Molecular Pathways of Disturbed Sleep and Depression: Studies on Adenosine and Gene Expression Patterns

Background: Adenosine is a potent sleep-promoting substance, and one of its targets is the basal forebrain. Fairly little is known about its mechanism of action in the basal forebrain and about the receptor subtype mediating its regulating effects on sleep homeostasis. Homeostatic deficiency might be one of the causes of the profoundly disturbed sleep pattern in major depressive disorder, which could explain the reduced amounts of delta-activity-rich stages 3 and 4. Since major depression has a relatively high heritability, and on the other hand adenosine regulates sleep homeostasis and might also be involved in mood modulation, adenosine-related genes should be considered for their possible contribution to a predisposition for depression and disturbed sleep in humans. Depression is a complex disorder likely involving the abnormal functioning of several genes. Novel target genes which could serve as the possible common substrates for depression and comorbid disturbed sleep should be identified. In this way specific brain areas related to sleep regulation should be studied by using animal model of depression which represents more homogenous phenotype as compared to humans. It is also important to study these brain areas during the development of depressive-like features to understand how early changes could facilitate pathophysiological changes in depression. Aims and methods: We aimed to find out whether, in the basal forebrain, adenosine induces recovery non-rapid eye movement (NREM) sleep after prolonged waking through the A1 or/and A2A receptor subtype. A1 and A2A receptor antagonists were perfused into the rat basal forebrain during 3 h of sleep deprivation, and the amount of NREM sleep and delta power during recovery NREM sleep were analyzed. We then explored whether polymorphisms in genes related to the metabolism, transport and signaling of adenosine could predispose to depression accompanied by signs of disturbed sleep. DNA from 1423 individuals representative of the Finnish population and including controls and cases with depression, depression accompanied by early morning awakenings and depression accompanied by fatigue, was used in the study to investigate the possible association between polymorphisms from adenosine-related genes and cases. Finally to find common molecular substrates of depression and disturbed sleep, gene expression changes were investigated in specific brain areas in the rat clomipramine model of depression. We focused on the basal forebrain of 3-week old clomipramine-treated rats which develop depressive-like symptoms later in adulthood and on the hypothalamus of adult female clomipramine-treated rats. Results: Blocking of the A1 receptor during sleep deprivation resulted in a reduction of the recovery NREM sleep amount and delta power, whereas A2A receptor antagonism had no effect. Polymorphisms in adenosine-related genes SLC29A3 (equilibrative nucleoside transporter type 3) in women and SLC28A1 (concentrative nucleoside transporter type 1) in men associated with depression alone as well as when accompanied by early morning awakenings and fatigue. In Study III the basal forebrain of postnatal rats treated with clomipramine displayed disturbances in gamma-aminobutyric acid (GABA) receptor type A signaling, in synaptic transmission and possible epigenetic changes. CREB1 was identified as a common transcription denominator which also mediates epigenetic regulation. In the hypothalamus the major changes included the expression of genes in GABA-A receptor pathway, K+ channel-related, glutamatergic and mitochondrial genes, as well as an overexpression of genes related to RNA and mRNA processing. Conclusions: Adenosine plays an important role in sleep homeostasis by promoting recovery NREM sleep via the A1 receptor subtype in the basal forebrain. Also adenosine levels might contribute to the risk of depression with disturbed sleep, since the genes encoding nucleoside transporters showed the strongest associations with depression alone and when accompanied by signs of disturbed sleep in both women and men. Sleep and mood abnormalities in major depressive disorder could be a consequence of multiple changes at the transcriptional level, GABA-A receptor signaling and synaptic transmission in sleep-related basal forebrain and the hypothalamus.

