Mgl2 cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice.

Fungal spores are abundant in the environment and a major cause of asthma. Originally characterised as a type 2 inflammatory disease, allergic airway inflammation that underpins asthma can also involve type 17 inflammation, which can exacerbate disease causing failure of treatments tailored to inhibit type 2 factors. However, the mechanisms that determine the host response to fungi, which can trigger both type 2 and type 17 inflammation in allergic airway disease, remain unclear.

Predictive Methods and Probabilistic Mapping of Subcortical Brain Components in Fossil Carnivora.

Paleoneurology reconstructs the evolutionary history of nervous systems through direct observations from the fossil record and comparative data from extant species. Although this approach can provide direct evidence of phylogenetic links among species, it is constrained by the availability and quality of data that can be gleaned from the fossil record. Here, we sought to translate brain component relationships in a sample of extant Carnivora to make inferences about brain structure in fossil species.

Maintenance oral steroids are not required in severe asthma.

https://bit.ly/4cgrJEL.

Targeting human plasma cells using regulated BCMA CAR T cells eliminates circulating antibodies in humanized mice.

Pathogenic long-lived plasma cells (LLPCs) secrete autoreactive antibodies, exacerbating autoimmune diseases and complicating solid organ transplantation. Targeted elimination of the autoreactive B cell pool represents a promising therapeutic strategy, yet current treatment modalities fall short in depleting mature PCs. Here, we demonstrate that chimeric antigen receptor (CAR) T cells, targeting B cell maturation antigen (BCMA) utilizing a split-receptor design, offer a controlled and effective therapeutic strategy against LLPCs.

A unified-field theory of genome organization and gene regulation.

Our aim is to predict how often genic and non-genic promoters fire within a cell. We first review a parsimonious pan-genomic model for genome organization and gene regulation, where transcription rate is determined by proximity in 3D space of promoters to clusters containing appropriate factors and RNA polymerases. This model reconciles conflicting results indicating that regulatory mammalian networks are both simple (as over-expressing just 4 transcription factors switches cell state) and complex (as genome-wide association studies show phenotypes like cell type are determined by thousands of loci rarely encoding such factors).

Aspergillus-mediated allergic airway inflammation is triggered by dendritic cell recognition of a defined spore morphotype.

Background: Exposure to fungi, especially Aspergillus fumigatus, can elicit potent allergic inflammation that triggers and worsens asthmatic disease. Dendritic cells (DCs) initiate allergic inflammatory responses to allergic stimuli. However, it is unclear if Af spores during isotropic growth (early spore swelling) can activate DCs to initiate allergic responses or if germination is required.

Attractiveness, longevity, and release rates of multilure wafers for trapping males of the oriental fruit fly and melon fly (Diptera: Tephritidae).

Invasive fruit flies (Diptera: Tephritidae) pose a serious threat to the production and export of many commercially important fruits and vegetables. Detection of the agricultural pests Bactrocera dorsalis (Hendel) and Zeugodacus cucurbitae (Coquillett) relies heavily on traps baited with male-specific attractants. For B.

Climate impacts of critical mineral supply chain bottlenecks for electric vehicle deployment.

New tailpipe emissions standards aim to increase electric vehicle (EV) sales in the United States. Here, we analyze the associated critical mineral supply chain constraints and enumerate the climate consequences of these constraints. Our work yields five findings.

Human plasma cells engineered to secrete bispecifics drive effective in vivo leukemia killing.

Bispecific antibodies are an important tool for the management and treatment of acute leukemias. As a next step toward clinical translation of engineered plasma cells, we describe approaches for secretion of bispecific antibodies by human plasma cells. We show that human plasma cells expressing either fragment crystallizable domain-deficient anti-CD19 × anti-CD3 (blinatumomab) or anti-CD33 × anti-CD3 bispecific antibodies mediate T cell activation and direct T cell killing of B acute lymphoblastic leukemia or acute myeloid leukemia cell lines in vitro.

Stable diffusion gradients in microfluidic conduits bounded by fluid walls.

Assays mimicking in vitro the concentration gradients triggering biological responses like those involved in fighting infections and blood clotting are essential for biomedical research. Microfluidic assays prove especially attractive as they allow precise control of gradient shape allied to a reduction in scale. Conventional microfluidic devices are fabricated using solid plastics that prevent direct access to responding cells.

