The importance of type I interferon in orchestrating the cytotoxic T-cell response to cancer.

Both type I interferon (IFN-I) and CD4 T-cell help are required to generate effective CD8 T-cell responses to cancer. We here outline based on existing literature how IFN-I signaling and CD4 T-cell help are connected. Both impact on the functional state of dendritic cells (DCs), particularly conventional (c)DC1.

Immune suppression by human thymus-derived effector Tregs relies on glucose/lactate-fueled fatty acid synthesis.

Regulatory T cells (Tregs) suppress pro-inflammatory conventional T cell (Tconv) responses. As lipids impact cell signaling and function, we compare the lipid composition of CD4 thymus-derived (t)Tregs and Tconvs. Lipidomics reveal constitutive enrichment of neutral lipids in Tconvs and phospholipids in tTregs.

Word Type and Frequency Effects on Lexical Decisions Are Process-dependent and Start Early.

When encountering letter strings, we rapidly determine whether they are words. The speed of such lexical decisions (LDs) is affected by word frequency. Apart from influencing late, decision-related, processing stages, frequency has also been shown to affect very early stages, and even the processing of nonwords.

Quantitative imaging reveals the role of MpARF proteasomal degradation during gemma germination.

The auxin signaling molecule controls a variety of growth and developmental processes in land plants. Auxin regulates gene expression through a nuclear auxin signaling pathway (NAP) consisting of the ubiquitin ligase auxin receptor TIR1/AFB, its Aux/IAA degradation substrate, and DNA-binding ARF transcription factors. Although extensive qualitative understanding of the pathway and its interactions has been obtained, mostly by studying the flowering plant Arabidopsis thaliana, it remains unknown how these translate to quantitative system behavior in vivo, a problem that is confounded by the large NAP gene families in most species.

A multifaceted kinase axis regulates plant organ abscission through conserved signaling mechanisms.

Plants have evolved mechanisms to abscise organs as they develop or when exposed to unfavorable conditions. Uncontrolled abscission of petals, fruits, or leaves can impair agricultural productivity. Despite its importance for abscission progression, our understanding of the IDA signaling pathway and its regulation remains incomplete.

Sodium salicylate improves detection of amplitude-modulated sound in mice.

Salicylate is commonly used to induce tinnitus in animals, but its underlying mechanism of action is still debated. We therefore tested its effects on the firing properties of neurons in the mouse inferior colliculus (IC). Salicylate induced a large decrease in the spontaneous activity and an increase of ∼20 dB SPL in the minimum threshold of single units.

Developmental fine-tuning of medial superior olive neurons mitigates their predisposition to contralateral sound sources.

Having two ears enables us to localize sound sources by exploiting interaural time differences (ITDs) in sound arrival. Principal neurons of the medial superior olive (MSO) are sensitive to ITD, and each MSO neuron responds optimally to a best ITD (bITD). In many cells, especially those tuned to low sound frequencies, these bITDs correspond to ITDs for which the contralateral ear leads, and are often larger than the ecologically relevant range, defined by the ratio of the interaural distance and the speed of sound.

Protein degradation in auxin response.

The signaling molecule auxin sits at the nexus of plant biology where it coordinates essentially all growth and developmental processes. Auxin molecules are transported throughout plant tissues and are capable of evoking highly specific physiological responses by inducing various molecular pathways. In many of these pathways, proteolysis plays a crucial role for correct physiological responses.

CD4 T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors.

CD4 T cells can "help" or "license" conventional type 1 dendritic cells (cDC1s) to induce CD8 cytotoxic T lymphocyte (CTL) anticancer responses, as proven in mouse models. We recently identified cDC1s with a transcriptomic imprint of CD4 T-cell help, specifically in T-cell-infiltrated human cancers, and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy. Here, we delineate the mechanism of cDC1 licensing by CD4 T cells in humans.

PD-1 or CTLA-4 blockade promotes CD86-driven Treg responses upon radiotherapy of lymphocyte-depleted cancer in mice.

Radiotherapy (RT) is considered immunogenic, but clinical data demonstrating RT-induced T cell priming are scarce. Here, we show in a mouse tumor model representative of human lymphocyte-depleted cancer that RT enhanced spontaneous priming of thymus-derived (FOXP3+Helios+) Tregs by the tumor. These Tregs acquired an effector phenotype, populated the tumor, and impeded tumor control by a simultaneous, RT-induced CD8+ cytotoxic T cell (CTL) response.

Tregs from human blood differentiate into nonlymphoid tissue-resident effector cells upon TNFR2 costimulation.

Tregs can facilitate transplant tolerance and attenuate autoimmune and inflammatory diseases. Therefore, it is clinically relevant to stimulate Treg expansion and function in vivo and to create therapeutic Treg products in vitro. We report that TNF receptor 2 (TNFR2) is a unique costimulus for naive, thymus-derived Tregs (tTregs) from human blood that promotes their differentiation into nonlymphoid tissue-resident (NLT-resident) effector Tregs, without Th-like polarization.

Immune checkpoints targeting dendritic cells for antibody-based modulation in cancer.