Aikakauslehtipapereiden pitkän aikavälin kulutus Yhdysvalloissa

The United States is the world s single biggest market area, where the demand for graphic papers has increased by 80 % during the last three decades. However, during the last two decades there have been very big unpredictable changes in the graphic paper markets. For example, the consumption of newsprint started to decline from the late 1980 s, which was surprising compared to the historical consumption and projections. The consumption has declined since. The aim of this study was to see how magazine paper consumption will develop in the United States until 2030. The long-term consumption projection was made using mainly two methods. The first method was to use trend analysis to see how and if the consumption has changed since 1980. The second method was to use qualitative estimate. These estimates are then compared to the so-called classical model projections, which are usually mentioned and used in forestry literature. The purpose of the qualitative analysis is to study magazine paper end-use purposes and to analyze how and with what intensity the changes in society will effect to magazine paper consumption in the long-term. The framework of this study covers theories such as technology adaptation, electronic substitution, electronic publishing and Porter s threat of substitution. Because this study deals with markets, which have showed signs of structural change, a very substantial part of this study covers recent development and newest possible studies and statistics. The following were among the key findings of this study. Different end-uses have very different kinds of future. Electronic substitution is very likely in some end-use purposes, but not in all. Young people i.e. future consumers have very different manners, habits and technological opportunities than our parents did. These will have substantial effects in magazine paper consumption in the long-term. This study concludes to the fact that the change in magazine paper consumption is more likely to be gradual (evolutionary) than sudden collapse (revolutionary). It is also probable that the years of fast growing consumption of magazine papers are behind. Besides the decelerated growth, the consumption of magazine papers will decline slowly in the long-term. The decline will be faster depending on how far in the future we ll extend the study to.

Impact of low temperature storage on active and storage forms of folate in choy sum (Brassica rapa subsp parachinensis)

Choy sum (Brassica rapa subsp. parachinensis) is a dark green leafy vegetable that contains high folate (vitamin B9) levels comparable to spinach. Folate is essential for the maintenance of human health and is obtained solely through dietary means. Analysis of the edible portion of choy sum by both microbiological assay and LC-MS/MS indicated that total folate activity remained significantly unchanged over 3 weeks storage at 4 degrees C. Inedible fractions consisted primarily of outer leaves, which showed signs of rotting after 14d, and a combination of rotting and yellowing after 21 d, contributing to 20% and 40% of product removal, respectively. Following deconjugation of the folate present in choy sum to monoglutamate and diglutamate derivatives, the principal forms (vitamers) of folate detected in choy sum were 5-methyltetrahydrofolate and 5-formyl tetrahydrofolate, followed by tetrahydrofolate (THF), 5,10-methenyl-THF, and 10-formyl folic acid. During storage, a significant decline in 5-formyl-THF was observed, with a slight but not significant increase in the combined 5-methyl-THF derivatives. The decline in 5-formyl-THF in relation to the other folate vitamers present may indicate that 5-formyl-THF is being utilised as a folate storage reserve, being interconverted to more metabolically active forms of folate, such as 5-methyl-THF. Although folate vitamer profile changed over the storage period, total folate activity did not significantly change. From a human nutritional perspective this is important, as while particular folate vitamers (e.g. 5-methyl-THF) are necessary for maintaining vital aspects of plant metabolism, it is less important to the human diet, as humans can absorb and interconvert multiple forms of folate. The current trial indicates that it is possible to store choy sum for up to 3 weeks at 4 degrees C without significantly affecting total folate concentration of the edible portion. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.

The state of the art of business process management research as published in the BPM Conference

The research field of Business Process Management (BPM) has gradually developed as a discipline situated within the computer, management and information systems sciences. Its evolution has been shaped by its own conference series, the BPM conference. Still, as with any other academic discipline, debates accrue and persist, which target the identity as well as the quality and maturity of the BPM field. In this paper, we contribute to the debate on the identity and progress of the BPM conference research community through an analysis of the BPM conference proceedings. We develop an understanding of signs of progress of research presented at this conference, where, how, and why papers in this conference have had an impact, and the most appropriate formats for disseminating influential research in this conference. Based on our findings from this analysis, we provide conclusions about the state of the conference series and develop a set of recommendations to further develop the conference community in terms of research maturity, methodological advance, quality, impact, and progression.

