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School counselors are needed now more than ever. Providing Catholic school counselors the specialized formation they need to be effective in the Catholic school context is essential. This study addressed two research questions in this regard: (1) What competencies (e.g., understanding, incorporating) and topics do Catholic school principals and school counselors believe are important for school counselors to fully contribute to the educational and faith-based mission of Catholic schools; and (2) How might the research findings inform pre-service education and/or continuing education and formation of school counselors for the Catholic school context? Online surveys were developed using the "Defining Characteristics of Catholic Schools" from NSBECS and researchbased, mission-centered competencies and topics. The surveys were sent to the 40 principals and 54 school counselors at the schools in one mid-size U.S. diocese that employ school counselors. The survey response rates were 87.5% for principals and 91% for school counselors. Findings confirmed high levels of support from both groups for school counselors understanding mission-related topics and incorporating these competencies into counseling practices and activities, although principals often rated the importance higher than did school counselors. Some between group differences were statistically significant on items such as the importance of incorporating Catholic teaching with current student and school issues. To reduce differences in perceptions, the authors recommend increased collaboration between principals and counselors to achieve unity of vision. Other recommendations to help school counselors contribute to mission include embedding mission-related topics or adding specialized courses to school counseling programs at Catholic universities, designing mission-centered professional development opportunities, and building networks of school counselors to support them in their complex and evolving role in support of Catholic school mission.

INTRODUCTION: Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke for select patients with large vessel occlusion (LVO). Although racial disparities in the utilization of thrombectomy have been previously identified, disparities in the utilization of thrombectomy in a single center with a standardized patient selection protocol have not been described in the literature. METHODS: Using the American Heart Association Quality Improvement Programs Registry, we retrospectively reviewed the records of 1,143 patients with LVO between December 1, 2014, and May 31, 2021. Patient records were assessed for demographic data, stroke risk factors, process metrics, and success of thrombectomy. A Pearson’s Chi-Squared and an independent two-sample t-test were used to determine the significance. Following this, a multivariate logistic regression was run to determine predictably of thrombectomy outcomes. RESULTS: Of the 1,143 LVO patients, 567 were male (49.6%), 576 were female, (50.4%), 963 were white (84.3%), and 180 were nonwhite (15.7%). Based on our Pearson’s Chi-squared analysis, female patients were more like to undergo thrombectomy compared to male patients (62.4% vs. 48.9%; P < 0.001). White patients were also more likely to undergo thrombectomy compared to nonwhite patients (58.7% vs. 39.7%; P < 0.001). After the multivariate logistic regression analysis and after controlling for comorbidities, insurance status, age, time to presentation (last known well to arrival), transfer from outside hospital, and zip codes, white patients were 2.29 times more likely to receive a thrombectomy compared to nonwhite patients (odds ratio [OR], 2.29, 95% confidence interval [CI], 1.33, 3.944). Patients with Medicare insurance were 33.57 times more likely to receive a thrombectomy compared to those without medicare (OR, 33.57, 95% CI, 20.37, 55.327). In the regression model, sex did not contribute significantly to the likelihood of receiving a thrombectomy. CONCLUSIONS: White patients were more likely to undergo MT. Female patients tended to have higher rates of MT, accounting for the fact that other variables could have influenced this. These disparities may result from a multitude of other factors such as eligibility for MT, delayed presentation, and adequate diagnosis of LVO in the emergency department. This study highlights the importance of and potential causes of these disparities. Further investigation with data from multiple centers is necessary to validate these findings and identify strategies for improving utilization of thrombectomy.

BACKGROUND: When medical students create their residency rank order lists, they consider a myriad of factors such as program reputation, research opportunities, and geographical location; however, it is unclear whether some factors such as the likelihood of acquiring an academic position, are adequately reflected in established ranking systems. The Doximity Reputation Navigator (DRN) reputation rank methodology is dubious. In this study, we aim to investigate the relationship between ranks of neurosurgical residency program ranks in DRN and Blue Ridge Institute for Medical Research (BRIMR) rankings, to identify potential underlying relationships between academic neurosurgeons and ranks. The primary objective of this study was to assess the relationship between established neurosurgical residency program rankings, specifically those from DRN and BRIMR, and the academic contributions of affiliated neurosurgeons. This was done by developing a new ranking system based on the proportion of neurosurgeons from these programs who hold academic positions. METHODS: We conducted a cross-sectional analysis of neurosurgical residency programs accredited by the Accreditation Council for Graduate Medical Education (ACGME). We included 1623 faculty members from these programs, focusing on those with publicly available education and training histories in our analysis. The newly developed ranking system, Residency Affiliated Academic Neurosurgeons (RAAN), was created to rank programs based on the proportion of neurosurgeons in academia. This study involved the development of Residency Affiliated Academic neurosurgeons ranking system, which was then compared to the existing DRN and BRIMR rankings. The correlations between these rankings and academic positions of neurosurgeons were analyzed to identify any significant relationships. RESULTS: We find that in our system, the program ranking had a significant correlation with Doximity Residency Navigator or Blue Ridge Institute for Medical Research (R=0.73, p

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During natural disasters, emergency communication systems become overloaded, and people are forced to turn to social media to make requests for help. This study employs machine learning and artificial intelligence to automatically detect, identify, and categorize tweets relevant to first responders during Hurricane Harvey. We curate a dataset of tweets, present a labeling scheme based on relevance and urgency, and develop neural and non-neural machine learning models to automatically categorize tweets. Our best relevance classifiers, language models BERT and XLNet, perform significantly better than non-neural models and the deep convolutional neural network (CNN) and achieve comparable F1 scores. Ultimately, this study furthers machine learning and crisis communication research by developing methods to automatically categorize tweets that can signal to first responders of individuals’ requests for help in urgent, life-threatening disasters. Our work also finds large pretrained language models promising for the development of well-performing disaster tweet classifiers in future work.

A determination of how the color of animal integument is produced is a starting point for investigations into the function and evolution of coloration. The mechanisms that give rise to the color of bare skin of New World vultures are largely unexplored. Here, we investigate the source of color production in the bare skin of Turkey Vultures (Cathartes aura) and Black Vultures (Coragyps atratus). Using UV–vis reflectance spectroscopy, we found evidence that hemoglobin is the primary pigment responsible for the red coloration of the bare skin on the heads of Turkey Vultures, and that eumelanin is responsible for the black coloration of the bare skin on the heads of Black Vultures. Light microscopy of incisional skin samples further supported these mechanisms of color production by revealing the presence of numerous blood vessels near the surface of the Turkey Vulture skin, and a high concentration of melanosomes in the skin of Black Vultures. Using high performance liquid chromatography (HPLC), we detected carotenoids within the skin of both species with significantly higher total concentrations of carotenoids in the skin of Turkey Vultures compared to the skin of Black Vultures. The carotenoids detected were dietary carotenoids that typically produce yellow coloration when accumulated in integument and were present in low concentrations. We hypothesize that the dietary carotenoids present do not contribute to the color of the skin, but rather help to compensate for the lack of melanosomes found in Turkey Vulture skin. The presence of additional carotenoids may act as an antioxidant to minimize UV damage when the bare Turkey Vulture head skin is exposed to direct sunlight for prolonged periods of time when soaring and scavenging for food.

In 2009, the International Soil Moisture Network (ISMN) was initiated as a community effort, funded by the European Space Agency, to serve as a centralised data hosting facility for globally available in situ soil moisture measurements (Dorigo et al., 2011b, a). The ISMN brings together in situ soil moisture measurements collected and freely shared by a multitude of organisations, harmonises them in terms of units and sampling rates, applies advanced quality control, and stores them in a database. Users can freely retrieve the data from this database through an online web portal (https://ismn.earth/en/, last access: 28 October 2021). Meanwhile, the ISMN has evolved into the primary in situ soil moisture reference database worldwide, as evidenced by more than 3000 active users and over 1000 scientific publications referencing the data sets provided by the network. As of July 2021, the ISMN now contains the data of 71 networks and 2842 stations located all over the globe, with a time period spanning from 1952 to the present. The number of networks and stations covered by the ISMN is still growing, and approximately 70 % of the data sets contained in the database continue to be updated on a regular or irregular basis. The main scope of this paper is to inform readers about the evolution of the ISMN over the past decade, including a description of network and data set updates and quality control procedures. A comprehensive review of the existing literature making use of ISMN data is also provided in order to identify current limitations in functionality and data usage and to shape priorities for the next decade of operations of this unique community-based data repository.

