Regulatory T-cell dysfunction and cutaneous exposure to Staphylococcus aureus underlie eczema in DOCK8 deficiency.

BACKGROUND: Dedicator of cytokinesis 8 (DOCK8)-deficient patients have severe eczema, elevated IgE, and eosinophilia, features of atopic dermatitis (AD). OBJECTIVE: We sought to understand the mechanisms of eczema in DOCK8 deficiency. METHODS: Skin biopsy samples were characterized by histology, immunofluorescence microscopy, and gene expression. Skin barrier function was measured by transepidermal water loss. Allergic skin inflammation was elicited in mice by epicutaneous sensitization with ovalbumin (OVA) or cutaneous application of Staphylococcus aureus. RESULTS: Skin lesions of DOCK8-deficient patients exhibited type 2 inflammation, and the patients' skin was colonized by Saureus, as in AD. Unlike in AD, DOCK8-deficient patients had a reduced FOXP3:CD4 ratio in their skin lesions, and their skin barrier function was intrinsically intact. Dock8-/- mice exhibited reduced numbers of cutaneous T regulatory (Treg) cells and a normal skin barrier. Dock8-/- and mice with an inducible Dock8 deletion in Treg cells exhibited increased allergic skin inflammation after epicutaneous sensitization with OVA. DOCK8 was shown to be important for Treg cell stability at sites of allergic inflammation and for the generation, survival, and suppressive activity of inducible Treg cells. Adoptive transfer of wild-type, but not DOCK8-deficient, OVA-specific, inducible Treg cells suppressed allergic inflammation in OVA-sensitized skin of Dock8-/- mice. These mice developed severe allergic skin inflammation and elevated serum IgE levels after topical exposure to Saureus. Both were attenuated after adoptive transfer of WT but not DOCK8-deficient Treg cells. CONCLUSION: Treg cell dysfunction increases susceptibility to allergic skin inflammation in DOCK8 deficiency and synergizes with cutaneous exposure to Saureus to drive eczema in DOCK8 deficiency.

Neoadjuvant systemic oncolytic vesicular stomatitis virus is safe and may enhance long-term survivorship in dogs with naturally occurring osteosarcoma.

Osteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection combined with multiagent chemotherapy, but many patients still suffer from metastatic disease progression. Neoadjuvant systemic oncolytic virus (OV) therapy has the potential to improve clinical outcomes by targeting primary and metastatic tumor sites and inducing durable antitumor immune responses. Here we describe the first evaluation of neoadjuvant systemic therapy with a clinical-stage recombinant oncolytic vesicular stomatitis virus (VSV), VSV-IFNß-NIS, in naturally occurring cancer, specifically appendicular osteosarcoma in companion dogs. Canine osteosarcoma has a similar natural disease history as its human counterpart. VSV-IFNß-NIS was administered prior to standard of care surgical resection, permitting microscopic and genomic analysis of tumors. Treatment was well-tolerated and a "tail" of long-term survivors (∼35%) was apparent in the VSV-treated group, a greater proportion than observed in two contemporary control cohorts. An increase in tumor inflammation was observed in VSV-treated tumors and RNA-seq analysis showed that all the long-term responders had increased expression of a T cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNß-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.

Hyperspectral imaging for estimating leaf, flower, and fruit macronutrient concentrations and predicting strawberry yields.

Managing the nutritional status of strawberry plants is critical for optimizing yield. This study evaluated the potential of hyperspectral imaging (400-1,000 nm) to estimate nitrogen (N), phosphorus (P), potassium (K), and calcium (Ca) concentrations in strawberry leaves, flowers, unripe fruit, and ripe fruit and to predict plant yield. Partial least squares regression (PLSR) models were developed to estimate nutrient concentrations. The determination coefficient of prediction (R2P) and ratio of performance to deviation (RPD) were used to evaluate prediction accuracy, which often proved to be greater for leaves, flowers, and unripe fruit than for ripe fruit. The prediction accuracies for N concentration were R2P = 0.64, 0.60, 0.81, and 0.30, and RPD = 1.64, 1.59, 2.64, and 1.31, for leaves, flowers, unripe fruit, and ripe fruit, respectively. Prediction accuracies for Ca concentrations were R2P = 0.70, 0.62, 0.61, and 0.03, and RPD = 1.77, 1.63, 1.60, and 1.15, for the same respective plant parts. Yield and fruit mass only had significant linear relationships with the Difference Vegetation Index (R2 = 0.256 and 0.266, respectively) among the eleven vegetation indices tested. Hyperspectral imaging showed potential for estimating nutrient status in strawberry crops. This technology will assist growers to make rapid nutrient-management decisions, allowing for optimal yield and quality.

Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigration.

T cell development proceeds via discrete stages that require both gene induction and gene repression. Transcription factors direct gene repression by associating with corepressor complexes containing chromatin-remodeling enzymes; the corepressors NCOR1 and NCOR2 recruit histone deacetylases to these complexes to silence transcription of target genes. Earlier work identified the importance of NCOR1 in promoting the survival of positively-selected thymocytes. Here, we used flow cytometry and single-cell RNA sequencing to identify a broader role for NCOR1 and NCOR2 in regulating thymocyte development. Using Cd4-cre mice, we found that conditional deletion of NCOR2 had no effect on thymocyte development, whereas conditional deletion of NCOR1 had a modest effect. In contrast, Cd4-cre x Ncor1f/f x Ncor2f/f mice exhibited a significant block in thymocyte development at the DP to SP transition. Combined NCOR1/2 deletion resulted in increased signaling through the T cell receptor, ultimately resulting in elevated BIM expression and increased negative selection. The NF-κB, NUR77, and MAPK signaling pathways were also upregulated in the absence of NCOR1/2, contributing to altered CD4/CD8 lineage commitment, TCR rearrangement, and thymocyte emigration. Taken together, our data identify multiple critical roles for the combined action of NCOR1 and NCOR2 over the course of thymocyte development.

Cytotoxic CD4 T cells in the mucosa and in cancer.

CD4 T cells were initially described as helper cells that promote either the cellular immune response (Th1 cells) or the humoral immune response (Th2 cells). Since then, a plethora of functionally distinct helper and regulatory CD4 T cell subsets have been described. CD4 T cells with cytotoxic function were first described in the setting of viral infections and autoimmunity, and more recently in cancer and gut dysbiosis. Regulatory CD4 T cell subsets such as Tregs and T-regulatory type 1 (Tr1) cells have also been shown to have cytotoxic potential. Indeed, Tr1 cells have been shown to be important for maintenance of stem cell niches in the bone marrow and the gut. This review will provide an overview of cytotoxic CD4 T cell development, and discuss the role of inflammatory and Tr1-like cytotoxic CD4 T cells in maintenance of intestinal stem cells and in anti-cancer immune responses.

Neoadjuvant systemic oncolytic vesicular stomatitis virus is safe and may enhance long-term survivorship in dogs with naturally occurring osteosarcoma.

Osteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection combined with multiagent chemotherapy, but many patients still suffer from metastatic disease progression. Neoadjuvant systemic oncolytic virus (OV) therapy has the potential to improve clinical outcomes by targeting primary and metastatic tumor sites and inducing durable antitumor immune responses. Here we described the first evaluation of neoadjuvant systemic therapy with a clinical-stage recombinant oncolytic Vesicular stomatitis virus (VSV), VSV-IFNß-NIS, in naturally occurring cancer, specifically appendicular osteosarcoma in companion dogs. Canine osteosarcoma has a similar natural disease history as its human counterpart. VSV-IFNß-NIS was administered prior to standard of care surgical resection, permitting microscopic and genomic analysis of tumors. Treatment was well-tolerated and a 'tail' of long-term survivors (~35%) was apparent in the VSV-treated group, a greater proportion than observed in two contemporary control cohorts. An increase in tumor inflammation was observed in VSV-treated tumors and RNAseq analysis showed that all the long-term responders had increased expression of a T-cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNß-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.

Open-circuit and short-circuit loss management in wide-gap perovskite p-i-n solar cells.

In this work, we couple theoretical and experimental approaches to understand and reduce the losses of wide bandgap Br-rich perovskite pin devices at open-circuit voltage (VOC) and short-circuit current (JSC) conditions. A mismatch between the internal quasi-Fermi level splitting (QFLS) and the external VOC is detrimental for these devices. We demonstrate that modifying the perovskite top-surface with guanidinium-Br and imidazolium-Br forms a low-dimensional perovskite phase at the n-interface, suppressing the QFLS-VOC mismatch, and boosting the VOC. Concurrently, the use of an ionic interlayer or a self-assembled monolayer at the p-interface reduces the inferred field screening induced by mobile ions at JSC, promoting charge extraction and raising the JSC. The combination of the n- and p-type optimizations allows us to approach the thermodynamic potential of the perovskite absorber layer, resulting in 1 cm2 devices with performance parameters of VOCs up to 1.29 V, fill factors above 80% and JSCs up to 17 mA/cm2, in addition to a thermal stability T80 lifetime of more than 3500 h at 85 °C.

