Observed humidity trends in dry regions contradict climate models.

Arid and semi-arid regions of the world are particularly vulnerable to greenhouse gas-driven hydroclimate change. Climate models are our primary tool for projecting the future hydroclimate that society in these regions must adapt to, but here, we present a concerning discrepancy between observed and model-based historical hydroclimate trends. Over the arid/semi-arid regions of the world, the predominant signal in all model simulations is an increase in atmospheric water vapor, on average, over the last four decades, in association with the increased water vapor-holding capacity of a warmer atmosphere. In observations, this increase in atmospheric water vapor has not happened, suggesting that the availability of moisture to satisfy the increased atmospheric demand is lower in reality than in models in arid/semi-arid regions. This discrepancy is most clear in locations that are arid/semi-arid year round, but it is also apparent in more humid regions during the most arid months of the year. It indicates a major gap in our understanding and modeling capabilities which could have severe implications for hydroclimate projections, including fire hazard, moving forward.

A bioenergy-focused versus a reforestation-focused mitigation pathway yields disparate carbon storage and climate responses.

Limiting global warming to 2 °C requires urgent action on land-based mitigation. This study evaluates the biogeochemical and biogeophysical implications of two alternative land-based mitigation scenarios that aim to achieve the same radiative forcing. One scenario is primarily driven by bioenergy expansion (SSP226Lu-BIOCROP), while the other involves re/afforestation (SSP126Lu-REFOREST). We find that overall, SSP126Lu-REFOREST is a more efficient strategy for removing CO2 from the atmosphere by 2100, resulting in a net carbon sink of 242 ~ 483 PgC with smaller uncertainties compared to SSP226Lu-BIOCROP, which exhibits a wider range of -78 ~ 621 PgC. However, SSP126Lu-REFOREST leads to a relatively warmer planetary climate than SSP226Lu-BIOCROP, and this relative warming can be intensified in certain re/afforested regions where local climates are not favorable for tree growth. Despite the cooling effect on a global scale, SSP226Lu-BIOCROP reshuffles regional warming hotspots, amplifying summer temperatures in vulnerable tropical regions such as Central Africa and Southeast Asia. Our findings highlight the need for strategic land use planning to identify suitable regions for re/afforestation and bioenergy expansion, thereby improving the likelihood of achieving the intended climate mitigation outcomes.

Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation.

Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices.

Large influence of soil moisture on long-term terrestrial carbon uptake.

Although the terrestrial biosphere absorbs about 25 per cent of anthropogenic carbon dioxide (CO2) emissions, the rate of land carbon uptake remains highly uncertain, leading to uncertainties in climate projections1,2. Understanding the factors that limit or drive land carbon storage is therefore important for improving climate predictions. One potential limiting factor for land carbon uptake is soil moisture, which can reduce gross primary production through ecosystem water stress3,4, cause vegetation mortality5 and further exacerbate climate extremes due to land-atmosphere feedbacks6. Previous work has explored the impact of soil-moisture availability on past carbon-flux variability3,7,8. However, the influence of soil-moisture variability and trends on the long-term carbon sink and the mechanisms responsible for associated carbon losses remain uncertain. Here we use the data output from four Earth system models9 from a series of experiments to analyse the responses of terrestrial net biome productivity to soil-moisture changes, and find that soil-moisture variability and trends induce large CO2 fluxes (about two to three gigatons of carbon per year; comparable with the land carbon sink itself1) throughout the twenty-first century. Subseasonal and interannual soil-moisture variability generate CO2 as a result of the nonlinear response of photosynthesis and net ecosystem exchange to soil-water availability and of the increased temperature and vapour pressure deficit caused by land-atmosphere interactions. Soil-moisture variability reduces the present land carbon sink, and its increase and drying trends in several regions are expected to reduce it further. Our results emphasize that the capacity of continents to act as a future carbon sink critically depends on the nonlinear response of carbon fluxes to soil moisture and on land-atmosphere interactions. This suggests that the increasing trend in carbon uptake rate may not be sustained past the middle of the century and could result in accelerated atmospheric CO2 growth.

