Mechanisms of Neuronal Death in a Transgenic Mouse Model for Amyotrophic Lateral Sclerosis

Neurons are large post-mitotic cells with a high metabolic activity and a highly complex morphology characterized by a dendritic tree that consists of a network of processes, and an axon that can have length of up to 104 times the diameter of the cell body. Because of this complexity the maintenance of the functional and structural integrity of neurons throughout life is a complex task that requires sophisticated transport, damage control and repair machineries. Hence, it is not surprising that aging is associated with structural and functional deterioration of the central nervous system and that neurodegenerative diseases (diseases that cause the premature loss of neurons) are among the dominant disorders associated with aging. The knowledge on processes involved in normal aging and neuronal death in neurodegerative diseases is increasing, but far from complete. Intervention in these processes is therefore not yet possible. Amyotrophic lateral sclerosis (ALS) is a fatal disease in which motoneurons in the spinal cord, brain stem and motor cortex degenerate. This disease has an incidence of 2-3 per 100.000 people, meaning that 300-450 people are diagnosed with the disease each year. The survival of ALS-patients is on average 3 years after diagnosis. The first symptoms are usually fatigue, muscle cramps, and weakness in the muscles of one of the limbs, progressing to paralysis and spreading to other parts of the body, eventually causing total body paralysis. In most patients (about 90%) no apparent genetic cause for their disease has been found, in those cases the disease is called sporadic ALS. In the other 10% a hereditary pattern has been found; familial ALS. In 1993 a mutation was found in the gene for superoxide dismutase 1 (SOD1) which causes ALS in some familial ALS families. By now more than 110 different mutations in the SOD1-gene have been linked to familial ALS and more recently mutations in 5 other genes have been found to cause familial ALS. The discovery of SOD1-mutations has enabled the production of transgenic mutant-SOD1 expressing mice that develop an ALS-like motoneuron disease. These SOD1-mutant mice develop a disease strongly resembling human ALS. These transgenic mice offer the possibility to study all stages of motoneuron death. In this thesis different aspects of ALS in the transgenic mouse model and in cultured motoneurons are studied and discussed