Confirmed case of encephalitis caused by Murray Valley encephalitis virus infection in a horse

A 5-year-old Australian stock horse in Monto, Queensland, Australia, developed neurological signs and was euthanized after a 6-day course of illness. Histological examination of the brain and spinal cord revealed moderate to severe subacute, nonsuppurative encephalomyelitis. Sections of spinal cord stained positively in immunohistochemistry with a flavivirus-specific monoclonal antibody. Reverse transcription polymerase chain reaction assay targeting the envelope gene of flavivirus yielded positive results from brain, spinal cord, cerebrospinal fluid, and facial nerve. A flavivirus was isolated from the cerebrum and spinal cord. Nucleotide sequences obtained from amplicons from both tissues and virus isolated in cell culture were compared with those in GenBank and had 96-98% identity with Murray Valley encephalitis virus. The partial envelope gene sequence of the viral isolate clustered into genotype 1 and was most closely related to a previous Queensland isolate.

Systemic toxoplasmosis in captive flying-foxes

Systemic toxoplasmosis caused by Toxoplasma gondii was diagnosed in two juvenile, captive flying-foxes (Pteropus conspicillatus and P. scapulatus), which died following respiratory distress. One animal displayed clinical signs suggestive of neurological disease. This is the first report of this disease in megachiropteran bats and adds to the list of differential diagnoses for both systemic and neurological disease in these animals. The role of captivity in the exposure and development of the disease is discussed.

Multiple liquid-crystals and NMR

The use of more than one liquid crystal solvents to determine molecular structure and conformation is discussed. Liquid crystals of similar and opposite signs of diamagnetic anisotropies are considered separately since they lead to different novel applications. Advantages of such experiments over those employing single solvents are pointed out with illustrative examples.

Short-term survival of discarded pearl perch (Glaucosoma scapulare Ramsay, 1881) caught by hook-and-line in Queensland, Australia

Post-release survival of line-caught pearl perch (Glaucosoma scapulare) was assessed via field experiments where fish were angled using methods similar to those used by commercial, recreational and charter fishers. One hundred and eighty-three individuals were caught during four experiments, of which >91% survived up to three days post-capture. Hook location was found to be the best predictor of survival, with the survival of throat- or stomach-hooked pearl perch significantly (P < 0.05) lower than those hooked in either the mouth or lip. Post-release survival was similar for both legal (≥35 cm) and sub-legal (<35 cm) pearl perch, while those individuals showing no signs of barotrauma were more likely to survive in the short term. Examination of the swim bladders in the laboratory, combined with observations in the field, revealed that swim bladders rupture during ascent from depth allowing swim bladder gases to escape into the gut cavity. As angled fish approach the surface, the alimentary tract ruptures near the anus allowing swim bladder gases to escape the gut cavity. As a result, very few pearl perch exhibit barotrauma symptoms and no barotrauma mitigation strategies were recommended. The results of this study show that pearl perch are relatively resilient to catch-and-release suggesting that post-release mortality would not contribute significantly to total fishing mortality. We recommend the use of circle hooks, fished actively on tight lines, combined with minimal handling in order to maximise the post-release survival of pearl perch.

Observation of a novel babesia spp. in eastern grey kangaroos (macropus giganteus) in australia

The roles and epidemiological features of tick-borne protozoans are not well elicited in wildlife. Babesia spp. are documented in many domestic animals, including cattle, horses, pigs, dogs and cats. Three cases affecting eastern grey kangaroos are described. The kangaroos exhibited neurological signs, depression and marked anaemia, and microscopic examination of blood smears revealed intraerythrocytic piroplasms. One to seven intraerythrocytic spherical, oval, pyriform and irregularly-shaped parasites consistent with Babesia spp. were seen in the blood smears and the percentage of infected erythrocytes was estimated to be approximately 7% in each case. Data suggest that the tick vector for this kangaroo Babesia sp. is a Haemaphysalis species. For Case 2, ultrastructural examination of the erythrocytes of the renal capillaries showed parasites resembling Babesia spp. and 18 of 33 erythrocytes were infected. DNA sequencing of the amplified 18S rDNA confirmed that the observed intraerythrocytic piroplasms belong to the genus Babesia. The phylogenetic position of this new kangaroo Babesia sp. (de novo Babesia macropus), as a sister species to the new Australian woylie Babesia sp., suggests a close affinity to the described Afro-Eurasian species Babesia orientalis and Babesia occultans suggesting perhaps a common ancestor for the Babesia in kangaroos. © 2012 Australian Society for Parasitology.

