Explore the vast range of titles available.

Terrestrial gross primary productivity (GPP) varies greatly over time and space. A better understanding of this variability is necessary for more accurate predictions of the future climate–carbon cycle feedback. Recent studies have suggested that variability in GPP is driven by a broad range of biotic and abiotic factors operating mainly through changes in vegetation phenology and physiological processes. However, it is still unclear how plant phenology and physiology can be integrated to explain the spatiotemporal variability of terrestrial GPP. Based on analyses of eddy–covariance and satellite-derived data, we decomposed annual terrestrial GPP into the length of the CO ₂ uptake period (CUP) and the seasonal maximal capacity of CO ₂ uptake (GPP ₘₐₓ). The product of CUP and GPP ₘₐₓ explained >90% of the temporal GPP variability in most areas of North America during 2000–2010 and the spatial GPP variation among globally distributed eddy flux tower sites. It also explained GPP response to the European heatwave in 2003 ( r ² = 0.90) and GPP recovery after a fire disturbance in South Dakota ( r ² = 0.88). Additional analysis of the eddy–covariance flux data shows that the interbiome variation in annual GPP is better explained by that in GPP ₘₐₓ than CUP. These findings indicate that terrestrial GPP is jointly controlled by ecosystem-level plant phenology and photosynthetic capacity, and greater understanding of GPP ₘₐₓ and CUP responses to environmental and biological variations will, thus, improve predictions of GPP over time and space. Significance Terrestrial gross primary productivity (GPP), the total photosynthetic CO ₂ fixation at ecosystem level, fuels all life on land. However, its spatiotemporal variability is poorly understood, because GPP is determined by many processes related to plant phenology and physiological activities. In this study, we find that plant phenological and physiological properties can be integrated in a robust index—the product of the length of CO ₂ uptake period and the seasonal maximal photosynthesis—to explain the GPP variability over space and time in response to climate extremes and during recovery after disturbance.

Removal of invasive exotic shrubs from mountaintop communities increased the number of pollinators and positively altered pollinator behaviour, which enhanced native fruit production, indicating that the degradation of ecosystem functions is partly reversible. Restoring plant communities boosts pollination Human activities often have damaging effects on biodiversity and ecosystem functions, but whether the targeted manipulation of ecological communities can successfully mitigate and reverse these impacts is the subject of much debate. Here, Christopher Kaiser-Bunbury et al . assess the effect of one form of restoration—the removal of all alien plant species—on the structure and function of plant–pollinator networks in mountain-top communities in the Seychelles. Vegetation restoration leads to a marked increase in the number of pollinator species and pollinator visits to flowers. There is also an increase in the diversity of pollinator interactions and, importantly, the pollination of fruit crops and native plants. The findings suggest that the degradation of ecosystem functions, in this case pollination, is at least partly reversible. Land degradation results in declining biodiversity and the disruption of ecosystem functioning worldwide, particularly in the tropics 1 . Vegetation restoration is a common tool used to mitigate these impacts and increasingly aims to restore ecosystem functions rather than species diversity 2 . However, evidence from community experiments on the effect of restoration practices on ecosystem functions is scarce 3 . Pollination is an important ecosystem function and the global decline in pollinators attenuates the resistance of natural areas and agro-environments to disturbances 4 . Thus, the ability of pollination functions to resist or recover from disturbance (that is, the functional resilience) 5 , 6 may be critical for ensuring a successful restoration process 7 . Here we report the use of a community field experiment to investigate the effects of vegetation restoration, specifically the removal of exotic shrubs, on pollination. We analyse 64 plant–pollinator networks and the reproductive performance of the ten most abundant plant species across four restored and four unrestored, disturbed mountaintop communities. Ecosystem restoration resulted in a marked increase in pollinator species, visits to flowers and interaction diversity. Interactions in restored networks were more generalized than in unrestored networks, indicating a higher functional redundancy in restored communities. Shifts in interaction patterns had direct and positive effects on pollination, especially on the relative and total fruit production of native plants. Pollinator limitation was prevalent at unrestored sites only, where the proportion of flowers producing fruit increased with pollinator visitation, approaching the higher levels seen in restored plant communities. Our results show that vegetation restoration can improve pollination, suggesting that the degradation of ecosystem functions is at least partially reversible. The degree of recovery may depend on the state of degradation before restoration intervention and the proximity to pollinator source populations in the surrounding landscape 5 , 8 . We demonstrate that network structure is a suitable indicator for pollination quality, highlighting the usefulness of interaction networks in environmental management 6 , 9 .

