Mary From Tipperary

https://digitalcommons.library.umaine.edu/mmb-vp/5194/thumbnail.jp

Can a systems approach produce a better understanding of mood disorders?

Background: One in twenty-five people suffer from a mood disorder. Current treatments are sub-optimal with poor patient response and uncertain modes-of-action. There is thus a need to better understand underlying mechanisms that determine mood, and how these go wrong in affective disorders. Systems biology approaches have yielded important biological discoveries for other complex diseases such as cancer, and their potential in affective disorders will be reviewed. Scope of review: This review will provide a general background to affective disorders, plus an outline of experimental and computational systems biology. The current application of these approaches in understanding affective disorders will be considered, and future recommendations made. Major conclusions: Experimental systems biology has been applied to the study of affective disorders, especially at the genome and transcriptomic levels. However, data generation has been slowed by a lack of human tissue or suitable animal models. At present, computational systems biology has only be applied to understanding affective disorders on a few occasions. These studies provide sufficient novel biological insight to motivate further use of computational biology in this field. General significance: In common with many complex diseases much time and money has been spent on the generation of large-scale experimental datasets. The next step is to use the emerging computational approaches, predominantly developed in the field of oncology, to leverage the most biological insight from these datasets. This will lead to the critical breakthroughs required for more effective diagnosis, stratification and treatment of affective disorders

Selvskading blant ungdom: Review og pilotstudie

The aim of this study was to review and summarize recent knowledge of deliberate self-harm among adolescents, which appear to be an increasing mental health problem. The study consisted of a review of essential literature and a pilot study where 3 pupils in senior high schools, who had experiences from deliberate self-harm, were interviewed. The review of 30 central and recent articles about deliberate self harm among adolescents in the period 1996-2005, identified risk factors for self-harm, protective factors, psychological mechanisms of self-harm, situation factors and triggers, functions, outcome, and maintaining factors of deliberate self-harm among adolescents. The qualitative pilot study, based on semi structured interviews, found that although several similarities among adolescents who self-harm can be identified, there are important individual differences. Main conclusions from the review and pilot study are: 1) The emotion regulation is a major function of self-harm. 2) Adolescents who self-harm have had experiences with psychological problems or problems with family, school, or behaviour. 3) Relations to peers are important since peers who had self-harmed was the strongest factor to influence self-harm, and since adolescents turn to their peers and friends for help and support when experiencing problems

A comparative study of regulatory biology of denitrifying bacteria of the genus Thauera