Optimal management of locally advanced vaginal mucosal melanoma is poorly understood because of its rarity and unique biology. Patients have a poor prognosis despite aggressive management approaches including pelvic exenteration and adjuvant radiation that carry major morbidities. We report a case of a patient in early 40’s who experienced complete pathologic response and organ preservation following immunotherapy consisting of 3 cycles of ipilimumab and nivolumab. Treatment was complicated by a high-grade immune mediated hepatitis that eventually resolved with immunosuppressive therapy. Immune monitoring studies utilizing vaginal tumor biopsies showed evidence of enhanced infiltration by CD3+/CD8+ cytotoxic T-cells and increased expression of MHC-I/PD-L1 within the tumor microenvironment following immunotherapy. The patient continues to be without evidence of disease recurrence by radiologic and gynecologic examinations with more than 2 years of follow up from the time of immunotherapy initiation. To our knowledge, this is the only case report in the literature of a patient with locally advanced vaginal mucosal melanoma experiencing a durable complete pathologic response and organ preservation following immune checkpoint blockade as the only treatment approach.

ABSTRACT Acinetobacter baumannii is an important hospital-associated pathogen that causes antibiotic resistant infections and reoccurring hospital outbreaks. A. baumannii’s ability to asymptomatically colonize patients is a risk factor for infection and exacerbates its spread. However, there is little information describing the mechanisms it employs to colonize patients. A. baumannii often colonizes the upper respiratory tract and skin. Antibiotic use is a risk factor for colonization and infection suggesting that A. baumannii likely competes with commensal bacteria to establish a niche. To begin to investigate this possibility, we cocultured A. baumannii and commensal bacteria of the upper respiratory tract and skin. In conditions that mimic iron starvation experienced in the host, we observed that A. baumannii inhibits Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus and Corynebacterium striatum. Then using an ordered transposon library screen we identified the A. baumannii siderophore acinetobactin as the causative agent of the inhibition phenotype. Using mass spectrometry, we show that acinetobactin is released from A. baumannii under our coculture conditions and that purified acinetobactin can inhibit C. striatum and S. hominis. Together our data suggest that acinetobactin may provide a competitive advantage for A. baumannii over some respiratory track and skin commensal bacteria and possibly support its ability to colonize patients. IMPORTANCE The ability of Acinetobacter baumannii to asymptomatically colonize patients is a risk factor for infection and exacerbates its clinical spread. However, there is minimal information describing how A. baumannii asymptomatically colonizes patients. Here we provide evidence that A. baumannii can inhibit the growth of many skin and upper respiratory commensal bacteria through iron competition and identify acinetobactin as the molecule supporting its nutritional advantage. Outcompeting endogenous commensals through iron competition may support the ability of A. baumannii to colonize and spread among patients.

A photoelectric color sorter—which can duplicate manual sorting practices— has been developed for use in lemon packing houses.

A sugar beet harvester developed at Davis and tested in dry, peat-loam soil at Clarksburg, October 16, 1947, gave 93.7% root recovery and only 6.8% dirt pickup.

The clinical utility of histone/protein deacetylase (HDAC) inhibitors in combinatorial regimens with proteasome inhibitors for patients with relapsed and refractory multiple myeloma (MM) is often limited by excessive toxicity due to HDAC inhibitor promiscuity with multiple HDACs. Therefore, more selective inhibition minimizing off-target toxicity may increase the clinical effectiveness of HDAC inhibitors. We demonstrated that plasma cell development and survival are dependent upon HDAC11, suggesting this enzyme is a promising therapeutic target in MM. Mice lacking HDAC11 exhibited markedly decreased plasma cell numbers. Accordingly, in vitro plasma cell differentiation was arrested in B cells lacking functional HDAC11. Mechanistically, we showed that HDAC11 is involved in the deacetylation of IRF4 at lysine103. Further, targeting HDAC11 led to IRF4 hyperacetylation, resulting in impaired IRF4 nuclear localization and target promoter binding. Importantly, transient HDAC11 knockdown or treatment with elevenostat, an HDAC11-selective inhibitor, induced cell death in MM cell lines. Elevenostat produced similar anti-MM activity in vivo, improving survival among mice inoculated with 5TGM1 MM cells. Elevenostat demonstrated nanomolar ex vivo activity in 34 MM patient specimens and synergistic activity when combined with bortezomib. Collectively, our data indicated that HDAC11 regulates an essential pathway in plasma cell biology establishing its potential as an emerging theraputic vulnerability in MM.

OBJECTIVE: Incomplete circle of Willis (CoW) configuration is an important risk factor for cerebrovascular pathology, namely aneurysm formation and ischemic stroke. This study was performed to characterize CoW variation using digital subtraction angiography and to identify demographic and physiologic features that may influence the risk of having an incomplete CoW configuration. MATERIALS AND METHODS: A retrospective review of 274 patients who underwent cerebral angiography by a single surgeon for any indication was conducted. Each CoW branch was graded as normal, hypoplastic, or aplastic. Univariate and multivariate regression analyses were conducted to assess the impact of age, gender, race, and certain comorbidities on CoW configuration. RESULTS: A complete CoW was identified in 37.23% of patients. In univariate analysis, patients

Abstract Background Everyday activities, such as walking or cycling, may be a feasible and practical way to integrate physical activity into everyday life. Walking and cycling for transport or recreation in the area local to a person’s home may have additional benefits. However, urban planning tends to prioritise car use over active modes. We explored the cross-sectional association between living near an urban motorway and local walking and cycling. Methods In 2013, residents living in an area (a) near a new urban motorway (M74), (b) near a longstanding urban motorway (M8), or (c) without a motorway, in Glasgow, Scotland, were invited to complete postal surveys assessing local walking and cycling journeys and socio-demographic characteristics. Using adjusted regression models, we assessed the association between motorway proximity and self-reported local walking and cycling, as well as the count of types of destination accessed. We stratified our analyses according to study area. Results One thousand three hundred forty-three residents (57% female; mean age: 54 years; SD: 16 years) returned questionnaires. There was no overall association between living near an urban motorway and the likelihood of local walking or cycling, or the number of types of local destination accessed by foot or bicycle. In stratified analyses, for those living in the area around the new M74 motorway, increasing residential proximity to the motorway was associated with lower likelihood of local recreational walking and cycling (OR 0.63, 95% CI: 0.39 to 1.00) a pattern not found in the area with the longstanding M8 motorway. In the area near the M8 motorway residential proximity was statistically significantly (p = 0.014) associated with a 12% decrease in the number of types of destination accessed, a pattern not found in the M74 study area. Conclusions Our findings suggest that associations between living near a motorway and local walking and cycling behaviour may vary by the characteristics of the motorway, and by whether the behaviour is for travel or recreation. The lack of associations seen in the study area with no motorway suggests a threshold effect whereby beyond a certain distance from a motorway, additional distance makes no difference.

Abstract An important component of life history theory is understanding how natural variation arises in populations. Both endogenous and exogenous factors contribute to organism survival and reproduction, and therefore, it is important to understand how such factors are both beneficial and detrimental to population dynamics. One ecologically relevant factor that influences the life history of aquatic organisms is ultraviolet (UV) radiation. While the majority of research has focused on the potentially detrimental effects that UV radiation has on aquatic organisms, few studies have evaluated hormetic responses stimulated by radiation under select conditions. The goal of this study was to evaluate the impact of UV‐A/B irradiation on life history characteristics in Tigriopus californicus copepods. After exposing copepods to UV‐A/B irradiation (control, 1‐, and 3‐hr UV treatments at 0.5 W/m2), we measured the impact of exposure on fecundity, reproductive effort, and longevity. We found that UV irradiation increased the size of the first clutch among all reproducing females in both the 1‐ and 3‐hr experimental groups and decreased longevity among all females that mated in the 1‐hr treatment. UV irradiation had no effect on the number of clutches females produced. These findings indicate a potential benefit of UV irradiation on reproductive performance early in life, although the same exposure came at a cost to longevity.

The etiology of acute lymphoblastic leukemia (ALL) remains unknown. A recent “two-hit” model for the occurrence of precursor B cell acute lymphoblastic leukemia propose that this disease arises through a two-step process, including predisposing genetic mutation and exposure to infections. While several genetic mutations are proposed, no infection category has been suggested. We have isolated a certain Aspergillus Flavus from residence of an ALL patient. This organism contains mycovirus and does not produce aflatoxin. The supernatant of culture of this mycovirus containing Aspergillus Flavus (SAF) was tested on the PBMCs of ALL patients in remission and controls. Cell surface phenotypes and genetic markers were examined. The effects of its combination with Epstein-Barr virus (EBV) was also investigated. For the SAF, positive and negative controls were aflatoxin and culture of Mycocladus corymbifer, respectively. Controls for ALL were sickle cell patients undergoing exchange transfusion. Incubation of the PMBCs from ALL patients in remission, or controls, with SAF resulted in re-development of ALL cell surface phenotypes and genetic markers in ALL patients in remission and not controls. These differentiating effects were not seen with aflatoxin or culture of Mycocladus Corymbifer. Addition of EBV did not alter effects of SAF. Currently, there are no techniques to discriminately reproduce characteristic leukemic genetic markers and cell surface phenotypes in cells from ALL patients in remission and not controls. These studies may provide a test for recognition of ALL patients in remission and new prospects for the investigation of leukemogenesis.

The marine copepod, Tigriopus californicus, produces the red carotenoid pigment astaxanthin from yellow dietary precursors. This 'bioconversion' of yellow carotenoids to red is hypothesized to be linked to individual condition, possibly through shared metabolic pathways with mitochondrial oxidative phosphorylation. Experimental inter-population crosses of lab-reared T. californicus typically produces low-fitness hybrids is due in large part to the disruption of coadapted sets nuclear and mitochondrial genes within the parental populations. These hybrid incompatibilities can increase variability in life history traits and energy production among hybrid lines. Here, we tested if production of astaxanthin was compromised in hybrid copepods and if it was linked to mitochondrial metabolism and offspring development. We observed no clear mitonuclear dysfunction in hybrids fed a limited, carotenoid-deficient diet of nutritional yeast. However, when yellow carotenoids were restored to their diet, hybrid lines produced less astaxanthin than parental lines. We observed that lines fed a yeast diet produced less ATP and had slower offspring development compared to lines fed a more complete diet of algae, suggesting the yeast-only diet may have obscured effects of mitonuclear dysfunction. Astaxanthin production was not significantly associated with development among lines fed a yeast diet but was negatively related to development in early generation hybrids fed an algal diet. In lines fed yeast, astaxanthin was negatively related to ATP synthesis, but in lines fed algae, the relationship was reversed. Although the effects of the yeast diet may have obscured evidence of hybrid dysfunction, these results suggest that astaxanthin bioconversion may still be related to mitochondrial performance and reproductive success.

Development of chronic lymphocytic leukemia (CLL) is associated with severe immune dysfunction. T-cell exhaustion, immune checkpoint upregulation, and increase of regulatory T cells contribute to an immunosuppressive tumor microenvironment. As a result, CLL patients are severely susceptible to infectious complications that increase morbidity and mortality. CLL B-cell survival is highly dependent upon interaction with the supportive tumor microenvironment. It has been postulated that the reversal of T-cell dysfunction in CLL may be beneficial to reduce tumor burden. Previous studies have also highlighted roles for histone deacetylase 6 (HDAC6) in regulation of immune cell phenotype and function. Here, we report for the first time that HDAC6 inhibition exerts beneficial immunomodulatory effects on CLL B cells and alleviates CLL-induced immunosuppression of CLL T cells. In the Eμ-TCL1 adoptive transfer murine model, genetic silencing or inhibition of HDAC6 reduced surface expression of programmed death-ligand 1 (PD-L1) on CLL B cells and lowered interleukin-10 (IL-10) levels. This occurred concurrently with a bolstered T-cell phenotype, demonstrated by alteration of coinhibitory molecules and activation status. Analysis of mice with similar tumor burden indicated that the majority of T-cell changes elicited by silencing or inhibition of HDAC6 in vivo are likely secondary to decrease of tumor burden and immunomodulation of CLL B cells. The data reported here suggest that CLL B cell phenotype may be altered by HDAC6-mediated hyperacetylation of the chaperone heat shock protein 90 (HSP90) and subsequent inhibition of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. Based on the beneficial immunomodulatory activity of HDAC6 inhibition, we rationalized that HDAC6 inhibitors could enhance immune checkpoint blockade in CLL. Conclusively, combination treatment with ACY738 augmented the antitumor efficacy of anti-PD-1 and anti-PD-L1 monoclonal antibodies in the Eμ-TCL1 adoptive transfer murine model. These combinatorial antitumor effects coincided with an increased cytotoxic CD8+ T-cell phenotype. Taken together, these data highlight a role for HDAC inhibitors in combination with immunotherapy and provides the rationale to investigate HDAC6 inhibition together with immune checkpoint blockade for treatment of CLL patients.

The asymmetric outer membrane (OM) of Gram-negative bacteria functions as a selective permeability barrier to the environment. Perturbations to OM lipid asymmetry sensitize the cell to antibiotics. As such, mechanisms involved in lipid asymmetry are fundamental to our understanding of OM lipid homeostasis. One such mechanism, the Maintenance of lipid asymmetry (Mla) pathway has been proposed to extract mislocalized glycerophospholipids from the outer leaflet of the OM and return them to the inner membrane (IM). Work on this pathway in Acinetobacter baumannii support conflicting models for the directionality of the Mla system being retrograde (OM to IM) or anterograde (IM to OM). Here, we show conclusively that A. baumannii mla mutants exhibit no defects in anterograde transport. Furthermore, we identify an allele of the GTPase obgE that is synthetically sick in the absence of Mla; providing another link between cell envelope homeostasis and stringent response.

Abstract Background Regulation of pre-mRNA splicing diversifies protein products and affects many biological processes. Arabidopsis thaliana Serine/Arginine-rich 45 (SR45), regulates pre-mRNA splicing by interacting with other regulatory proteins and spliceosomal subunits. Although SR45 has orthologs in diverse eukaryotes, including human RNPS1, the sr45–1 null mutant is viable. Narrow flower petals and reduced seed formation suggest that SR45 regulates genes involved in diverse processes, including reproduction. To understand how SR45 is involved in the regulation of reproductive processes, we studied mRNA from the wild-type and sr45–1 inflorescences using RNA-seq, and identified SR45-bound RNAs by immunoprecipitation. Results Using a variety of bioinformatics tools, we identified a total of 358 SR45 differentially regulated (SDR) genes, 542 SR45-dependent alternative splicing (SAS) events, and 1812 SR45-associated RNAs (SARs). There is little overlap between SDR genes and SAS genes, and neither set of genes is enriched for flower or seed development. However, transcripts from reproductive process genes are significantly overrepresented in SARs. In exploring the fate of SARs, we found that a total of 81 SARs are subject to alternative splicing, while 14 of them are known Nonsense-Mediated Decay (NMD) targets. Motifs related to GGNGG are enriched both in SARs and near different types of SAS events, suggesting that SR45 recognizes this motif directly. Genes involved in plant defense are significantly over-represented among genes whose expression is suppressed by SR45, and sr45–1 plants do indeed show enhanced immunity. Conclusion We find that SR45 is a suppressor of innate immunity. We find that a single motif (GGNGG) is highly enriched in both RNAs bound by SR45 and in sequences near SR45- dependent alternative splicing events in inflorescence tissue. We find that the alternative splicing events regulated by SR45 are enriched for this motif whether the effect of SR45 is activation or repression of the particular event. Thus, our data suggests that SR45 acts to control splice site choice in a way that defies simple categorization as an activator or repressor of splicing.

