Regulation of cell death: the calcium-apoptosis link

To live or to die? This crucial question eloquently reflects the dual role of Ca2+ in living organisms--survival factor or ruthless killer. It has long been known that Ca2+ signals govern a host of vital cell functions and so are necessary for cell survival. However, more recently it has become clear that cellular Ca2+ overload, or perturbation of intracellular Ca2+ compartmentalization, can cause cytotoxicity and trigger either apoptotic or necrotic cell death.     

Compound heterozygosity for two different amino-acid substitution mutations in the thrombopoietin receptor (c-mpl gene) in congenital amegakaryocytic thrombocytopenia (CAMT)

Congenital amegakaryocytic thrombocytopenia (CAMT) without physical anomalies is a rare disease, presenting isolated thrombocytopenia and megakaryocytopenia in infancy, which can evolve into aplastic anemia and leukemia. Recently, two heterozygous truncating mutations of the thrombopoietin (TPO) receptor MPL, coded by the c-mpl gene, were identified in a 10-year-old Japanese patient with CAMT transmitted in an autosomal recessive manner. Here, we report for the first time two different MPL amino-acid substitutions in a 2-year-old Italian boy with CAMT and compound heterozygosis for two (c-mpl point mutations. C-to-T transitions were detected on exons 5 and 12 at the 769 and 1904 cDNA nucleotide positions, respectively. The mutation in exon 5 substitutes an arginine with a cysteine (R257C) in the extracellular domain, 11 amino acids distant from the WSXWS motif conserved in the cytokine-receptor superfamily. The mutation in exon 12 substitutes a proline with a leucine (P635L) in the last amino acid of the C-terminal intracellular domain, responsible for signal transduction. As in the Japanese family, the mutations were both transmitted from the parents. TPO plasma levels were highly increased in the patient. The patient's 7-year-old brother, who was a candidate donor for allografting, turned out to be an asymptomatic heterozygous carrier of P635L and showed defective megakaryocyte colony formation from bone-marrow progenitor cells. The present study provides important confirmation that CAMT can be associated with (c-mpl) mutations.     

Botanical nematicides in the mediterranean basin

Achieving food sufficiency in a sustainable manner is a major challenge for farmers, agro-industries, researchers and governments. Amongst agricultural pests supressing crops, root-knot nematodes (Meloidogyne spp.) represent possibly the world’s most damaging one, the control of which has been mainly based on chemical nematicides. In the recent years the environmental, food safety and animal welfare issues pose the need for alternative nematode control measures. Screening naturally occurring compounds in plants, involved in the complex chemical-mediated interactions between a plant and other organisms in its environment, can provide with innovative nematode control measures that can be safely used in integrated pest management programs. The Mediterranean Basin is an area where various soils and climatic conditions allow a vast plant biodiversity providing with chemical botanicals of significant nematicidal potency. This is a review on the Mediterranean botanicals that can control Meloidogyne spp.     

New statistical software for intralaboratory and interlaboratory quality control in clinical cytology. Validation in a simulation study on clinical samples

OBJECTIVE: To design a statistical software package to provide automated calculations of normal and weighted and 3 indices. STUDY DESIGN: Prompted by the lack of commonly available software to compute weighted kappa and the nonproportionate workload needed to calculate our 3 variability indices manually, the new statistical software package was designed. To demonstrate the performance of the new CONQUISTADOR software, a simulation study (both intralaboratory and interlaboratory) was designed using 5,000 clinical samples randomly selected from a data file of > or = 200,000 conventional Pap smears and programmed to become "analyzed" by 12 cytologists in 5 imaginary laboratories. RESULTS: A representative set of both complete and partial outputs provided by the software, in Excel format (Microsoft, Redmond, Washington, U.S.A.) are shown to illustrate the different functions of the program. In the interlaboratory mode, the software calculates accuracy indicators (sensitivity, specificity, positive and negative predictive value, and their 95% CI), which are not common features of regular statistical packages; kappa and weighted kappa; and their 95% CI (comparison of single laboratories to all laboratories and pairwise comparisons between single laboratories). The 3 diagnostic variability indices can be computed separately for all samples or for only the positive samples. In the intralaboratory mode, the software calculates the same indices for individual cytologists. CONCLUSION: The CONQUISTADOR statistical package has properties that are useful in monitoring cytologic laboratory quality in both intralaboratory and interlaboratory settings. The software will be distributed by the National Institute of Health, Rome, for the delivery costs only.     