Denitrifikasjon er en viktig del av den globale nitrogensyklusen der nitrat (NO3 -) eller nitritt (NO2-) blir redusert trinnvis til nitrogen monoksid (NO), lystgass (N2O) og til slutt nitrogen i gassform (N2) under anoksiske eller semi-anoksiske forhold som et alternativ til aerob respirasjon. Reduksjonen av N-oksidene skjer ved benyttelse av reduktasene nitratreduktase (Nar/Nap, gen: nar/nap), nitrittreduktase (Nir, gen: nirS eller nirK), NO reduktase (Nor, gen:nor) og N2O reduktase (Nos, gen: nosZ). Prosessen utføres av bakterier i over 60 ulike phyla, samt enkelte Archaea og eukaryote organismer, og er en viktig kilde til utslipp av NO og N2O. N2O er en ozonnedbryter og en drivhusgass som er omtrent 300 ganger mer potent enn CO2, og har en halveringstid på 160 år i atmosfæren. I denne oppgaven ble det fokusert på karakteriseringen av denitrification regulatory phenotype (DRP) hos ulike stammer innen slekten Thauera. DRP er en samlebetegnelse på en rekke fenotypiske og regulatoriske karakteristika som har implikasjoner for en gitt denitrifiserende organismes overlevelse og N2O/NO utslipp til omgivelsene. I denne oppgaven ble det særlig fokusert på akkumulering av NO og N2O, samt transkripsjon av reduktasegenene (nir, nor, nos) under og etter overgang fra aerob respirasjon til denitrifikasjon. Enkelte stammer innenfor slekten Thauera innehar to distinkte utgaver av genet som koder for cytokrom cd1 –nitrittreduktase, nirS. Tre stammer ble dermed valgt for å representere slekten T.sp 27, som har genene nirS1 og nirS2, T.sp 28 som kun har nirS2 og T.linaloolentis kun har nirS1. De ulike stammene av Thauera ble dyrket i renkulturer i et semiautomatisk inkubasjonssystem der det ble målt konsentrasjoner av O2, NO, N2O og N2 i kulturene. På bakgrunn av gasskinetikken, ble prøver tatt ut på interessante tidspunkter og transkripsjon av nirS1 og/eller nirS2, norB og nosZ ble kvantifisert ved hjelp av real-time PCR. Etchebehere og Tiedje rapporterte 2005 at nirS1 var uttrykt konstitutivt i T.sp 27 . Dette var derimot ikke tilfelle i følge våre resultater. Funnene i denne oppgaven viste for de stammene som hadde nirS1 at ble uttrykt allerede ved lav konsentrasjon av oksygen i kulturen, og økte kraftig ekspresjonen under anoksiske forhold i kulturen, og at nirS2 var uttrykt kun under anoksiske forhold i kulturen. T.sp 27 var den stammen som hadde den høyeste ekspresjonen av nirS. Alle stammene hadde en stringent kontroll av NO, noe som betyr at de undersøkte stammene er følsomme for gassen og har en kontrollert regulering av NO akkumulering. N2O så ikke ut til å være gjenstand for like streng regulering og stammene akkumulerte varierende mengder under denitrifikasjon. Det eksperimentelle oppsettet som er beskrevet her gir et unikt innblikk i dynamikken rundt denitrifikasjon. Tette, presise målinger av headspace-gasser i kombinasjon med hyppig transkripsjonsanalyse danner grunnlaget for detaljert karakterisering av denitrifiserende bakterier, med videre implikasjoner for deres overlevelse og bidrag til N2O og NO utslipp fra mer komplekse systemer. Denitrification is an important part of the global nitrogen cycle. Nitrate (NO3-) or nitrite (NO2-) is reduced stepwise to nitric oxide (NO), laughing gas (N2O) and finally nitrogen in gasous form (N2) under anoxic or semi-anoxic conditions. The process is executed as an alternative to aerobic respiration. The reduction of the N-oxides is executed by the reductases nitrate reductase (Nar/Nap, gene nar/nap), nitrite reductase (Nir, gene nirS or nirK), nitric oxide reductase (Nor, gene:nor), and nitrous oxidereductase (Nos, gene: nosZ). The process is carried out by bacteria spread over 60 different phyla, as well as some Archaea and eukaryote organisms. It is also an important process in the emission of NO and N2O. Denitrification is responsible for 70 % of the total N2O emissions. N2O is a green house gas that is 300 times more potent than CO2, and has a residence time of 160 years in the atmosphere. In this thesis, it was focused on the characterization of denitrification regulatory phenotype (DRP) of different strains within the genus Thauera. DRP is a collective term for a variety of phenotypic and regulatory characteristics that have implications for the survival for a given denitrifying organism and emission of NO and N2O to the environment. I this task, it was focused on accumulation of NO and N2O, and the transcription of the reductase genes (nirS, norB and nosZ) during the transition from aerobic respiration to denitrification. Some strains within the genus Thauera possesses two distinct versions of the gene coding for cytochrome cd1-nitrite reductase, NirS. Three strains were thus selected to represent the genus T.sp 27, who has the genes and nirS1 and nirS2, T.sp 28 that has only nirS2 and T.linaloolentis only nirS1. It was also focused on the nitrite reductase nirS, which is responsible for the reduction of nitrite to NO. Three Thauera strains was chosen in this task; T.sp 27 expresses the genes nirS1 and nirS2, T.sp 28 nirS2, and T.linaloolentis expresses nirS1. The threeThauera strains were incubated in pure cultures in a semi automatic incubation system. The concentrations of O2, NO, N2O and N2 were measured. On the basis of gas kinetics, the samples taken out in interesting times and transcription of nirS1 and / or nirS2, norB and nosZ were quantified using real-time PCR. Etchebehere and Tiedje reported in 2005 that nirS1 was expressed constitutitly in the T.sp 27. This was however not the case according to our results. The results from this study showed for the strains that nirS1 was expressed already at low concentration of oxygen in the culture, and increased expression under anoxic conditions in culture, and that nirS2 was expressed only under anoxic conditions in culture. T.sp 27 was the strain that had the highest expression of both of the nirS types. All strains had a strict control of NO, which means that the investigated strains are sensitive to the gas and has a controlled regulation of NO accumulation. Variation in regulation of accumulated N2O, and in general, the gas accumulated faster than it was reduced. I non closed environments, the denitrification carried out by Thauera would have contributed to emission of the green house gas N2O. This experiment gives us a unique insight into the dynamics around denitrification. Precise measurements of gasses in headspace in combination with rapid analysis of expression gives us an detailed characterization of denitrifying bacterias, with further implications of their survival and contribution to N2O and NO emissions from more complex systems

