Human apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is an essential DNA repair enzyme which uses a single active site to process DNA damage via two distinct activities: (1) AP-endonuclease and (2) ...3' to 5' exonuclease. The AP-endonuclease activity cleaves at AP-sites, while the exonuclease activity excises bulkier 3' mismatches and DNA damage to generate clean DNA ends suitable for downstream repair. Molecular details of the exonuclease reaction and how one active site can accommodate various toxic DNA repair intermediates remains elusive despite being biologically important. Here, we report multiple high-resolution APE1-DNA structural snapshots revealing how APE1 removes 3' mismatches and DNA damage by placing the 3' group within the intra-helical DNA cavity via a non-base flipping mechanism. This process is facilitated by a DNA nick, instability of a mismatched/damaged base, and bending of the DNA. These results illustrate how APE1 cleanses DNA dirty-ends to generate suitable substrates for downstream repair enzymes.
We integrate climatic niche models and dated phylogenies to characterize the evolution of climatic niches inOenotherasectionsAnograandKleinia(Onagraceae), and from that we make inferences on ...diversification in relation to climate. The evolution of climatic tolerances inAnogra+Kleiniahas been heterogeneous, across phylogenetic groups and across different dimensions of climate. All the extant taxa occur in semiarid to arid conditions (annual precipitation of 10.1–49.1 cm and high temperatures in the warmest month of 28.5°–40.1°C), but there is striking variation among taxa in their climatic tolerances, especially temperature (minimum temperatures in the coldest month of −14.0° to 5.3°C) and summer versus winter precipitation (precipitation in the warmest quarter of 0.6–19.4 cm). Climatic disparity is especially pronounced in two subclades (californica,deltoides) that radiated in the southwestern United States and California, apparently including both divergent and convergent evolution of climatic tolerances. This niche evolution is remarkable, given the probable timescale of the radiation (∼1 million years). We suggest that the spatiotemporal climatic heterogeneity of western North America has served as a driver of diversification. Our data are also consistent with Axelrod’s hypothesis that the spread of arid conditions in western North America stimulated diversification of arid‐adapted lineages.
Family-systems interventions have been proposed as one way of supporting families of people with an intellectual disability (ID) or who are autistic. This systematic review aimed to summarise what ...family-systems interventions have been studied with this population, what evidence there is for their effectiveness and families' experiences of the interventions.
The review was preregistered on PROSPERO (CRD42022297516). We searched five electronic databases, identified 6908 records and screened 72 full texts. Study quality was evaluated using the Mixed Methods Appraisal Tool, and a narrative synthesis was used.
We identified 13 eligible articles with 292 participating families. Most studies reported positive effects of the interventions on wellbeing and family relationships, and families reported positive experiences. However, research quality was poor and there are no any sufficiently powered randomised controlled trials demonstrating family-systems interventions' effectiveness for this population.
There is a need for higher-quality research to establish whether family-systems interventions are beneficial for families of people who have an ID or who are autistic.
Photosynthetic electron transport rates in higher plants and green algae are light-saturated at approximately one quarter of full sunlight intensity. This is due to the large optical cross section of ...plant light harvesting antenna complexes which capture photons at a rate nearly 10-fold faster than the rate-limiting step in electron transport. As a result, 75% of the light captured at full sunlight intensities is reradiated as heat or fluorescence. Previously, it has been demonstrated that reductions in the optical cross-section of the light-harvesting antenna can lead to substantial improvements in algal photosynthetic rates and biomass yield. By surveying a range of light harvesting antenna sizes achieved by reduction in chlorophyll b levels, we have determined that there is an optimal light-harvesting antenna size that results in the greatest whole plant photosynthetic performance. We also uncover a sharp transition point where further reductions or increases in antenna size reduce photosynthetic efficiency, tolerance to light stress, and impact thylakoid membrane architecture. Plants with optimized antenna sizes are shown to perform well not only in controlled greenhouse conditions, but also in the field achieving a 40% increase in biomass yield.
Short sleep duration is a known risk factor for suicidality in the general population, yet it is unclear how short sleep interacts with autism traits in predicting suicidality. In this ...cross-sectional online study, a general population sample (
N
= 650) completed measures assessing autism traits, suicidal ideation, and sleep duration. Moderated hierarchical regressions demonstrated that higher autism traits and shorter sleep were independent predictors of increased suicide ideation. However, sleep duration did not significantly moderate the autism trait to suicide ideation relationship. Future work should explore this relationship longitudinally using objective measures before considering intervention work to increase sleep duration in those with elevated autism traits.
Background
Family members caring for children with intellectual disability (ID) routinely report heightened levels of psychological distress. However, families of children with Down syndrome ...typically report better outcomes (known as the Down syndrome advantage). We examined whether the Down syndrome advantage would be present for maternal psychological distress, impact of caregiving, life satisfaction and perceived positive impact of the child with ID when controlling for external variables.
Methods
Mothers of children with Down syndrome (n = 111) and mothers of children with ID of mixed aetiologies (n = 196) completed measures about their own mental health, perceived impact of caregiving, life satisfaction and perceived positive impact of their child on themselves and the family unit.
Results
A series of group comparisons revealed small to moderate differences supporting the presence of a putative Down syndrome advantage in relation to personal maternal well‐being outcomes. However, when child‐related characteristics and external variables were controlled, the Down syndrome advantage was no longer present, with reduced, small effect sizes observed for all maternal outcomes.
Conclusions
Initial group differences in psychological distress and life satisfaction were largely associated with family poverty, indicating that the Down syndrome advantage may be less robust than previously thought. Future research should seek to move beyond examining the existence of the putative Down syndrome advantage and focus on how families of children with Down syndrome experience family life, including longitudinal research exploring responses to life cycle and transition challenges.
