Imitation of Management Practices in Supply Networks: Relational and Environmental Effects

This study investigates the imitative use of management practices across a multitier supply network. Although imitation may take the form of any management practice, operationally, we focus on whether the buyer’s control practices used with first-tier suppliers results in similar control practices being used by these first-tier suppliers with the second-tier suppliers. Drawing on institutional theory, we identify relational context (i.e., affective commitment) and environmental context (i.e., environmental uncertainty) as two important factors influencing the extent to which such imitation takes place. Using unique survey data of vertically linked supply chain triads, we generally find support for the occurrence of imitation and more so in cases of high affective commitment. The results regarding environmental uncertainty further reveal selectivity in imitative behavior, calling attention to the level of deliberateness in imitation decisions in supply networks. Besides contributing to theory on imitative behaviors in the supply chain, this study also generates practical implications on the spread of management practices across multiple tiers

Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice

This work was supported by 55007419 (HHMI) and 2151 (EMBO) to L.M.F., D.P.-N., F.B., and F.G.; FCT fellowships to S.T., F.R.-F., and F.A.-B. (SFRH/BPD/89833/2012, SFRH/BD/51286/2010, and SFRH/BD/80718/2011, respectively); Wellcome Trust grant (093228), MRC MR/M020118/1, and European Community Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED) to S.A.Y. and T.K.S.; and PAI 7/41 (Belspo) and ERC-NANOSYM to J.V.D.A.Trypanosoma brucei is an extracellular parasite that causes sleeping sickness. In mammalian hosts, trypanosomes are thought to exist in two major niches: early in infection, they populate the blood; later, they breach the blood-brain barrier. Working with a well-established mouse model, we discovered that adipose tissue constitutes a third major reservoir for T. brucei. Parasites from adipose tissue, here termed adipose tissue forms (ATFs), can replicate and were capable of infecting a naive animal. ATFs were transcriptionally distinct from bloodstream forms, and the genes upregulated included putative fatty acid β-oxidation enzymes. Consistent with this, ATFs were able to utilize exogenous myristate and form β-oxidation intermediates, suggesting that ATF parasites can use fatty acids as an external carbon source. These findings identify the adipose tissue as a niche for T. brucei during its mammalian life cycle and could potentially explain the weight loss associated with sleeping sickness.Publisher PDFPeer reviewe

Vagus nerve stimulation for depression: efficacy and safety in a European study

Background Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression. Method An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically. Results The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%). Conclusions VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European stud

Trypanosoma brucei Modifies the Tsetse Salivary Composition, Altering the Fly Feeding Behavior That Favors Parasite Transmission

Tsetse flies are the notorious transmitters of African trypanosomiasis, a disease caused by the Trypanosoma parasite that affects humans and livestock on the African continent. Metacyclic infection rates in natural tsetse populations with Trypanosoma brucei, including the two human-pathogenic subspecies, are very low, even in epidemic situations. Therefore, the infected fly/host contact frequency is a key determinant of the transmission dynamics. As an obligate blood feeder, tsetse flies rely on their complex salivary potion to inhibit host haemostatic reactions ensuring an efficient feeding. The results of this experimental study suggest that the parasite might promote its transmission through manipulation of the tsetse feeding behavior by modifying the saliva composition. Indeed, salivary gland Trypanosoma brucei-infected flies display a significantly prolonged feeding time, thereby enhancing the likelihood of infecting multiple hosts during the process of a single blood meal cycle. Comparison of the two major anti-haemostatic activities i.e. anti-platelet aggregation and anti-coagulation activity in these flies versus non-infected tsetse flies demonstrates a significant suppression of these activities as a result of the trypanosome-infection status. This effect was mainly related to the parasite-induced reduction in salivary gland gene transcription, resulting in a strong decrease in protein content and related biological activities. Additionally, the anti-thrombin activity and inhibition of thrombin-induced coagulation was even more severely hampered as a result of the trypanosome infection. Indeed, while naive tsetse saliva strongly inhibited human thrombin activity and thrombin-induced blood coagulation, saliva from T. brucei-infected flies showed a significantly enhanced thrombinase activity resulting in a far less potent anti-coagulation activity. These data clearly provide evidence for a trypanosome-mediated modification of the tsetse salivary composition that results in a drastically reduced anti-haemostatic potential and a hampered feeding performance which could lead to an increase of the vector/host contact and parasite transmission in field conditions

Influence of probiotic bacteria on gut microbiota composition and gut wall function in an in-vitro model in patients with Parkinson's disease

