Two closely related ABC transporters in streptococcus mutans are involved in disaccharide and/or oligosaccharide uptake.

Streptococcus mutans has a large number of transporters apparently involved in the uptake of carbohydrates. At least two of these, the multiple sugar metabolism transporter, MsmEFGK, and the previously uncharacterized MalXFGK, are members of the ATP-binding cassette (ABC) superfamily. Mutation analysis revealed that the MsmEFGK and MalXFGK transporters are principally involved in the uptake of distinct disaccharides and/or oligosaccharides. Furthermore, the data also indicated an unusual protein interaction between the components of these two related transporters. Strains lacking msmE (which encodes a solute binding protein) can no longer utilize raffinose or stachyose but grow normally on maltodextrins in the absence of MalT, a previously characterized EII(mal) phosphotransferase system component. In contrast, a mutant of malX (which encodes a solute binding protein) cannot utilize maltodextrins but grows normally on raffinose or stachyose. Radioactive uptake assays confirmed that MalX, but not MsmE, is required for uptake of [U-14C]maltotriose and that MalXFGK is principally involved in the uptake of maltodextrins with as many as 7 glucose units. Surprisingly, inactivation of the corresponding ATPase components did not result in an equivalent abolition of growth: the malK mutant can grow on maltotetraose as a sole carbon source, and the msmK mutant can utilize raffinose. We propose that the ATPase domains of these ABC transporters can interact with either their own or the alternative transporter complex. Such unexpected interaction of ATPase subunits with distinct membrane components to form complete multiple ABC transporters may be widespread in bacteria

An orthologue of bacteroides fragilis NanH is the principal sialidase in tannerella forsythia

Sialidase activity is a putative virulence factor of the anaerobic periodontal pathogen Tannerella forsythia, but it is uncertain which genes encode this activity. Characterization of a putative sialidase, SiaHI, by others, indicated that this protein alone may not be responsible for all of the sialidase activity. We describe a second sialidase in T. forsythia (TF0035), an orthologue of Bacteroides fragilis NanH, and its expression in Escherichia coli. Sialidase activity of the expressed NanH was confirmed by using 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid as a substrate. Biochemical characterization of the recombinant T. forsythia NanH indicated that it was active over a broad pH range, with optimum activity at pH 5.5. This enzyme has high affinity for 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid (Km of 32.9 ± 10.3 μM) and rapidly releases 4-methylumbelliferone (Vmax of 170.8 ± 11.8 nmol of 4-methylumbelliferone min−1 mg of protein−1). E. coli lysates containing recombinant T. forsythia NanH cleave sialic acid from a range of substrates, with a preference for α2-3 glycosidic linkages. The genes adjacent to nanH encode proteins apparently involved in the metabolism of sialic acid, indicating that the NanH sialidase is likely to be involved in nutrient acquisition

Anger, Quality of Life and Mood in Multiple Sclerosis

This research was funded by The Multiple Sclerosis Society (UK).Peer reviewedPublisher PD

Neutralising antibody response in domestic cats immunised with a commercial feline immunodeficiency virus (FIV) vaccine

Across human and veterinary medicine, vaccines against only two retroviral infections have been brought to market successfully, the vaccines against feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV). FeLV vaccines have been a global success story, reducing virus prevalence in countries where uptake is high. In contrast, the more recent FIV vaccine was introduced in 2002 and the degree of protection afforded in the field remains to be established. However, given the similarities between FIV and HIV, field studies of FIV vaccine efficacy are likely to advise and inform the development of future approaches to HIV vaccination.<p></p> Here we assessed the neutralising antibody response induced by FIV vaccination against a panel of FIV isolates, by testing blood samples collected from client-owned vaccinated Australian cats. We examined the molecular and phenotypic properties of 24 envs isolated from one vaccinated cat that we speculated might have become infected following natural exposure to FIV. Cats vaccinated against FIV did not display broadly neutralising antibodies, suggesting that protection may not extend to some virulent recombinant strains of FIV circulating in Australia.<p></p&gt

Exploring customers’ zone of tolerance for B2B professional service quality

Purpose: This paper aims to extend the current research on zone of tolerance (ZOT) and its antecedents, to the context of business-to-business (B2B) professional services from both client and service firms’ perspectives, with a modified ZOT framework including five client and service firms attributes as antecedents of desired (DSL) and adequate (ASL) service levels. Prior research on zone of tolerance (ZOT) and its antecedents mostly focuses on business-to-consumer services and customers’ perspective. The authors address these gaps with a modified ZOT framework with five attributes of client and service firms as antecedents of customer expectations, namely, desired service level (DSL) and adequate service level (ASL), for business-to-business (B2B) professional services. Design/methodology/approach: A combination of qualitative (focus groups) and quantitative (online survey) research methods with managers of professional audit firms and their clients, using a reduced AUDITQUAL instrument with 39 items and seven dimensions.Findings: Professional firm size and fee premium have a positive effect on DSL; service tenure positively influences both DSL and ASL; client firm size has a negative effect on DSL; both client and service firm sizes positively moderate each other’s influence on the DSL; and DSL positively influences ASL. Research limitations/implications: The authors study a single B2B professional service (audit) in a single city (Hong Kong) from a single perspective (customers) that may limit the generalizability of the findings. Future research should validate the findings for other B2B professional services in diverse locations and also include service providers’ expectations and perceptions. Practical implications: Managers in professional service firms should understand the factors influencing different levels of expectations for their customers and develop suitable strategies (e.g. customer education and employee training) to manage these expectations more effectively. Originality/value: The authors extend current research on customer expectations and ZOT by identifying five unique attributes of professional service and client firms and testing their roles as antecedents of adequate and DSLs using AUDITQUAL instrument

Truncation of TRIM5 in the <i>Feliformia</i> explains the absence of retroviral restriction in cells of the domestic cat

TRIM5[alpha] mediates a potent retroviral restriction phenotype in diverse mammalian species. Here, we identify a TRIM5 transcript in cat cells with a truncated B30.2 capsid binding domain and ablated restrictive function which, remarkably, is conserved across the &lt;i&gt;Feliformia&lt;/i&gt;. Cat TRIM5 displayed no restriction activity, but ectopic expression conferred a dominant negative effect against human TRIM5[alpha]. Our findings explain the absence of retroviral restriction in cat cells and suggest that disruption of the TRIM5 locus has arisen independently at least twice in the &lt;i&gt;Carnivora&lt;/i&gt;, with implications concerning the evolution of the host and pathogen in this taxon

The complete mitochondrial genome and phylogenetic position of the critically endangered Trinidad Piping Guan, Pipile pipile synonym Aburria pipile (Aves: Galliformes).

This is an Author's Accepted Manuscript of an article published in Mitochondrial DNA Part B on 04/09/2016, copyright of Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/23802359.2016.1219622The complete mitochondrial genome of the Critically Endangered Trinidad Piping Guan, Pipile pipile (Jacquin 1784) synonym Aburria pipile was sequenced for the first time in this study. The genome is 16,665 bp in length with overall base compositions of 30.1, 23.7, 32.3 and 13.9% for A, T, C, and G, respectively. Structurally, the P. pipile mitogenome is comparable to that of other Galliformes, thereby demonstrating typical avian gene organization. The mitogenome was subsequently used to produce a revised phylogenetic placement of P. pipile within the Galliforme order, positioning the Pipile genus basal within the Cracidae family. It is further envisaged that this novel genomic data will contribute to a wider understanding of genetic relationships within the genus Pipile and the analysis of the evolutionary relationships of the Galliforme order in a wider avian context

A systematic review of the overlap of fluid biomarkers in delirium and advanced cancer-related syndromes.

BACKGROUND:Delirium is a serious and distressing neurocognitive disorder of physiological aetiology that is common in advanced cancer. Understanding of delirium pathophysiology is largely hypothetical, with some evidence for involvement of inflammatory systems, neurotransmitter alterations and glucose metabolism. To date, there has been limited empirical consideration of the distinction between delirium pathophysiology and that of the underlying disease, for example, cancer where these mechanisms are also common in advanced cancer syndromes such as pain and fatigue. This systematic review explores biomarker overlap in delirium, specific advanced cancer-related syndromes and prediction of cancer prognosis. METHODS:A systematic review (PROSPERO CRD42017068662) was conducted, using MEDLINE, PubMed, Embase, CINAHL, CENTRAL and Web of Science, to identify body fluid biomarkers in delirium, cancer prognosis and advanced cancer-related syndromes of interest. Studies were excluded if they reported delirium tremens only; did not measure delirium using a validated tool; the sample had less than 75% of participants with advanced cancer; measured tissue, genetic or animal biomarkers, or were conducted post-mortem. Articles were screened for inclusion independently by two authors, and data extraction and an in-depth quality assessment conducted by one author, and checked by two others. RESULTS:The 151 included studies were conducted in diverse settings in 32 countries between 1985 and 2017, involving 28130 participants with a mean age of 69.3 years. Seventy-one studies investigated delirium biomarkers, and 80 studies investigated biomarkers of an advanced cancer-related syndrome or cancer prognosis. Overall, 41 biomarkers were studied in relation to both delirium and either an advanced cancer-related syndrome or prognosis; and of these, 24 biomarkers were positively associated with either delirium or advanced cancer syndromes/prognosis in at least one study. The quality assessment showed large inconsistency in reporting. CONCLUSION:There is considerable overlap in the biomarkers in delirium and advanced cancer-related syndromes. Improving the design of delirium biomarker studies and considering appropriate comparator/controls will help to better understanding the discrete pathophysiology of delirium in the context of co-existing illness

Restriction of the felid lentiviruses by a synthetic feline TRIM5-CypA fusion

Gene therapy approaches to the treatment of HIV infection have targeted both viral gene expression and the cellular factors that are essential for virus replication. However, significant concerns have been raised regarding the potential toxic effects of such therapies, the emergence of resistant viral variants and unforeseen biological consequences such as enhanced susceptibility to unrelated pathogens. Novel restriction factors formed by the fusion of the tripartite motif protein (TRIM5) and cyclophilin A (CypA), or "TRIMCyps", offer an effective antiviral defence strategy with a very low potential for toxicity. In order to investigate the potential therapeutic utility of TRIMCyps in gene therapy for AIDS, a synthetic fusion protein between feline TRIM5 and feline CypA was generated and transduced into cells susceptible to infection with feline immunodeficiency virus (FIV). The synthetic feline TRIMCyp was highly efficient at preventing infection with both HIV and FIV and the cells resisted productive infection with FIV from either the domestic cat or the puma. Feline TRIMCyp and FIV infection of the cat offers a unique opportunity to evaluate TRIMCyp-based approaches to genetic therapy for HIV infection and the treatment of AIDS