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The 852/3 CE eruption of Mount Churchill, Alaska, was one of the largest first-millennium volcanic events, with a magnitude of 6.7 (VEI 6) and a tephra volume of 39.4–61.9 km3 (95 % confidence). The spatial extent of the ash fallout from this event is considerable and the cryptotephra (White River Ash east; WRAe) extends as far as Finland and Poland. Proximal ecosystem and societal disturbances have been linked with this eruption; however, wider eruption impacts on climate and society are unknown. Greenland ice core records show that the eruption occurred in winter 852/3 ± 1 CE and that the eruption is associated with a relatively moderate sulfate aerosol loading but large abundances of volcanic ash and chlorine. Here we assess the potential broader impact of this eruption using palaeoenvironmental reconstructions, historical records and climate model simulations. We also use the fortuitous timing of the 852/3 CE Churchill eruption and its extensively widespread tephra deposition of the White River Ash (east) (WRAe) to examine the climatic expression of the warm Medieval Climate Anomaly period (MCA; ca. 950–1250 CE) from precisely linked peatlands in the North Atlantic region. The reconstructed climate forcing potential of the 852/3 CE Churchill eruption is moderate compared with the eruption magnitude, but tree-ring-inferred temperatures report a significant atmospheric cooling of 0.8 ∘C in summer 853 CE. Modelled climate scenarios also show a cooling in 853 CE, although the average magnitude of cooling is smaller (0.3 ∘C). The simulated spatial patterns of cooling are generally similar to those generated using the tree-ring-inferred temperature reconstructions. Tree-ring-inferred cooling begins prior to the date of the eruption suggesting that natural internal climate variability may have increased the climate system's susceptibility to further cooling. The magnitude of the reconstructed cooling could also suggest that the climate forcing potential of this eruption may be underestimated, thereby highlighting the need for greater insight into, and consideration of, the role of halogens and volcanic ash when estimating eruption climate forcing potential. Precise comparisons of palaeoenvironmental records from peatlands across North America and Europe, facilitated by the presence of the WRAe isochron, reveal no consistent MCA signal. These findings contribute to the growing body of evidence that characterises the MCA hydroclimate as time-transgressive and heterogeneous rather than a well-defined climatic period. The presence of the WRAe isochron also demonstrates that no long-term (multidecadal) climatic or societal impacts from the 852/3 CE Churchill eruption were identified beyond areas proximal to the eruption. Historical evidence in Europe for subsistence crises demonstrate a degree of temporal correspondence on interannual timescales, but similar events were reported outside of the eruption period and were common in the 9th century. The 852/3 CE Churchill eruption exemplifies the difficulties of identifying and confirming volcanic impacts for a single eruption, even when the eruption has a small age uncertainty.

Abstract Bovine adenovirus 7 (BAdV-7) is an unclassified member of the genus Atadenovirus with a worldwide distribution and has been reported to induce clinical disease of varying severity in infected cattle, ranging from asymptomatic infections to severe enteric or respiratory disease. In this study, we used next-generation sequencing to obtain the first complete genome sequence of a European strain of BadV-7, from pooled spleen and liver tissue obtained from a deceased newborn Limousin calf. Histopathological analysis and electron microscopy showing systemic lesions in multiple organs with intranuclear amphophilic inclusions observed in endothelial cells in multiple peripheral tissues. Virus isolation was readily achieved from tissue homogenate using bovine esophagus cells (KOP-R), a strategy which should facilitate future in vitro or in vivo BAdV-7 studies. Phylogenetic analysis of available genome sequences of BAdV-7 showed that the newly identified strain groups most closely with a recent BAdV-7 strain, SD18-74, from the USA, confirming that this newly identified strain is a member of the Atadenovirus genus. The fiber gene was found to be highly conserved within BAdV-7 strains but was highly divergent in comparison to Ovine adenovirus 7 (OAdV-7) (39.56% aa sequence identity). Furthermore, we report a variable region of multiple tandem repeats between the coding regions of E4.1 and RH5 genes. In summary, the presented pathological and molecular characterization of this case suggests that further research into the worldwide molecular epidemiology and disease burden of BAdV-7 is warranted.