A fluid-walled microfluidic platform for human neuron microcircuits and directed axotomy.

In our brains, different neurons make appropriate connections; however, there remain few models of such circuits. We use an open microfluidic approach to build and study neuronal circuits in ways that fit easily into existing bio-medical workflows. Dumbbell-shaped circuits are built in minutes in standard Petri dishes; the aqueous phase is confined by fluid walls - interfaces between cell-growth medium and an immiscible fluorocarbon, FC40.

The Hydraulic Evolution of Groundwater-Fed Pit Lakes After Mine Closure.

Open pit mining frequently requires regional water tables to be lowered to access ore deposits. When mines close, dewatering ceases allowing the water table to recover. In arid and semi-arid mining regions, the developing pit lakes are predominantly fed by groundwater during this recovery phase and pit lakes develop first into "terminal sinks" for the surrounding groundwater system.

GNTI-122: an autologous antigen-specific engineered Treg cell therapy for type 1 diabetes.

Tregs have the potential to establish long-term immune tolerance in patients recently diagnosed with type 1 diabetes (T1D) by preserving β cell function. Adoptive transfer of autologous thymic Tregs, although safe, exhibited limited efficacy in previous T1D clinical trials, likely reflecting a lack of tissue specificity, limited IL-2 signaling support, and in vivo plasticity of Tregs. Here, we report a cell engineering strategy using bulk CD4+ T cells to generate a Treg cell therapy (GNTI-122) that stably expresses FOXP3, targets the pancreas and draining lymph nodes, and incorporates a chemically inducible signaling complex (CISC).

An Ecological and Neural Argument for Developing Pursuit-Based Cognitive Enrichment for Sea Lions in Human Care.

While general enrichment strategies for captive animals attempt to elicit variable and species-typical behaviors, approaches to cognitive enrichment have been disappointingly one-size-fits-all. In this commentary, we address the potential benefit of tailoring cognitive enrichment to the "cognitive niche" of the species, with a particular focus on a reasonably well-studied marine carnivore, the sea lion. Sea lions likely share some cognitive evolutionary pressures with primates, including complex social behavior.

Bridging condensins mediate compaction of mitotic chromosomes.

Eukaryotic chromosomes compact during mitosis into elongated cylinders-and not the spherical globules expected of self-attracting long flexible polymers. This process is mainly driven by condensin-like proteins. Here, we present Brownian-dynamic simulations involving two types of such proteins with different activities.

Corrigendum: Dynamics of host immune response development during infection.

[This corrects the article DOI: 10.3389/fimmu.2022.

Comparative phenotype of circulating versus tissue immune cells in human lung and blood compartments during health and disease.

The lung is a dynamic mucosal surface constantly exposed to a variety of immunological challenges including harmless environmental antigens, pollutants, and potentially invasive microorganisms. Dysregulation of the immune system at this crucial site is associated with a range of chronic inflammatory conditions including asthma and Chronic Pulmonary Obstructive Disease (COPD). However, due to its relative inaccessibility, our fundamental understanding of the human lung immune compartment is limited.

Dual-locus, dual-HDR editing permits efficient generation of antigen-specific regulatory T cells with robust suppressive activity.

Adoptive regulatory T (Treg) cell therapy is predicted to modulate immune tolerance in autoimmune diseases, including type 1 diabetes (T1D). However, the requirement for antigen (ag) specificity to optimally orchestrate tissue-specific, Treg cell-mediated tolerance limits effective clinical application. To address this challenge, we present a single-step, combinatorial gene editing strategy utilizing dual-locus, dual-homology-directed repair (HDR) to generate and specifically expand ag-specific engineered Treg (EngTreg) cells derived from donor CD4+ T cells.

A platform for modular assembly and feeding of micro-organoids on standard Petri dishes.

Organoids grow in vitro to reproduce structures and functions of corresponding organs in vivo. As diffusion delivers nutrients over only ∼200 µm, refreshing flows through organoids are required to avoid necrosis at their cores; achieving this is a central challenge in the field. Our general aim is to develop a platform for culturing micro-organoids fed by appropriate flows that is accessible to bioscientists.