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Viral capsid assembly involves the oligomerization of the capsid nucleoprotein (NP), which is an essential step in viral replication and may represent a potential antiviral target. An in vitro transcription-translation reaction using a wheat germ (WG) extr

Deep-sea ferromanganese nodules accumulate trace elements from seawater and underlying sediment porewaters during the growth of concentric mineral layers over millions of years. These trace elements have the potential to record past ocean geochemical conditions. The goal of this study was to determine whether Fe mineral alteration occurs and how the speciation of trace elements responds to alteration over ~3.7Ma of marine ferromanganese nodule (MFN) formation, a timeline constrained by estimates from 9Be/10Be concentrations in the nodule material. We determined Fe-bearing phases and Fe isotope composition in a South Pacific Gyre (SPG) nodule. Specifically, the distribution patterns and speciation of trace element uptake by these Fe phases were investigated. The time interval covered by the growth of our sample of the nodule was derived from 9Be/10Be accelerator mass spectrometry (AMS). The composition and distribution of major and trace elements were mapped at various spatial scales, using micro-X-ray fluorescence (μXRF), electron microprobe analysis (EMPA), and inductively coupled plasma mass spectrometry (ICP-MS). Fe phases were characterized by micro-extended X-ray absorption fine structure (μEXAFS) spectroscopy and micro-X-ray diffraction (μXRD). Speciation of Ti and V, associated with Fe, was measured using micro-X-ray absorption near edge structure (μXANES) spectroscopy. Iron isotope composition (δ56/54Fe) in subsamples of 1-3mm increments along the radius of the nodule was determined with multiple-collector ICP-MS (MC-ICP-MS). The SPG nodule formed through primarily hydrogeneous inputs at a rate of 4.0±0.4mm/Ma. The nodule exhibited a high diversity of Fe mineral phases: feroxyhite (δ-FeOOH), goethite (α-FeOOH), lepidocrocite (γ-FeOOH), and poorly ordered ferrihydrite-like phases. These findings provide evidence that Fe oxyhydroxides within the nodule undergo alteration to more stable phases over millions of years. Trace Ti and V were spatially correlated with Fe and found to be adsorbed to Fe-bearing minerals. Ti/Fe and V/Fe ratios, and Ti and V speciation, did not vary along the nodule radius. The δ56/54Fe values, when averaged over sample increments representing 0.25-0.75Ma, were homogeneous within uncertainty along the nodule radius, at -0.12±0.07‰ (2sd, n=10). Our results indicate that the Fe isotope composition of the nodule remained constant during nodule growth and that mineral alteration did not affect the primary Fe isotope composition of the nodule. Furthermore, the average δ56/54Fe value of -0.12‰ we find is consistent with Fe sourced from continental eolian particles (dust). Despite mineral alteration, the trace element partitioning of Ti and V, and Fe isotope composition, do not appear to change within the sensitivity of our measurements. These findings suggest that Fe oxyhydroxides within hydrogenetic ferromanganese nodules are out of geochemical contact with seawater once they are covered by subsequent concentric mineral layers. Even though Fe-bearing minerals are altered, trace element ratios, speciation and Fe isotope composition are preserved within the nodule.

High-density single nucleotide polymorphism (SNP) genotyping arrays are a powerful tool for studying genomic patterns of diversity, inferring ancestral relationships between individuals in populations and studying marker-trait associations in mapping experiments. We developed a genotyping array including about 90 000 gene-associated SNPs and used it to characterize genetic variation in allohexaploid and allotetraploid wheat populations. The array includes a significant fraction of common genome-wide distributed SNPs that are represented in populations of diverse geographical origin. We used density-based spatial clustering algorithms to enable high-throughput genotype calling in complex data sets obtained for polyploid wheat. We show that these model-free clustering algorithms provide accurate genotype calling in the presence of multiple clusters including clusters with low signal intensity resulting from significant sequence divergence at the target SNP site or gene deletions. Assays that detect low-intensity clusters can provide insight into the distribution of presence-absence variation (PAV) in wheat populations. A total of 46 977 SNPs from the wheat 90K array were genetically mapped using a combination of eight mapping populations. The developed array and cluster identification algorithms provide an opportunity to infer detailed haplotype structure in polyploid wheat and will serve as an invaluable resource for diversity studies and investigating the genetic basis of trait variation in wheat. © 2014 The Authors Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Meiotic crossovers (COs) generate genetic diversity and are crucial for viable gamete production. Plant COs are typically limited to 1-3 per chromosome pair, constraining the development of improved varieties, which in wheat is exacerbated by an extreme distal localisation bias. Advances in wheat genomics and related technologies provide new opportunities to investigate, and possibly modify, recombination in this important crop species. Here, we investigate the disruption of FIGL1 in tetraploid and hexaploid wheat as a potential strategy for modifying CO frequency/position. We analysed figl1 mutants and virus-induced gene silencing lines cytogenetically. Genetic mapping was performed in the hexaploid. FIGL1 prevents abnormal meiotic chromosome associations/fragmentation in both ploidies. It suppresses class II COs in the tetraploid such that CO/chiasma frequency increased 2.1-fold in a figl1 msh5 quadruple mutant compared with a msh5 double mutant. It does not appear to affect class I COs based on HEI10 foci counts in a hexaploid figl1 triple mutant. Genetic mapping in the triple mutant suggested no significant overall increase in total recombination across examined intervals but revealed large increases in specific individual intervals. Notably, the tetraploid figl1 double mutant was sterile but the hexaploid triple mutant was moderately fertile, indicating potential utility for wheat breeding., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Advances in synthetic peptide synthesis have enabled rapid and cost-effective peptide drug manufacturing. For this reason, peptide drugs that were first produced using recombinant DNA (rDNA) technology are now being produced using solid- and liquid-phase peptide synthesis. While peptide synthesis has some advantages over rDNA expression methods, new peptide-related impurities that differ from the active pharmaceutical ingredient (API) may be generated during synthesis. These impurity byproducts of the original peptide sequence feature amino acid insertions, deletions, and side-chain modifications that may alter the immunogenicity risk profile of the drug product. Impurities resulting from synthesis have become the special focus of regulatory review and approval for human use, as outlined in the FDA's Center for Drug Evaluation and Research guidance document, "ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin," published in 2021. This case study illustrates how in silico and in vitro methods can be applied to assess the immunogenicity risk of impurities that may be present in synthetic generic versions of the salmon calcitonin (SCT) drug product. Sponsors of generic drug abbreviated new drug applications (ANDAs) should consider careful control of these impurities (for example, keeping the concentration of the immunogenic impurities below the cut-off recommended by FDA regulators). Twenty example SCT impurities were analyzed using in silico tools and assessed as having slightly more or less immunogenic risk potential relative to the SCT API peptide. Class II human leukocyte antigen (HLA)-binding assays provided independent confirmation that a 9-mer sequence present in the C-terminus of SCT binds promiscuously to multiple HLA DR alleles, while T-cell assays confirmed the expected T-cell responses to SCT and selected impurities. In silico analysis combined with in vitro assays that directly compare the API to each individual impurity peptide may be a useful approach for assessing the potential immunogenic risk posed by peptide impurities that are present in generic drug products., Competing Interests: ADG and WM are senior officers and majority shareholders of EpiVax, a privately held immunoinformatics and vaccine design company. BR, AM, and SL are current employees. All of these authors acknowledge that there is a potential conflict of interest related to their employment status and/or ownership relationship with EpiVax and attest that the work contained in this research report is free of any bias that might be associated with the commercial goals of the company. The findings and conclusion in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Roberts, Mattei, Howard, Weaver, Liu, Lelias, Martin, Verthelyi, Pang, Edwards and De Groot.)