The mid-17th century is characterized by a cluster of explosive volcanic eruptions in the 1630s and 1640s, climatic conditions culminating in the Maunder Minimum, and political instability and famine in regions of western and northern Europe as well as China and Japan. This contribution investigates the sources of the eruptions of the 1630s and 1640s and their possible impact on contemporary climate using ice core, tree-ring, and historical evidence but will also look into the socio-political context in which they occurred and the human responses they may have triggered. Three distinct sulfur peaks are found in the Greenland ice core record in 1637, 1641–1642, and 1646. In Antarctica, only one unambiguous sulfate spike is recorded, peaking in 1642. The resulting bipolar sulfur peak in 1641–1642 can likely be ascribed to the eruption of Mount Parker (6∘ N, Philippines) on 26 December 1640, but sulfate emitted from Komaga-take (42∘ N, Japan) volcano on 31 July 1641 has potentially also contributed to the sulfate concentrations observed in Greenland at this time. The smaller peaks in 1637 and 1646 can be potentially attributed to the eruptions of Hekla (63∘ N, Iceland) and Shiveluch (56∘ N, Russia), respectively. To date, however, none of the candidate volcanoes for the mid-17th century sulfate peaks have been confirmed with tephra preserved in ice cores. Tree-ring and written sources point to cold conditions in the late 1630s and early 1640s in various parts of Europe and to poor harvests. Yet the early 17th century was also characterized by widespread warfare across Europe – and in particular the Thirty Years' War (1618–1648) – rendering any attribution of socio-economic crisis to volcanism challenging. In China and Japan, historical sources point to extreme droughts and famines starting in 1638 (China) and 1640 (Japan), thereby preceding the eruptions of Komaga-take (31 July 1640) and Mount Parker (4 January 1641). The case of the eruption cluster between 1637 and 1646 and the climatic and societal conditions recorded in its aftermath thus offer a textbook example of difficulties in (i) unambiguously distinguishing volcanically induced cooling, wetting, or drying from natural climate variability and (ii) attributing political instability, harvest failure, and famines solely to volcanic climatic impacts. This example shows that while the impacts of past volcanism must always be studied within the contemporary socio-economic contexts, it is also time to move past reductive framings and sometimes reactionary oppositional stances in which climate (and environment more broadly) either is or is not deemed an important contributor to major historical events.

While paleoclimate simulations have been a priority for Earth system modelers over the past three decades, little attention has been paid to the period between the mid-Holocene and the Last Millennium, although this is an important period for the emergence of complex societies. Here, we consider the climate of 2500 BP (550 BCE), a period when compared to late preindustrial time, greenhouse gas concentrations were slightly lower, and orbital forcing led to a stronger seasonal cycle in high latitude insolation. To capture the influence of land cover on climate, we asynchronously coupled the NASA GISS ModelE Earth system model with the LPJ-LMfire dynamic global vegetation model. We simulated global climate and assessed our results in the context of independent paleoclimate reconstructions. We also explored a set of combinations of model performance parameters (bias and variability) and demonstrated their importance for the asynchronous coupling framework. The coupled model system shows substantial vegetation albedo feedback to climate. In the absence of a bias correction, while driving LPJ-LMfire in the coupling process, ModelE drifts towards colder conditions in the high latitudes of the Northern Hemisphere in response to land cover simulated by LPJ-LMfire. A regional precipitation response is also prominent in the various combinations of the coupled model system, with a substantial intensification of the Summer Indian Monsoon and a drying pattern over Europe. Evaluation of the simulated climate against reconstructions of temperature from multiple proxies and the isotopic composition of precipitation (δ18Op) from speleothems demonstrated the skill of ModelE in simulating past climate. A regional analysis of the simulated vegetation-climate response further confirmed the validity of this approach. The coupled model system is sensitive to the representation of shrubs and this land cover type requires particular attention as a potentially important driver of climate in regions where shrubs are abundant. Our results further demonstrate the importance of bias correction in coupled paleoclimate simulations. [ABSTRACT FROM AUTHOR]