Nuclear corepressors NCOR1/NCOR2 regulate B cell development, maintain genomic integrity and prevent transformation.

The nuclear corepressors NCOR1 and NCOR2 interact with transcription factors involved in B cell development and potentially link these factors to alterations in chromatin structure and gene expression. Herein, we demonstrate that Ncor1/2 deletion limits B cell differentiation via impaired recombination, attenuates pre-BCR signaling and enhances STAT5-dependent transcription. Furthermore, NCOR1/2-deficient B cells exhibited derepression of EZH2-repressed gene modules, including the p53 pathway. These alterations resulted in aberrant Rag1 and Rag2 expression and accessibility. Whole-genome sequencing of Ncor1/2 DKO B cells identified increased number of structural variants with cryptic recombination signal sequences. Finally, deletion of Ncor1 alleles in mice facilitated leukemic transformation, whereas human leukemias with less NCOR1 correlated with worse survival. NCOR1/2 mutations in human leukemia correlated with increased RAG expression and number of structural variants. These studies illuminate how the corepressors NCOR1/2 regulate B cell differentiation and provide insights into how NCOR1/2 mutations may promote B cell transformation.

Tracking Regulatory T Cell Development in the Thymus Using Single-Cell RNA Sequencing/TCR Sequencing.

Recent studies have demonstrated that regulatory T cells (Tregs) develop in the thymus via two pathways involving distinct Treg progenitors (TregP): CD25+FOXP3- (CD25+ TregP) and CD25-FOXP3lo (FOXP3lo TregP) Treg progenitors. To examine this process in more detail, we carried out single-cell RNA sequencing (scRNA-Seq) and TCR-Seq on sorted murine CD4+CD8+ double-positive (DP) thymocytes, CD4+ single-positive (CD4SP) thymocytes, CD25+FOXP3-CD73- TregP, CD25-FOXP3loCD73- TregP, newly generated mature CD25+FOXP3+CD73- Tregs, and FOXP3+CD73+ recirculating/long-term resident Tregs (RT-Tregs). Sorted populations were individually hashtagged and then combined into one scRNA-Seq/TCR-Seq library before sequencing and subsequent analysis. We found that both CD25+ TregP and FOXP3lo TregP arise via an initial agonist-activated state that gives rise to a second transitional stage before differentiating into mature Tregs Using both scRNA-Seq and bulk RNA-Seq on sorted thymocyte subsets, we demonstrate that CD25+ TregP are significantly enriched for Il2 production, suggesting that they are the major source of IL-2 needed to convert TregP into mature Tregs Using TCR-Seq, we found that several TCRs were clearly biased in favor of the conventional or Treg lineages, but that a large fraction of TCRs were found in both these lineages. Finally, we found that RT-Tregs in the thymus are not monomorphic but are composed of multiple distinct subsets and that these RT-Tregs express the most diverse TCR repertoire of all CD4SP thymocytes. Thus, our studies define multiple stages of Treg differentiation within the murine thymus and serve as a resource for future studies on CD4+ thymocyte development and Treg differentiation.

An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism.

The immunosuppressive regulatory T (Treg) cells exert emerging effects on adipose tissue homeostasis and systemic metabolism. However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. Here, we investigate the O-GlcNAc transferase (OGT)-STAT5 axis in driving the immunomodulatory function of Treg cells for metabolic homeostasis. Treg cell-specific OGT deficiency renders mice more vulnerable to high-fat diet (HFD)-induced adiposity and insulin resistance. Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. Treg cell function can be augmented by targeting the OGT-STAT5 axis to combat obesity and related metabolic disorders.

Combining nilotinib and PD-L1 blockade reverses CD4+ T-cell dysfunction and prevents relapse in acute B-cell leukemia.

