Comparison of Allogeneic Stem Cell Transplantation and Non-Transplant Approaches in Elderly Patients with Advanced Myelodysplastic Syndrome: Optimal Statistical Approaches and a Critical Appraisal of Clinical Results Using Non-Randomized Data

Allogeneic stem cell transplantation (ASCT) from related or unrelated donors may cure patients with myelodysplastic syndromes (MDS), a heterogeneous group of clonal stem cell disorders. We analysed 384 elderly patients (55-69 years) with advanced MDS who received either ASCT (n=247) and were reported to The European Group for Blood and Marrow Transplantation (EBMT) or a non –transplant approach (n=137) reported to the Düsseldorf registry. Besides an attempt to answer the question of „comparison“, the purpose of this work is to explain the difficulties in comparing a non-transplant with a transplant cohort, when death before transplant is likely but unknown and the selection of patients for transplant is based on assumptions. It shows which methods are almost always biased and that even the most sophisticated approaches crucially rely on clinical assumptions. Using the most appropriate model for our data, we derive an overall univariate non-significant survival disadvantage for the transplant cohort (HR: 1.29, p = 0.11). We show that such an “average” hazard ratio is however misleading due to non-proportionality of the hazards reflecting early treatment related mortality, the occurring of which is logically correlated with the interval between diagnosis and transplant creating a disproportional drop in the (reconstructed) survival curve of the transplanted patients. Also in multivariate analysis (correcting for age > 60 (HR: 1.4, p = 0.02) and abnormal cytogenetics (HR: 1.46, p = 0.01)), transplantation seems to be worse (HR: 1.39, p = 0.05) but only in the (incorrect but commonly applied) model without time varying covariates. The long term (time depending) hazard ratio is shown to be virtually 1 and overall survival is virtually identical in both groups. Nonetheless no conclusion can be reached from a clinical point of view without assumptions which are by their very nature untestable unless all patients would be followed from diagnosis.     

Biosorption of Heavy Metals (Cd2+, Cu2+, Co2+, and Mn2+) by Thermophilic Bacteria,Geobacillus thermantarcticus and Anoxybacillus amylolyticus: Equilibrium and Kinetic Studies

ABSTRACT

Two strains of thermophilic bacteria, Geobacillus thermantarcticus and Anoxybacillus amylolyticus, were employed to investigate the biosorption of heavy metals including Cd²⁺, Cu²⁺, Co²⁺, and Mn²⁺ ions. The effects of different biosorption parameters such as pH (2.0–10.0), initial metal concentrations (10.0–300.0 mg L^?1), amount of biomass (0.25–10 g L^?1), temperature (30–80°C), and contact time (15–120 min) were investigated. Concentrations of metal ions were determined by using an inductively coupled plasma optical emission spectrometry (ICP-OES). Optimum pHs for Cd²⁺, Cu²⁺, Co²⁺, and Mn²⁺ biosorption by Geobacillus thermantarcticus were found to be 4.0, 4.0, 5.0, and 6.0, respectively. For Anoxybacillus amylolyticus, the optimum pHs for Cd²⁺, Cu²⁺, Co²⁺, and Mn²⁺ biosorption were found to be 5.0, 4.0, 5.0, and 6.0, respectively. The Cd²⁺, Cu²⁺, Co²⁺, and Mn²⁺ removals at 50 mg L^?1 in 60 min by 50 mg dried cells of Geobacillus thermantarcticus were 85.4%, 46.3%, 43.6%, and 65.1%, respectively, whereas 74.1%, 39.8%, 35.1%, and 36.6%, respectively, for Anoxybacillus amylolyticus. The optimum temperatures for heavy metal biosorption were near the optimum growth temperatures for both strains. Scatchard plot analysis was employed to obtain more compact information about the interaction between metal ions and biosorbents. The plot results were further studied to determine if they fit Langmuir and Freundlich models.     

Molasses as fermentation substrate for levan production by <Emphasis Type="Italic">Halomonas</Emphasis> sp.