6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment. The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing. 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1–78·2) for the 3 month group and 77·1% (75·6–78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909–1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group). In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care. Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK.

Diurnal oscillation of intracellular redox potential is known to couple metabolism with the circadian clock, yet the responsible mechanisms are not well understood. We show here that chemical activation of NRF2 modifies circadian gene expression and rhythmicity, with phenotypes similar to genetic NRF2 activation. Loss of Nrf2 function in mouse fibroblasts, hepatocytes and liver also altered circadian rhythms, suggesting that NRF2 stoichiometry and/or timing of expression are important to timekeeping in some cells. Consistent with this concept, activation of NRF2 at a circadian time corresponding to the peak generation of endogenous oxidative signals resulted in NRF2-dependent reinforcement of circadian amplitude. In hepatocytes, activated NRF2 bound specific enhancer regions of the core clock repressor gene Cry2, increased Cry2 expression and repressed CLOCK/BMAL1-regulated E-box transcription. Together these data indicate that NRF2 and clock comprise an interlocking loop that integrates cellular redox signals into tissue-specific circadian timekeeping. Like many other animals, our behavior often follows a familiar pattern each day. We tend to wake up with the morning sunlight and start by eating breakfast to satisfy our hunger. Then, at night, most of us sleep, and our bodies use chemical building blocks from the day's meals to replenish and repair our tissues. As such, its not just our behavior that shows a daily cycle. The countless chemical reactions that keep us alive, collectively referred to as our metabolism, also change over the course of each day. Daily patterns of activity, known as circadian rhythms, can be seen even at the level of individual cells. Each cell in the body has its own molecular clock that works by rhythmically cycling the levels of different molecules. Proteins called CLOCK and BMAL1 trigger the production of proteins PER and CRY. As levels of PER and CRY rise, they interfere with CLOCK and BMAL1, essentially switching off their own production. Then, levels of PER and CRY fall and the cycle starts again. Thus, these molecules rise and fall throughout the day to drive circadian rhythms, similar to how a pendulum swings back and forth to keep a clock ticking. Metabolism and circadian rhythms are clearly linked, but it is not well understood how this works. Now, Wible, Ramanathan et al. identify a protein called NRF2 as an important bridge between the molecular clock and metabolism. NRF2 is a activated by hydrogen peroxide, a byproduct of cell metabolism, and when activated this protein grabs hold of DNA to increase the activity of specific genes. A combination of experiments revealed that mouse liver cells need NRF2 to maintain a normal circadian rhythm, and a closer inspection of the liver cells revealed that NRF2 specifically attaches to part of the gene for a clock protein called CRY2. This enhances the production of this protein, which in turn, switches CLOCK and BMAL1 off. In this way, NRF2 links metabolism signals to the ticking of the circadian clock. Previous research has shown a link between shift work, which disrupt these rhythms, and metabolic diseases like obesity and diabetes. Understanding more about the underlying molecular biology that links metabolism to circadian rhythms could help scientists to find new ways to improve public health.

Andrew Wilkie and colleagues report that activating paternal-effect mutations in FGFR3 and HRAS promote clonal expansion in the testis, leading to spermatocytic seminomas. The same mutation in FGFR3 leads to the lethal disorder thanatophoric dysplasia, revealing a shared genetic mechanism for congenital disorders and testicular tumors. Genes mutated in congenital malformation syndromes are frequently implicated in oncogenesis 1 , 2 , but the causative germline and somatic mutations occur in separate cells at different times of an organism's life. Here we unify these processes to a single cellular event for mutations arising in male germ cells that show a paternal age effect 3 . Screening of 30 spermatocytic seminomas 4 , 5 for oncogenic mutations in 17 genes identified 2 mutations in FGFR3 (both 1948A>G, encoding K650E, which causes thanatophoric dysplasia in the germline) 6 and 5 mutations in HRAS . Massively parallel sequencing of sperm DNA showed that levels of the FGFR3 mutation increase with paternal age and that the mutation spectrum at the Lys650 codon is similar to that observed in bladder cancer 7 , 8 . Most spermatocytic seminomas show increased immunoreactivity for FGFR3 and/or HRAS. We propose that paternal age-effect mutations activate a common 'selfish' pathway supporting proliferation in the testis, leading to diverse phenotypes in the next generation including fetal lethality, congenital syndromes and cancer predisposition.

