Growth and enzyme production by three Penicillium species on monosaccharides

The growth and preference for utilisation of various sugar by the Penicillium species Penicillium pinophilum IBT 4186, Penicillium persicinum IBT 13226 and Penicillium brasilianum IBT 20888 was studied in batch cultivations using various monosaccharides as carbon source, either alone or in mixtures. P. pinophilum IBT 4186 and P. persicinum IBT 13226 had a micro(max) around 0.08-0.09 h(-1) using either glucose or xylose as carbon source. The micro(max) of P. brasilianum IBT 20888 was 0.16 and 0.14 h(-1) on glucose and xylose, respectively. Glucose was found to exert repression on the catabolism of mannose, galactose, xylose and arabinose. The three species were able to utilise all the tested monosaccharides, but arabinose was only slowly metabolised. Glucose was also found to repress the production of endoglucanases, endoxylanases and beta-xylosidases. After glucose depletion, the fungi started producing beta-glucosidase and endoglucanases. Xylose did not repress the enzyme production and it induced the production of endoxylanases and beta-xylosidases.     

High molecular weight kininogen regulates platelet-leukocyte interactions by bridging Mac-1 and glycoprotein Ib

Leukocyte-platelet interaction is important in mediating leukocyte adhesion to a thrombus and leukocyte recruitment to a site of vascular injury. This interaction is mediated at least in part by the beta2-integrin Mac-1 (CD11b/CD18) and its counter-receptor on platelets, glycoprotein Ibalpha (GPIbalpha). High molecular weight kininogen (HK) was previously shown to interact with both GPIbalpha and Mac-1 through its domains 3 and 5, respectively. In this study we investigated the ability of HK to interfere with the leukocyte-platelet interaction. In a purified system, HK binding to GPIbalpha was inhibited by HK domain 3 and the monoclonal antibody (mAb) SZ2, directed against the epitope 269-282 of GPIbalpha, whereas mAb AP1, directed to the region 201-268 of GPIbalpha had no effect. In contrast, mAb AP1 inhibited the Mac-1-GPIbalpha interaction. Binding of GPIbalpha to Mac-1 was enhanced 2-fold by HK. This effect of HK was abrogated in the presence of HK domains 3 or 5 or peptides from the 475-497 region of the carboxyl terminus of domain 5 as well as in the presence of mAb SZ2 but not mAb AP1. Whereas no difference in the affinity of the Mac-1-GPIbalpha interaction was observed in the absence or presence of HK, maximal binding of GPIbalpha to Mac-1 doubled in the presence of HK. Moreover, HK/HKa increased the Mac-1-dependent adhesion of myelomonocytic U937 cells and K562 cells transfected with Mac-1 to immobilized GPIbalpha or to GPIbalpha-transfected Chinese hamster ovary cells. Finally, Mac-1-dependent adhesion of neutrophils to surface-adherent platelets was enhanced by HK. Thus, HK can bridge leukocytes with platelets by interacting via its domain 3 with GPIbalpha and via its domain 5 with Mac-1 thereby augmenting the Mac-1-GPIbalpha interaction. These distinct molecular interactions of HK with leukocytes and platelets contribute to the regulation of the adhesive behavior of vascular cells and provide novel molecular targets for reducing atherothrombotic pathologies.     

In field damage of high and low cyanogenic cassava due to a generalist insect herbivore Cyrtomenus bergi (Hemiptera: Cydnidae)

The hypothesis that cyanogenic potential in cassava roots deters polyphagous insects in the field is relevant to current efforts to reduce or eliminate the cyanogenic potential in cassava. To test this hypothesis, experiments were conducted in the field under natural selection pressure of the polyphagous root feeder Cyrtomenus bergi Froeschner (Hemiptera: Cydnidae). A number of cassava varieties (33) as well as 13 cassava siblings and their parental clone, each representing a determined level of cyanogenic potential (CNP), were scored for damage caused by C. bergi and related to CNP and nonglycosidic cyanogens, measured as hydrogen cyanide. Additionally, 161 low-CNP varieties (< 50 ppm hydrogen cyanide, fresh weight) from the cassava germplasm core collection at Centro Internacional de Agricultura Tropical (CIAT) were screened for resistance/tolerance to C. bergi. Low root damage scores were registered at all levels of CNP. Nevertheless, CNP and yield (or root size) partly explained the damage in cassava siblings (r2 = 0.82) and different cassava varieties (r2 = 0.42), but only when mean values of damage scores were used. This relation was only significant in one of two crop cycles. A logistic model describes the underlying negative relation between CNP and damage. An exponential model describes the underlying negative relation between root size and damage. Damage, caused by C. bergi feeding, released nonglycosidic cyanogens, and an exponential model fits the underlying positive relation. Fifteen low-CNP clones were selected for potential resistance/tolerance against C. bergi.     