Patients with acute lymphoblastic leukemia have experienced significantly improved outcomes due to the advent of chimeric antigen receptor (CAR) T cells and bispecific T-cell engagers, although a proportion of patients still relapse despite these advances. T-cell exhaustion has been recently suggested to be an important driver of relapse in these patients. Indeed, phenotypic exhaustion of CD4+ T cells is predictive of relapse and poor overall survival in B-cell acute lymphoblastic leukemia (B-ALL). Thus, therapies that counter T-cell exhaustion, such as immune checkpoint blockade, may improve leukemia immunosurveillance and prevent relapse. Here, we used a murine model of Ph+ B-ALL as well as human bone marrow biopsy samples to assess the fundamental nature of CD4+ T-cell exhaustion and the preclinical therapeutic potential for combining anti-PD-L1 based checkpoint blockade with tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein. Single-cell RNA-sequence analysis revealed that B-ALL induces a unique subset of CD4+ T cells with both cytotoxic and helper functions. Combination treatment with the tyrosine kinase inhibitor nilotinib and anti-PD-L1 dramatically improves long-term survival of leukemic mice. Depletion of CD4+ T cells prior to therapy completely abrogates the survival benefit, implicating CD4+ T cells as key drivers of the protective anti-leukemia immune response. Indeed, treatment with anti-PD-L1 leads to clonal expansion of leukemia-specific CD4+ T cells with the aforementioned helper/cytotoxic phenotype as well as reduced expression of exhaustion markers. These findings support efforts to use PD1/PD-L1 checkpoint blockade in clinical trials and highlight the importance of CD4+ T-cell dysfunction in limiting the endogenous anti-leukemia response.

Combined effects of biochar and fertilizer applications on yield: A review and meta-analysis.

The use of biochar is changing, and the combined application of biochar with fertilizer is increasingly gaining acceptance. However, the yield gains results reported in the existing literature through the co-application of fertilizer with biochar are conflicting. To resolve this, we utilized a meta-analysis of 627 paired data points extracted from 57 published articles to assess the performance of the co-application of biochar and fertilizers on crop yield compared with the corresponding controls. We also studied the impact of biochar characteristics, experimental conditions, and soil properties on crop yield. Our analysis showed that individually, biochar and inorganic fertilizer increased crop yield by 25.3% ± 3.2 (Bootstrap CI 95%) and 21.9% ± 4.4, respectively. The co-application of biochar with both inorganic and organic fertilizers increased crop yield by 179.6% ± 18.7, however, this data needs to be treated with caution due to the limited dataset. The highest yield increase was observed with amendments to very acidic soils (pH ≤5), but the benefits of biochar were not affected by the rate and the time after the application. In addition, the effects of biochar are enhanced when it is produced at 401-500 °C with a C:N ratio of 31-100. Our results suggest that the co-application of biochar with either inorganic and/or organic fertilizers in acidic soils increase crop productivity compared to amendment with either fertilizer or biochar. Our meta-analysis supports the utilization of biochar to enhance the efficiency and profitability of fertilizers.

Biochar compound fertilisers increase plant potassium uptake 2 years after application without additional organic fertiliser.

Biochar compound fertilisers (BCFs) are an emerging technology that combine biochar with nutrients, clays and minerals and can be formulated to address specific issues in soil-plant systems. However, knowledge of BCF performance over consecutive crops and without re-application is limited. This study aims to assess the residual effect of organic BCFs soil-plant nutrient cycling 2 years after application and without additional fertiliser inputs. We applied BCFs and biochar with organic fertiliser amendments and established a crop of ginger and a second crop of turmeric (Curcuma longa) without re-application or additional fertilisation. All treatment formulations included bamboo-biochar and organic fertiliser amendments; however, two novel BCFs were formulated to promote agronomic response in an intensive cropping system. We report here on the effect of treatments on soil and plant macronutrient and micronutrient cycling and turmeric growth, biomass and yield at harvest. Both BCFs (enriched (10 t ha-1) and organo-mineral biochar (8.6 t ha-1) increased foliar K (+155% and +120%) and decreased foliar Mg (-20% and -19%) concentration compared with all other treatments, suggesting antagonism between K and Mg. Plants were limited for K, P and B at harvest but not N, Ca or Mg. Foliar K was dependent on the biochar formulation rather than the rate of application. Biochar-clay aggregates increased K retention and cycling in the soil solution 2 years after application. Clay blended BCFs reduced K limitation in turmeric compared to biochar co-applied with organic amendments, suggesting these blends can be used to manage organic K nutrition. All formulations and rates of biochar increased leaf biomass and shoot-to-root ratio. Novel BCFs should be considered as an alternative to co-applying biochar with organic fertiliser amendments to decrease application rates and increase economic feasibility for farmers. Applying BCFs without re-application or supplementary fertiliser did not provide sufficient K or P reserves in the second year for consecutive cropping. Therefore, supplementary fertilisation is recommended to avoid nutrient deficiency and reduced yield for consecutive organic rhizome crops.

Single-cell analysis identifies dynamic gene expression networks that govern B cell development and transformation.

