Trypanocidal activity of a new pterocarpan and other secondary metabolites of plants from Northeastern Brazil flora

Two hundred fifteen compounds isolated from plants of Northeastern Brazil flora have been assayed against epimastigote forms of Trypanosoma cruzi, using the tetrazolium salt MTT as an alternative method. Eight compounds belonging to four different species: Harpalyce brasiliana (Fabaceae), Acnistus arborescens and Physalis angulata (Solanaceae), and Cordia globosa (Boraginaceae) showed significant activity. Among them, a novel and a known pterocarpan, a chalcone, four withasteroids, and a meroterpene benzoquinone were the represented chemical classes.     

Leishmania mexicana: Inhibition of camptothecin-induced apoptosis of monocyte-derived dendritic cells

Macrophages (M?) and dendritic cells (DC) are the major target cell populations of the obligate intracellular parasite Leishmania. Inhibition of host cell apoptosis is a method employed by multiple pathogens to ensure their survival in the infected cell. Leishmania has been shown to protect M? and neutrophils from both natural and induced apoptosis. As shown in this study, apoptosis in monocyte-derived dendritic cells (moDC) induced by treatment with camptothecin was downregulated by coincubation with L. mexicana, as detected by morphological analysis of cell nuclei, TUNEL assay, gel electrophoresis of low molecular weight DNA fragments, and annexin V binding to phosphatidylserine. The observed antiapoptotic effect was found to be associated with a significant reduction of caspase-3 activity in moDC. The capacity of L. mexicana to delay apoptosis induction in the infected moDC may have implications for Leishmania pathogenesis by favoring the invasion of its host and the persistence of the parasite in the infected cells.     

Influence of nutrient status and grazing pressure on the fate of Francisella tularensis in lake water

The natural reservoir of Francisella tularensis , the causative agent of tularaemia, is yet to be identified. We investigated the possibility that Francisella persists in natural aquatic ecosystems between outbreaks. It was hypothesized that nutrient-rich environments, with strong protozoan predation, favour the occurrence of the tularaemia bacterium. To investigate the differences in adaptation to aquatic environments of the species and subspecies of Francisella , we screened 23 strains for their ability to survive grazing by the ciliate Tetrahymena pyriformis . All the Francisella strains tested were consumed at a low rate, although significant differences between subspecies were found. The survival and virulence of gfp -labelled F. tularensis ssp. holarctica were then studied in a microcosm experiment using natural lake water, with varying food web complexities and nutrient availabilities. High nutrient conditions in combination with high abundances of nanoflagellates were found to favour F. tularensis ssp. holarctica . The bacterium was observed both free-living and within the cells of a nanoflagellate. Francisella tularensis entered a viable but nonculturable state during the microcosm experiment. When studied over a longer period of time, F. tularensis ssp. holarctica survived in the lake water, but loss of virulence was not prevented by either high nutrient availability or the presence of predators.     

Facilitating the Recruitment of Minority Ethnic People into Research: Qualitative Case Study of South Asians and Asthma

Background

There is international interest in enhancing recruitment of minority ethnic people into research, particularly in disease areas with substantial ethnic inequalities. A recent systematic review and meta-analysis found that UK South Asians are at three times increased risk of hospitalisation for asthma when compared to white Europeans. US asthma trials are far more likely to report enrolling minority ethnic people into studies than those conducted in Europe. We investigated approaches to bolster recruitment of South Asians into UK asthma studies through qualitative research with US and UK researchers, and UK community leaders.

Methods and Findings

Interviews were conducted with 36 researchers (19 UK and 17 US) from diverse disciplinary backgrounds and ten community leaders from a range of ethnic, religious, and linguistic backgrounds, followed by self-completion questionnaires. Interviews were digitally recorded, translated where necessary, and transcribed. The Framework approach was used for analysis. Barriers to ethnic minority participation revolved around five key themes: (i) researchers'' own attitudes, which ranged from empathy to antipathy to (in a minority of cases) misgivings about the scientific importance of the question under study; (ii) stereotypes and prejudices about the difficulties in engaging with minority ethnic populations; (iii) the logistical challenges posed by language, cultural differences, and research costs set against the need to demonstrate value for money; (iv) the unique contexts of the two countries; and (v) poorly developed understanding amongst some minority ethnic leaders of what research entails and aims to achieve. US researchers were considerably more positive than their UK counterparts about the importance and logistics of including ethnic minorities, which appeared to a large extent to reflect the longer-term impact of the National Institutes of Health''s requirement to include minority ethnic people.