Tripling of western US particulate pollution from wildfires in a warming climate.

SignificanceRecord-setting fires in the western United States over the last decade caused severe air pollution, loss of human life, and property damage. Enhanced drought and increased biomass in a warmer climate may fuel larger and more frequent wildfires in the coming decades. Applying an empirical statistical model to fires projected by Earth System Models including climate-ecosystem-socioeconomic interactions, we show that fine particulate pollution over the US Pacific Northwest could double to triple during late summer to fall by the late 21st century under intermediate- and low-mitigation scenarios. The historic fires and resulting pollution extremes of 2017-2020 could occur every 3 to 5 y under 21st-century climate change, posing challenges for air quality management and threatening public health.

Extending the new era of genomic testing into pregnancy management: A proposed model for Australian prenatal services.

BACKGROUND: Trio exome sequencing can be used to investigate congenital abnormalities identified on pregnancy ultrasound, but its use in an Australian context has not been assessed. AIMS: Assess clinical outcomes and changes in management after expedited genomic testing in the prenatal period to guide the development of a model for widespread implementation. MATERIALS AND METHODS: Forty-three prospective referrals for whole exome sequencing, including 40 trios (parents and pregnancy), two singletons and one duo were assessed in a tertiary hospital setting with access to a state-wide pathology laboratory. Diagnostic yield, turn-around time (TAT), gestational age at reporting, pregnancy outcome, change in management and future pregnancy status were assessed for each family. RESULTS: A clinically significant genomic diagnosis was made in 15/43 pregnancies (35%), with an average TAT of 12 days. Gestational age at time of report ranged from 16 + 5 to 31 + 6 weeks (median 21 + 3 weeks). Molecular diagnoses included neuromuscular and skeletal disorders, RASopathies and a range of other rare Mendelian disorders. The majority of families actively used the results in pregnancy decision making as well as in management of future pregnancies. CONCLUSIONS: Rapid second trimester prenatal genomic testing can be successfully delivered to investigate structural abnormalities in pregnancy, providing crucial guidance for current and future pregnancy management. The time-sensitive nature of this testing requires close laboratory and clinical collaboration to ensure appropriate referral and result communication. We found the establishment of a prenatal coordinator role and dedicated reporting team to be important facilitators. We propose this as a model for genomic testing in other prenatal services.

The association between child maltreatment and health risk behaviours and conditions throughout life in the Australian Child Maltreatment Study.

OBJECTIVE: To estimate associations between all five types of child maltreatment (emotional abuse, neglect, physical abuse, sexual abuse, and exposure to domestic violence) and health risk behaviours and conditions. DESIGN, SETTING, PARTICIPANTS: Nationally representative survey of Australian residents aged 16 years and older conducted by computer-assisted telephone interviewing. MAIN OUTCOME MEASURES: Associations between child maltreatment and the following health risk behaviours and conditions: current smoker, binge drinking (at least weekly in past 12 months), cannabis dependence (according to the Cannabis Severity of Dependence Scale), obesity (based on body mass index), self-harm in past 12 months, and suicide attempt in past 12 months. RESULTS: A total of 8503 participants completed the survey. All five types of child maltreatment were associated with increased rates of all of the health risk behaviours and conditions that we considered. The strongest associations were in the youngest age group (16-24-year-olds). Sexual abuse and emotional abuse were associated with the highest odds of health risk behaviours and conditions. Cannabis dependence, self-harm and suicide attempts were most strongly associated with child maltreatment. Experiencing more than one type of child maltreatment was associated with higher rates of health risk behaviours and conditions than experiencing one type of child maltreatment. CONCLUSIONS: Child maltreatment is associated with substantially increased rates of health risk behaviours and conditions. Prevention and intervention efforts should be informed by trauma histories, and holistic psychosocial care should be incorporated into programs focusing on behaviour change.

The Australian Child Maltreatment Study (ACMS), a national survey of the prevalence of child maltreatment and its correlates: methodology.