Integration of external signals and B-lymphoid transcription factor activities organise B cell lineage commitment through alternating cycles of proliferation and differentiation, producing a diverse repertoire of mature B cells. We use single-cell transcriptomics/proteomics to identify differentially expressed gene networks across B cell development and correlate these networks with subtypes of B cell leukemia. Here we show unique transcriptional signatures that refine the pre-B cell expansion stages into pre-BCR-dependent and pre-BCR-independent proliferative phases. These changes correlate with reciprocal changes in expression of the transcription factor EBF1 and the RNA binding protein YBX3, that are defining features of the pre-BCR-dependent stage. Using pseudotime analysis, we further characterize the expression kinetics of different biological modalities across B cell development, including transcription factors, cytokines, chemokines, and their associated receptors. Our findings demonstrate the underlying heterogeneity of developing B cells and characterise developmental nodes linked to B cell transformation.

Phenotypic and Functional Diversity in Regulatory T Cells.

The concept that a subset of T cells exists that specifically suppresses immune responses was originally proposed over 50 years ago. It then took the next 30 years to solidify the concept of regulatory T cells (Tregs) into the paradigm we understand today - namely a subset of CD4+ FOXP3+ T-cells that are critical for controlling immune responses to self and commensal or environmental antigens that also play key roles in promoting tissue homeostasis and repair. Expression of the transcription factor FOXP3 is a defining feature of Tregs, while the cytokine IL2 is necessary for robust Treg development and function. While our initial conception of Tregs was as a monomorphic lineage required to suppress all types of immune responses, recent work has demonstrated extensive phenotypic and functional diversity within the Treg population. In this review we address the ontogeny, phenotype, and function of the large number of distinct effector Treg subsets that have been defined over the last 15 years.

Revealing Ultrafast Charge-Carrier Thermalization in Tin-Iodide Perovskites through Novel Pump-Push-Probe Terahertz Spectroscopy.

Tin-iodide perovskites are an important group of semiconductors for photovoltaic applications, promising higher intrinsic charge-carrier mobilities and lower toxicity than their lead-based counterparts. Controllable tin vacancy formation and the ensuing hole doping provide interesting opportunities to investigate dynamic intraband transitions of charge carriers in these materials. Here, we present for the first time an experimental implementation of a novel Optical-Pump-IR-Push-THz-Probe spectroscopic technique and demonstrate its suitability to investigate the intraband relaxation dynamics of charge carriers brought into nonequilibrium by an infrared "push" pulse. We observe a push-induced decrease of terahertz conductivity for both chemically- and photodoped FA0.83Cs0.17SnI3 thin films and show that these effects derive from stimulated THz emission. We use this technique to reveal that newly photogenerated charge carriers relax within the bands of FA0.83Cs0.17SnI3 on a subpicosecond time scale when a large, already fully thermalized (cold) population of charge-carriers is present. Such rapid dissipation of the initial charge-carrier energy suggests that the propensity of tin halide perovskites toward unintentional self-doping resulting from tin vacancy formation makes these materials less suited to implementation in hot-carrier solar cells than their lead-based counterparts.

Identification of mutations that cooperate with defects in B cell transcription factors to initiate leukemia.

The transcription factors PAX5, IKZF1, and EBF1 are frequently mutated in B cell acute lymphoblastic leukemia (B-ALL). We demonstrate that compound heterozygous loss of multiple genes critical for B and T cell development drives transformation, including Pax5+/-xEbf1+/-, Pax5+/-xIkzf1+/-, and Ebf1+/-xIkzf1+/- mice for B-ALL, or Tcf7+/-xIkzf1+/- mice for T-ALL. To identify genetic defects that cooperate with Pax5 and Ebf1 compound heterozygosity to initiate leukemia, we performed a Sleeping Beauty (SB) transposon screen that identified cooperating partners including gain-of-function mutations in Stat5b (~65%) and Jak1 (~68%), or loss-of-function mutations in Cblb (61%) and Myb (32%). These findings underscore the role of JAK/STAT5B signaling in B cell transformation and demonstrate roles for loss-of-function mutations in Cblb and Myb in transformation. RNA-Seq studies demonstrated upregulation of a PDK1>SGK3>MYC pathway; treatment of Pax5+/-xEbf1+/- leukemia cells with PDK1 inhibitors blocked proliferation in vitro. In addition, we identified a conserved transcriptional gene signature between human and murine leukemias characterized by upregulation of myeloid genes, most notably involving the GM-CSF pathway, that resemble a B cell/myeloid mixed-lineage leukemia. Thus, our findings identify multiple mechanisms that cooperate with defects in B cell transcription factors to generate either progenitor B cell or mixed B/myeloid-like leukemias.

