Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy.

Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based spatial analysis. In acute myeloid leukemia (AML) DLI responders, we identified clonally expanded CD8 cytotoxic T lymphocytes with in vitro specificity for patient-matched AML.

Representational geometry explains puzzling error distributions in behavioral tasks.

Measuring and interpreting errors in behavioral tasks is critical for understanding cognition. Conventional wisdom assumes that encoding/decoding errors for continuous variables in behavioral tasks should naturally have Gaussian distributions, so that deviations from normality in the empirical data indicate the presence of more complex sources of noise. This line of reasoning has been central for prior research on working memory.

A Novel Hybrid Improved RIME Algorithm for Global Optimization Problems.

The RIME algorithm is a novel physical-based meta-heuristic algorithm with a strong ability to solve global optimization problems and address challenges in engineering applications. It implements exploration and exploitation behaviors by constructing a rime-ice growth process. However, RIME comes with a couple of disadvantages: a limited exploratory capability, slow convergence, and inherent asymmetry between exploration and exploitation.

Neuroeconomically dissociable forms of mental accounting are altered in a mouse model of diabetes.

Those with diabetes mellitus are at high-risk of developing psychiatric disorders, especially mood disorders, yet the link between hyperglycemia and altered motivation has not been thoroughly explored. Here, we characterized value-based decision-making behavior of a streptozocin-induced diabetic mouse model on Restaurant Row, a naturalistic neuroeconomic foraging paradigm capable of behaviorally capturing multiple decision systems known to depend on dissociable neural circuits. Mice made self-paced choices on a daily limited time-budget, accepting or rejecting reward offers based on cost (delays cued by tone pitch) and subjective value (flavors), in a closed-economy system tested across months.

Glioma-induced alterations in excitatory neurons are reversed by mTOR inhibition.

Gliomas are aggressive neoplasms that diffusely infiltrate the brain and cause neurological symptoms, including cognitive deficits and seizures. Increased mTOR signaling has been implicated in glioma-induced neuronal hyperexcitability, but the molecular and functional consequences have not been identified. Here, we show three types of changes in tumor-associated neurons: (1) downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development and upregulation of cytoskeletal transcripts via neuron-specific profiling of ribosome-bound mRNA, (2) marked decreases in dendritic spine density via light and electron microscopy, and (3) progressive functional alterations leading to neuronal hyperexcitability via in vivo calcium imaging.

Iberian ribbed newts.

Matheson et al. introduce the Iberian ribbed newt (Pleurodeles waltl), a species of salamander that lives some of its adult life on land and some in water, requiring remarkable physiological and behavioral plasticity to adapt to these very different environments.

CalciumZero: a toolbox for fluorescence calcium imaging on iPSC derived brain organoids.

Calcium plays an important role in regulating various neuronal activities in human brains. Investigating the dynamics of the calcium level in neurons is essential not just for understanding the pathophysiology of neuropsychiatric disorders but also as a quantitative gauge to evaluate the influence of drugs on neuron activities. Accessing human brain tissue to study neuron activities has historically been challenging due to ethical concerns.

Nutrition and Huntington's Disease- A Review of Current Practice and Theory.

Purpose Of Review: Nutition has long been of importance in the care of Huntington's disease (HD). The purpose of this review is to summarize recent research relevant to HD nutrition, and to describe some emerging theoretical approaches to research in this area.

Recent Findings: Clinical studies have identified swallowing problems and fear of choking as major impediments to maintaining nutritional status with HD.

Random noise promotes slow heterogeneous synaptic dynamics important for robust working memory computation.

Recurrent neural networks (RNNs) based on model neurons that communicate via continuous signals have been widely used to study how cortical neural circuits perform cognitive tasks. Training such networks to perform tasks that require information maintenance over a brief period (i.e.

Coordination and persistence of aggressive visual communication in Siamese fighting fish.

Outside acoustic communication, little is known about how animals coordinate social turn taking and how the brain drives engagement in these social interactions. Using Siamese fighting fish (Betta splendens), we discover dynamic visual features of an opponent and behavioral sequences that drive visually driven turn-taking aggressive behavior. Lesions of the telencephalon show that it is unnecessary for coordinating turn taking but is required for persistent participation in aggressive interactions.