Levan is a homopolymer of fructose with many outstanding properties like high solubility in oil and water, strong adhesiveness, good biocompatibility, and film-forming ability. However, its industrial use has long been hampered by costly production processes which rely on mesophilic bacteria and plants. Recently, Halomonas sp. AAD6 halophilic bacteria were found to be the only extremophilic species producing levan at high titers in semi-chemical medium containing sucrose, and in this study, pretreated sugar beet molasses and starch molasses were both found to be feasible substitutes for sucrose. Five different pretreatment methods and their combinations were applied to both molasses types. Biomass and levan concentrations reached by the Halomonas sp. AAD6 cells cultivated on 30 g/L of pretreated beet molasses were 6.09 g dry cells/L and 12.4 g/L, respectively. When compared with literature, Halomonas sp. was found to stand out with its exceptionally high levan production yields on available fructose. Molecular characterization and monosaccharide composition studies confirmed levan-type fructan structure of the biopolymers. Rheological properties under different conditions pointed to the typical characteristics of low viscosity and pseudoplastic behaviors of the levan polymers. Moreover, levan polymer produced from molasses showed high biocompatibility and affinity with both cancerous and non-cancerous cell lines.     

Experimental evidence for adaptive personalities in a wild passerine bird

Individuals of the same species differ consistently in risky actions. Such ‘animal personality’ variation is intriguing because behavioural flexibility is often assumed to be the norm. Recent theory predicts that between-individual differences in propensity to take risks should evolve if individuals differ in future fitness expectations: individuals with high long-term fitness expectations (i.e. that have much to lose) should behave consistently more cautious than individuals with lower expectations. Consequently, any manipulation of future fitness expectations should result in within-individual changes in risky behaviour in the direction predicted by this adaptive theory. We tested this prediction and confirmed experimentally that individuals indeed adjust their ‘exploration behaviour’, a proxy for risk-taking behaviour, to their future fitness expectations. We show for wild great tits (Parus major) that individuals with experimentally decreased survival probability become faster explorers (i.e. increase risk-taking behaviour) compared to individuals with increased survival probability. We also show, using quantitative genetics approaches, that non-genetic effects (i.e. permanent environment effects) underpin adaptive personality variation in this species. This study thereby confirms a key prediction of adaptive personality theory based on life-history trade-offs, and implies that selection may indeed favour the evolution of personalities in situations where individuals differ in future fitness expectations.     

Senescence-induced iron mobilization in source leaves of barley (Hordeum vulgare) plants

? Retranslocation of iron (Fe) from source leaves to sinks requires soluble Fe binding forms. As much of the Fe is protein-bound and associated with the leaf nitrogen (N) status, we investigated the role of N in Fe mobilization and retranslocation under N deficiency- vs dark-induced leaf senescence. ? By excluding Fe retranslocation from the apoplastic root pool, Fe concentrations in source and sink leaves from hydroponically grown barley (Hordeum vulgare) plants were determined in parallel with the concentrations of potential Fe chelators and the expression of genes involved in phytosiderophore biosynthesis. ? N supply showed opposing effects on Fe pools in source leaves, inhibiting Fe export out of source leaves under N sufficiency but stimulating Fe export from source leaves under N deficiency, which partially alleviated Fe deficiency-induced chlorosis. Both triggers of leaf senescence, shading and N deficiency, enhanced NICOTIANAMINE SYNTHASE2 gene expression, soluble Fe pools in source leaves, and phytosiderophore and citrate rather than nicotianamine concentrations. ? These results indicate that Fe mobilization within senescing leaves is independent of a concomitant N sink in young leaves and that phytosiderophores enhance Fe solubility in senescing source leaves, favoring subsequent Fe retranslocation.     