First records of the summerfruit tοrticid, Adoxophyes oranα F. ν .R. in Greece

Το πολυφάγο Αεπιδόπτερο Adoxophyes orana F.v.R. της οικογένειας Tortricidae παρατηρήθηκε για πρώτη φορά στην περιοχή της Νάουσας το 1985, σε μηλιές, ροδακινιές και κερασιές, όπου προσέβαλε την άνοιξη τους οφθαλμούς και αργότερα τα φύλλα και τους καρπούς. Πιθανότατα εισήλθε στην Ελλάδα από τη γειτονική Γιουγκοσλαβία, όπου ήταν γνωστό και προκαλούσε ζημιά στα οπωροφόρα δέντρα τουλάχιστον από το 1975. Το ενήλικο σε γενικό χρωματισμό και μορφή μοιάζει με το επίσης πολυφάγο φυλλοδετικό Λεπιδόπτερο.4Γί7φί rosanus L. Το άνοιγμα των πτερύγων στο ενήλικο αρσενικό είναι 15-20 mm και το θηλυκό 19-22 mm. Οι πρόσθιες πτέρυγες στο αρσενικό έχουν βασικό χρώμα κίτρινο ώχρας και στο θηλυκό σκοτεινότερο, συχνά καστανόμαυρο. Οι πτέρυγες αυτές και στα δύο φύλλα, έχουν χαρακτηριστικές κηλίδες και λωρίδες σκοτεινότερες από το βασικό χρώμα. Η πλήρως αναπτυγμένη προνύμφη είναι πράσινη και μήκους 18-20 mm.In spring 1985, buds of apple and peach trees in the Naoussa area of northern Greece were severely damaged by larvae of a tortricid moth. Adults emerged in late May and early June. Later in the season, we found larvae of the same species established and feeding on leaves and green or ripe fruits of apple and peach, as well as on ripe cherries. Larvae collected in late June were reared in the laboratory on peach leaves and on an artificial diet. The adults obtained were identified as Adoxophyes orana Fischer von Rosslerstamm (Lepidoptera. Tortricidae). A. orana is a synonym of A. reticulates Huebner, A.tripsiana Eversmann, A. fasciata Walsh., or Capua or Cacoecia reticulana Huebner and most probably, is a recent introduction to Greece. The damage it causes to fruits such as apples, peaches and cherries is such that it could not have escaped the attention of fruit growers and plant protection specialists if the insect had earlier been present in the country. A. orana has been established and caused damage to fruit trees in northwest and central Europe for approximately fifty years and in southern Yugoslavia for at least the last ten years. It is probable that it spread to northern Greece from neighboring Yugoslavia. In the Naoussa area, the moths laid their eggs in batches on fruits or leaves. On peach and cherry the eggs were laid on both sides of the leaves, whereas on apple on the upper side as was observed also in other countries. In early October, the larvae abandoned their feeding sites and went next to auxiliary buds and crevices of the bark of branches to spin their hibernating webs. The adult maleof A. orana has a wingspan of 15-20 mm and the female one of 19-22 mm. The fore wings of the male are yellow ochre reddish, and have distinct rusty-red designs. There is a basal darker (brown) area, and two large darker stripes. The median one departs from the basal third of the costa and terminates, widening or divided in two branches, at the tornus. The other stripe is preapical and may take the form of a triangular spot of which sometimes only the borders are visible. The fore wings of the female are normally darker than those of the male, often blackish-brown, and have darker and dimmer stripes and other markings. The hind wings are light grey in the male and grey-brown in the female. The ground colour in the specimens of northwestern Europe is varying from light brown to dark brown. The fully grown larva is 18-20 mm long, green, with a light brown head. It somewhat resembles the larva of another tortricid, Archipsrosanus L. which is a monovoltine polyphagous species common in Greek orchards in spring. A. orana is polyvoltine and feeds on buds, leaves and fruits of a great number of cultivated and wild plants. Among its reported many hosts are species of Betula, Crataegus, Cydonia, Gossypium, Ligustrum, Lonicera, Malus, Medicago, Pyrus, Populus, Pistacia, Parrotia, Proms,Quercus, Ribes, Rubus, Rosa, Salix, Solanum, Syringa, Tilia, Ulmus, Vaccinium and the grapevine Vitis vinifera

Bone Resorption Is Increased in Pheochromocytoma Patients and Normalizes following Adrenalectomy

Context: The sympathetic nervous system (SNS) controls bone turnover in rodents, but it is uncertain whether a similar role for the SNS exists in humans. Pheochromocytomas are catecholamine-producing neuroendocrine tumors. Because catecholamines are the neurotransmitters of the SNS, we hypothesized that pheochromocytoma patients have increased bone turnover. Objective: Our objective was to compare bone turnover in pheochromocytoma patients and controls. Design and Setting: This retrospective case-control study was performed at the Endocrine Department of the Academic Medical Center of the University of Amsterdam in The Netherlands from 2007 until 2011. Patients: All patients were screened for pheochromocytoma. Cases (n = 21) were identified by 24-h urinary excretion of fractionated metanephrines above the institutional reference value and confirmed by histology after adrenalectomy. All patients screened and diagnosed as not having pheochromocytoma served as controls (n = 126). Main Outcome Measure: The difference in bone turnover markers C-terminal cross-linking telopeptides of collagen type I (CTx) and procollagen type 1 N propeptide (P1NP) between cases and controls was the main outcome measure. Results: CTx concentrations were higher in cases [343 ng/liter; interquartile range (IQR), 295 ng/liter] than in controls (232 ng/liter; IQR, 168 ng/liter; P <0.001) and decreased after adrenalectomy [before, 365 ng/liter (IQR, 450 ng/liter); after, 290 ng/liter (IQR, 241 ng/liter); P = 0.044]. The effect remained after adjustment for possible confounders. P1NP concentrations did not differ. Conclusions: This study shows that pheochromocytoma patients have increased bone resorption, which normalizes after adrenalectomy. This finding supports the concept of regulation of bone remodeling by the SNS in humans. (J Clin Endocrinol Metab 97: E2093-E2097, 2012