The bone and the kidney

Renal tubular diseases may present with osteopenia, osteoporosis or osteomalacia, as a result of significant derangements in body electrolytes. In case of insufficient synthesis of calcitriol, as in renal failure, the more complex picture of renal osteodystrophy may develop. Hypothetically, also disturbed renal production of BMP-7 and Klotho could cause bone disease. However, the acknowledgment that osteocytes are capable of producing FGF23, a phosphaturic hormone at the same time modulating renal synthesis of calcitriol, indicates that it is also bone that can influence renal function. Importantly, a feed-back mechanism exists between FGF23 and calcitriol synthesis, while Klotho, produced by the kidney, determines activity and selectivity of FGF23. Identification of human diseases linked to disturbed production of FGF23 and Klotho underlines the importance of this new bone-kidney axis. Kidney and bone communicate reciprocally to regulate the sophisticated machinery responsible for divalent ions homeostasis and for osseous or extraosseous mineralisation processes.     

Coherent optical spatial filtering of diatoms in water pollution monitoring

Summary The use of Fourier transform coherent optical techniques in the pattern recognition of microscopic algae, i.e., diatoms, is described. The results of the construction of complex-valued filters for diatoms and their usefulness in algal identification are presented. Some general applications to water pollution monitoring and control are discussed.     

Ecological comparison between duckweeds in central Italy: The invasive Lemna minuta vs the native L. minor

The American duckweed Lemna minuta shows an invasive behaviour in Europe, causing weed problems in aquatic habitats there. Few studies addressed this species’ ecological requirements for a suitable establishment in a site. In this paper, L. minuta populations were analysed through field surveys so as (1) to define the autoecology of this duckweed as regards the main environmental factors characterizing invaded habitats, and (2) to identify possible overlaps/differences in ecological requirements between the alien L. minuta and the common native L. minor, with which it is often associated and in direct competition. The occurrence/abundance of the two species and environmental data were collected from 41 wetlands in central Italy. Currently, L. minuta is more common and abundant than L. minor in the study-area, despite its recent arrival there (2007). The two species have a partially overlapped autoecology. However, L. minuta differs from L. minor since it occurs in waters which are less alkaline, slightly less warm, and richer in nitrates. It shows tolerance for environmental conditions which are limiting for most of macrophytes, including L. minor, such as high shading and low water oxygenation. This enables L. minuta to increase its invasion potentiality and thus to enlarge its distribution area.     

Bioinformatic Characterization of the Trimeric Intracellular Cation-Specific Channel Protein Family

Trimeric intracellular cation-specific (TRIC) channels are integral to muscle excitation–contraction coupling. TRIC channels provide counter-ionic flux when calcium is rapidly transported from intracellular stores to the cell cytoplasm. Until recently, knowledge of the presence of these proteins was limited to animals. We analyzed the TRIC family and identified a profusion of prokaryotic family members with topologies and motifs similar to those of their eukaryotic counterparts. Prokaryotic members far outnumber eukaryotic members, and although none has been functionally characterized, the evidence suggests that they function as secondary carriers. The presence of fused N- or C-terminal domains of known biochemical functions as well as genomic context analyses provide clues about the functions of these prokaryotic homologs. They are proposed to function in metabolite (e.g., amino acid/nucleotide) efflux. Phylogenetic analysis revealed that TRIC channel homologs diverged relatively early during evolutionary history and that horizontal gene transfer was frequent in prokaryotes but not in eukaryotes. Topological analyses of TRIC channels revealed that these proteins possess seven putative transmembrane segments (TMSs), which arose by intragenic duplication of a three-TMS polypeptide-encoding genetic element followed by addition of a seventh TMS at the C terminus to give the precursor of all current TRIC family homologs. We propose that this family arose in prokaryotes.     

Metabolic Profiling of Alternative NAD Biosynthetic Routes in Mouse Tissues

NAD plays essential redox and non-redox roles in cell biology. In mammals, its de novo and recycling biosynthetic pathways encompass two independent branches, the “amidated” and “deamidated” routes. Here we focused on the indispensable enzymes gating these two routes, i.e. nicotinamide mononucleotide adenylyltransferase (NMNAT), which in mammals comprises three distinct isozymes, and NAD synthetase (NADS). First, we measured the in vitro activity of the enzymes, and the levels of all their substrates and products in a number of tissues from the C57BL/6 mouse. Second, from these data, we derived in vivo estimates of enzymes''rates and quantitative contributions to NAD homeostasis. The NMNAT activity, mainly represented by nuclear NMNAT1, appears to be high and nonrate-limiting in all examined tissues, except in blood. The NADS activity, however, appears rate-limiting in lung and skeletal muscle, where its undetectable levels parallel a relative accumulation of the enzyme''s substrate NaAD (nicotinic acid adenine dinucleotide). In all tissues, the amidated NAD route was predominant, displaying highest rates in liver and kidney, and lowest in blood. In contrast, the minor deamidated route showed higher relative proportions in blood and small intestine, and higher absolute values in liver and small intestine. Such results provide the first comprehensive picture of the balance of the two alternative NAD biosynthetic routes in different mammalian tissues under physiological conditions. This fills a gap in the current knowledge of NAD biosynthesis, and provides a crucial information for the study of NAD metabolism and its role in disease.     