Conclusions

Most researchers and community leaders view the broadening of participation in research as important and are reasonably optimistic about the feasibility of recruiting South Asians into asthma studies provided that the barriers can be overcome. Suggested strategies for improving recruitment in the UK included a considerably improved support structure to provide academics with essential contextual information (e.g., languages of particular importance and contact with local gatekeepers), and the need to ensure that care is taken to engage with the minority ethnic communities in ways that are both culturally appropriate and sustainable; ensuring reciprocal benefits was seen as one key way of avoiding gatekeeper fatigue. Although voluntary measures to encourage researchers may have some impact, greater impact might be achieved if UK funding bodies followed the lead of the US National Institutes of Health requiring recruitment of ethnic minorities. Such a move is, however, likely in the short- to medium-term, to prove unpopular with many UK academics because of the added “hassle” factor in engaging with more diverse populations than many have hitherto been accustomed to. Please see later in the article for the Editors'' Summary     

Preserved MHC Class II Antigen Processing in Monocytes from HIV-Infected Individuals

Background

MHC-II restricted CD4+ T cells are dependent on antigen presenting cells (APC) for their activation. APC dysfunction in HIV-infected individuals could accelerate or exacerbate CD4+ T cell dysfunction and may contribute to increased levels of immunodeficiency seen in some patients regardless of their CD4+ T cell numbers. Here we test the hypothesis that APC from HIV-infected individuals have diminished antigen processing and presentation capacity.

Methodology/Principal Findings

Monocytes (MN) were purified by immuno-magnetic bead isolation techniques from HLA-DR1.01+ or DR15.01+ HIV-infected and uninfected individuals. MN were analyzed for surface MHC-II expression and for antigen processing and presentation capacity after overnight incubation with soluble antigen or peptide and HLA-DR matched T cell hybridomas. Surface expression of HLA-DR was 20% reduced (p<0.03) on MN from HIV-infected individuals. In spite of this, there was no significant difference in antigen processing and presentation by MN from 14 HIV-infected donors (8 HLA-DR1.01+ and 6 HLA-DR15.01+) compared to 24 HIV-uninfected HLA-matched subjects.

Conclusions/Significance

We demonstrated that MHC class II antigen processing and presentation is preserved in MN from HIV-infected individuals. This further supports the concept that this aspect of APC function does not further contribute to CD4+ T cell dysfunction in HIV disease.     

Mesenchymal stem cell therapy: A promising cell‐based therapy for treatment of myocardial infarction

For decades, mesenchymal stem (MSCs) cells have been used for cardiovascular diseases as regenerative therapy. This review is an attempt to summarize the types of MSCs involved in myocardial infarction (MI) therapy, as well as its possible mechanisms effects, especially the paracrine one in MI focusing on the studies (human and animal) conducted within the last 10 years. Recently, reports showed that MSC therapy could have infarct‐limiting effects after MI in both experimental and clinical trials. In this context, various types of MSCs can help cardiac regeneration by either revitalizing the cardiac stem cells or revascularizing the arteries and veins of the heart. Furthermore, MSCs could produce paracrine growth factors that increase the survival of nearby cardiomyocytes, as well as increase angiogenesis through recruitment of stem cell from bone marrow or inducing vessel growth from existing capillaries. Recent research suggests that the paracrine effects of MSCs could be mediated by extracellular vesicles including exosomes. Exosomal microRNAs (miRNAs) released by MSCs are promising therapeutic hotspot target for MI. This could be attributed to the role of miRNA in cardiac biology, including cardiac regeneration, stem cell differentiation, apoptosis, neovascularization, cardiac contractility and cardiac remodeling. Furthermore, gene‐modified MSCs could be a recent promising therapy for MI to enhance the paracrine effects of MSCs, including better homing and effective cell targeted tissue regeneration. Although MSC therapy has achieved considerable attention and progress, there are critical challenges that remains to be overcome to achieve the most effective successful cell‐based therapy in MI.     