High-throughput genotyping arrays have provided a cost-effective, reliable and interoperable system for genotyping hexaploid wheat and its relatives. Existing, highly cited arrays including our 35K Wheat Breeder's array and the Illumina 90K array were designed based on a limited amount of varietal sequence diversity and with imperfect knowledge of SNP positions. Recent progress in wheat sequencing has given us access to a vast pool of SNP diversity, whilst technological improvements have allowed us to fit significantly more probes onto a 384-well format Axiom array than previously possible. Here we describe a novel Axiom genotyping array, the 'Triticum aestivum Next Generation' array (TaNG), largely derived from whole genome skim sequencing of 204 elite wheat lines and 111 wheat landraces taken from the Watkins 'Core Collection'. We used a novel haplotype optimization approach to select SNPs with the highest combined varietal discrimination and a design iteration step to test and replace SNPs which failed to convert to reliable markers. The final design with 43 372 SNPs contains a combination of haplotype-optimized novel SNPs and legacy cross-platform markers. We show that this design has an improved distribution of SNPs compared to previous arrays and can be used to generate genetic maps with a significantly higher number of distinct bins than our previous array. We also demonstrate the improved performance of TaNGv1.1 for Genome-wide association studies (GWAS) and its utility for Copy Number Variation (CNV) analysis. The array is commercially available with supporting marker annotations and initial genotyping results freely available., (© 2024 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Harnessing genetic diversity in major staple crops through the development of new breeding capabilities is essential to ensure food security 1 . Here we examined the genetic and phenotypic diversity of the A. E. Watkins landrace collection 2 of bread wheat (Triticum aestivum), a major global cereal, by whole-genome re-sequencing of 827 Watkins landraces and 208 modern cultivars and in-depth field evaluation spanning a decade. We found that modern cultivars are derived from two of the seven ancestral groups of wheat and maintain very long-range haplotype integrity. The remaining five groups represent untapped genetic sources, providing access to landrace-specific alleles and haplotypes for breeding. Linkage disequilibrium-based haplotypes and association genetics analyses link Watkins genomes to the thousands of identified high-resolution quantitative trait loci and significant marker-trait associations. Using these structured germplasm, genotyping and informatics resources, we revealed many Watkins-unique beneficial haplotypes that can confer superior traits in modern wheat. Furthermore, we assessed the phenotypic effects of 44,338 Watkins-unique haplotypes, introgressed from 143 prioritized quantitative trait loci in the context of modern cultivars, bridging the gap between landrace diversity and current breeding. This study establishes a framework for systematically utilizing genetic diversity in crop improvement to achieve sustainable food security., (© 2024. The Author(s).)

Genome-wide introgression and substitution lines have been developed in many plant species, enhancing mapping precision, gene discovery, and the identification and exploitation of variation from wild relatives. Created over multiple generations of crossing and/or backcrossing accompanied by marker-assisted selection, the resulting introgression lines are a fixed genetic resource. In this study we report the development of spring wheat (Triticum aestivum L.) chromosome segment substitution lines (CSSLs) generated to systematically capture genetic variation from tetraploid (T. turgidum ssp. dicoccoides) and diploid (Aegilops tauschii) progenitor species. Generated in a common genetic background over four generations of backcrossing, this is a base resource for the mapping and characterization of wheat progenitor variation. To facilitate further exploitation the final population was genetically characterized using a high-density genotyping array and a range of agronomic and grain traits assessed to demonstrate the potential use of the populations for trait localization in wheat., (© 2023 The Authors. The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America.)

Objectives: Health and care resources are under increasing pressure, partly due to the ageing population. Physical activity supports healthy ageing, but motivating exercise is challenging. We aimed to explore staff perceptions towards a virtual reality (VR) omnidirectional treadmill (MOTUS), aimed at increasing physical activity for older adult care home residents., Design: Interactive workshops and qualitative evaluation., Settings: Eight interactive workshops were held at six care homes and two university sites across Cornwall, England, from September to November 2021., Participants: Forty-four staff participated, including care home, supported living, clinical care and compliance managers, carers, activity coordinators, occupational therapists and physiotherapists., Interventions: Participants tried the VR treadmill system, followed by focus groups exploring device design, potential usefulness or barriers for care home residents. Focus groups were audio-recorded, transcribed verbatim and thematically analysed. We subsequently conducted a follow-up interview with the technology developer (September 2022) to explore the feedback impact., Results: The analysis produced seven key themes: anticipated benefits, acceptability, concerns of use, concerns of negative effects, suitability/unsuitability, improvements and current design. Participants were generally positive towards VR to motivate care home residents' physical activity and noted several potential benefits (increased exercise, stimulation, social interaction and rehabilitation). Despite the reported potential, staff had safety concerns for frail older residents due to their standing position. Participants suggested design improvements to enhance safety, usability and accessibility. Feedback to the designers resulted in the development of a new seated VR treadmill to address concerns about falls while maintaining motivation to exercise. The follow-up developer interview identified significant value in academia-industry collaboration., Conclusion: The use of VR-motivated exercise holds the potential to increase exercise, encourage reminiscence and promote meaningful activity for care home residents. Staff concerns resulted in a redesigned seated treadmill for those too frail to use the standing version. This novel study demonstrates the importance of stakeholder feedback in product design., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Circadian rhythms coordinate the responses of organisms with their daily fluctuating environments, by establishing a temporal program of gene expression. This schedules aspects of metabolism, physiology, development and behaviour according to the time of day. Circadian regulation in plants is extremely pervasive, and is important because it underpins both productivity and seasonal reproduction. Circadian regulation extends to the control of environmental responses through a regulatory process known as circadian gating. Circadian gating is the process whereby the circadian clock regulates the response to an environmental cue, such that the magnitude of response to an identical cue varies according to the time of day of the cue. Here, we show that there is genome-wide circadian gating of responses to cold temperatures in plants. By using bread wheat as an experimental model, we establish that circadian gating is crucial to the programs of gene expression that underlie the environmental responses of a crop of major socioeconomic importance. Furthermore, we identify that circadian gating of cold temperature responses are distributed unevenly across the three wheat subgenomes, which might reflect the geographical origins of the ancestors of modern wheat., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Graham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The UK is facing a nationwide staffing crisis within adult social care, due to difficulties in recruiting and retaining registered nurses. Current interpretation of legislation means nursing homes must always have the physical presence of a registered nurse on duty within the home. With the shortage of registered nurses increasing, reliance on agency workers is commonplace, a practice impacting service cost and continuity of care. Lack of innovation to tackle this issue means the question of how to transform service delivery to combat staffing shortages is open for debate. The potential for technology to augment the provision of care was highlighted during the COVID-19 pandemic. In this article the authors present one possible solution focused on the provision of digital nursing care within nursing homes. Anticipated benefits include enhanced accessibility of nursing roles, reduced risk of viral spread and opportunities for upskilling staff. However, challenges include the current interpretation of legislation.

Background: There is limited literature on security and access for social care settings despite policy highlighting importance, and no published research exploring facial recognition lock technology (FRLT) for potential improvements. This study explored FRLT device implementation, use, barriers and benefits., Methods: One residential care home with 43 older adults and 68 staff members (Site A), and one supported living facility caring for six individuals with mental health issues with 18 staff members (Site B) were provided with FRLT for six months. Nine pre-implementation staff interviews explored existing access and security perceptions. Ten post-implementation staff interviews and one staff focus group were conducted; all were analysed using content analysis to understand, alongside process mapping, the use and impact of the FRLT. Interview participants included site care staff and other visiting healthcare professionals. We additionally report feedback from the technology developers to demonstrate impact of industry-academia collaboration., Results: Pre-implementation interviews highlighted issues with current pin-pad or lock-box systems, including; code sharing; code visibility, ineffective code changes, security issues following high staff turnover, lack of efficiency for visitors including NHS staff and lack of infection control suggesting requirement for innovation and improvement. Pre-implementation interviews showed openness and interest in FRLT, although initial queries were raised around cost effectiveness and staff skills. Following implementation, good levels of adoption were achieved with 72% and 100% (49/68 and 18/18) of staff members uploading their face at the two sites, and 100% of residents at Site B using the system (6/6). Additionally, Site B made a positive procurement decision and continues to discuss wider rollout. Post implementation interviews suggested FRLT was useful and acceptable for improving security and access. Benefits identified included staff/visitor time saving, enhanced security, team ease of access, resident autonomy and fewer shared touch points. Integration was suggested including with fire alarm systems, staff clocking in/out, and Covid monitoring to improve usefulness. The developers have since responded to feedback with design iterations., Conclusion: We identified concerns on security and access in social care settings, which warrant further exploration and research. FRLT could increase resident autonomy and reduce staff burden, particularly considering frequent multi-agency health and care visits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bradwell, Edwards, Baines, Page, Chatterjee and Jones.)

Increasing crop yields through plant breeding is time consuming and laborious, with the generation of novel combinations of alleles being limited by chromosomal linkage blocks and linkage-drag. Meiotic recombination is essential to create novel genetic variation via the reshuffling of parental alleles. The exchange of genetic information between homologous chromosomes occurs at crossover (CO) sites but CO frequency is often low and unevenly distributed. This bias creates the problem of linkage-drag in recombination 'cold' regions, where undesirable variation remains linked to useful traits. In plants, programmed meiosis-specific DNA double-strand breaks, catalysed by the SPO11 complex, initiate the recombination pathway, although only ~5% result in the formation of COs. To study the role of SPO11-1 in wheat meiosis, and as a prelude to manipulation, we used CRISPR/Cas9 to generate edits in all three SPO11-1 homoeologues of hexaploid wheat. Characterization of progeny lines shows plants deficient in all six SPO11-1 copies fail to undergo chromosome synapsis, lack COs and are sterile. In contrast, lines carrying a single copy of any one of the three wild-type homoeologues are phenotypically indistinguishable from unedited plants both in terms of vegetative growth and fertility. However, cytogenetic analysis of the edited plants suggests that homoeologues differ in their ability to generate COs and in the dynamics of synapsis. In addition, we show that the transformation of wheat mutants carrying six edited copies of SPO11-1 with the TaSPO11-1B gene, restores synapsis, CO formation, and fertility and hence opens a route to modifying recombination in this agronomically important crop., (© 2022 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Purpose: Despite the success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies, successful targeting of solid tumors with CAR T cells has been limited by a lack of durable responses and reports of toxicities. Our understanding of the limited therapeutic efficacy in solid tumors could be improved with quantitative tools that allow characterization of CAR T-targeted antigens in tumors and accurate monitoring of response., Experimental Design: We used a radiolabeled FAP inhibitor (FAPI) [18F]AlF-FAPI-74 probe to complement ongoing efforts to develop and optimize FAP CAR T cells. The selectivity of the radiotracer for FAP was characterized in vitro, and its ability to monitor changes in FAP expression was evaluated using rodent models of lung cancer., Results: [18F]AlF-FAPI-74 showed selective retention in FAP+ cells in vitro, with effective blocking of the uptake in presence of unlabeled FAPI. In vivo, [18F]AlF-FAPI-74 was able to detect FAP expression on tumor cells as well as FAP+ stromal cells in the tumor microenvironment with a high target-to-background ratio. We further demonstrated the utility of the tracer to monitor changes in FAP expression following FAP CAR T-cell therapy, and the PET imaging findings showed a robust correlation with ex vivo analyses., Conclusions: This noninvasive imaging approach to interrogate the tumor microenvironment represents an innovative pairing of a diagnostic PET probe with solid tumor CAR T-cell therapy and has the potential to serve as a predictive and pharmacodynamic response biomarker for FAP as well as other stroma-targeted therapies. A PET imaging approach targeting FAP expressed on activated fibroblasts of the tumor stroma has the potential to predict and monitor therapeutic response to FAP-targeted CAR T-cell therapy. See related commentary by Weber et al., p. 5241., (©2022 American Association for Cancer Research.)

Abstract: Immune checkpoint inhibitors (ICI) have been effective in treating a subset of refractory solid tumors, but only a small percentage of treated patients benefit from these therapies. Thus, there is a clinical need for reliable tools that allow for the early assessment of response to ICIs, as well as a preclinical need for imaging tools that aid in the future development and understanding of immunotherapies. Here we demonstrate that CD69, a canonical early-activation marker expressed on a variety of activated immune cells, including cytotoxic T cells and natural killer (NK) cells, is a promising biomarker for the early assessment of response to immunotherapies. We have developed a PET probe by radiolabeling a highly specific CD69 mAb, H1.2F3, with Zirconium-89 (89Zr), [89Zr]-deferoxamine (DFO)-H1.2F3. [89Zr]-DFO-H1.2F3 detected changes in CD69 expression on primary mouse T cells in vitro and detected activated immune cells in a syngeneic tumor immunotherapy model. In vitro uptake studies with [89Zr]-DFO-H1.2F3 showed a 15-fold increase in CD69 expression for activated primary mouse T cells, relative to untreated resting T cells. In vivo PET imaging showed that tumors of ICI-responsive mice had greater uptake than the tumors of nonresponsive and untreated mice. Ex vivo biodistribution, autoradiography, and IHC analyses supported the PET imaging findings. These data suggest that the CD69 PET imaging approach detects CD69 expression with sufficient sensitivity to quantify immune cell activation in a syngeneic mouse immunotherapy model and could allow for the prediction of therapeutic immune responses to novel immunotherapies., (©2022 American Association for Cancer Research.)

Objective: The objective of this review was to map the knowledge related to the use of mobile health (mHealth) as a primary mode of intervention for the prevention and management of gestational diabetes mellitus and its long-term implications among women at risk of or diagnosed with gestational diabetes mellitus. We also sought to understand if mHealth for women at risk of or diagnosed with gestational diabetes mellitus incorporated relevant behavior change theory and techniques., Introduction: Prevention and management of gestational diabetes mellitus and its associated adverse outcomes are important to maternal and infant health. Women with gestational diabetes mellitus report high burden of disease management and barriers to lifestyle change post-delivery, which mHealth interventions may help to overcome. Evidence suggests apps could help gestational diabetes mellitus prevention and management; however, less is known about broader applications of mHealth from preconception to interconception, and whether relevant behavior change techniques are incorporated., Inclusion Criteria: Studies that focused on mHealth use as the primary mode of intervention for the prevention and management of gestational diabetes mellitus and its long-term implications were considered for inclusion. Telehealth or telemedicine were excluded as these have been reviewed elsewhere., Methods: Six databases were searched: MEDLINE, CINAHL, Embase, Cochrane Library, Scopus, and TRIP. No limits were applied to database exploration periods to ensure retrieval of all relevant studies. Gray literature sources searched were OpenGrey, ISRCTN Registry, ClinicalTrials.gov, EU Clinical Trials Register, and ANZCTR. Two reviewers independently screened abstracts and assessed full texts against the inclusion criteria. Data were extracted using an adapted version of the JBI data extraction instrument. Data are presented in narrative form accompanied by tables and figures., Results: This review identified 2166 sources, of which 96 full texts were screened. Thirty eligible reports were included, covering 25 different mHealth interventions. Over half (n = 14) of the interventions were for self-managing blood glucose during pregnancy. Common features included tracking blood glucose levels, real-time feedback, communication with professionals, and educational information. Few (n = 6) mHealth interventions were designed for postpartum use and none for interconception use. Five for postpartum use supported behavior change to reduce the risk oftype 2 diabetes and included additional features such as social support functions and integrated rewards. Early development and feasibility studies used mixed methods to assess usability and acceptability. Later stage evaluations of effectiveness typically used randomized controlled trial designs to measure clinical outcomes such as glycemic control and reduced body weight. Three mHealth interventions were developed using behavior change theory. Most mHealth interventions incorporated two behavior change techniques shown to be optimal when combined, and those delivering behavior change interventions included a wider range. Nevertheless, only half of the 26 techniques listed in a published behavior change taxonomy were tried., Conclusions: mHealth for gestational diabetes mellitus focuses on apps to improve clinical outcomes. This focus could be broadened by incorporating existing resources that women value, such as social media, to address needs, such as peer support. Although nearly all mHealth interventions incorporated behavior change techniques, findings suggest future development should consider selecting techniques that target women's needs and barriers to engagement. Lack of mHealth interventions for prevention of gestational diabetes mellitus recurrence and type 2 diabetes mellitus suggests further development and evaluation are required., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 JBI.)

Wheat is a major cereal crop that possesses a large allopolyploid genome formed through hybridisation of tetraploid and diploid progenitors. During meiosis, crossovers (COs) are constrained in number to 1-3 per chromosome pair that are predominantly located towards the chromosome ends. This reduces the probability of advantageous traits recombining onto the same chromosome, thus limiting breeding. Therefore, understanding the underlying factors controlling meiotic recombination may provide strategies to unlock the genetic potential in wheat. In this mini-review, we will discuss the factors associated with restricted CO formation in wheat, such as timing of meiotic events, chromatin organisation, pre-meiotic DNA replication and dosage of CO genes, as a means to modulate recombination., (© 2022 The Author(s).)

Background: Robot pets may assist in the challenges of supporting an aging population with growing dementia prevalence. Prior work has focused on the impacts of the robot seal Paro on older adult well-being, but recent studies have suggested the good acceptability and implementation feasibility of more affordable devices (Joy for All [JfA] cats and dogs)., Objective: We aimed to address the limited effectiveness research on JfA devices., Methods: We conducted an 8-month, stratified, cluster randomized controlled trial in 8 care homes in Cornwall, United Kingdom. Over 4 months, 4 care homes each received 2 JfA devices (1 cat and 1 dog; intervention group), and 4 homes received care as usual (control group). Psychometrics were collected before and after the intervention to compare the change from baseline to follow-up between the groups. In the final 4 months, all 8 care homes received devices, but only qualitative data were collected owing to COVID-19 and reduced capacity. The primary outcome was neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI] Nursing Home version). Care provider burden was a secondary outcome (occupational disruptiveness NPI subscale), alongside the Challenging Behavior scale, the Holden communication scale, the Campaign to End Loneliness questionnaire, and medication use. Qualitative data were collected through care staff observation calendars and end-of-study interviews to understand use, experience, and impact. We also collected demographic data and assessed dementia severity. In total, 253 residents had robot interaction opportunities, and 83 were consented for direct data collection., Results: There was a significant difference in the total change from baseline to follow-up between the intervention and control groups for NPI (P<.001) and occupational disruptiveness (P=.03). Neuropsychiatric symptoms increased in the control group and decreased in the intervention group. No significant difference was seen for communication issues or challenging behavior. For NPI subdomains, there were significant differences from baseline to follow-up in delusions (P=.03), depression (P=.01), anxiety (P=.001), elation (P=.02), and apathy (P=.009), all of which decreased in the intervention group and increased slightly in the control group. The summative impact results suggested that most residents (46/54, 85%) who interacted with robots experienced a positive impact. Those who interacted had significantly higher dementia severity scores (P=.001). The qualitative results suggested good adoption, acceptability, and suitability for subjectively lonely individuals and lack of a novelty effect through sustained use, and demonstrated that the reasons for use were entertainment, anxiety, and agitation., Conclusions: Affordable robot pets hold potential for improving the well-being of care home residents and people with dementia, including reducing neuropsychiatric symptoms and occupational disruptiveness. This work suggests no novelty effect and contributes toward understanding robot pet suitability. Moreover, interactions were more common among residents with more moderate/severe dementia and those subjectively lonely., Trial Registration: ClinicalTrials.gov NCT04168463; https://www.clinicaltrials.gov/ct2/show/NCT04168463., (©Hannah Bradwell, Katie J Edwards, Rhona Winnington, Serge Thill, Victoria Allgar, Ray B Jones. Originally published in JMIR Aging (https://aging.jmir.org), 24.08.2022.)

Mentorship is a fundamental aspect that contributes to the success of a career in science, technology, engineering, and mathematics (STEM), particularly in academia. Research suggests that underrepresented minorities (URMs) often experience less quality mentorship and face barriers to finding successful mentor-mentee relationships. URM trainees in STEM face challenges that are not encountered by their majority peers or mentors, adding another level of complexity to establishing important relationships. Mentors of URM trainees must therefore mentor beyond general scientific training and tailor their mentorship to be more culturally appropriate and inclusive, allowing URM trainees to bring their whole selves to the table and leading to their effective socialization. Herein, we present the perspectives of group leaders and trainees from around the globe to highlight key aspects of creating successful mentor-mentee relationships that are sustainable and productive for both parties., (© 2022. World Molecular Imaging Society.)

FANCM suppresses crossovers in plants by unwinding recombination intermediates. In wheat, crossovers are skewed toward the chromosome ends, thus limiting generation of novel allelic combinations. Here, we observe that FANCM maintains the obligate crossover in tetraploid and hexaploid wheat, thus ensuring that every chromosome pair exhibits at least one crossover, by localizing class I crossover protein HEI10 at pachytene. FANCM also suppresses class II crossovers that increased 2.6-fold in fancm msh5 quadruple mutants. These data are consistent with a role for FANCM in second-end capture of class I designated crossover sites, whilst FANCM is also required to promote formation of non-crossovers. In hexaploid wheat, genetic mapping reveals that crossovers increase by 31% in fancm compared to wild type, indicating that fancm could be an effective tool to accelerate breeding. Crossover rate differences in fancm correlate with wild type crossover distributions, suggesting that chromatin may influence the recombination landscape in similar ways in both wild type and fancm., (© 2022. The Author(s).)

Racial, ethnic, and gender representation in an academic setting means that teachers, professors, and other leaders reflect the demographics of the student body in the educational and professional spaces that they serve. This form of representation, which is often intersectional, strengthens communities and improves student outcomes, from as early as primary and secondary education, through to college education and beyond. Representation matters because it can shape the reputation and self-image of women and Black, Indigenous, and People of Color (BIPOC) within environments dominated by over-represented majorities (ORMs). From the perspective of BIPOC women trainees, the lack of BIPOC faculty who are visible minorities, particularly at the most senior level positions, often conjures questions of whether academia is a realistic career path for aspiring minority students. This article focuses on the key component of representation in the United States (U.S.), highlighting our vision for a solution for the so-called "leaky pipeline" for BIPOC in science, technology, engineering, and mathematic with action items to end it., (© 2021. World Molecular Imaging Society.)

The bread wheat ( Triticum aestivum ) pangenome is a patchwork of variable regions, including translocations and introgressions from progenitors and wild relatives. Although a large number of these have been documented, it is likely that many more remain unknown. To map these variable regions and make them more traceable in breeding programs, wheat accessions need to be genotyped or sequenced. The wheat genome is large and complex and consequently, sequencing efforts are often targeted through exome capture. In this study, we employed exome capture prior to sequencing 12 wheat varieties; 10 elite T. aestivum cultivars and two T. aestivum landrace accessions. Sequence coverage across chromosomes was greater toward distal regions of chromosome arms and lower in centromeric regions, reflecting the capture probe distribution which itself is determined by the known telomere to centromere gene gradient. Superimposed on this general pattern, numerous drops in sequence coverage were observed. Several of these corresponded with reported introgressions. Other drops in coverage could not be readily explained and may point to introgressions that have not, to date, been documented., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Burridge, Winfield, Wilkinson, Przewieslik-Allen, Edwards and Barker.)

Immuno-PET is a powerful tool to noninvasively characterize the in vivo biodistribution of engineered antibodies. Methods: L1 cell adhesion molecule-targeting humanized (HuE71) IgG 1 and IgG 4 antibodies bearing identical variable heavy- and light-chain sequences but different fragment crystallizable (Fc) portions were radiolabeled with 89 Zr, and the in vivo biodistribution was studied in SKOV3 ovarian cancer xenografted nude mice. Results: In addition to showing uptake in L1 cell adhesion molecule-expressing SKOV3 tumors, as does its parental counterpart HuE71 IgG 1 , the afucosylated variant having enhanced Fc-receptor affinity showed high nonspecific uptake in lymph nodes. On the other hand, aglycosylated HuE71 IgG 1 with abrogated Fc-receptor binding did not show lymphoid uptake. The use of the IgG 4 subclass showed high nonspecific uptake in the kidneys, which was prevented by mutating serine at position 228 to proline in the hinge region of the IgG 4 antibody to mitigate in vivo fragment antigen-binding arm exchange. Conclusion: Our findings highlight the influence of Fc modifications and the choice of IgG subclass on the in vivo biodistribution of antibodies and the potential outcomes thereof., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Video consultations (VCs) were rapidly implemented in response to COVID-19 despite modest progress before., Objective: We aim to explore staff and patient experiences with VCs implemented during COVID-19 and use feedback insights to support quality improvement and service development., Methods: Secondary data analysis was conducted on 955 patient and 521 staff responses (from 4234 consultations; 955/4234, 22.6% and 521/4234, 12.3%, respectively) routinely collected following a VC between June and July 2020 in a rural, older adult, and outpatient care setting at a National Health Service Trust. Responses were summarized using descriptive statistics and inductive thematic analysis and presented to Trust stakeholders., Results: Most patients (890/955, 93.2%) reported having good (210/955, 22%) or very good (680/955, 71.2%) experience with VCs and felt listened to and understood (904/955, 94.7%). Most patients accessed their VC alone (806/955, 84.4%) except for those aged ≥71 years (23/58, 40%), with ease of joining VCs negatively associated with age (P<.001). Despite more difficulties joining, older adults were most likely to be satisfied with the technology (46/58, 79%). Patients and staff generally felt that patients' needs had been met (860/955, 90.1% and 453/521, 86.9%, respectively), although staff appeared to overestimate patient dissatisfaction with VC outcomes (P=.02). Patients (848/955, 88.8%) and staff (419/521, 80.5%) felt able to communicate everything they wanted, although patients were significantly more positive than staff (P<.001). Patient satisfaction with communication was positively associated with technical performance satisfaction (P<.001). Most staff members (466/521, 89.4%) reported positive (185/521, 35.5%) or very positive (281/521, 53.9%) experiences with joining and managing VCs. Staff reported reductions in carbon footprint (380/521, 72.9%) and time (373/521, 71.6%). Most patients (880/955, 92.1%) would choose VCs again. We identified three themes in responses: barriers, including technological difficulties, patient information, and suitability concerns; potential benefits, including reduced stress, enhanced accessibility, cost, and time savings; and suggested improvements, including trial calls, turning music off, photo uploads, expanding written character limit, supporting other internet browsers, and shared online screens. This routine feedback, including evidence to suggest that patients were more satisfied than clinicians had anticipated, was presented to relevant Trust stakeholders, allowing for improved processes and supporting the development of a business case to inform the Trust decision on continuing VCs beyond COVID-19 restrictions., Conclusions: The findings highlight the importance of regularly reviewing and responding to routine feedback following digital service implementation. The feedback helped the Trust improve the VC service, challenge clinician-held assumptions about patient experience, and inform future use of VCs. It has focused improvement efforts on patient information; technological improvements such as blurred backgrounds and interactive whiteboards; and responding to the needs of patients with dementia, communication or cognitive impairment, or lack of appropriate technology. These findings have implications for other health care providers., (©Hannah Bradwell, Rebecca Baines, Katie J Edwards, Sebastian Stevens, Kate Atkinson, Ellen Wilkinson, Arunangsu Chatterjee, Ray B Jones. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.03.2022.)

Purpose: Advances in our understanding of the contribution of aberrant glycosylation to the pro-oncogenic signaling and metastasis of tumor cells have reinvigorated the development of mucin-targeted therapies. Here, we validate the tumor-targeting ability of a novel monoclonal antibody (mAb), AR9.6, that binds MUC16 and abrogates downstream oncogenic signaling to confer a therapeutic response., Experimental Design: The in vitro and ex vivo validation of the binding of AR9.6 to MUC16 was achieved via flow cytometry, radioligand binding assay (RBA), and immunohistochemistry (IHC). The in vivo MUC16 targeting of AR9.6 was validated by creating a 89Zr-labeled radioimmunoconjugate of the mAb and utilizing immunoPET and ex vivo biodistribution studies in xenograft models of human ovarian and pancreatic cancer., Results: Flow cytometry, RBA, and IHC revealed that AR9.6 binds to ovarian and pancreatic cancer cells in an MUC16-dependent manner. The in vivo radiopharmacologic profile of 89Zr-labeled AR9.6 in mice bearing ovarian and pancreatic cancer xenografts confirmed the MUC16-dependent tumor targeting by the radioimmunoconjugate. Radioactivity uptake was also observed in the distant lymph nodes (LNs) of mice bearing xenografts with high levels of MUC16 expression (i.e., OVCAR3 and Capan-2). IHC analyses of these PET-positive LNs highlighted the presence of shed antigen as well as necrotic, phagocytized, and actively infiltrating neoplastic cells. The humanization of AR9.6 did not compromise its ability to target MUC16-expressing tumors., Conclusions: The unique therapeutic mechanism of AR9.6 combined with its excellent in vivo tumor targeting makes it a highly promising theranostic agent. huAR9.6 is poised for clinical translation to impact the management of metastatic ovarian and pancreatic cancers., (©2021 The Authors; Published by the American Association for Cancer Research.)

According to Catholic theology, God offers a gift of love, known as divine grace, to all of humanity. This gift of divine grace is the gift of redemption and forgiveness of sins from God that is offered to everyone who decides to acknowledge and accept it. Grace is central to the lived experience of many Christians. This qualitative study examined how Catholics perceive and experience divine grace using interviews that assessed perceptions of divine grace in 29 practicing adult Catholics. A grounded theory analysis resulted in themes indicating that these Catholics view God's divine grace as a tangible gift that is undeserved though continuously offered. The participants' experience of God's grace is not just an abstract theological concept but an embodied aspect of religious life with which believers can interact in many powerful ways. Three characteristics of God's divine grace (i.e., salvific grace, cooperation through free will, primacy of conscience and the afterlife) and three mechanisms to experiencing God's grace (i.e., sacraments, prayer and meditation, saints) are presented., Competing Interests: Conflicts of InterestResearchers have no known conflicts of interest to disclose., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Background: The use of smart speakers to improve well-being had been trialed in social care by others; however, we were not aware of their implementation in most care homes across a region in the Southwest of the United Kingdom. For the widespread adoption of new technology, it must be locally demonstrable and become normalized., Objective: The aim of this study was to install smart speakers in care homes in a rural and coastal region and to explore if and how the devices were being used, the barriers to their implementation, and their potential benefits., Methods: Email, workshops, drop-in sessions, phone, and cold calling was used to contact all 230 care homes, offering a free smart speaker and some advisory support. Care homes accepting the devices were asked to complete a feedback diary. Nonresponse rate for diary completion was high and was thus supplemented with a telephone survey., Results: Over the course of 7 months, we installed 156 devices in 92 care homes for older people, 50 devices for people with physical or mental health needs, and 8 for others. The devices were used mainly for music but also for poetry, recipes, light controls, jokes, and video calls. Care home managers reported the benefits for the residents, including enhanced engagement with home activities, enjoyment, calming effects, and the acquisition of new skills. Implementation problems included internet connectivity, staff capacity, and skills., Conclusions: Affordable consumer devices such as smart speakers should be installed in all care homes to benefit residents. Voice-activated technologies are easy to use and promote interaction. This study indicates that implementation in care homes was possible and that smart speakers had multifaceted benefits for residents and staff. Most care homes in this region now use smart speakers for their residents, thereby normalizing this practice., (©Katie J Edwards, Ray B Jones, Deborah Shenton, Toni Page, Inocencio Maramba, Alison Warren, Fiona Fraser, Tanja Križaj, Tristan Coombe, Hazel Cowls, Arunangsu Chatterjee. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 20.12.2021.)

The hexaploid bread wheat genome comprises over 16 gigabases of sequence across 21 chromosomes. Meiotic crossovers are highly polarized along the chromosomes, with elevation in the gene-dense distal regions and suppression in the Gypsy retrotransposon-dense centromere-proximal regions. We profiled the genomic landscapes of the meiotic recombinase DMC1 and the chromosome axis protein ASY1 in wheat and investigated their relationships with crossovers, chromatin state, and genetic diversity. DMC1 and ASY1 chromatin immunoprecipitation followed by sequencing (ChIP-seq) revealed strong co-enrichment in the distal, crossover-active regions of the wheat chromosomes. Distal ChIP-seq enrichment is consistent with spatiotemporally biased cytological immunolocalization of DMC1 and ASY1 close to the telomeres during meiotic prophase I. DMC1 and ASY1 ChIP-seq peaks show significant overlap with genes and transposable elements in the Mariner and Mutator superfamilies. However, DMC1 and ASY1 ChIP-seq peaks were detected along the length of each chromosome, including in low-crossover regions. At the fine scale, crossover elevation at DMC1 and ASY1 peaks and genes correlates with enrichment of the Polycomb histone modification H3K27me3. This indicates a role for facultative heterochromatin, coincident with high DMC1 and ASY1, in promoting crossovers in wheat and is reflected in distalized H3K27me3 enrichment observed via ChIP-seq and immunocytology. Genes with elevated crossover rates and high DMC1 and ASY1 ChIP-seq signals are overrepresented for defense-response and immunity annotations, have higher sequence polymorphism, and exhibit signatures of selection. Our findings are consistent with meiotic recombination promoting genetic diversity, shaping host-pathogen co-evolution, and accelerating adaptation by increasing the efficiency of selection., (© 2021 Tock et al.; Published by Cold Spring Harbor Laboratory Press.)

Free asparagine is the precursor for acrylamide, which forms during the baking, toasting and high-temperature processing of foods made from wheat. In this study, CRISPR/Cas9 was used to knock out the asparagine synthetase gene, TaASN2, of wheat (Triticum aestivum) cv. Cadenza. A 4-gRNA polycistronic gene was introduced into wheat embryos by particle bombardment and plants were regenerated. T1 plants derived from 11 of 14 T0 plants were shown to carry edits. Most edits were deletions (up to 173 base pairs), but there were also some single base pair insertions and substitutions. Editing continued beyond the T1 generation. Free asparagine concentrations in the grain of plants carrying edits in all six TaASN2 alleles (both alleles in each genome) were substantially reduced compared with wildtype, with one plant showing a more than 90 % reduction in the T2 seeds. A plant containing edits only in the A genome alleles showed a smaller reduction in free asparagine concentration in the grain, but the concentration was still lower than in wildtype. Free asparagine concentration in the edited plants was also reduced as a proportion of the free amino acid pool. Free asparagine concentration in the T3 seeds remained substantially lower in the edited lines than wildtype, although it was higher than in the T2 seeds, possibly due to stress. In contrast, the concentrations of free glutamine, glutamate and aspartate were all higher in the edited lines than wildtype. Low asparagine seeds showed poor germination but this could be overcome by exogenous application of asparagine., (© 2021 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Immuno-PET using desferrioxamine (DFO)-conjugated zirconium-89 ([ 89 Zr]Zr 4+ )-labeled antibodies is a powerful tool used for preclinical and clinical molecular imaging. However, a comprehensive study evaluating the variables involved in DFO-conjugation and 89 Zr-radiolabeling of antibodies and their impact on the in vitro and in vivo behavior of the resulting radioimmunoconjugates has not been adequately performed. Here, we synthesized different DFO-conjugates of the HER2-targeting antibody (Ab)-trastuzumab, dubbed T5, T10, T20, T60, and T200-to indicate the molar equivalents of DFO used for bioconjugation. Next we radiolabeled the immunoconjugates with ([ 89 Zr]Zr 4+ ) under a comprehensive set of reaction conditions including different buffers (PBS, chelexed-PBS, TRIS/HCl, HEPES; ± radioprotectants), different reaction volumes (0.1-1 mL), variable amounts of DFO-conjugated Ab (5, 25, 50 μg), and radioactivity (0.2-1.0 mCi; 7.4-37 MBq). We evaluated the effects of these variables on radiochemical yield (RCY), molar activity ( A m )/specific activity ( A s ), immunoreactive fraction, and ultimately the in vivo biodistribution profile and tumor targeting ability of the trastuzumab radioimmunoconjugates. We show that increasing the degree of DFO conjugation to trastuzumab increased the RCY (∼90%) and A m / A s (∼194 MBq/nmol; 35 mCi/mg) but decreased the HER2-binding affinity (3.5×-4.6×) and the immunoreactive fraction of trastuzumab down to 50-64%, which translated to dramatically inferior in vivo performance of the radioimmunoconjugate. Cell-based immunoreactivity assays and standard binding affinity analyses using surface plasmon resonance (SPR) did not predict the poor in vivo performance of the most extreme T200 conjugate. However, SPR-based concentration free calibration analysis yielded active antibody concentration and was predictive of the in vivo trends. Positron emission tomography (PET) imaging and biodistribution studies in a HER2-positive xenograft model revealed activity concentrations of 38.7 ± 3.8 %ID/g in the tumor and 6.3 ± 4.1 %ID/g in the liver for ([ 89 Zr]Zr 4+ )-T5 (∼1.4 ± 0.5 DFOs/Ab) at 120 h after injection of the radioimmunoconjugates. On the other hand, ([ 89 Zr]Zr 4+ )-T200 (10.9 ± 0.7 DFOs/Ab) yielded 16.2 ± 3.2 %ID/g in the tumor versus 27.5 ± 4.1 %ID/g in the liver. Collectively, our findings suggest that synthesizing trastuzumab immunoconjugates bearing 1-3 DFOs per Ab (T5 and T10) combined with radiolabeling performed in low reaction volumes using Chelex treated PBS or HEPEs without a radioprotectant provided radioimmunoconjugates having high A m / A s (97 MBq/nmol; 17.5 ± 2.2 mCi/mg), highly preserved immunoreactive fractions (86-93%), and favorable in vivo biodistribution profile with excellent tumor uptake.

Delta-like ligand 3 (DLL3) is a therapeutic target for the treatment of small cell lung cancer, neuroendocrine prostate cancer, and isocitrate dehydrogenase mutant glioma. In the clinic, DLL3-targeted 89 Zr-immunoPET has the potential to aid in the assessment of disease burden and facilitate the selection of patients suitable for therapies that target the antigen. The overwhelming majority of 89 Zr-labeled radioimmunoconjugates are synthesized via the random conjugation of desferrioxamine (DFO) to lysine residues within the immunoglobulin. While this approach is admittedly facile, it can produce heterogeneous constructs with suboptimal in vitro and in vivo behavior. In an effort to circumvent these issues, we report the development and preclinical evaluation of site-specifically labeled radioimmunoconjugates for DLL3-targeted immunoPET. To this end, we modified a cysteine-engineered variant of the DLL3-targeting antibody SC16-MB1 with two thiol-reactive variants of DFO: one bearing a mal eimide moiety (Mal-DFO) and the other containing a p henyl o xa d iazolyl methyl s ulfone group (PODS-DFO). In an effort to obtain immunoconjugates with a D FO-to- a ntibody r atio (DAR) of 2, we explored both the reduction of the antibody with tris(2-carboxyethyl) phosphine (TCEP) as well as the use of a combination of glutathione and arginine as reducing and stabilizing agents, respectively. While exerting control over the DAR of the immunoconjugate proved cumbersome using TCEP, the use of glutathione and arginine enabled the selective reduction of the engineered cysteines and thus the formation of homogeneous immunoconjugates. A head-to-head comparison of the resulting 89 Zr-radioimmunoconjugates in mice bearing DLL3-expressing H82 xenografts revealed no significant differences in tumoral uptake and showed comparable radioactivity concentrations in most healthy nontarget organs. However, 89 Zr-DFO PODS - DAR2 SC16-MB1 produced 30% lower uptake (3.3 ± 0.5 %ID/g) in the kidneys compared to 89 Zr-DFO Mal - DAR2 SC16-MB1 (4.7 ± 0.5 %ID/g). In addition, H82-bearing mice injected with a 89 Zr-labeled isotype-control radioimmunoconjugate synthesized using PODS exhibited ∼40% lower radioactivity in the kidneys compared to mice administered its maleimide-based counterpart. Taken together, these results demonstrate the improved in vivo performance of the PODS-based radioimmunoconjugate and suggest that a stable, well-defined DAR2 radiopharmaceutical may be suitable for the clinical immunoPET of DLL3-expressing cancers.

Background: Women experiencing gestational diabetes face challenges during and after pregnancy that could be supported with mobile health. Mobile health isn't routinely implemented and little is known regarding its use to aid information seeking, peer support and behaviour change. Understanding women's experiences of mHealth is critical to ensuring acceptance and use, particularly with relation to postpartum and interconception periods, where support is currently lacking. This study therefore aimed to explore the views and experiences of women with previous gestational diabetes, on using mHealth resources before, during and after pregnancy.Women's expectations for future mHealth were also explored., Setting: Ten female participants from across the United Kingdom, experiencing GDM within the past five years, were convenience sampled from a group of individuals participating in a webinar. The webinar about technology to support GDM management was advertised online and all of those who registered were invited, via email, to take part., Design: Women's views and experiences were explored using semi-structured telephone interviews. Audio recorded data were transcribed, coded and analysed using NVivo 12. Thematic analysis was used to analyse data, creating main and sub-themes. Data are presented in narrative form., Participants: Ten women living across the United Kingdom who had experienced gestational diabetes within the past five years, participated., Findings: All ten women used mHealth, valuing social media for dietary information and peer support. Few mHealth resources were recommended by professionals and women discussed discontentment with the information they provided. Information found online was often valued over that provided by professionals. Some women used apps for behaviour change, but disliked certain features and poor engagement hindered their use. Women desired an app to overcome lack of motivation and prepare them for future healthy pregnancies., Key Conclusions: Information provided to women by professionals was viewed as 'limited' and mHealth resources were rarely recommended. In response, women used social media to meet informational and emotional needs. Postpartum behaviour change is important to women and could be facilitated with tailored mHealth focused on increasing motivation. To maximise adoption and engagement future mHealth should be integrated with existing resources women value and be co-produced with professionals., Implications for Practice: Current lack of engagement in mHealth for GDM by healthcare professionals means opportunities to influence or contest poor information are missed. We recommend increased participation by professionals to reduce opportunities for information miss-spread and reliance on peer driven information. Increasing digital confidence among professionals to support women navigate online spaces and take part in co-design is recommended., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Poly (ADP-ribose) (PAR) is a negatively charged polymer that is biosynthesized by Poly (ADP-ribose) Polymerase-1 (PARP-1) and regulates various cellular processes. Alpha-synuclein (αSyn) is an intrinsically disordered protein (IDP) that has been directly implicated with driving the onset and progression of Parkinson's disease (PD). The mechanisms by which α-synuclein (αSyn) elicits its neurotoxic effects remain unclear, though it is well established that the main components of Lewy bodies (LBs) and Lewy neurites (LNs) in PD patients are aggregated hyperphosphorylated (S129) forms of αSyn (pαSyn). In the present study, we used immunofluorescence-based assays to explore if PARP-1 enzymatic product (PAR) promotes the aberrant cytoplasmic accumulation of pαSyn. We also performed quantitative measurements using in situ proximity ligation assays (PLA) on a transgenic murine model of α-synucleinopathy (M83-SNCA ∗ A53T) and post mortem PD/PDD patient samples to characterize PAR-pαSyn interactions. Additionally, we used bioinformatic approaches and site-directed mutagenesis to identify PAR-binding regions on αSyn. In summary, our studies show that PAR-pαSyn interactions are predominantly observed in PD-relevant transgenic murine models of αSyn pathology and post mortem PD/PDD patient samples. Moreover, we confirm that the interactions between PAR and αSyn involve electrostatic forces between negatively charged PAR and lysine residues on the N-terminal region of αSyn., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Puentes, Lengyel-Zhand, Lee, Hsieh, Schneider, Edwards, Luk, Lee, Trojanowski and Mach.)

Recent events in America in 2020 have stimulated a worldwide movement to dismantle anti-Black racism in all facets of our lives. Anti-Black racism is, as defined by the Movement for Black Lives, a "term used to specifically describe the unique discrimination, violence, and harm imposed on and impacting Black people specifically." In science, technology, engineering, and mathematics (STEM), we have yet to achieve the goal and responsibility to ensure that the field reflects the diversity of our lived experiences. Members of the Women in Molecular Imaging Network (WIMIN) have come together to take a stand on diversity, equity, and inclusion in the field of molecular imaging. We strongly condemn oppression in all its forms and strive to identify and dismantle barriers that lead to inequities in the molecular imaging community and STEM as a whole. In this series coined "Visions" (Antiracism and Allyship in Action), we identify and discuss specific actionable items for improving diversity and representation in molecular imaging and ensuring inclusion of all members of the community, inclusive of race, disability, ethnicity, religion, or LGBTQ+ identity. Although the issues highlighted here extend to other under-recruited and equity-seeking groups, for this first article, we are focusing on one egregious and persistent form of discrimination: anti-Black racism. In this special article, Black women residing in America present their lived experiences in the molecular imaging field and give candid insights into the challenges, frustrations, and hopes of our Black friends and colleagues. While this special article focuses on the experiences of Black women, we would like the readers to reflect on their anti-Blackness toward men, transgender, nonbinary, and gender non-conforming people. From the vulnerability we have asked of all our participants, these stories are meant to inspire and invoke active antiracist work among the readership. We present strategies for dismantling systemic racism that research centers and universities can implement in the recruitment, retention, mentorship, and development of Black trainees and professionals. We would like to specifically acknowledge the Black women who took the time to be interviewed, write perspectives, and share their lived experiences in hopes that it will inspire genuine and lasting change.

Soil bioavailability of phosphorus (P) is a major concern for crop productivity worldwide. As phosphatic fertilizers are a non-renewable resource associated with economic and environmental issues so, the sustainable option is to develop P use efficient crop varieties. We phenotyped 82 diverse wheat (Triticum aestivum L.) accessions in soil and hydroponics at low and sufficient P. To identify the genic regions for P efficiency traits, the accessions were genotyped using the 35 K-SNP array and genome-wide association study (GWAS) was performed. The high-quality SNPs across the genomes were evenly distributed with polymorphic information content values varying between 0.090 and 0.375. Structure analysis revealed three subpopulations (C1, C2, C3) and the phenotypic responses of these subpopulations were assessed for P efficiency traits. The C2 subpopulation showed the highest genetic variance and heritability values for numerous agronomically important traits as well as strong correlation under both P levels in soil and hydroponics. GWAS revealed 78 marker-trait associations (MTAs) but only 35 MTAs passed Bonferroni Correction. A total of 297 candidate genes were identified for these MTAs and their annotation suggested their involvement in several biological process. Out of 35, nine (9) MTAs were controlling polygenic trait (two controlling four traits, one controlling three traits and six controlling two traits). These multi-trait MTAs (each controlling two or more than two correlated traits) could be utilized for improving bread wheat to tolerate low P stress through marker-assisted selection (MAS).

Objective: To synthesize current knowledge on the use of mHealth as a primary mode of intervention for the prevention and management of gestational diabetes mellitus and its long-term implications among women at risk of, or diagnosed with, gestational diabetes mellitus., Introduction: Prevention and management of gestational diabetes mellitus and its associated adverse outcomes are of paramount importance to both maternal and infant health. However, women with experience of gestational diabetes mellitus report several barriers to effective disease management and lifestyle change. Supporting women through use of mHealth technology may help overcome these barriers. Recent evidence suggests mobile apps may be useful for the prevention and management of gestational diabetes mellitus, however, less is known about the broader application of mHealth from preconception to interconception., Inclusion Criteria: Studies considered for inclusion are those focused on the use of mHealth as the primary mode of intervention for the prevention and management of gestational diabetes mellitus and its long-term implications among women at risk of, or diagnosed with, gestational diabetes mellitus. Studies will be limited to those published in English, with no date restrictions., Methods: The following databases will be searched: MEDLINE (Ovid), CINAHL (EBSCO), EMBASE (Ovid), Cochrane Database (Wiley), Scopus, and TRIP. Unpublished studies and gray literature will be searched using Open Grey, ISRCTN Registry, ClinicalTrials.gov, EU Clinical Trials register, and ANZCTR. Two reviewers will independently screen abstracts. Reviewers will assess full texts of selected citations against the inclusion criteria. Any disagreements will be discussed with a third reviewer. Data will be extracted and presented in diagrammatic or tabular form with an accompanying narrative in line with review objectives., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 JBI.)

Meiotic recombination generates genetic variation and provides physical links between homologous chromosomes (crossovers) essential for accurate segregation. In cereals the distribution of crossovers, cytologically evident as chiasmata, is biased toward the distal regions of chromosomes. This creates a bottleneck for plant breeders in the development of varieties with improved agronomic traits, as genes situated in the interstitial and centromere proximal regions of chromosomes rarely recombine. Recent advances in wheat genomics and genome engineering combined with well-developed wheat cytogenetics offer new opportunities to manipulate recombination and unlock genetic variation. As a basis for these investigations we have carried out a detailed analysis of meiotic progression in hexaploid wheat ( Triticum aestivum ) using immunolocalization of chromosome axis, synaptonemal complex and recombination proteins. 5-Bromo-2'-deoxyuridine (BrdU) labeling was used to determine the chronology of key events in relation to DNA replication. Axis morphogenesis, synapsis and recombination initiation were found to be spatio-temporally coordinated, beginning in the gene-dense distal chromosomal regions and later occurring in the interstitial/proximal regions. Moreover, meiotic progression in the distal regions was coordinated with the conserved chromatin cycles that are a feature of meiosis. This mirroring of the chiasma bias was also evident in the distribution of the gene-associated histone marks, H3K4me3 and H3K27me3; the repeat-associated mark, H3K27me1; and H3K9me3. We believe that this study provides a cytogenetic framework for functional studies and ongoing initiatives to manipulate recombination in the wheat genome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Osman, Algopishi, Higgins, Henderson, Edwards, Franklin and Sanchez-Moran.)

Bread wheat (Triticum aestivum) is one of the world's most important crops; however, a low level of genetic diversity within commercial breeding accessions can significantly limit breeding potential. In contrast, wheat relatives exhibit considerable genetic variation and so potentially provide a valuable source of novel alleles for use in breeding new cultivars. Historically, gene flow between wheat and its relatives may have contributed novel alleles to the bread wheat pangenome. To assess the contribution made by wheat relatives to genetic diversity in bread wheat, we used markers based on single nucleotide polymorphisms to compare bread wheat accessions, created in the past 150 years, with 45 related species. We show that many bread wheat accessions share near-identical haplotype blocks with close relatives of wheat's diploid and tetraploid progenitors, while some show evidence of introgressions from more distant species and structural variation between accessions. Hence, introgressions and chromosomal rearrangements appear to have made a major contribution to genetic diversity in cultivar collections. As gene flow from relatives to bread wheat is an ongoing process, we assess the impact that introgressions might have on future breeding strategies.

Purpose: Targeted delivery in vivo remains an immense roadblock for the translation of nanomaterials into the clinic. The greatest obstacle is the mononuclear phagocyte system (MPS), which sequesters foreign substances from general circulation and causes accumulation in organs such as the liver and spleen. The purpose of this study was to determine whether attaching an active targeting antibody, 5B1, to the surface of gold nanoparticles and using clodronate liposomes to deplete liver and splenic macrophages could help to minimize uptake by MPS organs, increase targeted delivery to CA19.9-positive pancreatic tumors, and enhance pancreatic tumor delineation., Procedures: To produce the antibody-gold nanoparticle conjugate (Ab-AuNP), the Ab was conjugated to p-isothiocyanatobenzyl-desferrioxamine (p-SCN-DFO) and subsequently conjugated to NHS-activated gold nanoparticles. The Ab-AuNP was characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Modified Lindmo assay was performed to assess binding affinity and internalization potential in vitro. The Ab-AuNP was radiolabeled with 89 Zr and injected into CA19.9-positive BxPc-3 pancreatic orthotopic tumor-bearing mice pretreated with or without clodronate liposomes for PET imaging and biodistribution studies. Inductively coupled plasma-optical emission spectrometry (ICP-OES) analysis was used to confirm delivery of gold nanoparticles to BxPc-3 pancreatic subcutaneous xenografts., Results: Mice pretreated with clodronate liposomes in an orthotopic setting demonstrated decreased liver uptake at early time points (12.2 ± 2.3 % ID/g vs. 22.8 ± 3.8 % ID/g at 24 h) and increased tumor uptake at 120 h (13.8 ± 8.0 % ID/g vs. 6.0 ± 1.2 % ID/g). This allowed for delineation of orthotopic pancreatic xenografts in significantly more mice treated with clodronate (6/6) than in mice not treated with clodronate (2/6) or mice injected with gold nanoparticles labeled with a nonspecific antibody (0/5)., Conclusions: The combination of clodronate liposomes and an active targeting antibody on the surface of gold nanoparticles allowed for PET/CT imaging of subcutaneous and orthotopic pancreatic xenografts in mice.

Analyses of high-resolution pollen data, coprophilous fungal spores, microscopic charcoal and sedimentology, combined with radiocarbon dating, allow the assessment of the impact of Sami and Nordic land use in the region surrounding the winter market town of Lycksele in northern Sweden. Such winter markets were established by the Crown during the seventeenth century AD to control the semi-nomadic movements of the Sami who traded here with Finnish settlers and were also taxed and educated. Little is known about Sami and Nordic co-existence beyond these market places, mainly due to a lack of archaeological evidence relating to Sami activity. Vegetation and land-use changes in the region between ~ AD 250 and 1825 reveal no signal for pre-seventeenth century agricultural activity, but the coprophilous fungal spore records suggest the increased regional presence of grazing herbivores (possibly reindeer) between ~ AD 800 and 1100. Sami activity in the parish of Lycksele has been suggested by rich metal finds dated to ~ AD 1000-1350 and they may have been attracted by an abundance of reindeer., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2021.)

The wild relatives of modern wheat represent an underutilized source of genetic and phenotypic diversity and are of interest in breeding owing to their wide adaptation to diverse environments. Leaf photosynthetic traits underpin the rate of production of biomass and yield and have not been systematically explored in the wheat relatives. This paper identifies and quantifies the phenotypic variation in photosynthetic, stomatal, and morphological traits in up to 88 wheat wild relative accessions across five genera. Both steady-state measurements and dynamic responses to step changes in light intensity are assessed. A 2.3-fold variation for flag leaf light and CO 2 -saturated rates of photosynthesis A max was observed. Many accessions showing higher and more variable A max , maximum rates of carboxylation, electron transport, and Rubisco activity when compared with modern genotypes. Variation in dynamic traits was also significant; with distinct genus-specific trends in rates of induction of nonphotochemical quenching and rate of stomatal opening. We conclude that utilization of wild relatives for improvement of photosynthesis is supported by the existence of a high degree of natural variation in key traits and should consider not only genus-level properties but variation between individual accessions., (©2020 The Authors New Phytologist ©2020 New Phytologist Trust.)