the upstream levels of the cascade exhibit much larger sensitivities to regulation by release of phosphorylated substrate protein and kinase than downstream reactions. On the other hand, for signals that decay through the cascade, downstream reactions exhibit larger sensitivity than upstream reactions. For regulation by phosphatase release, all reactions within the cascade show large sensitivity for amplified signals but lose this sensitivity for decaying signals. We use the analysis to develop a simple model of endosome-mediated regulation of cell signaling. The results demonstrate that signal regulation by the modeled endosome is most effective when the endosome is positioned in the vicinity of the nucleus. The present findings may explain at least in part why endosomes in many cell types localize near the nucleus.