OBJECTIVES: To describe the aims, design, methodology, and respondent sample representativeness of the Australian Child Maltreatment Study (ACMS). DESIGN, SETTING: Cross-sectional, retrospective survey; computer-assisted mobile telephone interviewing using random digit dialling (computer-generated), Australia, 9 April - 11 October 2021. PARTICIPANTS: People aged 16 years or more. The target sample size was 8500 respondents: 3500 people aged 16-24 years and 1000 respondents each from five further age groups (25-34, 35-44, 45-54, 55-64, 65 years or more). MAIN OUTCOME MEASURES: Primary outcomes: Emotional abuse, neglect, physical abuse, sexual abuse, exposure to domestic violence during childhood, assessed with the Juvenile Victimization Questionnaire-R2 Adapted Version (Australian Child Maltreatment Study). SECONDARY OUTCOMES: selected mental disorder diagnoses (Mini International Neuropsychiatric Interview, MINI), selected physical health conditions, health risk behaviours, health service use. RESULTS: The demographic characteristics of the ACMS sample were similar to those of the Australian population in 2016 with respect to gender, Indigenous status, region and remoteness category of residence, and marital status, but larger proportions of participants were born in Australia, lived in areas of higher socio-economic status, had tertiary qualifications, and had income greater than $1250 per week. Population weights were derived to adjust for these differences. Associations between the number of calls required to recruit participants and maltreatment rates and health outcomes were not statistically significant. CONCLUSIONS: The ACMS provides the first reliable estimates of the prevalence of each type of child maltreatment in Australia. These estimates, and those of associated mental health and health risk behaviours reported in this supplement can inform policy and practice initiatives for reducing the prevalence of child maltreatment and its consequences. Our benchmark study also provides baseline data for repeated waves of the ACMS that will assess the effectiveness of these initiatives.

The prevalence of child maltreatment in Australia: findings from a national survey.

OBJECTIVES: To estimate the prevalence in Australia of each type of child maltreatment; to identify gender- and age group-related differences in prevalence. DESIGN, SETTING: Cross-sectional national survey; mobile telephone interviews using random digit dialling (computer-generated), Australia, 9 April - 11 October 2021. Retrospective self-report data using validated questionnaire (Juvenile Victimisation Questionnaire-R2 Adapted Version (Australian Child Maltreatment Study). PARTICIPANTS: People aged 16 years or more. The target sample size was 8500 respondents: 3500 people aged 16-24 years and 1000 respondents each from five further age groups (25-34, 35-44, 45-54, 55-64, 65 years or more). MAIN OUTCOME MEASURES: Proportions of respondents reporting physical abuse, sexual abuse, emotional abuse, neglect, and exposure to domestic violence to age 18 years, assessed with the Juvenile Victimization Questionnaire-R2 Adapted Version (Australian Child Maltreatment Study), overall and by gender and age group, and weighted to reflect characteristics of the Australian population aged 16 years or more in 2016. RESULTS: Complete survey data were available for 8503 eligible participants (14% response rate). Physical abuse was reported by 32.0% of respondents (95% confidence interval [CI], 30.7-33.3%), sexual abuse by 28.5% (95% CI, 27.3-29.8%), emotional abuse by 30.9% (95% CI, 29.7-32.2%), neglect by 8.9% (95% CI, 8.1-9.7%), and exposure to domestic violence by 39.6% (95% CI, 38.3-40.9%). The proportions of respondents who reported sexual abuse, emotional abuse, or neglect were each statistically significantly larger for women than men. The reported prevalence of physical abuse by respondents aged 16-24 years was lower than for those aged 25-34 years, and that of sexual abuse was lower than for those aged 35-44 years, suggesting recent declines in the prevalence of these maltreatment types. CONCLUSIONS: Child maltreatment is common in Australia, and larger proportions of women than men report having experienced sexual abuse, emotional abuse, and neglect during childhood. As physical and sexual abuse may have declined recently, public health policy and practice may have positive effects, justifying continued monitoring and prevention activities.