Israel State Lottery Commemorative Medal

Obverse: The Lottery emblem, the Hebrew letter "P" entwined with the Star of David and surrounding it. In the left side of the medal symbols for medicine and education, a test tube, a serpent and a book. Reverse: Around the rim twelve signs of the zodiac, in the center a schematic design of a lottery selling kiosk.

Israel's 25th anniversary Commemorative Medal

Obverse: Official emblem of the Israel's 25th Anniversary, menorah entwined by ribbon creating the number 25. Reverse: The twelve signs of Zodiac seen on the mosaic of a 6th century synagogue floor discovered in Beth Alpha.

Masada Commemorative Medal

Obverse: In the center, an ancient shield and on its raised center, an inscription. Reverse: Design of Masada. At the mountain base, the signs of the Roman legions siege.

Competitive performance of Cabomba caroliniana

Cabomba caroliniana A.Gray (cabomba) is an invasive aquatic species causing serious environmental and socio-economic impacts. In particular, cabomba has a tendency to create large monospecific stands once introduced and appears to negatively affect native macrophyte diversity. Experiments have shown that cabomba, when cultured in isolation, grew significantly faster than any of the other macrophytes tested. However, competitive superiority over other macrophytes declined with increasing pH. Contrary to this, cabomba seemed to be a weak competitor in co-culture and few macrophytes showed signs of being affected by negative competitive interactions with cabomba. The reduction in growth performance at pH >7.5 and the fact that cabomba appears to be a weak competitor means that cabomba might not be able to establish everywhere and displace other plants. This weakness of cabomba could potentially be exploited in future management and rehabilitation efforts.

Selma's saga [1916-1948]

The memoirs were written in 1982 in Sydney, Australia and include excerpts of letters from various relatives during the years 1938-1941. Early childhood recollections of World War One. The family was living in the 6th district of Vienna. Description of domestic life with maids, laundresses and a French governess. Death of her mother in 1918. Trip with her stepmother Ida Plohn to Prague. Recollections of a stay in the countryside at their maid's family, where Selma and her older sister Martha awaited the birth of their younger sister Trude. Memories of Christmas celebrations. Summer vacations in the mountains. Description of the extended family. Inflation and economic depression in the 1920s. Strict upbringing by her stepmother. Children recreation trip to Grado, Italy in 1925. Selma was accepted at the "Bundeserziehungsanstalt" for gifted students. Only few fellow Jewish students. Religious education with beloved rabbi Diamant. Recovery from tonsilitis in a senatorium in Aflenz, Austria. Celebration of Jewish holidays and visits at the Synagogue on Yom Kippur. Transfer to Realschule. Due to a sudden onset of various illnesses Selma was unable to continue school and had put an end to her father's dream of an university education for her. Difficult to find a position in the depression times of the early 1930s. Only few working options for a Jewish woman. Position as a secretary in a Jewish firm. Outings in the Vienna Woods. Membership in the Zionist group Betar.

Infection and pathology in Queensland grouper, Epinephelus lanceolatus, (Bloch), caused by exposure to Streptococcus agalactiae via different routes

Since 2007, 96 wild Queensland groupers, Epinephelus lanceolatus, (Bloch), have been found dead in NE Australia. In some cases, Streptococcus agalactiae (Group B Streptococcus, GBS) was isolated. At present, a GBS isolate from a wild grouper case was employed in experimental challenge trials in hatchery-reared Queensland grouper by different routes of exposure. Injection resulted in rapid development of clinical signs including bilateral exophthalmia, hyperaemic skin or fins and abnormal swimming. Death occurred in, and GBS was re-isolated from, 98% fish injected and was detected by PCR in brain, head kidney and spleen from all fish, regardless of challenge dose. Challenge by immersion resulted in lower morbidity with a clear dose response. Whilst infection was established via oral challenge by admixture with feed, no mortality occurred. Histology showed pathology consistent with GBS infection in organs examined from all injected fish, from fish challenged with medium and high doses by immersion, and from high-dose oral challenge. These experimental challenges demonstrated that GBS isolated from wild Queensland grouper reproduced disease in experimentally challenged fish and resulted in pathology that was consistent with that seen in wild Queensland grouper infected with S. agalactiae.