Micronuclei frequency in children exposed to environmental mutagens: a review

Cytogenetic monitoring has been traditionally used for the surveillance of populations exposed to genotoxic agents. In recent years sensitivity problems emerged in surveys of populations exposed to low levels of mutagens, and therefore alternative approaches have been explored. Biomonitoring studies in children are a promising field, since because of evident differences in the uptake, metabolism, distribution and excretion of mutagens this population seems to be more susceptible than adults. Further, the effect of major confounders such as cigarettes smoking, occupation, life-style, and dietary factors plays a minor role. Among cytogenetic assays, the micronucleus assay (MN) has several advantages and is increasingly used. A review was then carried out to synthesize the published data on the occurrence of MN in children and adolescents (age range 0-18 years), and to assess the impact of genotoxic exposure on MN frequency. Overall, 20 papers from international literature and 8 Russian papers were included. An effect of age was found within this age range, while the influence of gender on MN frequency was irrelevant. These results were confirmed by the re-analysis of data for 448 children selected from the HUMN database. An effect of chronic and infectious diseases on MN levels has been reported by various authors. Most studies describing the effect of exposure to genotoxic agents (ionizing radiation, chemicals, drugs, environmental tobacco smoke) found an increase of MN in exposed children. The limited number of published papers indicates that the conduct of properly designed studies on the effect of environmental pollutants in children may be difficult. This review confirmed the usefulness of MN assay in biomonitoring studies conducted in children, revealing that in many circumstances investigating children increases the sensitivity of the study, even with low dose exposures.     

Experimental investigations of multiple steady states in aerobic continuous cultivations of Saccharomyces cerevisiae

The steady-state behavior of a glucose-limited, aerobic, continuous cultivation of Saccharomyces cerevisiae CEN.PK113-7D was investigated around the critical dilution rate. Oxido-reductive steady states were obtained at dilution rates up to 0.09 h(-1) lower than the critical dilution rate by operating the bioreactor as a productostat, where the dilution rate was controlled on the basis of an ethanol measurement. Thus, the experimental investigations revealed that multiple steady states exist in a region of dilution rates below the critical dilution rate. The existence of multiple steady states was attributed to two distinct physiological effects occurring when growth changed from oxidative to oxido-reductive: (i) a decrease in the efficiency of ATP production and utilization (at ethanol concentrations below 3 g/L) and (ii) repression of the oxidative metabolism (at higher ethanol concentrations). The first effect was best observed at low ethanol concentrations, where multiple steady states were observed even when no repression of the oxidative metabolism was evident, i.e., the oxidative capacity was constant. However, at higher ethanol concentrations repression of the oxidative metabolism was observed (the oxidative capacity decreased), and this resulted in a broader range of dilution rates where multiple steady states could be found.     

Interpretation of small angle X-ray measurements guided by molecular dynamics simulations of lipid bilayers

Reconstruction and interpretation of lipid bilayer structure from X-ray scattering often rely on assumptions regarding the molecular distributions across the bilayer. It is usually assumed that changes in head-head spacings across the bilayer, as measured from electron density profiles, equal the variations in hydrocarbon thicknesses. One can then determine the structure of a bilayer by comparison to the known structure of a lipid with the same headgroup. Here we examine this procedure using simulated electron density profiles for the benchmark lipids DMPC and DPPC. We compare simulation and experiment in both real and Fourier space to address two main aspects: (i) the measurement of head-head spacings from relative electron density profiles, and (ii) the determination of the absolute scale for these profiles. We find supporting evidence for the experimental procedure, thus explaining the robustness and consistency of experimental structural results derived from electron density profiles. However, we also expose potential pitfalls in the Fourier reconstruction that are due to the limited number of scattering peaks. Volumetric analysis of simulated bilayers allows us to propose an improved, yet simple method for scale determination. In this way we are able to remove some of the restrictions imposed by limited scattering data in constructing reliable electron density profiles.     

The synthesis of pseudomycin C' via a novel acid promoted side-chain deacylation of pseudomycin A

The gamma hydroxyl present in the aliphatic side chain of the natural products pseudomycin A and C' provided a unique handle for the pH dependent side-chain deacylation. Low pH reaction conditions were used to cleave the side chain with minimal degradation of the peptide core. The pseudomycin nucleus intermediate obtained from the deacylation of pseudomycin A was pivotal in the synthesis of novel side-chain analogues. A practical synthesis of a minor fermentation factor pseudomycin C' and related analogues is reported.     

A new global commitment to disease control in Africa

Despite the availability of effective therapies in developed nations, infectious diseases continue to take a grave toll on the population and economy of sub-Saharan Africa. Aside from a few successes, the global donor community has not adequately helped African governments meet these health challenges. However, if annual donor contributions increased approximately 10-20-fold, millions of lives could be saved, helping Africa escape the cycle of disease and impoverishment.