The prevalence and nature of multi-type child maltreatment in Australia.

OBJECTIVES: To determine the prevalence in Australia of multi-type child maltreatment, defined as two or more maltreatment types (physical abuse, sexual abuse, emotional abuse, neglect, or exposure to domestic violence) and to examine its nature, family risk factors, and gender and age cohort differences. DESIGN: Retrospective cross-sectional survey using a validated questionnaire. SETTING AND PARTICIPANTS: Mobile phone random digit-dial sample of the Australian population aged 16 years and older. MAIN OUTCOME MEASURES: National estimates of multi-type child maltreatment up to age 18 years using the Juvenile Victimisation Questionnaire-R2: Adapted Version (Australian Child Maltreatment Study). RESULTS: Of 8503 participants, 62.2% (95% CI, 60.9-63.6%) experienced one or more types of child maltreatment. Prevalence of single-type maltreatment was 22.8% (95% CI, 21.7-24.0%), whereas 39.4% (95% CI, 38.1-40.7%) of participants reported multi-type maltreatment and 3.5% (95% CI, 3.0-4.0%) reported all five types. Multi-type maltreatment was more common for gender diverse participants (66.1% [95% CI, 53.7-78.7%]) and women (43.2% [95% CI, 41.3-45.1%]) than for men (34.9% [95% CI, 33.0-36.7%]). Multi-type maltreatment prevalence was highest for those aged 25-44 years. Family-related adverse childhood experiences - especially mental illness and alcohol or substance misuse - increased risk. Exposure to domestic violence was the maltreatment type most often present in multi-type maltreatment patterns. CONCLUSIONS: Multi-type child maltreatment is prevalent in Australia and more common in women and gender diverse individuals. Child protection services, health practitioners, and prevention and intervention services must assess and manage multi-type maltreatment in children and address its health consequences across the lifespan. Public health policy should consider prevention services or strategies that target multi-type child maltreatment.

Child maltreatment and health service use: findings of the Australian Child Maltreatment Study.

OBJECTIVES: To examine associations between child maltreatment and health service use, both overall, by type and by the number of types of maltreatment reported. DESIGN, SETTING: Cross-sectional, retrospective survey using the Juvenile Victimization Questionnaire-R2: Adapted Version (Australian Child Maltreatment Study); computer-assisted mobile telephone interviews using random digit dialling, Australia, 9 April - 11 October 2021. PARTICIPANTS: Australians aged 16 years or more. The target sample size was 8500 respondents: 3500 people aged 16-24 years and 1000 respondents each from the five age groups (25-34, 35-44, 45-54, 55-64, 65 years or more). MAIN OUTCOME MEASURES: Self-reported health service use during the past twelve months: hospital admissions, length of stay, and reasons for admission; and numbers of consultations with health care professionals, overall and by type. Associations between maltreatment and health service use are reported as odds ratios adjusted for age group, gender, socio-economic status, financial hardship (childhood and current), and geographic remoteness. RESULTS: A total of 8503 participants completed the survey. Respondents who had experienced child maltreatment were significantly more likely than those who had not to report a hospital admission during the preceding twelve months (adjusted odds ratio [aOR], 1.39; 95% confidence interval [CI], 1.16-1.66), particularly admission with a mental disorder (aOR, 2.4; 95% CI, 1.03-5.6). The likelihood of six or more visits to general practitioners (aOR, 2.37; 95% CI, 1.87-3.02) or of a consultation with a mental health nurse (aOR, 2.67; 95% CI, 1.75-4.06), psychologist (aOR, 2.40; 95% CI, 2.00-2.88), or psychiatrist (aOR, 3.02; 95% CI, 2.25-4.04) were each higher for people who reported maltreatment during childhood. People who reported three or more maltreatment types were generally most likely to report greater health service use. CONCLUSIONS: Child maltreatment has a major impact on health service use. Early, targeted interventions are vital, not only for supporting children directly, but also for their longer term wellbeing and reducing their health system use throughout life.