This work considers the impact of resolution in the construction of mock observations of simulated galaxies. In particular, when building mock integral field spectroscopic observations from galaxy formation models in cosmological simulations, we investigate the possible systematics that may arise given the assumption that all galaxies above some stellar mass limit will provide unbiased and meaningful observable stellar kinematics. We build a catalogue of N -body simulations to sample the range of stellar particle resolutions within the Eagle Ref0050N0752 simulation box and examine how their observable kinematics vary relative to a higher-resolution N -body control. We use these models to compile a table of the minimum number of particles-per-pixel to reach a given uncertainty in the fitted line-of-sight velocity distribution parameters. Further, we introduce a Voronoi-binning module to the mock observation code, SimSpin , in order to meet these minimum numbers. Using Eagle , we show the impact of this shot noise on the observed spin–ellipticity plane and the recovery of this space when observations are binned with increasing numbers of particles. In conclusion, we advise binning mock images to meet at least 200 particles-per-pixel to avoid systematically under-estimating the velocity dispersion along a given line-of-sight. We demonstrate that this is important for comparing galaxies extracted from the same simulation, as well as between simulations of varying mass resolution and observations of real galaxies. [ABSTRACT FROM AUTHOR]

The Western Han dynasty (206 BCE–8 CE) experienced periods of extreme climate, accompanied by the evolving concept of the "mandate of heaven" that shaped societal response to disasters. While recent studies suggest that certain climate anomalies during the Han era are related to the atmospheric impacts of explosive volcanic eruptions, this paper employs both quantitative and qualitative methods to establish these associations more systematically. It categorizes and quantifies climatic stressors and selected societal events and applies superposed epoch analysis to examine the timing and statistical significance of their potential associations with ice-core-based dates of explosive eruptions. The paper then selects two historical periods, 180–150 BCE and 60–30 BCE, and offers a comparative analysis of recorded climatic and societal stresses, atmospheric optical anomalies, and societal responses to consecutive natural disasters. These periods are chosen because of the occurrence of massive volcanic eruptions known from polar ice-cores. For instance, in 43 BCE, when the Okmok volcano in Alaska erupted, a pale-blue sun and extreme summer cold are documented. Similarly, ice-cores identify a cluster of substantial eruptions in 168 BCE, 164 BCE, 161 BCE and 158 BCE that may have heavily impacted societies such as Egypt. Comparing the responses to the disasters of these periods also allow us to incorporate historical materials not suitable for quantification and to evaluate the effectiveness of Han dynasty disaster prevention and mitigation measures, thereby identifying factors that may contribute to better resilience to sudden and drastic environmental changes. [ABSTRACT FROM AUTHOR]

Selective mutism (SM) and autism frequently co-occur together, exacerbating social communication deficits and associated anxiety. However, professionals have lacked a readiness to diagnose SM and autism together, making the need to understand parental experiences of caring for a child with SM and autism crucial. The current study utilised Interpretative Phenomenological Analysis (IPA) to explore parents' experience of caring for children with SM and autism. Semi-structured interviews were conducted with eleven mothers and one father of children aged between 5 and 18 years. All children were diagnosed with SM and had undertaken, or were currently undertaking, an autism diagnostic process. Analysis of the transcripts resulted in the following themes: Complexities from co-occurring issues; The overwhelming impact of SM; The diagnostic journey; Finding solutions and advocacy. Judgements and minimisation of symptoms from educational and healthcare systems exacerbated delays in diagnosis preventing appropriate intervention. The complexities of caring for a child with SM and autism, alongside wider misunderstandings, exacerbated parental stress, impacting the family. Parental advocacy and safe environments provided opportunities for children to better manage contextually based mutism. Improvements in identification and compassionate understanding from wider systems by involving parents as key stakeholders are essential to improve this situation. [ABSTRACT FROM AUTHOR]

The transition from primary to secondary school is a stressful period for autistic individuals. However, less is known about parental experiences of the school transition, and its impact on the family. This study explored mothers' perspectives on the psychological impact of the transition to secondary school for their autistic children and their families. Using Interpretative Phenomenological Analysis, semi-structured interviews were analysed to explore the experiences of eight mothers of autistic children at the end of their child's first year in secondary school. The analysis revealed two superordinate themes: lack of available support and detrimental psychological impact on the family. Mothers reported the negative impact the transition had on themselves, their child, and the wider family. The importance of pre- and ongoing transition support was highlighted to reduce the concerns of children and their parents throughout the transition process. The findings highlighted the need for autism-specific individualized guidance, as well as considering the potential for transition issues to impact on siblings. [ABSTRACT FROM AUTHOR]

Introduction: Chyme reinfusion therapy (CRT) is a safe and effective method to improve nutritional outcomes and promote intestinal adaptation in patients with stomas. This practice involves refeeding the proximal stoma output, down the distal limb, and mimics a state of intestinal continuity; thereby promoting growth and adaption of the distal bowel. Despite its promise, CRT in neonates is a relatively underutilised practice and can be of significant value in neonates with congenital bowel anomalies or necrotising enterocolitis. We aimed to identify the frequency, methodology and adverse effects associated with CRT in our neonatal population. We aimed to identify the frequency, methodology and adverse events associated with CRT in our neonatal population. Methods: A ten-year retrospective cohort study was conducted using database searches at two major paediatric hospitals in New Zealand. All patients with suitable anatomy were identified, and data on CRT methodology and outcomes were recorded. Results: Of the 49 eligible neonates, 23 (47%) underwent CRT. Indications for CRT included high stoma output, malnutrition with poor weight gain, and routine refeeding prior to stoma reversal. A nasogastric feeding tube was inserted into the distal limb and collected chyme was reinfused via manual bolus or automated syringe driver. The median (IQR) weight gain increased from 13.9 (3.50–22.89) to 24.37 (19.68–29.99) g/day during CRT (p = 0.04). 18 infections requiring medical intervention but unrelated to CRT occurred in 13 patients (56%). Amongst our cohort, there was a high rate of non-infectious events, including peri-stomal skin irritation (60%), stoma prolapse (43%) and stomal bleeding (26%). Conclusion: CRT is an underutilised method of improving nutrition in neonates with intestinal failure. Premature neonates requiring double enterostomy formation are at high risk of infectious and non-infectious complications, but few of these are related to CRT. Standardised protocols providing clear eligibility criteria and detailed methodology for CRT are required to promote uniform utilisation of this practice. [ABSTRACT FROM AUTHOR]

Background: Many women of childbearing age with inflammatory bowel disease (IBD) require advanced therapies. While biologics are largely low risk during pregnancy, the novel small molecules tofacitinib, filgotinib, upadacitinib and ozanimod (TFUO) have shown concerning teratogenic effects, and decreased fertility in animal studies. Therefore, their use in women of childbearing age needs careful consideration. Design: RAND/University of California Los Angeles (UCLA) Appropriateness Method (RAM). Objective: To evaluate the appropriateness of TFUO in women of childbearing age. Methods: We convened a panel of six gastroenterologists, two IBD nurses, one IBD pharmacist and three expert patients. Following a literature review, 13 statements were drafted and voted upon in 2 rounds. Results: All 13 statements were deemed appropriate. The panel concluded that women with IBD of childbearing age who wish to commence therapy with TFUO, need to use effective contraception and be counselled regarding the risk in unplanned pregnancies. For women using contraception while on Janus kinase inhibitor (JAKi) therapy, we suggest the preferred use of progesterone-only or non-hormonal long-acting contraception. TFUO are contraindicated during pregnancy and breast feeding. We recommend that women receiving TFUO cease therapy in time to establish clinical remission for at least 3 months prior to conception. Therapies other than TFUO should be considered as first-line therapy in women with IBD of childbearing age, except in select individual circumstances. TFUO may be appropriate for women of childbearing age after failure of, intolerance or contraindications to one biological agent. Conclusion: TFUO should be avoided during pregnancy and breastfeeding, and alternative therapies should be considered as first-line treatments. Summary: We provide clinical practice recommendations regarding the use of TFUO for IBD in women of childbearing age. Plain language summary: Small Molecules for Patients with IBD of Childbearing Age The maintenance of remission is vital for good fetal and maternal outcomes in IBD pregnancies and biological therapies used in IBD have been associated with favourable pregnancy outcomes. The safety profile of novel small molecules in human pregnancy is however largely unknown. We conducted a RAND appropriateness panel to agree recommendation son the use of Tofacitinib, Filgotinib, Upadacitinib and Ozanimod in women of childbearing age. Tofacitinib, Filgotinib, Upadacitinib and Ozanimod should be avoided during pregnancy due to serious concerns regarding birth defects. Small molecule therapies Tofacitinib, Filgotinib, Upadacitinib and Ozanimod should be given due consideration in the management of IBD in women of childbearing age, provided there are no immediate plans for conception. Counselling about potential risk of adverse effects during pregnancy, risk of venous thromboembolism and effective contraception are needed. Clinicians need to consider time to establish alternative therapies when switching away from Tofacitinib, Filgotinib, Upadacitinib and Ozanimod in the pre-conception period. Future research should examine pregnancy outcomes in cases where Tofacitinib, Filgotinib, Upadacitinib and Ozanimod exposure occurred but data may be difficult to compare to biologics due to differences in exposure duration. Guidelines should be updated as further maternal and fetal safety data become available [ABSTRACT FROM AUTHOR]

Background: Older adults in residential aged care facilities (RACFs) experience disproportionate levels of poor oral health relative to other groups in the general population, affecting their physical and mental wellbeing. The Oral Health Assessment Tool (OHAT) is a validated and widely used dental assessment tool; however, recent systematic reviews have identified shortcomings with respect to its measurement properties. Objective: The objective of this protocol is to provide a detailed overview of a multidisciplinary qualitative study that aims to (a) co-design and develop a modified OHAT for RACFs and (b) inform the development of an OHAT training package and implementation strategies. Methods: This study will utilize a co-design methodology with aged care residents, caregivers, staff members, and health professionals. The co-design workshops will: (1) investigate the barriers to and enablers of optimal oral healthcare in RACFs; and (2) co-design a modified version of the Oral Health Assessment Tool and a referral to treatment pathway that is appropriate for use in RACFs. The co-design workshops will facilitate group discussion and involve interactive activities using, for example, mind mapping and Sticky Notes. Qualitative data (transcripts and artefacts from co-design activities) will be analyzed in NVivo using an inductive codebook thematic analysis, specifically a template analysis. Conclusion: The findings of this study will inform a modified OHAT (M-OHAT), as well as future study phases regarding training and implementation strategies. It is expected that the M-OHAT will have enhanced usability and relevance to RACFs, facilitating the identification of poor oral health and timely referral to dental treatment. [ABSTRACT FROM AUTHOR]

Understanding of past droughts has been mostly shaped by meteorological data, with relatively less known about the human aspects of droughts, their socio‐economic impacts, as well as choices people make in response to droughts in different environmental and socio‐political contexts. The lack of data that systematically record and categorize drought impacts is an important reason for this disparity. In this paper, we present an Irish drought impacts database (IDID) containing 6094 newspaper reports and 11,351 individual impact records for the island of Ireland, covering the period 1733–2019. Relevant articles were identified through systematic searching of the Irish Newspaper Archives, and recorded impacts were categorized using a modified version of the classification scheme employed by the European drought impact inventory (EDII). Drawing on the wealth and diversity of content provided by the newspapers, the IDID database provides information on the documented temporal and geographical extent of drought events, their socio‐economic and political contexts, their consequences, mitigation strategies employed and their change over time. The IDID also facilitates analysis of long‐term patterns in drought incidence, individual impact categories, as well as detailed insight into the impacts of individual drought events over nearly three centuries of Ireland's history. In addition, by allowing an examination of the coherence between meteorological records and identified impacts, it advances our understanding of the influences that contemporary economic, political, environmental and societal events had on the human experience, perception and impact of droughts. This new open‐access database, therefore, provides opportunities for improving understanding of drought vulnerability and is an important step in developing greater capacity to cope with and respond to future droughts on the island of Ireland. [ABSTRACT FROM AUTHOR]

Controlled human infection models (CHIMs) are a critical tool for the understanding of infectious disease progression, characterising immune responses to infection and rapid assessment of vaccines or drug treatments. There is increasing interest in using CHIMs for vaccine development and an obvious need for widely available and fit‐for‐purpose challenge agents. Inno4Vac is a large European consortium working towards accelerating and de‐risking the development of new vaccines, including development of CHIMs for influenza, respiratory syncytial virus and Clostridium difficile. This report (in two parts) summarises a workshop held at the MHRA in 2021, focused on how to select CHIM candidate strains of influenza and respiratory syncytial virus (RSV) based on desirable virus characteristics and which immune assays would provide relevant information for assessing pre‐existing and post‐infection immune responses and defining correlates of protection. This manuscript (part 2) summarises presentations and discussions centred around RSV CHIMs and immune assays (an additional manuscript summarises influenza CHIM and immune assays: Inno4Vac workshop report Part 1: Controlled human influenza virus infection model (CHIVIM) strain selection and immune assays for CHIVIM studies, November 2021, MHRA, UK). [ABSTRACT FROM AUTHOR]

Parental involvement (PI) in the education of their children is an important factor which should be taken into account when assessing and predicting children's school outcomes. However, PI encompasses numerous operationalizations from checking homework, to communication with school, to organizing cultural outings. This study describes a Rasch/Guttman scenario-based scale designed to provide a holistic approach to measuring the PI construct. The Parental Involvement SCenarios scale (PISC-9) was administered to 1,930 parents of primary school children from a sample representative of a Russian region. The scale has very good technical and construct validity characteristics. More specifically, raw scores on the PISC-9 may be represented as locations along a hierarchical continuum from relatively less to increasingly more time consuming and demanding parental behaviors.

Student perceptions of instructor availability outside of class are examined both as a predictor of instructor quality and as an outcome of student, instructor, and course characteristics. Data represent a 30-year case study record of course evaluations and instructor professional and personal variables. Student perceptions of instructor availability have a statistically significant positive relationship with student ratings of instruction beyond what is explained by other sets of instructional variables. These results suggest that faculty members' ratings of instructional quality may improve with increased availability to students outside of class; however, it is not entirely clear what exactly it looks like to students for faculty to be available outside of class.

Abstract Background Falls in older adults remain a pressing health concern. With advancements in data analytics and increasing uptake of electronic health records, developing comprehensive predictive models for fall risk is now possible. We aimed to systematically identify studies involving the development and implementation of predictive falls models which used routinely collected electronic health record data in home-based, community and residential aged care settings. Methods A systematic search of entries in Cochrane Library, CINAHL, MEDLINE, Scopus, and Web of Science was conducted in July 2020 using search terms relevant to aged care, prediction, and falls. Selection criteria included English-language studies, published in peer-reviewed journals, had an outcome of falls, and involved fall risk modelling using routinely collected electronic health record data. Screening, data extraction and quality appraisal using the Critical Appraisal Skills Program for Clinical Prediction Rule Studies were conducted. Study content was synthesised and reported narratively. Results From 7,329 unique entries, four relevant studies were identified. All predictive models were built using different statistical techniques. Predictors across seven categories were used: demographics, assessments of care, fall history, medication use, health conditions, physical abilities, and environmental factors. Only one of the four studies had been validated externally. Three studies reported on the performance of the models. Conclusions Adopting predictive modelling in aged care services for adverse events, such as falls, is in its infancy. The increased availability of electronic health record data and the potential of predictive modelling to document fall risk and inform appropriate interventions is making use of such models achievable. Having a dynamic prediction model that reflects the changing status of an aged care client is key to this moving forward for fall prevention interventions.

It appears that indexicals must have fine-grained senses for us to explain things involving human action and emotions, and we typically identify these different senses with different modes of expression. On the other hand, we also express the very same thought in very different ways. The first problem is the problem of cognitive significance. The second problem is what Branquinho (1999) has called the problem of cognitive dynamics. The question is how we can solve both of those problems at the same time. Vojislav Božičković (2021) offers one solution in which the cognitive dynamics runs through the objects of the attitudes. I discuss this solution and offer an alternative in which the theory of cognitive dynamics has no use for the objects of the attitudes to unify expressions of attitudes. When we say or believe "the same thing" using different modes of expressions, it is by virtue of our deploying a dynamic theory of attitude expression. Like Lewis Carrol's Red Queen, we must run to stay in place.

Part of the regulation of telomerase activity includes the alternative splicing (AS) of the catalytic subunit telomerase reverse transcriptase (TERT). Although a therapeutic window for telomerase/TERT inhibition exists between cancer cells and somatic cells, stem cells express TERT and rely on telomerase activity for physiological replacement of cells. Therefore, identifying differences in TERT regulation between stem cells and cancer cells is essential for developing telomerase inhibition-based cancer therapies that reduce damage to stem cells. In this study, we measured TERT splice variant expression and telomerase activity in induced pluripotent stem cells (iPSCs), neural progenitor cells (NPCs), and non-small cell lung cancer cells (NSCLC, Calu-6 cells). We observed that a NOVA1-PTBP1-PTBP2 axis regulates TERT alternative splicing (AS) in iPSCs and their differentiation into NPCs. We also found that splice-switching of TERT, which regulates telomerase activity, is induced by different cell densities in stem cells but not cancer cells. Lastly, we identified cell type-specific splicing factors that regulate TERT AS. Overall, our findings represent an important step forward in understanding the regulation of TERT AS in stem cells and cancer cells.

Rosa roxburghii Tratt. is an important commercial horticultural crop endemic to China, which is recognized for its extremely high content of L-ascorbic acid (AsA). To understand the mechanisms underlying AsA overproduction in fruit of R. roxburghii, content levels, accumulation rate, and the expression of genes putatively in the biosynthesis of AsA during fruit development have been characterized. The content of AsA increased with fruit weight during development, and AsA accumulation rate was found to be highest between 60 and 90 days after anthesis (DAA), with approximately 60% of the total amount being accumulated during this period. In vitro incubating analysis of 70DAA fruit flesh tissues confirmed that AsA was synthesized mainly via the L-galactose pathway although L-Gulono-1, 4-lactone was also an effective precursor elevating AsA biosynthesis. Furthermore, in transcript level, AsA content was significantly associated with GDP-L-galactose phosphorylase (RrGGP2) gene expression. Virus-induced RrGGP2 silencing reduced the AsA content in R. roxburghii fruit by 28.9%. Overexpressing RrGGP2 increased AsA content by 8-12-fold in tobacco leaves and 2.33-3.11-fold in tomato fruit, respectively, and it showed enhanced resistance to oxidative stress caused by paraquat in transformed tobacco. These results further justified the importance of RrGGP2 as a major control step to AsA biosynthesis in R. roxburghii fruit.