In vitro models of multiple system atrophy from primary cells to induced pluripotent stem cells

Multiple system atrophy (MSA) is a rare neurodegenerative disease with a fatal outcome. Nowadays, only symptomatic treatment is available for MSA patients. The hallmarks of the disease are glial cytoplasmic inclusions (GCIs), proteinaceous aggregates mainly composed of alpha‐synuclein, which accumulate in oligodendrocytes. However, despite the extensive research efforts, little is known about the pathogenesis of MSA. Early myelin dysfunction and alpha‐synuclein deposition are thought to play a major role, but the origin of the aggregates and the causes of misfolding are obscure. One of the reasons for this is the lack of a reliable model of the disease. Recently, the development of induced pluripotent stem cell (iPSC) technology opened up the possibility of elucidating disease mechanisms in neurodegenerative diseases including MSA. Patient specific iPSC can be differentiated in glia and neurons, the cells involved in MSA, providing a useful human disease model. Here, we firstly review the progress made in MSA modelling with primary cell cultures. Subsequently, we focus on the first iPSC‐based model of MSA, which showed that alpha‐synuclein is expressed in oligodendrocyte progenitors, whereas its production decreases in mature oligodendrocytes. We then highlight the opportunities offered by iPSC in studying disease mechanisms and providing innovative models for testing therapeutic strategies, and we discuss the challenges connected with this technique.     

Epidermal growth factor binding and steroid receptor content in human benign prostatic hyperplasia

The receptor for epidermal growth factor (EGF-R) was characterized on membrane fractions from human benign prostatic hyperplasia (BPH). Specific binding of [125I]EGF reached equilibrium after 40 min at 25 degrees C and was stable for up to 120 min. Saturation analysis of EGF-R, performed by incubating the membranes with 0.0156-15 nM [125I]EGF in the presence and in the absence of 100-fold excess of cold EGF for 60 min, revealed the presence of two classes of binding sites with high and low affinities (Kd = 0.35 +/- 0.23 and 9.60 +/- 2.87 nM respectively). Competition experiments revealed that FSH, insulin and calcitonin did not compete with [125I]EGF. The simultaneous determination of EGF-R and that of estradiol (ER), progesterone (PR) and androgen receptors (AR) was performed using the same buffer to homogenate the tissues and to obtain cellular membranes. The steroid receptors (SR) were determined by means of the dextran-coated charcoal method. There was a significant negative correlation between nuclear SR and binding capacity of EGF-R. The presence of specific and high affinity binding sites for EGF and the modulation of the level of these sites by steroid receptors suggest a possible role of EGF in prostatic hyperplasia.     

Pityriasis versicolor in the aged: A clinical investigation and epidemiological survey in 190 elderly hospitalized patients

190 subjects over 60 yrs of age, hospitalized for long stays were checked for scaling and hyperpigmented patches of P. versicolor. 20 patients (10.5%) showed no clinical lesions; 170 patients (89.5%) showed scaling and/or hyperpigmented patches of which 13 patients (6.8%) on direct microscopic exam showed hyphae and yeasts of M. furfur, 64 (33.6%) only globular forms of P. orbiculare and 113 cases (59.4%) showed no fungal elements. Wood's light examination showed that 38 subjects (20%) were 6 positive for M. furfur and 23 for P. orbiculare while in the other 9 no fungal elements were observed on microscopic exam. Whereas 48/132 patients negative to Wood's light were positive for yeasts on microscopic exam (false negative). This study indicates that P. versicolor is not rare in the elderly and that Wood's light examination is not diagnostic. There was no relationship between P. versicolor and underlying illness.     

Electrically induced phase transitions via the dipole model in excitable membranes

Calculations based upon the membrane dipole model have been carried out and indicate the possibility of cooperative behavior during the membrane excitation process. An explicit expression is obtained for the critical electric field,E, which must be present to initiate the cooperative structural transition assumed to occur during membrane excitation. An hypothesis concerning the occurrence of two distinct phase transitions in the membrane resulting in the rapid influx of sodium ions and sodium ion inactivation, respectively, is presented.