En komparativ studie av regulatorisk biologi hos denitrifiserende bakterier i slekten Thauera

Denitrifikasjon er en viktig del av den globale nitrogensyklusen der nitrat (NO3 -) eller nitritt (NO2-) blir redusert trinnvis til nitrogen monoksid (NO), lystgass (N2O) og til slutt nitrogen i gassform (N2) under anoksiske eller semi-anoksiske forhold som et alternativ til aerob respirasjon. Reduksjonen av N-oksidene skjer ved benyttelse av reduktasene nitratreduktase (Nar/Nap, gen: nar/nap), nitrittreduktase (Nir, gen: nirS eller nirK), NO reduktase (Nor, gen:nor) og N2O reduktase (Nos, gen: nosZ). Prosessen utføres av bakterier i over 60 ulike phyla, samt enkelte Archaea og eukaryote organismer, og er en viktig kilde til utslipp av NO og N2O. N2O er en ozonnedbryter og en drivhusgass som er omtrent 300 ganger mer potent enn CO2, og har en halveringstid på 160 år i atmosfæren. I denne oppgaven ble det fokusert på karakteriseringen av denitrification regulatory phenotype (DRP) hos ulike stammer innen slekten Thauera. DRP er en samlebetegnelse på en rekke fenotypiske og regulatoriske karakteristika som har implikasjoner for en gitt denitrifiserende organismes overlevelse og N2O/NO utslipp til omgivelsene. I denne oppgaven ble det særlig fokusert på akkumulering av NO og N2O, samt transkripsjon av reduktasegenene (nir, nor, nos) under og etter overgang fra aerob respirasjon til denitrifikasjon. Enkelte stammer innenfor slekten Thauera innehar to distinkte utgaver av genet som koder for cytokrom cd1 –nitrittreduktase, nirS. Tre stammer ble dermed valgt for å representere slekten T.sp 27, som har genene nirS1 og nirS2, T.sp 28 som kun har nirS2 og T.linaloolentis kun har nirS1. De ulike stammene av Thauera ble dyrket i renkulturer i et semiautomatisk inkubasjonssystem der det ble målt konsentrasjoner av O2, NO, N2O og N2 i kulturene. På bakgrunn av gasskinetikken, ble prøver tatt ut på interessante tidspunkter og transkripsjon av nirS1 og/eller nirS2, norB og nosZ ble kvantifisert ved hjelp av real-time PCR. Etchebehere og Tiedje rapporterte 2005 at nirS1 var uttrykt konstitutivt i T.sp 27 . Dette var derimot ikke tilfelle i følge våre resultater. Funnene i denne oppgaven viste for de stammene som hadde nirS1 at ble uttrykt allerede ved lav konsentrasjon av oksygen i kulturen, og økte kraftig ekspresjonen under anoksiske forhold i kulturen, og at nirS2 var uttrykt kun under anoksiske forhold i kulturen. T.sp 27 var den stammen som hadde den høyeste ekspresjonen av nirS. Alle stammene hadde en stringent kontroll av NO, noe som betyr at de undersøkte stammene er følsomme for gassen og har en kontrollert regulering av NO akkumulering. N2O så ikke ut til å være gjenstand for like streng regulering og stammene akkumulerte varierende mengder under denitrifikasjon. Det eksperimentelle oppsettet som er beskrevet her gir et unikt innblikk i dynamikken rundt denitrifikasjon. Tette, presise målinger av headspace-gasser i kombinasjon med hyppig transkripsjonsanalyse danner grunnlaget for detaljert karakterisering av denitrifiserende bakterier, med videre implikasjoner for deres overlevelse og bidrag til N2O og NO utslipp fra mer komplekse systemer. Denitrification is an important part of the global nitrogen cycle. Nitrate (NO3-) or nitrite (NO2-) is reduced stepwise to nitric oxide (NO), laughing gas (N2O) and finally nitrogen in gasous form (N2) under anoxic or semi-anoxic conditions. The process is executed as an alternative to aerobic respiration. The reduction of the N-oxides is executed by the reductases nitrate reductase (Nar/Nap, gene nar/nap), nitrite reductase (Nir, gene nirS or nirK), nitric oxide reductase (Nor, gene:nor), and nitrous oxidereductase (Nos, gene: nosZ). The process is carried out by bacteria spread over 60 different phyla, as well as some Archaea and eukaryote organisms. It is also an important process in the emission of NO and N2O. Denitrification is responsible for 70 % of the total N2O emissions. N2O is a green house gas that is 300 times more potent than CO2, and has a residence time of 160 years in the atmosphere. In this thesis, it was focused on the characterization of denitrification regulatory phenotype (DRP) of different strains within the genus Thauera. DRP is a collective term for a variety of phenotypic and regulatory characteristics that have implications for the survival for a given denitrifying organism and emission of NO and N2O to the environment. I this task, it was focused on accumulation of NO and N2O, and the transcription of the reductase genes (nirS, norB and nosZ) during the transition from aerobic respiration to denitrification. Some strains within the genus Thauera possesses two distinct versions of the gene coding for cytochrome cd1-nitrite reductase, NirS. Three strains were thus selected to represent the genus T.sp 27, who has the genes and nirS1 and nirS2, T.sp 28 that has only nirS2 and T.linaloolentis only nirS1. It was also focused on the nitrite reductase nirS, which is responsible for the reduction of nitrite to NO. Three Thauera strains was chosen in this task; T.sp 27 expresses the genes nirS1 and nirS2, T.sp 28 nirS2, and T.linaloolentis expresses nirS1. The threeThauera strains were incubated in pure cultures in a semi automatic incubation system. The concentrations of O2, NO, N2O and N2 were measured. On the basis of gas kinetics, the samples taken out in interesting times and transcription of nirS1 and / or nirS2, norB and nosZ were quantified using real-time PCR. Etchebehere and Tiedje reported in 2005 that nirS1 was expressed constitutitly in the T.sp 27. This was however not the case according to our results. The results from this study showed for the strains that nirS1 was expressed already at low concentration of oxygen in the culture, and increased expression under anoxic conditions in culture, and that nirS2 was expressed only under anoxic conditions in culture. T.sp 27 was the strain that had the highest expression of both of the nirS types. All strains had a strict control of NO, which means that the investigated strains are sensitive to the gas and has a controlled regulation of NO accumulation. Variation in regulation of accumulated N2O, and in general, the gas accumulated faster than it was reduced. I non closed environments, the denitrification carried out by Thauera would have contributed to emission of the green house gas N2O. This experiment gives us a unique insight into the dynamics around denitrification. Precise measurements of gasses in headspace in combination with rapid analysis of expression gives us an detailed characterization of denitrifying bacterias, with further implications of their survival and contribution to N2O and NO emissions from more complex systems