Novel Comparative Efficiency of Ozone and Gamma Sterilization on Fungal Deterioration of Archeological Painted Coffin,Saqqara Excavation,Egypt

An archeological wooden painted coffin was excavated in Tety tomb from Saqqara excavation. It belonged to the Ministry of Antiquities. This coffin was discovered in a bad state of conservation with many destroyed big and small pieces in Saqqara stores. Analyses and investigation study were performed on the ground layer of the coffin by X-ray diffraction (XRD), Energy dispersive X ray analysis (EDX) equipped with environmental scanning electron microscopy (ESEM) and Fourier transform infrared spectroscopy (FTIR). Results confirmed that the degradation factors affecting the wooden painted coffin are essentially attributed to direct effects of microbial phenomena, which have lead to many deterioration forms as: macro- and microcracks, hydrated salts, flaking, coloration, scaling and defoliation microbiological spots. Nine deteriorating fungal species were isolated from the painted and ground layers of the tested coffin. Fusarium moniliforme followed by Aspergillus flavus able to significantly solublize calcium salts as major components of the ground layer of archeological wooden coffin. Effect of ozone and Gamma sterilization on growth; lipid, tryptophan oxidation and protein, nucleic acid leakage in the most dominant toxigenic deteriorated fungal species were detected. No mycelial growth was observed at 4 ppm of ozone at all exposure times. As Gamma radiation dose increased over 250 Gy, the growth parameter gradually decreased to reach the lethal dose at 2000 Gy. The production of mycotoxins by the tested toxigenic fungi was completely disappeared under the exposure to 3 ppm and 90 min to ozone.     

Prospective survey of veterinary practitioners’ primary assessment of equine colic: clinical features,diagnoses, and treatment of 120 cases of large colon impaction

Background

Large colon impactions are a common cause of colic in the horse. There are no scientific reports on the clinical presentation, diagnostic tests and treatments used in first opinion practice for large colon impaction cases. The aim of this study was to describe the presentation, diagnostic approach and treatment at the primary assessment of horses with large colon impactions.

Methods

Data were collected prospectively from veterinary practitioners on the primary assessment of equine colic cases over a 12 month period. Inclusion criteria were a diagnosis of primary large colon impaction and positive findings on rectal examination. Data recorded for each case included history, signalment, clinical and diagnostic findings, treatment on primary assessment and final case outcome. Case outcomes were categorised into three groups: simple medical (resolved with single treatment), complicated medical (resolved with multiple medical treatments) and critical (required surgery, were euthanased or died). Univariable analysis using one-way ANOVA and Tukey’s post-hoc test, Kruskal Wallis with Dunn’s post-hoc test and Chi squared analysis were used to compare between different outcome categories.

Results

1032 colic cases were submitted by veterinary practitioners: 120 cases met the inclusion criteria for large colon impaction. Fifty three percent of cases were categorised as simple medical, 36.6% as complicated medical, and 9.2% as critical. Most cases (42.1%) occurred during the winter. Fifty nine percent of horses had had a recent change in management, 43% of horses were not ridden, and 12.5% had a recent / current musculoskeletal injury. Mean heart rate was 43bpm (range 26-88) and most cases showed mild signs of pain (67.5%) and reduced gut sounds (76%). Heart rate was significantly increased and gut sounds significantly decreased in critical compared to simple medical cases (p<0.05). Fifty different treatment combinations were used, with NSAIDs (93%) and oral fluids (71%) being administered most often.

Conclusions

Large colon impactions typically presented with mild signs of colic; heart rate and gut sounds were the most useful parameters to distinguish between simple and critical cases at the primary assessment. The findings of seasonal incidence and associated management factors are consistent with other studies. Veterinary practitioners currently use a wide range of different treatment combinations for large colon impactions.

     

Evolutionary History of the PER3 Variable Number of Tandem Repeats (VNTR): Idiosyncratic Aspect of Primate Molecular Circadian Clock

The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR) locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns.