Search

The responses of Acala cotton (Gossypium hirsutum L.) in California to a range of applied nitrogen (N) treatments were investigated in a 5-year, multisite experiment. The experiment’s goals were to identify crop growth and yield responses to applied N and provide information to better assess the utility of soil residual N estimates in improving fertilizer management. Baseline fertilizer application rates for the lowest applied N treatments were based on residual soil nitrate-N (NO3-N) levels determined on soil samples from the upper 0.6 m of the soil collected prior to spring N fertilization and within 1 week postplanting each year. Results have shown positive cotton lint yield responses to increases in applied N across the 56 to 224 kg N/ha range in only 41% (16 out of 39) of test sites. Soil NO3-N monitoring to a depth of 2.4 m in the spring (after planting) and fall (postharvest) indicate most changes in soil NO3- occur within the upper 1.2 m of soil. However, some sites (those most prone to leaching losses of soluble nutrients) also exhibited net increases in soil NO3-N in the 1.2- to 2.4-m depth zone when comparing planting time vs. postharvest data. The lack of yield responses and soil NO3-N accumulations at some sites indicate that more efforts should be put into identifying the amount of plant N requirements that can be met from residual soil N, rather than solely from fertilizer N applications.

Abstract Background Treatment for osteosarcoma, a paediatric bone cancer with no therapeutic advances in over three decades, is limited by a lack of targeted therapies. Osteosarcoma frequently metastasises to the lungs, and only 20% of patients survive 5 years after the diagnosis of metastatic disease. We found that WNT5B is the most abundant WNT expressed in osteosarcoma tumours and its expression correlates with metastasis, histologic subtype and reduced survival. Methods Using tumor‐spheroids to model cancer stem‐like cells, we performed qPCR, immunoblotting, and immunofluorescence to monitor changes in gene and protein expression. Additionally, we measured sphere size, migration and forming efficiency to monitor phenotypic changes. Therefore, we characterised WNT5B's relevance to cancer stem‐like cells, metastasis, and chemoresistance and evaluated its potential as a therapeutic target. Results In osteosarcoma cell lines and patient‐derived spheres, WNT5B is enriched in stem cells and induces the expression of the stemness gene SOX2. WNT5B promotes sphere size, sphere‐forming efficiency, and cell proliferation, migration, and chemoresistance to methotrexate (but not cisplatin or doxorubicin) in spheres formed from conventional cell lines and patient‐derived xenografts. In vivo, WNT5B increased osteosarcoma lung and liver metastasis and inhibited the glycosaminoglycan hyaluronic acid via upregulation of hyaluronidase 1 (HYAL1), leading to changes in the tumour microenvironment. Further, we identified that WNT5B mRNA and protein correlate with the receptor ROR1 in primary tumours. Targeting WNT5B through inhibition of WNT/ROR1 signalling with an antibody to ROR1 reduced stemness properties, including chemoresistance, sphere size and SOX2 expression. Conclusions Together, these data define WNT5B's role in driving osteosarcoma cancer stem cell expansion and methotrexate resistance and provide evidence that the WNT5B pathway is a promising candidate for treating osteosarcoma patients. Key points WNT5B expression is high in osteosarcoma stem cells leading to increased stem cell proliferation and migration through SOX2. WNT5B expression in stem cells increases rates of osteosarcoma metastasis to the lungs and liver in vivo. The hyaluronic acid degradation enzyme HYAL1 is regulated by WNT5B in osteosarcoma contributing to metastasis. Inhibition of WNT5B with a ROR1 antibody decreases osteosarcoma stemness.

IntroductionLamb production systems are under increasing pressure to reduce their environmental footprint, particularly emissions of greenhouse gases (GHGs) such as methane. However, the metrics used to express the carbon footprint of lamb seldom consider its nutritional density and contribution to balanced diets in humans. Lamb production systems vary considerably, from low-input pastoral systems to higher-input systems feeding concentrates for the latter ‘finishing’ period. To date, no studies have explored the effect of finishing diet on the carbon footprint of lamb meat on a nutritional basis.MethodsData from 444 carcasses were collected from four abattoirs across Wales, United Kingdom. Lambs were derived from 33 farms with one of four distinct finishing diets: forage crops (n = 5), grass (n = 11), concentrates (n = 7), and grass and concentrates (n = 15). Carcass data were analysed using mixed effects models. Significant differences were found in fatty acid composition of two large commercial cuts of meat from different finishing diets. To illustrate the effect of different measures of footprint, mass (kg dwt) and omega-3 polyunsaturated fatty acid content (g omega-3) were selected as functional units. GHG emission estimates were calculated using Agrecalc.ResultsThe concentrates diet had the lowest average mass-based product emissions [25.0 kg CO2e/kg deadweight (dwt)] while the grass systems had the highest (28.1 kg CO2e/kg dwt; p < 0.001). The semimembranosus muscle cut from the forage crops diet had the lowest average nutrition-based product emissions (19.2 kg CO2e/g omega-3); whereas the same muscle cut from lambs finished on the grass and concentrates diet had the highest nutrition-based product emissions (29.4 kg CO2e/g omega-3; p < 0.001).DiscussionWhile mass-based functional units can be useful for comparing efficiencies of different farming systems, they do not reflect how farming systems impact the nutritional differences of the final product. This study demonstrates the importance of considering nutrition when expressing and comparing the carbon footprints of nutrient-dense foods such as lamb. This approach could also help inform discussions around the optimal diets for lamb production systems from both a human nutrition and environmental sustainability perspective.

In Hawai’i, ecosystem conservation practitioners are increasingly considering the potential ecohydrological benefits from applied conservation action to mitigate the degrading impacts of runoff on native and restored ecosystems. One determinant of runoff is excess rainfall events where rainfall rates exceed the infiltration capacity of soils. To help understand runoff risks, we calculated the probability of excess rainfall events across the Hawaiian landscape by comparing the probability distributions of projected rainfall frequency and land-cover-specific infiltration capacity. We characterized soil infiltration capacity based on different land cover types (bare soil, grasses, and woody vegetation) and compared them to the frequency of large rainfall events under current and future climate scenarios. We then mapped the potential risk of excess rainfall across the main Hawaiian Islands. Our results show that land cover type has a very large effect on runoff risk as excess rainfall conditions are 234% more likely in bare soil and 75% more likely in grasslands compared to woody forests and shrublands. In contrast, projected shifts in rainfall intensity by end-of-century show little impact on these probabilities and thus, the risk of runoff. This indicates that the probability of excess rainfall is primarily driven by differences in land cover and not by current or potential shifts in rainfall patterns across the Hawaiian landscape. The ability to estimate the risk of potentially ecologically and economically costly runoff based on changes of land cover is useful for managers focused on invasive species control and restoration planning, especially for native and endemic ecosystems unique to the State of Hawai’i.

Background. Rheumatic heart disease (RHD) is a preventable chronic cardiac condition that causes over 350 000 deaths annually, largely in low and middle-income countries, as a direct result of structural inequalities and inadequate access to comprehensive healthcare. People living with and affected by this disease are a key stakeholder group and need to be directing research priorities. Objective. To improve care and provide direction for future research, a group of qualitative researchers and pe living with RHD from six countries convened in Cape Town in 2016. Methods. People with RHD shared their lived experiences while RHD researchers, clinicians and advocates presented a spectrum of qualitative research methods to explore these experiences. The Continuum of Care© (CoC, developed by the Medtronic Foundation) was used as a framework to guide participant discussions. Thematic summaries of the discussions were undertaken in an iterative process throughout the workshop. Results. Three themes emerged in the summaries: there is no ‘typical’ patient journey; a biomedical focus on RHD does not reflect people’s lived experiences; and a diversity of research methods is required to investigate experiences of people living with RHD. Practice implications. Qualitative research methods are invaluable for allowing patient ‘voices’ to be heard. To this end, qualitative approaches should be incorporated in all RHD research to ensure maximum benefit for patients. Conclusion. Greater understanding of the patient journey was gained for strengthening and expanding the global RHD research agenda. Future research should reflect on and incorporate the realities of patients’ lived experiences, and these experiences should be integrated into healthcare models for chronic conditions.

Abstract Wildfire is a growing concern as climate shifts. The hydrologic effects of wildfire, which include elevated hazards and changes in water quantity and quality, are increasingly assessed using numerical models. Post‐wildfire application of physically based distributed models provides unique insight into the underlying processes that affect water resources after wildfire. This work reviews and synthesizes post‐wildfire applications of physically based distributed models by examining the scales and geographic/ecohydrologic distribution of model applications, hydrologic response process representation, model parameterization, and model performance metrics. Highlighted gaps and opportunities for advancing physically based distributed hydrologic response modeling after wildfire include the following: (a) applying models in under‐represented geographic (S. America, Africa, Asia) and ecohydrologic regions (arid or dry subhumid climates), (b) incorporating all four major streamflow generation mechanisms (infiltration excess, saturation excess, subsurface storm flow, and groundwater flow), (c) representing integrated vadose zone and saturated zone processes to better capture subsurface streamflow generation, (d) building new remotely sensed model parameterization methods for precipitation interception, infiltration, and overland flow that account for burn severity and recovery, (e) incorporating distributed state variables (e.g., soil moisture, groundwater levels) in model performance assessment, (f) designing model intercomparison studies, including field datasets specifically for post‐wildfire model development and validation, (g) linking mechanistic vegetation regrowth models with hydrologic models to improve simulation of process shifts as ecosystems recover, and (h) creating a new community modeling framework to integrate modeling advances across the wildfire science community.

WNT10B, a member of the WNT family of secreted glycoproteins, activates the WNT/β-catenin signaling cascade to control proliferation, stemness, pluripotency, and cell fate decisions. WNT10B plays roles in many tissues, including bone, adipocytes, skin, hair, muscle, placenta, and the immune system. Aberrant WNT10B signaling leads to several diseases, such as osteoporosis, obesity, split-hand/foot malformation (SHFM), fibrosis, dental anomalies, and cancer. We reviewed WNT10B a decade ago, and here we provide a comprehensive update to the field. Novel research on WNT10B has expanded to many more tissues and diseases. WNT10B polymorphisms and mutations correlate with many phenotypes, including bone mineral density, obesity, pig litter size, dog elbow dysplasia, and cow body size. In addition, the field has focused on the regulation of WNT10B using upstream mediators, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). We also discussed the therapeutic implications of WNT10B regulation. In summary, research conducted during 2012–2022 revealed several new, diverse functions in the role of WNT10B in physiology and disease.

Estrogens, which bind to estrogen receptor alpha (ERα), are important for proper bone mineral density. When women go through menopause, estrogen levels decrease, and there is a decrease in bone quality, along with an increased risk for fractures. We previously identified an enhancer near FOXC1 as the most significantly enriched binding site for estrogen receptor alpha (ERα) in osteoblasts. FOXC1 is a transcription factor belonging to a large group of proteins known as forkhead box genes and is an important regulator of bone formation. Here, we demonstrate that 17β-estradiol (E2) increases the mRNA and protein levels of FOXC1 in primary mouse and human osteoblasts. GATA4 is a pioneer factor for ERα and it is also recruited to enhancers near Foxc1. Knockdown of Gata4 in mouse osteoblasts in vitro decreases Foxc1 expression as does knockout of Gata4 in vivo. Functionally, GATA4 and FOXC1 interact and regulate osteoblast proteins such as RUNX2, as demonstrated by ChIP-reChIP and luciferase assays. The most enriched motif in GATA4 binding sites from ChIP-seq is for FOXC1, supporting the notion that GATA4 and FOXC1 cooperate in regulating osteoblast differentiation. Together, these data demonstrate the interactions of the transcription factors ERα, GATA4, and FOXC1 to regulate each other’s expression and other osteoblast differentiation genes.

Progestins, synthetic compounds designed to mimic the activity of natural progesterone (P4), are used globally in menopausal hormone therapy. Although the older progestins medroxyprogesterone acetate (MPA) and norethisterone (NET) have been implicated in increased breast cancer risk, little is known regarding newer progestins, and no significant risk has been associated with P4. Considering that breast cancer is the leading cause of mortality in women, establishing which progestins increase breast cancer incidence and elucidating the underlying mechanisms is a global priority. We showed for the first time that the newer-generation progestin drospirenone (DRSP) is the least potent progestin in terms of proliferation of the estrogen-responsive MCF-7 BUS breast cancer cell line, while NET and P4 have similar potencies to estradiol (E2), the known driver of breast cancer cell proliferation. Notably, MPA, the progestin most frequently associated with increased breast cancer risk, was significantly more potent than E2. While all the progestogens enhanced the anchorage-independent growth of the MCF-7 BUS cell line, MPA promoted a greater number of colonies than P4, NET or DRSP. None of the progestogens inhibited E2-induced proliferation and anchorage-independent growth. We also showed that under non-estrogenic conditions, MPA and NET, unlike P4 and DRSP, increased the expression of the estrogen receptor (ER) target gene, cathepsin D, via a mechanism requiring the co-recruitment of ERα and the progesterone receptor (PR) to the promoter region. In contrast, all progestogens promoted the association of the PR and ERα on the promoter of the PR target gene, MYC, thereby increasing its expression under non-estrogenic and estrogenic conditions. These results suggest that progestins differentially regulate the way the PR and ER converge to modulate the expression of PR and ER-regulated genes. Our novel findings indicating similarities and differences between P4 and the progestins, emphasize the importance of comparatively investigating effects of individual progestins rather than grouping them as a class. Further studies are required to underpin the clinical relevance of PR/ERα crosstalk in response to different progestins in both normal and malignant breast tissue, to either confirm or refute their suitability in combination therapy for ER-positive breast cancer.

The Fermi Large Area Telescope (LAT) lightcurve repository (LCR) is a publicly available, continually updated library of gamma-ray lightcurves of variable Fermi-LAT sources generated over multiple timescales. The Fermi-LAT LCR aims to provide publication-quality lightcurves binned on timescales of 3, 7, and 30 days for 1525 sources deemed variable in the source catalog of the first 10 yr of Fermi-LAT observations. The repository consists of lightcurves generated through full likelihood analyses that model the sources and the surrounding region, providing fluxes and photon indices for each time bin. The LCR is intended as a resource for the time-domain and multimessenger communities by allowing users to search LAT data quickly to identify correlated variability and flaring emission episodes from gamma-ray sources. We describe the sample selection and analysis employed by the LCR and provide an overview of the associated data access portal.

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

Unsaturated zone properties and processes are central to understanding the interacting effects of land-use change, contamination, and hydroclimate on our ability to grow food, sustain clean water supplies, and minimize loss of life and property. Advances in unsaturated zone science are being achieved through collaborations across traditional boundaries where information from biological, physical, and chemical disciplines is combined for new insights. The Unsaturated Zone Interest Group (UZIG) is an organization that exists principally to promote multidisciplinary collaborations and the sharing of ideas, expertise, and technical assets. Here we summarize key findings from 14 papers, several of which originated from a meeting convened by UZIG in 2017 at the University of Florida in Gainesville titled “Land-Use Change, Climate Change, and Hydrologic Extremes: Unsaturated Zone Responses and Feedbacks.” This special section of contains multidisciplinary research in three general categories relevant to measuring and understanding unsaturated zone responses to changing land uses and climate: (i) unsaturated zone properties and processes; (ii) soil–plant–atmosphere interactions; and (iii) novel field sampling devices. A strong cross-cutting theme in these papers is the value of continuous monitoring data and ways of utilizing them to discover novel hydrologic, biologic, and pedologic information. As climatic and land-use conditions change and demands for resources and stresses on ecosystems continue to intensify, it is vital to improve our fundamental understanding of the processes at work in the unsaturated zone. Toward that goal, we discuss the need for improved ground-based unsaturated zone monitoring networks.

The title compound, C19H12Cl2N2O4S3, is related to a ditosylated 2-iminobenzothiazole with the two methyl groups on the two phenyl rings replaced by chlorine. There is a weak intramolecular π–π contact between the two phenyl rings, with a centroid-to-centroid distance of 4.004 (2) Å. The dihedral angle between the rings is 9.96 (13)°. An intramolecular C—H...O hydrogen bond stabilizes the molecular conformation.