Leukemia escapes immunity by imposing a Type-1 regulatory program on neoantigen-specific CD4+ T cells.

The significance of endogenous immune surveillance in acute lymphoblastic leukemia (ALL) remains controversial. Using clinical B-ALL samples and a novel mouse model, we show that neoantigen-specific CD4+ T cells are induced to adopt type-1 regulatory (Tr1) function in the leukemia microenvironment. Tr1s then inhibit cytotoxic CD8+ T cells, preventing effective leukemia clearance.

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.

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.

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.

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.

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 (V) and short-circuit current (J) conditions. A mismatch between the internal quasi-Fermi level splitting (QFLS) and the external V 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-V mismatch, and boosting the V.

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.

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

Recent studies have demonstrated that regulatory T cells (T) develop in the thymus via two pathways involving distinct T progenitors (TP): CD25FOXP3 (CD25 TP) and CD25FOXP3 (FOXP3 TP) T progenitors. To examine this process in more detail, we carried out single-cell RNA sequencing (scRNA-Seq) and TCR-Seq on sorted murine CD4CD8 double-positive (DP) thymocytes, CD4 single-positive (CD4SP) thymocytes, CD25FOXP3CD73 TP, CD25FOXP3CD73 TP, newly generated mature CD25FOXP3CD73 T, and FOXP3CD73 recirculating/long-term resident T (RT-T). Sorted populations were individually hashtagged and then combined into one scRNA-Seq/TCR-Seq library before sequencing and subsequent analysis.

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, STAT5 O-GlcNAcylation and activation.

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.

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.

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.

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 Pax5xEbf1, Pax5xIkzf1, and Ebf1xIkzf1 mice for B-ALL, or Tcf7xIkzf1 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%).

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.

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.

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.

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.

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.

B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage.

B-1a cells are long-lived, self-renewing innate-like B cells that predominantly inhabit the peritoneal and pleural cavities. In contrast to conventional B-2 cells, B-1a cells have a receptor repertoire that is biased towards bacterial and self-antigens, promoting a rapid response to infection and clearing of apoptotic cells. Although B-1a cells are known to primarily originate from fetal tissues, the mechanisms by which they arise has been a topic of debate for many years.

Regulatory T Cell Development in the Thymus.

Development of a comprehensive regulatory T (T) cell compartment in the thymus is required to maintain immune homeostasis and prevent autoimmunity. In this study, we review cellular and molecular determinants of T cell development in the thymus. We focus on the evidence for a self-antigen-focused T cell repertoire as well as the APCs responsible for presenting self-antigens to developing thymocytes.

Microsecond Carrier Lifetimes, Controlled p-Doping, and Enhanced Air Stability in Low-Bandgap Metal Halide Perovskites.

Mixed lead-tin halide perovskites have sufficiently low bandgaps (∼1.2 eV) to be promising absorbers for perovskite-perovskite tandem solar cells. Previous reports on lead-tin perovskites have typically shown poor optoelectronic properties compared to neat lead counterparts: short photoluminescence lifetimes (<100 ns) and low photoluminescence quantum efficiencies (<1%).