5-Hydroxytryptamine-Stimulated Inositol Phospholipid Hydrolysis in the Mouse Cortex Has Pharmacological Characteristics Compatible with Mediation via 5-HT2 Receptors but This Response Does Not Reflect Altered 5-HT2 Function After 5,7-Dihydroxytryptamine Lesioning or Repeated Antidepressant Treatments

5-Hydroxytryptamine (5-HT; 3 x 10(-8)-1 x 10(-5)M) produced a dose-dependent increase in phosphatidylinositol/polyphosphoinositide (PI) turnover in mouse cortical slices, as measured by following production of 3H-labelled inositol phosphates (IPs) in the presence of 10 mM LiCl. Analysis of individual IPs, in slices stimulated for 45 min, indicated substantial increases in inositol monophosphate (IP1; 140%) and inositol bisphosphate (IP2; 95%) contents with smaller increases in inositol trisphosphate (IP3; 51%) and inositol tetrakisphosphate (IP4; 48%) contents. The increase in IP3 level was solely in the 1,3,4-isomer. This response was inhibited by the nonselective 5-HT antagonists methysergide, metergoline, and spiperone. It was also inhibited by the selective 5-HT2 antagonists ketanserin and ritanserin but not by the 5-HT1 antagonists isapirone, (-)-propranolol, or pindolol. 5-HT-stimulated IP formation was also unaltered by atropine, prazosin, and mepyramine. Lesioning brain 5-HT neurones using 5,7-dihydroxytryptamine (5,7-DHT; 50 micrograms i.c.v.) produced a 210% (p less than 0.01) increase in the number of 5-HT2-mediated head-twitches induced by 5-methoxy-N,N-dimethyltryptamine (2 mg/kg). However, 5,7-DHT lesioning had no effect on 5-HT-stimulated PI turnover in these mice. Similarly, an electroconvulsive shock (90 V, 1 s) given five times over a 10-day period caused an 85% (p less than 0.01) increase in head-twitch responses but no change in 5-HT-stimulated PI turnover. Decreasing 5-HT2 function by twice-a-day injection of 5 mg/kg of zimeldine or desipramine (DMI) produced 50% (p less than 0.01) and 56% (p less than 0.01), respectively, reductions in head-twitch behaviour.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association between transfusion of whole blood and recurrence of cancer.

Transfusion affects the immune response to renal transplantation and may be associated with recurrence of various human neoplasms. Data from patients with colonic, rectal, cervical, and prostate tumours showed an association between transfusion of any amount of whole blood or larger amounts of red blood cells at the time of surgery and later recurrence of cancer. Recipients of one unit of whole blood had a significantly higher incidence of recurrence (45%) than recipients of a single unit of red cells (12%) (p = 0.03). Recipients of two units of whole blood also had a higher rate of recurrence (52%) than those receiving two units of red cells (23%) (p = 0.03). Recipients of any amount of whole blood had similar recurrence rates (38-52%). Recipients of four or more units of red blood cells had a higher rate of recurrence (55%) than those receiving three or fewer units of red blood cells (20%) (p = 0.005). Mortality due to cancer in patients receiving three or fewer units of red blood cells (2%) was similar to that in patients who did not have transfusions (7%) and significantly lower than that observed in patients receiving three or fewer units of whole blood (20%) (p = 0.003). A proportional hazards risk analysis showed that transfusion of any whole blood or more than three units of red blood cells was significantly associated with earlier recurrence and death due to cancer. These data support an association between transfusion and recurrence of cancer. They also suggest that some factor present in greater amounts in whole blood, such as plasma, may contribute to the increased risk of recurrence in patients who have undergone transfusion. Until the questions raised by retrospective studies of cancer recurrence and transfusion can be answered by prospective interventional trials with washed red blood cells, red blood cells should be transfused to patients with cancer in preference to whole blood when clinically feasible.     