We report here the potential role of a 4-strain probiotic suspension for use with patients with Parkinson's disease (PD). Stool samples from a group of three patients with diagnosed PD were used to create microbiotas in an in-vitro gut model. The effects of dosing with an oral probiotic suspension (Symprove) on bacterial composition and metabolic activity in the microbiotas was evaluated over 48 h and compared with healthy controls. Additionally, the effect of probiotic dosing on epithelial tight-junction integrity, production of inflammatory markers and wound healing were evaluated in cell culture models. In general, the relative proportions of the main bacterial phyla in the microbiotas of PD patients differed from those of healthy subjects, with levels of Firmicutes raised and levels of Bacteroidetes reduced. Dosing with probiotic resulted in a change in bacterial composition in the microbiotas over a 48 h period. Several other indicators of gut health changed upon dosing with the probiotic; production of short chain fatty acids (SCFAs) and lactate was stimulated, levels of anti-inflammatory cytokines (IL-6, IL-10) increased and levels of pro-inflammatory cytokines and chemokines (MCP-1 and IL-8) decreased. Tight junction integrity was seen to improve with probiotic dosing and wound healing was seen to occur faster than a control. The data suggest that if development and/or progression of PD is influenced by gut microbiota dysbiosis then supplementation of the diet with a properly formulated probiotic may be a useful adjunct to standard treatment in clinic

Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants.

Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut

The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate

Purpose: Gastrointestinal stromal tumours (GIST) are mesenchymal neoplasms of the gastrointestinal tract that are unresponsive to standard sarcoma chemotherapy. Imaging of GIST patients is done with structural and functional methods such as contrast-enhanced helical computed tomography (ceCT) and positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG). The aim of this study was to compare the prognostic power of PET and ceCT and to evaluate the clinical role of PET/CT imaging. Methods: All patients with GIST undergoing PET or PET/CT examinations were prospectively included in this study, and the median overall survival, time to progression and treatment duration were documented. The prognostic significance of PET and ceCT criteria of treatment response was assessed and PET/CT was compared with PET and ceCT imaging. Data for 34 patients (19 male, 15 female, 21-76 years) undergoing PET or PET/CT for staging or restaging were analysed. Results: In 28 patients, PET/CT and ceCT were available after introduction of treatment with the tyrosine kinase inhibitor imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). Patients without FDG uptake after the start of treatment had a better prognosis than patients with residual activity. In contrast, ceCT criteria provided insufficient prognostic power. However, more lesions were found on ceCT images than on PET images, and FDG uptake was sometimes very variable. PET/CT delineated active lesions better than did the combination of PET and ceCT imaging. Conclusion: Both PET and PET/CT provide important prognostic information and have an impact on clinical decision-making in GIST patients. PET/CT precisely delineates lesions and thus allows for the correct planning of surgical intervention

Tsetse GmmSRPN10 has anti-complement activity and is important for successful establishment of trypanosome infections in the fly midgut

The complement cascade in mammalian blood can damage the alimentary tract of haematophagous arthropods. As such, these animals have evolved their own repertoire of complement-inactivating factors, which are inadvertently exploited by blood-borne pathogens to escape complement lysis. Unlike the bloodstream stages, the procyclic (insect) stage of Trypanosoma brucei is highly susceptible to complement killing, which is puzzling considering that a tsetse takes a bloodmeal every 2–4 days. In this study, we identified four tsetse (Glossina morsitans morsitans) serine protease inhibitors (serpins) from a midgut expressed sequence tag (EST) library (GmmSRPN3, GmmSRPN5, GmmSRPN9 and GmmSRPN10) and investigated their role in modulating the establishment of a T. brucei infection in the midgut. Although not having evolved in a common blood-feeding ancestor, all four serpins have an active site sharing remarkable homology with the human complement C1-inhibitor serpin, SerpinG1. RNAi knockdown of individual GmmSRPN9 and GmmSRPN10 genes resulted in a significant decreased rate of infection by procyclic form T. brucei. Furthermore, recombinant GmmSRPN10 was both able to inhibit the activity of human complement-cascade serine proteases, C1s and Factor D, and to protect the in vitro killing of procyclic trypanosomes when incubated with complement-activated human serum. Thus, the secretion of serpins, which may be part of a bloodmeal complement inactivation system in tsetse, is used by procyclic trypanosomes to evade an influx of fresh trypanolytic complement with each bloodmeal. This highlights another facet of the complicated relationship between T. brucei and its tsetse vector, where the parasite takes advantage of tsetse physiology to further its chances of propagation and transmission

Vagus nerve stimulation for depression: efficacy and safety in a European study

Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression

Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio