Explore the vast range of titles available.

In this study, the authors use measures of carbon-14 in neuronal DNA from human stroke patient cortical tissue samples to show that, unlike previous studies done in rodents, they do not find any evidence of increased neurogenesis after an ischemic injury. In addition, DNA damage assays suggest that there is no increase in DNA rearrangement after this insult. It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA rearrangements in the human neocortex. Using immunohistochemistry; transcriptome, genome and ploidy analyses; and determination of nuclear bomb test–derived 14 C concentration in neuronal DNA, we found neither to be the case. A large proportion of cortical neurons displayed DNA fragmentation and DNA repair a short time after stroke, whereas neurons at chronic stages after stroke showed DNA integrity, demonstrating the relevance of an intact genome for survival.

ObjectivesTo test if impaired oxygenation or major haemodynamic instability at the time of emergency intensive care transport, from a smaller admitting hospital to a tertiary care centre, are predictors of long-term mortality.DesignRetrospective observational study. Impaired oxygenation was defined as oxyhaemoglobin %–inspired oxygen fraction ratio (S/F ratio)<100. Major haemodynamic instability was defined as a need for treatment with norepinephrine infusion to sustain mean arterial pressure (MAP) at or above 60 mm Hg or having a mean MAP <60. Logistic regression was used to assess mortality risk with impaired oxygenation or major haemodynamic instability.SettingSparsely populated Northern Sweden. A fixed-wing interhospital air ambulance system for critical care serving 900 000 inhabitants.ParticipantsIntensive care cases transported in fixed-wing air ambulance from outlying hospitals to a regional tertiary care centre during 2000–2016 for adults (16 years old or older). 2142 cases were included.Primary and secondary outcome measuresAll-cause mortality at 3 months after transport was the primary outcome, and secondary outcomes were all-cause mortality at 1 and 7 days, 1, 6 and 12 months.ResultsS/F ratio <100 was associated with increased mortality risk compared with S/F>300 at all time-points, with adjusted OR 6.3 (2.5 to 15.5, p<0.001) at 3 months. Major haemodynamic instability during intensive care unit (ICU) transport was associated with increased adjusted OR of all-cause mortality at 3 months with OR 2.5 (1.8 to 3.5, p<0.001).ConclusionMajor impairment of oxygenation and/or major haemodynamic instability at the time of ICU transport to get to urgent tertiary intervention is strongly associated with increased mortality risk at 3 months in this cohort. These findings support the conclusion that these conditions are markers for many fold increase in risk for death notable already at 3 months after transport for patients with these conditions.

Genome integrity depends on correct chromosome segregation, which in turn relies on cohesion between sister chromatids from S phase until anaphase. S phase cohesion, together with DNA double-strand break (DSB) recruitment of cohesin and formation of damage-induced (DI) cohesion, has previously been shown to be required also for efficient postreplicative DSB repair. The budding yeast acetyltransferase Eco1 (Ctf7) is a common essential factor for S phase and DI-cohesion. The fission yeast Eco1 ortholog, Eso1, is expressed as a fusion protein with the translesion synthesis (TLS) polymerase Polη. The involvement of Eso1 in S phase cohesion was attributed to the Eco1 homologous part of the protein and bypass of UV-induced DNA lesions to the Polη part. Here we describe an additional novel function for budding yeast Polη, i.e. formation of postreplicative DI genome-wide cohesion. This is a unique Polη function not shared with other TLS polymerases. However, Polη deficient cells are DSB repair competent, as Polη is not required for cohesion locally at the DSB. This reveals differential regulation of DSB-proximal cohesion and DI genome-wide cohesion, and challenges the importance of the latter for DSB repair. Intriguingly, we found that specific inactivation of DI genome-wide cohesion increases chromosomal mis-segregation at the entrance of the next cell cycle, suggesting that S phase cohesion is not sufficient for correct chromosome segregation in the presence of DNA damage.

Suicide is a serious public health issue, with clear differences across gender and age. In Sweden, progress in reducing suicide rates has been limited, particularly among younger individuals. While unemployment and broader economic conditions are well-established risk factors, the potential role of economic uncertainty has received relatively little attention. This thesis examines whether short-term economic uncertainty is associated with suicide rates in Sweden, and whether these associations differ by age and gender. A time series framework is employed using monthly data on suicide from 1997 to 2024, broken down by gender and age group. Economic uncertainty is measured using the Swedish Economic Policy Uncertainty (EPU) Index, along with the OMXS30 stock market index and household sentiment indicator. The results indicate a positive association between EPU and suicide among young men (0–34), and a negative association among older men (65+), though the latter may partly reflect a long-term downward trend. No clear patterns are found for women. One explanation is that younger people face greater life-stage insecurity, while men are less likely to seek support, often lacking strong social safety nets. These findings suggest that economic uncertainty affects mental health differently across groups, providing an important insight into how macroeconomic shocks influence public health.

Introduction: The first aim of this study is to gain more knowledge about why public libraries choose to organize reading groups for adults. The second aim is to shed light on the possible transformative potential of public libraries’reading groups for adults.Method: Semi-structured interviews with six librarians at Bibliotek Uppsala were conducted. Three of the librarians had an overall responsibility for the reading group activities within the organization. The other three librarians led reading groups themselves. The interviews were recorded and transcribed.Analysis: A thematic content analysis was conducted to interpret the transcripts of the interviews.Results: The librarians’ thoughts regarding what participants can gain from reading groups were categorized within the following themes: They can inspire more or more extensive reading, they can promote democracy and participation, they can encourage people to meet and fulfill an important social function, they can promote health, personal growth, and can give the participants new perspectives. This is largely consistent with previous studies reagarding what participants themselves state reading groups contribute to their lives. The result further shows that there are many favorable conditions for transformative learning within the library’s reading groups.Conclusion: The librarians see that the reading groups can fulfill more functions than promoting reading. Among other things, they point out that the reading groups, for several different reasons, are in line with the library’s democratic mission. Based on the theory of transformative learning, it is possible to see the potential of reading grups to promote critical reflection. According to the theory of transformative learning, it is believed that it is of the utmost importance that citizens of democratic societies develop their critical thinking. Thus, reading groups that develop the participants' ability to reflect could therefore also be justified on the basis of the library's democracy mission.This is a two years master’s thesis in Library and Information Science.

BackgroundAndrogens have anabolic effects that may contribute to enhanced physical performance and a decreased risk of injury in athletes. The role of endogenous androgens for athletic performance in female athletes is not yet fully elucidated.ObjectiveTo examine the profile of serum androgens in relation to body composition and physical performance in female Olympic athletes and compared to sedentary controls.DesignCross-sectional study, recruitment 2011–2015.SettingThe Women's Health Research Unit, Karolinska University Hospital.Participants106 female Swedish Olympic athletes (summer and winter sports) and 117 controls (maximum 2 hours training per week, no prior participation in elite-level sports).AssessmentParticipants were examined at one occasion at rest and in a fasting state for blood sampling. Serum androgen levels were established by liquid chromatography-mass spectrometry. Body composition was evaluated by DXA. Physical performance tests (Squat jump (SJ), Counter Movement Jump (CMJ)) were made at the Sports Institute, Bosön, as part of the “Physical Profile” offered by the Swedish Olympic Committee.Main Outcome MeasurementsThe profile of serum androgens, body composition, physical performance.ResultsFemale Olympic athletes demonstrated significantly higher androgen levels of dehydroepiandrosterone (DHEA) and androstandiol (5-ADIOL), lower levels of estrone, and a more anabolic body composition compared to controls. Athletes in power sports had significantly higher bone mineral density compared to endurance and technical athletes, whereas endurance athletes had the highest values of lean mass. Serum levels of DHEA and 5-ADIOL correlated positively to lean mass in female athletes (R=0.25–0.33). Furthermore, DHEA, 5-ADIOL and dihydrotestosterone correlated positively to CMJ and SJ in the athletes (R=0.27–0.39).ConclusionsWe suggest that endogenous androgens contribute to a more anabolic body composition and increased physical performance in female athletes. Furthermore, the anabolic effect on body composition could play a role for the risk of injury.

Genome integrity depends on correct chromosome segregation, which in turn relies on cohesion between sister chromatids from S phase until anaphase. S phase cohesion, together with DNA double-strand break (DSB) recruitment of cohesin and formation of damage-induced (DI) cohesion, has previously been shown to be required also for efficient postreplicative DSB repair. The budding yeast acetyltransferase Eco1 (Ctf7) is a common essential factor for S phase and DI-cohesion. The fission yeast Eco1 ortholog, Eso1, is expressed as a fusion protein with the translesion synthesis (TLS) polymerase Polη. The involvement of Eso1 in S phase cohesion was attributed to the Eco1 homologous part of the protein and bypass of UV-induced DNA lesions to the Polη part. Here we describe an additional novel function for budding yeast Polη, i.e. formation of postreplicative DI genome-wide cohesion. This is a unique Polη function not shared with other TLS polymerases. However, Polη deficient cells are DSB repair competent, as Polη is not required for cohesion locally at the DSB. This reveals differential regulation of DSB-proximal cohesion and DI genome-wide cohesion, and challenges the importance of the latter for DSB repair. Intriguingly, we found that specific inactivation of DI genome-wide cohesion increases chromosomal mis-segregation at the entrance of the next cell cycle, suggesting that S phase cohesion is not sufficient for correct chromosome segregation in the presence of DNA damage.

Correct segregation of sister chromatids is an important mechanism for keeping the genome intact. The cohesin complex holds the sister chromatids together from the time of their formation during replication, until separation at anaphase and is thereby mediating cohesion between the sister chromatids, essential for correct chromatid segregation. Members of the cohesin network in addition play essential roles in the repair of double strand breaks (DSBs), and have been shown to be involved in regulation of transcription. Thus, cohesin is a master regulator of a majority of the cellular processes required for transfer of the correct genetic information from one cell generation to the next. The aim with this thesis was to further elucidate the function(s) of the cohesin network in genome integrity. In doing so, either budding yeast or human cell cultures were used. In budding yeast, cohesin is recruited to the vicinity of an induced DSB and cohesion is established genome wide. This phenomenon of re-­?establishment of cohesion is called Damage induced (DI-­) cohesion. By investigating the function of Polymerase ? in DI-­?cohesion, we found that it is differentially regulated at the break site and genome-­?wide. We also suggeste that the function of break proximal DI-­?cohesion is to support DSB repair, while the genome wide DI-­ cohesion is important for correct chromosomal segregation and for survival following repeated break induction. A gene regulatory role of cohesin and its loading complex Scc2/4 has been described in several organisms, but not investigated thoroughly in yeast.Thus, we investigated the gene transcription profiles in Scc2-­deficient cells in the absence and presence of DNA damage. We conclude that Scc2 is indeed instrumental for gene regulation also in budding yeast, both globally in an undamaged situation, and in response to DSB induction. Our data also indicate that the difference in gene response between WT and Scc2-­ deficient cells is not based on overt changes in cohesin binding. Mutations in NIPBL (human ortholog of SCC2), are frequent in Cornelia de Lange syndrome (CdLS) patients. By studying the DSB repair in B-­cells originated from CdLS patient, we found a shift towards the alternative, microhomology-­?based, end joining pathway during class switch recombination, implicating that NIPBL is important for classical Non Homologous End Joining (NHEJ).Our results suggest that NIPBL plays an important and conserved role for NHEJ, in addition to its previously known function in homologous recombination. Altogether I have with this thesis highlighted the importance of the cohesin network in DI-­cohesion and DNA DSB repair, as well as in the transcriptional regulation, all important components of the systems used for maintenance of genome integrity.

Genome integrity depends on correct chromosome segregation, which in turn relies on cohesion between sister chromatids from S phase until anaphase. S phase cohesion, together with DNA double-strand break (DSB) recruitment of cohesin and formation of damage-induced (DI) cohesion, has previously been shown to be required also for efficient postreplicative DSB repair. The budding yeast acetyltransferase Eco1 (Ctf7) is a common essential factor for S phase and DI-cohesion. The fission yeast Eco1 ortholog, Eso1, is expressed as a fusion protein with the translesion synthesis (TLS) polymerase Pol eta . The involvement of Eso1 in S phase cohesion was attributed to the Eco1 homologous part of the protein and bypass of UV-induced DNA lesions to the Pol eta part. Here we describe an additional novel function for budding yeast Pol eta , i.e. formation of postreplicative DI genome-wide cohesion. This is a unique Pol eta function not shared with other TLS polymerases. However, Pol eta deficient cells are DSB repair competent, as Pol eta is not required for cohesion locally at the DSB. This reveals differential regulation of DSB-proximal cohesion and DI genome-wide cohesion, and challenges the importance of the latter for DSB repair. Intriguingly, we found that specific inactivation of DI genome-wide cohesion increases chromosomal mis-segregation at the entrance of the next cell cycle, suggesting that S phase cohesion is not sufficient for correct chromosome segregation in the presence of DNA damage.

Dopamine transmission has been implicated in motor and cognitive function. In Parkinson’s disease (PD), dopamine replacement using the precursor drug l -DOPA is the predominant treatment approach, but long-term exposure leads to the onset of dyskinesias (LIDs). Chronic l -DOPA exposure has been associated with changes in gene expression and altered cortico-striatal plasticity. The aim of this research was to assess the functional consequence of long-term l -DOPA exposure on cognitive and motor function using a rodent model of PD. Across two independent experiments, we assessed the impact of chronic l -DOPA exposure, or a control D 2 R agonist, on motor and cognitive function in intact and in hemi parkinsonian rats, in the absence of drug. Abnormal involuntary movements associated with LID were measured and brain tissues were subsequently harvested for immunohistochemical analysis. Exposure to chronic l -DOPA, but not the D 2 R agonist, impaired motor and cognitive function, when animals were tested in the absence of drug. A meta-analysis of the two experiments allowed further dissociation of l -DOPA -treated rats into those that developed LIDs (dyskinetic) and those that did not develop LIDs (non-dyskinetic). This analysis revealed impaired cognitive and motor performance were evident only in dyskinetic, but not in non-dyskinetic, rats. These data reveal a functional consequence of the altered plasticity associated with LID onset and have implications for understanding symptom progression in the clinic.