Studies toward the comprehension of fungal-macroalgae interaction in cold marine regions from a biotechnological perspective

In marine ecosystems, macroalgae are the habitat for several microorganisms, fungi being among them. In the Antarctic benthic coastal ecosystem, macroalgae play a key role in organic matter cycling. In this study, 13 different macroalgae from Potter Cove and surrounding areas were sampled and 48 fungal isolates were obtained from six species, four Rhodophyta Ballia callitricha, Gigartina skottsbergii, Neuroglossum delesseriae and Palmaria decipiens, and two Phaeophyceae: Adenocystis utricularis and Ascoseira mirabilis. Fungal isolates mostly belonged to the Ascomycota phylum (Antarctomyces, Cadophora, Cladosporium, Penicillium, Phialocephala, and Pseudogymnoascus) and only one to the phylum Mucoromycota. Two of the isolates could not be identified to genus level, implying that Antarctica is a source of probable novel fungal taxa with enormous bioprospecting and biotechnological potential. 73% of the fungal isolates were moderate eurypsychrophilic (they grew at 5–25 °C), 12.5% were eurypsychrophilic and grew in the whole range, 12.5% of the isolates were narrow eurypsychrophilic (growth at 15–25 °C), and Mucoromycota AUe4 was classified as stenopsychrophilic as it grew at 5–15 °C. Organic extracts of seven macroalgae from which no fungal growth was obtained (three red algae Georgiella confluens, Gymnogongrus turquetii, Plocamium cartlagineum, and four brown algae Desmarestia anceps, D. Antarctica, Desmarestia menziesii, Himantothallus grandifolius) were tested against representative fungi of the genera isolated in this work. All extracts presented fungal inhibition, those from Plocamium cartilagineum and G. turquetii showed the best results, and for most of these macroalgae, this represents the first report of antifungal activity and constitute a promising source of compounds for future evaluation.     

Mixed planting with a leguminous plant outperforms bacteria in promoting growth of a metal remediating plant through histidine synthesis

The effectiveness of plant growth promoting bacteria (PGPB) in improving metal phytoremediation is still limited by stunted plant growth under high soil metal concentrations. Meanwhile, mixed planting with leguminous plants is known to improve yield in nutrient deficient soils but the use of a metal tolerant legume to enhance metal tolerance of a phytoremediator has not been explored. We compared the use of Pseudomonas brassicacearum, Rhizobium leguminosarum, and the metal tolerant leguminous plant Vicia sativa to promote the growth of Brassica juncea in soil contaminated with 400 mg Zn kg^–1, and used synchrotron based microfocus X-ray absorption spectroscopy to probe Zn speciation in plant roots. B. juncea grew better when planted with V. sativa than when inoculated with PGPB. By combining PGPB with mixed planting, B. juncea recovered full growth while also achieving soil remediation efficiency of >75%, the maximum ever demonstrated for B. juncea. μXANES analysis of V. sativa suggested possible root exudation of the Zn chelates histidine and cysteine were responsible for reducing Zn toxicity. We propose the exploration of a legume-assisted-phytoremediation system as a more effective alternative to PGPB for Zn bioremediation.     

Prochlorococcus extracellular vesicles: molecular composition and adsorption to diverse microbes

Extracellular vesicles are small (~50–200 nm diameter) membrane-bound structures released by cells from all domains of life. While vesicles are abundant in the oceans, their functions, both for cells themselves and the emergent ecosystem, remain a mystery. To better characterize these particles – a prerequisite for determining function – we analysed the lipid, protein, and metabolite content of vesicles produced by the marine cyanobacterium Prochlorococcus. We show that Prochlorococcus exports a diverse array of cellular compounds into the surrounding seawater enclosed within discrete vesicles. Vesicles produced by two different strains contain some materials in common, but also display numerous strain-specific differences, reflecting functional complexity within vesicle populations. The vesicles contain active enzymes, indicating that they can mediate extracellular biogeochemical reactions in the ocean. We further demonstrate that vesicles from Prochlorococcus and other bacteria associate with diverse microbes including the most abundant marine bacterium, Pelagibacter. Together, our data point toward hypotheses concerning the functional roles of vesicles in marine ecosystems including, but not limited to, possibly mediating energy and nutrient transfers, catalysing extracellular biochemical reactions, and mitigating toxicity of reactive oxygen species.     