Effects of biochar, compost, and biochar-compost on soil total nitrogen and available phosphorus concentrations in a corn field in Papua New Guinea.

Replenishing soil nutrient particularly total nitrogen (TN) and available phosphorus (P) is important to sustain soil health for food production. Organic amendments such as compost and biochar are commonly applied to improve soil nutrient retention especially N and P. In farms, biochar is usually applied once followed by applying other organic amendment applied in their full rates. Both form and rate of organic amendments can affect soil nutrient concentrations particularly in short term. This study aimed to examine the effects of compost and mixture of compost with biochar (both at full rates) on soil nutrient concentrations in short term. A randomised complete block filed experiment with eight replicates was used for this study. The effects of biochar (5 t/ha) only, compost (at the rates of 10 t/ha, 25 t/ha and 35 t/ha) and biochar mixed with compost (5 t/ha and 10 t/ha, respectively) on soil nutrient concentrations compared with control were explored in a corn field. Compost treatment at the rate of 35 t/ha had significantly higher TN, available P, calcium (Ca) and iron (Fe) compared with other treatments and control. Soil potassium (K) levels remained unchanged among all treatments. Biochar only treatment had significantly higher available P and Ca concentrations compared with biochar mixed with compost treatment. Compost application at higher rate (35 t/ha) proved best practice to significantly increase TN and available P concentrations in short term. Significantly higher available P concentration in biochar only treatment compared with the biochar mixed with compost treatment could have been associated with stimulation of P immobilisation when biochar was mixed with compost. Our results indicated that the form and rate of organic amendments in short term cropping systems are important to be considered while applying to a volcanic soil to ensure N and P availability for plants are not compromised.

NCOR1 Orchestrates Transcriptional Landscapes and Effector Functions of CD4+ T Cells.

The differentiation of naïve CD4+ T cells into T helper (Th) subsets is key for a functional immune response and has to be tightly controlled by transcriptional and epigenetic processes. However, the function of cofactors that connect gene-specific transcription factors with repressive chromatin-modifying enzymes in Th cells is yet unknown. Here we demonstrate an essential role for nuclear receptor corepressor 1 (NCOR1) in regulating naïve CD4+ T cell and Th1/Th17 effector transcriptomes. Moreover, NCOR1 binds to a conserved cis-regulatory element within the Ifng locus and controls the extent of IFNγ expression in Th1 cells. Further, NCOR1 controls the survival of activated CD4+ T cells and Th1 cells in vitro, while Th17 cell survival was not affected in the absence of NCOR1. In vivo, effector functions were compromised since adoptive transfer of NCOR1-deficient CD4+ T cells resulted in attenuated colitis due to lower frequencies of IFNγ+ and IFNγ+IL-17A+ Th cells and overall reduced CD4+ T cell numbers. Collectively, our data demonstrate that the coregulator NCOR1 shapes transcriptional landscapes in CD4+ T cells and controls Th1/Th17 effector functions.

Short-term application of mulch, roundup and organic herbicides did not affect soil microbial biomass or bacterial and fungal diversity.

Application of synthetic herbicides is currently the most widely used and cost-effective methods to assist with revegetation programs. However, the effects of short-term application of herbicides such as Roundup®, acetic acid, BioWeed™ and Slasher® as compared with mulch, on soil microbial biomass and microbial diversity remain unknown. This study examined the effects of short-term herbicide application on soil microbial biomass, C:N ratio, and fungal and bacterial communities at months 2 and 8 following initiation of treatment application. No effects of treatments on soil pH, C:N and microbial biomass were found. No segregation among treatments in the community structure of bacteria and fungi was observed. However, the fungal phylum Basiodiomycota had one unidentified class, which was only found in the mulch treatment, suggesting the C quality in the mulch treatment may differ compared with the other treatments. The dry and hot conditions experienced throughout the study period may have resulted in fast degradation of the herbicides and may have minimised the impacts of the herbicides on microbial diversity and community structure. Given that the research was undertaken at a single site and over only a short time frame, the results should be extrapolated with caution. Herbicides may have greater impact with long-term use. Future research will need to assess the revegetation success of each treatment and determine if the observed change in Basidiomycota profile and C quality identified in this study becomes significant over the long-term. We hypothesise that mulching may be a preferred treatment to facilitate weed control in riparian zone revegetation.