The association between child maltreatment and mental disorders in the Australian Child Maltreatment Study.

OBJECTIVES: To examine the associations between experiences of child maltreatment and mental disorders in the Australian population. DESIGN: Population-representative survey conducted by computer-assisted telephone interviewing. SETTING, PARTICIPANTS: Australian residents aged 16 years and older. MAIN OUTCOME MEASURES: Mental disorder diagnoses of lifetime major depressive disorder, current alcohol use disorder (mild, moderate and severe), current generalised anxiety disorder and current post-traumatic stress disorder. RESULTS: More than one in three Australians (3606/8503 surveyed participants; 38.0%; 95% CI, 36.7-39.3%) met the diagnostic criteria for a mental disorder. The prevalence of mental disorders in non-maltreated participants was 21.6% (95% CI, 19.9-23.3%; n = 851). This increased to 36.2% (95% CI, 33.5-38.9%; n = 764) for those who experienced a single type of maltreatment and 54.8% (95% CI, 52.6-56.9%; n = 1991) for participants who experienced multi-type maltreatment. Compared with non-maltreated Australians, maltreated participants had about three times the odds of any mental disorder (odds ratio [OR], 2.82; 95% CI, 2.47-3.22), generalised anxiety disorder (OR, 3.14; 95% CI, 2.48-3.97), major depressive disorder (OR, 3.19; 95% CI, 2.68-3.80) and severe alcohol use disorder (OR, 2.62; 95% CI, 1.83-3.76), and almost five times the odds of post-traumatic stress disorder (OR, 4.60; 95% CI, 3.00-7.07). Associations between experiences of child maltreatment and mental disorders were strongest for sexual abuse, emotional abuse and multi-type maltreatment. The strength of the associations did not differ by gender. Adjustment for childhood and current financial hardship and for current socio-economic status did not significantly attenuate the associations. CONCLUSIONS: Mental disorders are significantly more likely to occur in individuals who experience child maltreatment, particularly multi-type maltreatment. Prevention of child maltreatment provides an opportunity to substantially reduce the prevalence of mental illness and improve the health of the Australian population.

miR-200/375 control epithelial plasticity-associated alternative splicing by repressing the RNA-binding protein Quaking.

Members of the miR-200 family are critical gatekeepers of the epithelial state, restraining expression of pro-mesenchymal genes that drive epithelial-mesenchymal transition (EMT) and contribute to metastatic cancer progression. Here, we show that miR-200c and another epithelial-enriched miRNA, miR-375, exert widespread control of alternative splicing in cancer cells by suppressing the RNA-binding protein Quaking (QKI). During EMT, QKI-5 directly binds to and regulates hundreds of alternative splicing targets and exerts pleiotropic effects, such as increasing cell migration and invasion and restraining tumour growth, without appreciably affecting mRNA levels. QKI-5 is both necessary and sufficient to direct EMT-associated alternative splicing changes, and this splicing signature is broadly conserved across many epithelial-derived cancer types. Importantly, several actin cytoskeleton-associated genes are directly targeted by both QKI and miR-200c, revealing coordinated control of alternative splicing and mRNA abundance during EMT These findings demonstrate the existence of a miR-200/miR-375/QKI axis that impacts cancer-associated epithelial cell plasticity through widespread control of alternative splicing.

GATA2 deficiency syndrome: A decade of discovery.