The poor health of deep-water species in the context of fishing activity and a warming climate: will populations of Molva species rebuild or collapse?

Many deep-water fish populations, being K-selected species, have little resilience to overexploitation and may be at serious risk of depletion as a consequence. Sea warming represents an additional threat. In this study, the condition, or health, of several populations of common ling (Molva molva), blue ling (Molva dypterygia) and Mediterranean or Spanish ling (Molva macrophthalma) inhabiting different areas in the North Atlantic and the Mediterranean was evaluated, to shed light on the challenges these deep-water species are facing in the context of fishing activity and a warming climate. The data on the condition of Molva populations which are analysed here have been complemented with data on abundance and, for the southernmost species (Mediterranean ling), with two other health indicators (parasitism and hepato-somatic index). Despite some exceptions (e.g., common ling in Icelandic waters), this study shows that the condition of many populations of Molva species in the northeastern Atlantic and the Mediterranean Sea has worsened, a trend which, in recent decades, has usually been found to be accompanied by a decline in their abundance. In addition, the poor health status of most populations of common ling, blue ling and Mediterranean ling considered in this analysis points to a lower sustainability of these populations in the future. Overall, the health status and abundance of Molva populations in the northeastern Atlantic and the Mediterranean suggest that only some populations located in the North Atlantic may be able to rebuild, whereas the populations in southern North Atlantic and the Mediterranean, which are probably most at risk from sea warming, are facing serious difficulties in doing so. In the context of fisheries and global warming, this study's results strongly indicate that management bodies need to consider the health status of many of the populations of Molva species, particularly in southern European waters, before implementing their decisions.     

Denitrification in a meromictic lake and its relevance to nitrogen flows within a moderately impacted forested catchment

We analysed the spatial and temporal variability of benthic nitrogen fluxes and denitrification rates in a sub-alpine meromictic lake (Lake Idro, Italy), and compared in-lake nitrogen retention and loss with the net anthropogenic nitrogen inputs to the watershed. We hypothesized a low nitrogen retention and denitrification capacity due to meromixis. This results from nitrate supply from the epilimnion slowing down during stratification and oxygen deficiency inhibiting nitrification and promoting ammonium recycling and its accumulation. We also hypothesized a steep vertical gradient of sedimentary denitrification capacity, decreasing with depth and oxygen deficiency. These are important and understudied issues in inland waters, as climate change and direct anthropic pressures may increase the extent of meromixis. Nearshore sediments had high denitrification rates (87 mg m^?2 day^?1) and efficiency (~ 100%), while in the monimolimnion denitrification was negligible. The littoral zone, covering 10% of the lake surface, contributed ~50% of total denitrification, while the monimolimnion, which covered 70% of the sediment surface, contributed to < 13% of total denitrification. The persistent and expanding meromixis of Lake Idro is expected to further decrease its nitrogen removal capacity (31% of the incoming nitrogen load) compared to what has been measured in other temperate lakes. Values up to 60% are generally reported for other such lakes. Results of this study are relevant as the combination of anthropogenic pressures, climate change and meromixis may threaten the nitrogen processing capacity of lakes.     

An antibody cross-reacting with LA and FOUR antigens of theHL-A system

A volunteer was immunized by planned blood transfusions from an LA and FOUR incompatible donor. Among the several antibodies produced, an antibody population was found that cross-reacts with both LA and FOUR antigens; both these crossreacting determinants were present in the immunizing donor. Monospecificity of the antibody has been proven by adsorptions and elutions. Resistance to lysis experiments excluded the possibility that this antibody does not react against LA and FOUR, but reacts instead against an antigen belonging to another independentHL-A locus with alleles in strong linkage disequilibrium withLA andFOUR alleles. The following hypotheses are therefore formulated: a)LA andFOUR factors have structural analogies; b) LA and FOUR molecules lie in close proximity on the cell surface so that the appearance of a “hybrid” antigenic determinant becomes possible.