Dendritic cells (DC) are professional antigen-presenting cells which link innate to adaptive immunity. DC play a central role in regulating antitumor T-cell responses in both tumor-draining lymph nodes (TDLN) and the tumor microenvironment (TME). They modulate effector T-cell responses via immune checkpoint proteins (ICPs) that can be either stimulatory or inhibitory.

Headplate Installation and Craniotomy for Awake In Vivo Electrophysiological Recordings or Two-Photon Imaging of the Mouse Inferior Colliculus.

The inferior colliculus (IC) is an important processing center in the auditory system, which also receives non-auditory sensory input. The IC consists of several subnuclei whose functional role in (non-) auditory processing and plastic response properties are best approached by studying awake animals, preferably in a longitudinal fashion. The increasing use of mice in auditory research, the availability of genetic models, and the superficial location of the IC in the mouse have made it an attractive species for studying IC function.

A whole-task brain model of associative recognition that accounts for human behavior and neuroimaging data.

Brain models typically focus either on low-level biological detail or on qualitative behavioral effects. In contrast, we present a biologically-plausible spiking-neuron model of associative learning and recognition that accounts for both human behavior and low-level brain activity across the whole task. Based on cognitive theories and insights from machine-learning analyses of M/EEG data, the model proceeds through five processing stages: stimulus encoding, familiarity judgement, associative retrieval, decision making, and motor response.

Neuronal responses in mouse inferior colliculus correlate with behavioral detection of amplitude-modulated sound.

Amplitude modulation (AM) is a common feature of natural sounds, including speech and animal vocalizations. Here, we used operant conditioning and in vivo electrophysiology to determine the AM detection threshold of mice as well as its underlying neuronal encoding. Mice were trained in a Go-NoGo task to detect the transition to AM within a noise stimulus designed to prevent the use of spectral side-bands or a change in intensity as alternative cues.

Corn Oil-Water Separation: Interfacial Behavior of Extended Surfactant and Glutelin.

The purification and collection of various products from oil/water mixtures are routine procedures. However, the presence of emulsifiers that can displace other surface active components in the mixtures can significantly influence the efficiency of such procedures. Previously, we investigated interfacial mechanisms of zein protein-induced emulsification and the opposing surfactant-induced demulsification related to corn oil refinement.

Somatic Integration of Incoherent Dendritic Inputs in the Gerbil Medial Superior Olive.

The medial superior olive (MSO) is a binaural nucleus that is specialized in detecting the relative arrival times of sounds at both ears. Excitatory inputs to its neurons originating from either ear are segregated to different dendrites. To study the integration of synaptic inputs both within and between dendrites, we made juxtacellular and whole-cell recordings from the MSO in anesthetized female gerbils, while presenting a "double zwuis" stimulus, in which each ear received its own set of tones, which were chosen in a way that all second-order distortion products (DP2s) could be uniquely identified.

Multiomics and spatial mapping characterizes human CD8 T cell states in cancer.

Clinically relevant immunological biomarkers that discriminate between diverse hypofunctional states of tumor-associated CD8 T cells remain disputed. Using multiomics analysis of CD8 T cell features across multiple patient cohorts and tumor types, we identified tumor niche-dependent exhausted and other types of hypofunctional CD8 T cell states. CD8 T cells in "supportive" niches, like melanoma or lung cancer, exhibited features of tumor reactivity-driven exhaustion (CD8 T).

Inter-individual single-trial classification of MEG data using M-CCA.

Neuroscientific studies often involve some form of group analysis over multiple participants. This requires alignment of recordings across participants. A naive solution is to assume that participants' recordings can be aligned anatomically in sensor space.

Decoding study-independent mind-wandering from EEG using convolutional neural networks.

. Mind-wandering is a mental phenomenon where the internal thought process disengages from the external environment periodically. In the current study, we trained EEG classifiers using convolutional neural networks (CNNs) to track mind-wandering across studies.

CD4 helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment.

Despite their low abundance in the tumor microenvironment (TME), classical type 1 dendritic cells (cDC1) play a pivotal role in anti-cancer immunity, and their abundance positively correlates with patient survival. However, their interaction with CD4 T-cells to potentially enable the cytotoxic T lymphocyte (CTL) response has not been elucidated. Here we show that contact with activated CD4 T-cells enables human ex vivo cDC1, but no other DC types, to induce a CTL response to cell-associated tumor antigens.

Multitasking While Driving: Central Bottleneck or Problem State Interference?

Objective: The objective of this work was to investigate if visuospatial attention and working memory load interact at a central control resource or at a task-specific, information processing resource during driving.

Background: In previous multitasking driving experiments, interactions between different cognitive concepts (e.g.

Proteomics reveals unique identities of human TGF-β-induced and thymus-derived CD4 regulatory T cells.

The CD4 regulatory T (Treg) cell lineage, defined by FOXP3 expression, comprises thymus-derived (t)Treg cells and peripherally induced (p)Treg cells. As a model for Treg cells, studies employ TGF-β-induced (i)Treg cells generated from CD4 conventional T (Tconv) cells in vitro. Here, we describe how human iTreg cells relate to human blood-derived tTreg and Tconv cells according to proteomic analysis.