GATA2 deficiency syndrome (G2DS) is a rare autosomal dominant genetic disease predisposing to a range of symptoms, of which myeloid malignancy and immunodeficiency including recurrent infections are most common. In the last decade since it was first reported, there have been over 480 individuals identified carrying a pathogenic or likely pathogenic germline GATA2 variant with symptoms of G2DS, with 240 of these confirmed to be familial and 24 de novo. For those that develop myeloid malignancy (75% of all carriers with G2DS disease symptoms), the median age of onset is 17 years (range 0-78 years) and myelodysplastic syndrome is the first diagnosis in 75% of these cases with acute myeloid leukemia in a further 9%. All variant types appear to predispose to myeloid malignancy and immunodeficiency. Apart from lymphedema in which haploinsufficiency seems necessary, the mutational requirements of the other less common G2DS phenotypes is still unclear. These predominantly loss-of-function variants impact GATA2 expression and function in numerous ways including perturbations to DNA binding, protein structure, protein:protein interactions, and gene transcription, splicing, and expression. In this review, we provide the first expert-curated ACMG/AMP classification with codes of published variants compatible for use in clinical or diagnostic settings.

Concordance between adolescents and parents on the Strengths and Difficulties Questionnaire: Analysis of an Australian nationally representative sample.

OBJECTIVE: Differences between adolescent self-reported and parent-reported emotional and behavioural difficulties may influence psychiatric epidemiological research. This study examined concordance between adolescents and their parents about mental health symptoms using the Strengths and Difficulties Questionnaire. METHODS: The study comprised a randomly selected, nationally representative sample of adolescents aged 11-17 years who participated in the Second Australian Child and Adolescent Survey of Mental Health and Wellbeing (N = 2967). Matched adolescent and parent responses across the five Strengths and Difficulties Questionnaire subscales (emotional problems, hyperactivity, peer problems, conduct problems and prosocial behaviour), as well as total difficulties and total impact scores were examined to estimate concordance. Concordance patterns were analysed by sex, after stratifying the sample by age group (younger adolescents: 11-14 years; older adolescents: 15-17 years). RESULTS: Concordance was 86.7% for total difficulties, 77.5% for total impact and ranged from 82.4% to 94.3% across the five Strengths and Difficulties Questionnaire subscales. There were no differences in concordance between sexes on the total difficulties score. Older females were more likely to disagree with their parents about emotional problems compared to males of the same age. Younger males were more likely to disagree with their parents compared to same-aged females about peer problems, hyperactivity, conduct problems and prosocial skills, as well as the impact of their problems. Older males were more likely to disagree with their parents about their prosocial skills compared to older females. CONCLUSION: Overall, concordance between adolescents and parents on the Strengths and Difficulties Questionnaire was largely driven by the high proportion of respondents who reported having no problems. Discordance on a subscale increased as the prevalence of problems in a sex and age demographic subgroup increased. These findings highlight the need for a multi-informant approach to detect emotional and behavioural difficulties in adolescents, particularly when assessing the impact of symptoms, as this subscale had the lowest concordance.

Dependence of the evolution of carbon dynamics in the northern permafrost region on the trajectory of climate change.

We conducted a model-based assessment of changes in permafrost area and carbon storage for simulations driven by RCP4.5 and RCP8.5 projections between 2010 and 2299 for the northern permafrost region. All models simulating carbon represented soil with depth, a critical structural feature needed to represent the permafrost carbon-climate feedback, but that is not a universal feature of all climate models. Between 2010 and 2299, simulations indicated losses of permafrost between 3 and 5 million km2 for the RCP4.5 climate and between 6 and 16 million km2 for the RCP8.5 climate. For the RCP4.5 projection, cumulative change in soil carbon varied between 66-Pg C (1015-g carbon) loss to 70-Pg C gain. For the RCP8.5 projection, losses in soil carbon varied between 74 and 652 Pg C (mean loss, 341 Pg C). For the RCP4.5 projection, gains in vegetation carbon were largely responsible for the overall projected net gains in ecosystem carbon by 2299 (8- to 244-Pg C gains). In contrast, for the RCP8.5 projection, gains in vegetation carbon were not great enough to compensate for the losses of carbon projected by four of the five models; changes in ecosystem carbon ranged from a 641-Pg C loss to a 167-Pg C gain (mean, 208-Pg C loss). The models indicate that substantial net losses of ecosystem carbon would not occur until after 2100. This assessment suggests that effective mitigation efforts during the remainder of this century could attenuate the negative consequences of the permafrost carbon-climate feedback.