Pre-mRNA alternative splicing is a conserved mechanism for eukaryotic cells to leverage existing genetic resources to create a diverse pool of protein products. It is regulated in coordination with other events in RNA metabolism such as transcription, polyadenylation, RNA transport, and nonsense-mediated decay via protein networks. SERINE/ARGININE-RICH 45 (SR45) is thought to be a neutral splicing regulator. It is orthologous to a component of the apoptosis and splicing-associated protein (ASAP) complex functioning to regulate RNA metabolism at multiple levels. Within this context, we try to understand why the sr45-1 mutant Arabidopsis has malformed flowers, delayed flowering time, and increased disease resistance. Prior studies revealed increased expression for some disease resistance genes and the flowering suppressor Flowering Locus C (FLC) in sr45-1 mutants and a physical association between SR45 and reproductive process-related RNAs. Here, we used Tandem Mass Tag-based quantitative mass spectrometry to compare the protein abundance from inflorescence between Arabidopsis wild-type (Col-0) and sr45-1 mutant plants. A total of 7,206 proteins were quantified, of which 227 proteins exhibited significantly different accumulation. Only a small percentage of these proteins overlapped with the dataset of RNAs with altered expression. The proteomics results revealed that the sr45-1 mutant had increased amounts of enzymes for glucosinolate biosynthesis which are important for disease resistance. Furthermore, the mutant inflorescence had a drastically reduced amount of the Sin3-associated protein 18 (SAP18), a second ASAP complex component, despite no significant reduction in SAP18 RNA. The third ASAP component protein, ACINUS, also had lower abundance without significant RNA changes in the sr45-1 mutant. To test the effect of SR45 on SAP18, a SAP18-GFP fusion protein was overproduced in transgenic Arabidopsis Col-0 and sr45-1 plants. SAP18-GFP has less accumulation in the nucleus, the site of activity for the ASAP complex, without SR45. Furthermore, transgenic sr45-1 mutants overproducing SAP18-GFP expressed even more FLC and had a more severe flowering delay than non-transgenic sr45-1 mutants. These results suggest that SR45 is required to maintain the wild-type level of SAP18 protein accumulation in the nucleus and that FLC-regulated flowering time is regulated by the correct expression and localization of the ASAP complex.

Abstract Willow species (Salix) are important as short‐rotation biomass crops for bioenergy, which creates a demand for faster genetic improvement and breeding through deployment of molecular marker‐assisted selection (MAS). To find markers associated with important adaptive traits, such as growth and phenology, for use in MAS, we genetically dissected the trait variation of a Salix viminalis (L.) population of 323 accessions. The accessions were sampled throughout northern Europe and were established at two field sites in Pustnäs, Sweden, and at Woburn, UK, offering the opportunity to assess the impact of genotype‐by‐environment interactions (G × E) on trait–marker associations. Field measurements were recorded for growth and phenology traits. The accessions were genotyped using 1536 SNP markers developed from phenology candidate genes and from genes previously observed to be differentially expressed in contrasting environments. Association mapping between 1233 of these SNPs and the measured traits was performed taking into account population structure and threshold selection bias. At a false discovery rate (FDR) of 0.2, 29 SNPs were associated with bud burst, leaf senescence, number of shoots or shoot diameter. The percentage of accession variation (Radj2) explained by these associations ranged from 0.3% to 4.4%, suggesting that the studied traits are controlled by many loci of limited individual impact. Despite this, a SNP in the EARLY FLOWERING 3 gene was repeatedly associated (FDR

Recent technological breakthroughs in our ability to derive and differentiate induced pluripotent stem cells, organoid biology, organ-on-chip assays, and 3-D bioprinting have all contributed to a heightened interest in the design, assembly, and manufacture of living systems with a broad range of potential uses. This white paper summarizes the state of the emerging field of “multi-cellular engineered living systems,” which are composed of interacting cell populations. Recent accomplishments are described, focusing on current and potential applications, as well as barriers to future advances, and the outlook for longer term benefits and potential ethical issues that need to be considered.

The median survival for metastatic melanoma is in the realm of 8–16 months and there are few therapies that offer significant improvement in overall survival. One of the recent advances in cancer treatment focuses on epigenetic modifiers to alter the survivability and immunogenicity of cancer cells. Our group and others have previously demonstrated that pan‐HDAC inhibitors induce apoptosis, cell cycle arrest and changes in the immunogenicity of melanoma cells. Here we interrogated specific HDACs which may be responsible for this effect. We found that both genetic abrogation and pharmacologic inhibition of HDAC6 decreases in vitro proliferation and induces G1 arrest of melanoma cell lines without inducing apoptosis. Moreover, targeting this molecule led to an important upregulation in the expression of tumor associated antigens and MHC class I, suggesting a potential improvement in the immunogenicity of these cells. Of note, this anti‐melanoma activity was operative regardless of mutational status of the cells. These effects translated into a pronounced delay of in vivo melanoma tumor growth which was, at least in part, dependent on intact immunity as evidenced by the restoration of tumor growth after CD4+ and CD8+ depletion. Given our findings, we provide the initial rationale for the further development of selective HDAC6 inhibitors as potential therapeutic anti‐melanoma agents.