The contribution of tandem repeat number to the O-glycosylation of mucins

The serine- and threonine-rich tandem repeat (TR) units that make up the characteristic feature of mucin glycoproteins are often polymorphic with substantial genetic variation in TR number. The precise effect of TR number on O-glycosylation is not fully understood, although the TR number of several mucins may be associated with apparent susceptibility to certain human diseases. To evaluate the contribution of TR number to O-glycosylation, we generated a series of chimeric mucins carrying increasing numbers of TR units from the MUC5B mucin in the context of an epitope-tagged MUC1 mucin backbone. These mucins were expressed in Caco2 colon carcinoma cell clones and purified by immunoprecipitation. O-Glycosylation was investigated by western blotting with antibodies to known carbohydrate structures and by fast atom bombardment-mass spectrometry. Additional carbohydrate epitopes were detected with antibodies on chimeric mucins with a higher TR number in comparison to those with fewer TRs. Using mass spectrometry, higher-molecular-weight glycans were detected more frequently on the mucins with extended TRs compared to those with fewer TRs. However no novel carbohydrate structures were seen, suggesting that TR number does not affect the specificity of O-glycosylation.     

Protein myristoylation in health and disease

N-myristoylation is the attachment of a 14-carbon fatty acid, myristate, onto the N-terminal glycine residue of target proteins, catalysed by N-myristoyltransferase (NMT), a ubiquitous and essential enzyme in eukaryotes. Many of the target proteins of NMT are crucial components of signalling pathways, and myristoylation typically promotes membrane binding that is essential for proper protein localisation or biological function. NMT is a validated therapeutic target in opportunistic infections of humans by fungi or parasitic protozoa. Additionally, NMT is implicated in carcinogenesis, particularly colon cancer, where there is evidence for its upregulation in the early stages of tumour formation. However, the study of myristoylation in all organisms has until recently been hindered by a lack of techniques for detection and identification of myristoylated proteins. Here we introduce the chemistry and biology of N-myristoylation and NMT, and discuss new developments in chemical proteomic technologies that are meeting the challenge of studying this important co-translational modification in living systems.     

The universal design, operation and maintenance guidelines for farm constructed wetlands (FCW) in temperate climates

This paper comprises the scientific justification for the Farm Constructed Wetland (FCW) Design Manual for Northern Ireland and Scotland. Moreover, this document addresses an international audience interested in applying wetland systems in the wider agricultural context. Farm constructed wetlands combine farm wastewater (predominantly farmyard runoff) treatment with landscape and biodiversity enhancements, and are a specific application and class of integrated constructed wetlands (ICW), which have wider applications in the treatment of other wastewater types such as domestic sewage. The aim of this review paper is to propose guidelines highlighting the rationale for FCW, including key water quality management and regulatory issues, important physical and biochemical wetland treatment processes, assessment techniques for characterizing potential FCW sites and discharge options to water bodies. The paper discusses universal design, construction, planting, maintenance and operation issues relevant specifically for FCW in a temperate climate, but highlights also catchment-specific requirements to protect the environment.     

Transfusion-induced immunomodulation and its possible role in cancer recurrence and perioperative bacterial infection

Over the last decade, it has become evident that homologous transfusions carry immunologic consequences beyond the well-understood ones of alloimmunization to blood cell antigens. Transfusions constitute temporary transplants of large amounts of allogeneic antigen given intravenously and cause down-regulation of many cellular immune functions. These changes may explain in part the association of transfusion with such clinically important events as (1) improved survival of renal allografts, (2) decreased recurrence rates for autoimmune disease, (3) increased frequency and earlier recurrences of solid tumors, (4) increased frequency of post-operative bacterial infection, and (5) increased severity of viral infection. Preliminary data suggest that, in animal models and clinical settings, syngeneic or autologous transfusions are not associated with such events. This finding supports the hypothesis that these associations are cause and effect and involve immunologic mechanisms.