Beyond Static Benchmarking: Using Experimental Manipulations to Evaluate Land Model Assumptions.

Land models are often used to simulate terrestrial responses to future environmental changes, but these models are not commonly evaluated with data from experimental manipulations. Results from experimental manipulations can identify and evaluate model assumptions that are consistent with appropriate ecosystem responses to future environmental change. We conducted simulations using three coupled carbon-nitrogen versions of the Community Land Model (CLM, versions 4, 4.5, and-the newly developed-5), and compared the simulated response to nitrogen (N) and atmospheric carbon dioxide (CO2) enrichment with meta-analyses of observations from similar experimental manipulations. In control simulations, successive versions of CLM showed a poleward increase in gross primary productivity and an overall bias reduction, compared to FLUXNET-MTE observations. Simulations with N and CO2 enrichment demonstrate that CLM transitioned from a model that exhibited strong nitrogen limitation of the terrestrial carbon cycle (CLM4) to a model that showed greater responsiveness to elevated concentrations of CO2 in the atmosphere (CLM5). Overall, CLM5 simulations showed better agreement with observed ecosystem responses to experimental N and CO2 enrichment than previous versions of the model. These simulations also exposed shortcomings in structural assumptions and parameterizations. Specifically, no version of CLM captures changes in plant physiology, allocation, and nutrient uptake that are likely important aspects of terrestrial ecosystems' responses to environmental change. These highlight priority areas that should be addressed in future model developments. Moving forward, incorporating results from experimental manipulations into model benchmarking tools that are used to evaluate model performance will help increase confidence in terrestrial carbon cycle projections.

Naturally existing isoforms of miR-222 have distinct functions.

Deep-sequencing reveals extensive variation in the sequence of endogenously expressed microRNAs (termed 'isomiRs') in human cell lines and tissues, especially in relation to the 3' end. From the immunoprecipitation of the microRNA-binding protein Argonaute and the sequencing of associated small RNAs, we observe extensive 3'-isomiR variation, including for miR-222 where the majority of endogenously expressed miR-222 is extended by 1-5 nt compared to the canonical sequence. We demonstrate this 3' heterogeneity has dramatic implications for the phenotype of miR-222 transfected cells, with longer isoforms promoting apoptosis in a size (but not 3' sequence)-dependent manner. The transfection of longer miR-222 isomiRs did not induce an interferon response, but did downregulate the expression of many components of the pro-survival PI3K-AKT pathway including PIK3R3, a regulatory subunit whose knockdown phenocopied the expression of longer 222 isoforms in terms of apoptosis and the inhibition of other PI3K-AKT genes. As this work demonstrates the capacity for 3' isomiRs to mediate differential functions, we contend more attention needs to be given to 3' variance given the prevalence of this class of isomiR.

Detecting regional patterns of changing CO2 flux in Alaska.

With rapid changes in climate and the seasonal amplitude of carbon dioxide (CO2) in the Arctic, it is critical that we detect and quantify the underlying processes controlling the changing amplitude of CO2 to better predict carbon cycle feedbacks in the Arctic climate system. We use satellite and airborne observations of atmospheric CO2 with climatically forced CO2 flux simulations to assess the detectability of Alaskan carbon cycle signals as future warming evolves. We find that current satellite remote sensing technologies can detect changing uptake accurately during the growing season but lack sufficient cold season coverage and near-surface sensitivity to constrain annual carbon balance changes at regional scale. Airborne strategies that target regular vertical profile measurements within continental interiors are more sensitive to regional flux deeper into the cold season but currently lack sufficient spatial coverage throughout the entire cold season. Thus, the current CO2 observing network is unlikely to detect potentially large CO2 sources associated with deep permafrost thaw and cold season respiration expected over the next 50 y. Although continuity of current observations is vital, strategies and technologies focused on cold season measurements (active remote sensing, aircraft, and tall towers) and systematic sampling of vertical profiles across continental interiors over the full annual cycle are required to detect the onset of carbon release from thawing permafrost.