Observations in psychiatric in-patient settings are used to reduce suicide, self-harm, violence and absconding risk. The study aims were to describe the characteristics of in-patients who died by ...suicide under observation and examine their service-related antecedents.
A national consecutive case series in England and Wales (2006-2012) was examined.
There were 113 suicides by in-patients under observation, an average of 16 per year. Most were under intermittent observation. Five deaths occurred while patients were under constant observation. Patient deaths were linked with the use of less experienced staff or staff unfamiliar with the patient, deviation from procedures and absconding.
We identified key elements of observation that could improve safety, including only using experienced and skilled staff for the intervention and using observation levels determined by clinical need not resources.
Schizophrenia unfolds during the late period of brain maturation, while myelination is still continuing. In the present study, we used MRI and T2 relaxation analysis to measure the myelin water ...fraction in schizophrenia. In schizophrenia (n=30) compared with healthy subjects (n=27), overall white matter showed 12% lower myelin water fraction (P=0.031), with the most prominent effects on the left genu of the corpus callosum (36% lower, P=0.002). The left anterior genu was affected in both first-episode (P=0.035) and chronic patients (P=0.011). In healthy subjects, myelin water fraction in total white matter and in frontal white matter increased with age, and with years of education, indicating ongoing maturation. In patients with schizophrenia, neither relation was statistically significant. Post-mortem studies of anterior frontal cortex demonstrated less immunoreactivity of two oligodendrocyte-associated proteins in schizophrenia (2',3'-cyclic nucleotide 3'-phosphodiesterase by 33%, P=0.05; myelin-associated glycoprotein by 27%, P=0.14). Impaired myelination in schizophrenia could contribute to abnormalities of neural connectivity and persistent functional impairment in the illness.
BACKGROUND
Although survivors of adolescent‐onset cancers are at risk of infertility, the majority desire children. Fertility preservation options are available for adolescents, but sperm banking ...remains underused. To the authors' knowledge, patient factors that influence decisions to bank sperm are poorly understood.
METHODS
A cross‐sectional study of 146 adolescent males who were newly diagnosed with cancer and who completed surveys within 1 week of treatment initiation was performed. Participants, 65% of whom were white, were aged 13 to 21 years (mean, 16.49 years; standard deviation, 2.02 years) and were at risk of infertility secondary to impending gonadotoxic treatment. Participating institutions included 8 leading pediatric oncology centers across the United States and Canada.
RESULTS
Of the patients approached, approximately 80.6% participated. Parent recommendation to bank (odds ratio OR, 4.88; 95% confidence interval 95% CI, 1.15‐20.71 P = .03), higher Tanner stage (OR, 4.25; 95% CI, 1.60‐11.27 P < .01), greater perceived benefits (OR, 1.41; 95% CI, 1.12‐1.77 P < .01), and lower social barriers to banking (OR, 0.88; 95% CI, 0.81‐0.96 P < .01) were found to be associated with adolescent collection attempts, whereas meeting with a fertility specialist (OR, 3.44; 95% CI, 1.00‐11.83 P = .05), parent (OR, 3.02; 95% CI, 1.12‐8.10 P = .03) or provider (OR, 2.67; 95% CI, 1.05‐6.77 P = .04) recommendation to bank, and greater adolescent self‐efficacy to bank (OR, 1.16; 95% CI, 1.01‐1.33 P = .03) were found to be associated with successful sperm banking.
CONCLUSIONS
Adolescents' perceived benefits of sperm banking, higher Tanner stage, and parent recommendation were associated with collection attempts, whereas perceived social barriers decreased this likelihood. Successful banking was associated with greater adolescent self‐efficacy, parent and provider recommendation to bank, and consultation with a fertility specialist. Providers should consult with both adolescents and parents regarding fertility preservation, and interventions should be tailored to address barriers to sperm banking while promoting its benefits.
Among at‐risk adolescent males newly diagnosed with cancer, sperm banking outcomes are associated with adolescent developmental (eg, Tanner stage) and psychological (eg, benefits to banking, self‐efficacy, and social barriers) factors, in addition to parent and provider recommendations and consultation with a fertility specialist. Because adolescent factors drive sperm banking outcomes, providers should prioritize patient participation and desires during the fertility preservation decision‐making process.
Flowback and produced water (FPW) is a complex, often brackish, solution formed during the process of hydraulic fracturing. Despite recent findings on the short-term toxicity of FPW on aquatic biota, ...longer-term impacts of FPW on fish have not yet been investigated and the mechanisms of chronic effects remain unknown. The aim of the present study was to observe the effect of a diluted FPW on ionoregulatory endpoints in the rainbow trout Oncorhynchus mykiss, following a 28-d sub-chronic exposure. A salinity-matched control solution (SW), recreating the salt content of the FPW, was used to differentiate the specific effect of the salts from the effects of the other FPW components (i.e. organics and metals). Overall, fish ionoregulation was not impacted by the chronic exposure. An accumulation of strontium (Sr) and bromide (Br) occurred in the plasma of the FPW-exposed fish only, however no change of plasma ions (Na, K, Cl, Ca, Mg) was observed in SW- or FPW-exposed fish. Similarly, exposures did not alter branchial activity of the osmoregulatory enzymes sodium/potassium ATPase and proton ATPase. Finally, FPW exposure resulted in modifications of gill morphology over time, with fish exposed to the fluid displaying shorter lamellae and increased interlamellar-cell mass. However, these effects were not distinct from morphological changes that also occurred in the gills of control groups.
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