Cognitive behavioral therapy for insomnia in euthymic bipolar disorder: study protocol for a randomized controlled trial

Background Patients with bipolar disorder experience sleep disturbance, even in euthymic phases. Changes in sleep pattern are frequent signs of a new episode of (hypo)mania or depression. Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment for primary insomnia, but there are no published results on the effects of CBT-I in patients with bipolar disorder. In this randomized controlled trial, we wish to compare CBT-I and treatment as usual with treatment as usual alone to determine its effect in improving quality of sleep, stabilizing minor mood variations and preventing new mood episodes in euthymic patients with bipolar disorder and comorbid insomnia. Methods Patients with euthymic bipolar I or II disorder and insomnia, as verified by the Structured Clinical Interview for DSM Disorders (SCID-1) assessment, will be included. The patients enter a three-week run-in phase in which they complete a sleep diary and a mood diary, are monitored for seven consecutive days with an actigraph and on two of these nights with polysomnography in addition before randomization to an eight-week treatment trial. Treatment as usual consists of pharmacological and supportive psychosocial treatment. In this trial, CBT-I will consist of sleep restriction, psychoeducation about sleep, stabilization of the circadian rhythm, and challenging and correcting sleep state misperception, in three to eight sessions. Discussion This trial could document a new treatment for insomnia in bipolar disorder with possible effects on sleep and on stability of mood. In addition, more precise information can be obtained about the character of sleep disturbance in bipolar disorder