Purpose There is substantial literature suggesting that the mental health benefits of marriage (compared to being single) are greater for those in ‘good-quality’ relationships in comparison to those in ‘poor-quality’ relationships. However, little of this research utilises large population-based surveys. Large surveys in psychiatric epidemiology have focused almost exclusively on the association between marital status and mental health. The current study explores some of the reasons for this gap in the literature, and adopts a large, representative community-based sample to investigate whether associations between relationship status and levels of depression and anxiety are moderated by relationship quality. Methods Participants were from Wave 3 of the PATH Survey, a longitudinal community survey assessing the health and well-being of residents of the Canberra region, Australia ( n  = 3,820). Relationship quality was measured using the 7 item Dyadic Adjustment Scale (DAS-7), and levels of depression and anxiety were measured using the Goldberg Scales. Results Both cross-sectional and prospective analyses showed that associations between relationship status and mental health were moderated by relationship quality for both men and women, such that only good-quality relationships bestowed mental health benefits over remaining single. For women, being in a poor-quality relationship was associated with greater levels of anxiety than being single. Conclusions Epidemiological studies need to measure relationship quality to qualify the effect of relationship status on mental health.

BACKGROUNDThe Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer.METHODSIn total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3–8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan–Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken.RESULTSThe 3 M arm is less costly (-£4881; 95% CI: -£6269; -£3492) and entails (non-significant) QALY gains (0.08; 95% CI: −0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant).CONCLUSIONSOverall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care.

SARS-CoV-2 neutralising antibodies provide protection against COVID-19. Evidence from early vaccine trials suggested binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether these thresholds predict sufficient neutralising capacity against variants of concern (VOCs), and whether this is impacted by vaccine or infection history remains unclear. Here we analyse individuals recovered from, vaccinated or with hybrid immunity against SARS-CoV-2. An NT50 ≥ 100 IU confers protection in vaccine trials, however, as VOC induce a reduction in NT50, we use NT50 ≥ 1000 IU as a cut off for WT NT50 that would retain neutralisation against VOC. In unvaccinated convalescent participants, a receptor binding domain (RBD) IgG of 456 BAU/mL predicts an NT50 against WT of 1000 IU with an accuracy of 80% (95%CI 73–86%). This threshold maintains accuracy in determining loss of protective immunity against VOC in two vaccinated cohorts. It predicts an NT50 < 100 IU against Beta with an accuracy of 80% (95%CI 67–89%) in 2 vaccine dose recipients. In booster vaccine recipients with a history of COVID-19 (hybrid immunity), accuracy is 87% (95%CI 77–94%) in determining an NT50 of <100 IU against BA.5. This analysis provides a discrete threshold that could be used in future clinical studies. Evidence from trials suggests SARS-CoV-2 binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether this is accurate in the context of variants of concerns, or in the event of prior infection or vaccination remains unclear. Authors explore the performance of receptor binding domain IgG thresholds in predicting a level of neutralising capacity that has demonstrated protection against infection in vaccine trials

Antarctica's weather and climate have global impacts, influencing weather patterns, ocean currents and sea levels worldwide. However, Antarctica is vast and complex, and the atmospheric processes that govern its climate are strongly influenced by its steep terrain, particularly around the coastal periphery. Our scientific understanding of this complex environment is hampered by the lack of reliable observations and gridded datasets at sufficiently high spatial and temporal resolution. High-resolution regional climate models, RCMs, can provide a solution to the sparsity of observational data and low resolution of reanalyses, facilitating more in-depth assessments of crucial climate variables like precipitation, wind and temperature that are strongly influenced by topography. Here we present and evaluate a comprehensive, high-quality, ∼ 11 km resolution RCM dataset, the PolarRES ensemble, for the period 2000–2019. We show that the ensemble largely out-performs ERA5, especially with regard to variables like coastal winds and precipitation. There are no consistent seasonal differences in biases, but there are persistent regional biases. Victoria Land and the Trans-Antarctic Mountains are the regions the RCMs and ERA5 struggle the most with, which suggests that further investigation and model development is needed in this area. Each RCM has strengths and limitations, but overall the ensemble captures the observed weather and climate of Antarctica well. The PolarRES ensemble offers a novel and exciting way of evaluating climate processes and features, and we encourage researchers to use the data, which are freely available, to explore pertinent climate questions of local, regional and global significance.