The prebiotic source influences the growth, biochemical features and survival under simulated gastrointestinal conditions of the probiotic Lactobacillus acidophilus

The viability of the probiotic strain Lactobacillus acidophilus DSM 20079, after its passage through the simulated gastric and pancreatic juices, was evaluated as function of its pre-growth in a medium containing the known prebiotics pectin or inulin, and was compared to glucose used as control. The presence of pectin or inulin did not affect the growth (12.11(log10) colony forming units/mL and 12.08(log10) colony forming units/mL for pectin and inulin respectively versus 12.22(log10) colony forming units/mL obtained for glucose). Pectin and inulin, in contrast to glucose, induced cell stress resistance against gastrointestinal juices (Δ(log10) 1 and 2 colony forming units/mL respectively, versus Δ(log10) 4.5 for glucose). The data were confirmed by the analysis of the protein pattern following stress treatments which, in the case of microbial cells grown with glucose, revealed a relevant protein degradation after the double passage through simulated gastric and intestinal juices. An impressive metabolic change, as function of the growth conditions, was demonstrated by analyzing the proteomic profile with a μ-2DE system, used herein for the first time as evaluation tool of prebiotic-probiotic interactions. The analysis revealed a different pH protein distribution that was mostly acidic in the presence of pectin and neutral-alkaline in the presence of inulin. Both prebiotics stimulated the production of butyrate, a relevant healthy bio-molecule not detectable in the presence of glucose, that was measured by HPLC analysis to be 14.5 fold higher after growth in the presence of inulin, as compared to pectin. Three specific proteins were detected at pH 6 after growth in the presence of pectin or inulin. They could be correlated to the stress resistance and/or to the production of butyrate, the common phenotypic characteristics induced in the bacterial strain by the two prebiotics.     

Gelrite plate technique for culturing Sulfolobus solfataricus,a thermoacidophilic archaebacterium

Summary A rapid procedure for plating the thermo-acidophilic archaebacterium Sulfolobus solfataricus using Gerlite as a gelling agent is reported. The technique uses a clear, single layer in which the colonies are grown.     

Mutual Mate Choice for Colorful Traits in King Penguins

While studies of mate choice based on male color pattern are ubiquitous, studies of mate choice based on ornamental color traits in sexually monomorphic species are less common. We conducted manipulative field experiments on two color ornaments of king penguins (Aptenodytes patagonicus), the size of auricular patches of orange feathers and degree of UV reflectance from beak spots, to determine how the degree of ornamentation influenced pairing rate. In a reduction of auricular patch size, females paired significantly more quickly than males in both control and experimental samples. When this bias was taken into account statistically, pairing of individuals with reduced auricular patches was significantly delayed. We also reduced, but did not eliminate, UV reflectance from beak spots by applying a UV filter; no sex difference in pairing rate was evident in this experiment. Treated birds paired significantly more slowly than untreated control individuals, taking more than a week longer to pair on average than their unmanipulated counterparts, a result that was significant for males and approached significance for females. Our results may indicate mutual mate choice via UV reflectance of the beak spot. Given that this is a species where breeding is extremely slow and considerable investment by both males and females is required for successful reproduction, our results support the hypothesis that in such species, sexual selection might act on the same ornament in both sexes.     

Isolation of extremely halotolerant cocci from Antarctica

Abstract Five non-motile Gram-positive cocci were isolated from saline located in geothermal regions of the Antarctic continent. The organisms were extremely halotolerant growing between 0 and 4.2 M NaCl. On the basis of the results of phenotypic characterizations, lipid and quinone analyses, and the amino acid composition of the cell the isolates have been assigned to the genus Micrococcus .     

A halophilic thermotolerant Bacillus isolated from a marine hot spring able to produce a new exopolysaccharide

A halophilic, thermotolerant Bacillus strain (B3-15), isolated from water of a shallow, marine hot spring at Vulcano Island (Eolian Islands, Italy), produced an exocellular polysaccharide at 165 mg l^–1. It grew on kerosene as sole carbon source and was resistant to Cd²⁺, Zn²⁺, As²⁺ and Hg²⁺. From 16S rDNA analysis, strain B3-15 was related to B. licheniformis. The exopolysaccharide was a tetrasaccharide repeating unit essentially constituted by sugars having a manno-pyranosidic configuration.