Auditory decision-making deficits after permanent noise-induced hearing loss.

Loud noise exposure is one of the leading causes of permanent hearing loss. Individuals with noise-induced hearing loss (NIHL) suffer from speech comprehension deficits and experience impairments to cognitive functions such as attention and decision-making. Here, we investigate the specific underlying cognitive processes during auditory perceptual decision-making that are impacted by NIHL.

The shape of cleaved tethered membranes.

A remarkable property of flexible self-avoiding elastic surfaces (membranes) is that they remain flat at all temperatures, even in the absence of a bending rigidity or in the presence of active fluctuations. Here, we report numerical results of these surfaces wherein we alter their topology by systematically cleaving internal bonds. While it is known that a random removal of membrane bonds does not disrupt the overall extended shape of the membrane, we find that cleaving an elastic surface with longitudinal parallel cuts leads to its systematic collapse into a number of complex morphologies that can be controlled by altering the number and length of the inserted cuts.

Codon bias, nucleotide selection, and genome size predict in situ bacterial growth rate and transcription in rewetted soil.

In soils, the first rain after a prolonged dry period represents a major pulse event impacting soil microbial community function, yet we lack a full understanding of the genomic traits associated with the microbial response to rewetting. Genomic traits such as codon usage bias and genome size have been linked to bacterial growth in soils-however, often through measurements in culture. Here, we used metagenome-assembled genomes (MAGs) with O-water stable isotope probing and metatranscriptomics to track genomic traits associated with growth and transcription of soil microorganisms over one week following rewetting of a grassland soil.

Structure of an LGR dimer - an evolutionary predecessor of glycoprotein hormone receptors.

The glycoprotein hormones of humans, produced in the pituitary and acting through receptors in the gonads to support reproduction and in the thyroid gland for metabolism, have co-evolved from invertebrate counterparts. These hormones are heterodimeric cystine-knot proteins; and their receptors bind the cognate hormone at an extracellular domain and transmit the signal of this binding through a transmembrane domain that interacts with a heterotrimeric G protein. Structures determined for the human receptors as isolated for cryogenic electron microscopy (cryo-EM) are all monomeric despite compelling evidence for their functioning as dimers.

The key role of cheaters in the persistence of cooperation.

Evolution of cooperation is a major, extensively studied problem in evolutionary biology. Cooperation is beneficial for a population as a whole but costly for the bearers of social traits such that cheaters enjoy a selective advantage over cooperators. Here we focus on coevolution of cooperators and cheaters in a multi-level selection framework, by modeling competition among groups composed of cooperators and cheaters.

Pathogenetic mechanisms of muscle-specific ribosomes in dilated cardiomyopathy.

The heart employs a specialized ribosome in its muscle cells to translate genetic information into proteins, a fundamental adaptation with an elusive physiological role. Its significance is underscored by the discovery of neonatal patients suffering from often fatal heart failure caused by severe dilated cardiomyopathy when both copies of the gene are mutated. RPL3L is a muscle-specific paralog of the ubiquitous ribosomal protein L3 (RPL3), which makes the closest contact of any protein to the ribosome's RNA-based catalytic center.

Donor Strand Complementation and Calcium Ion Coordination Drive the Chaperone-free Polymerization of Archaeal Cannulae.

Cannulae are tubular protein filaments that accumulate on the extracellular surface of the hyperthermophilic archaeon during cell division. Cannulae have been postulated to act as a primitive extracellular matrix through which cells could communicate or exchange material, although their native biological function remains obscure. Here, we report cryoEM structural analyses of cannulae and of protein assemblies derived from recombinant cannula-like proteins.

Magnitude of Potential Biases in COVID-19 Vaccine Effectiveness Studies due to Differential Healthcare seeking following Home Testing: Implications for Test Negative Design Studies.

The test-negative design (TND) is widely used to estimate COVID-19 vaccine effectiveness (VE). Biased estimates of VE may result from effects of at-home SARS-CoV-2 rapid diagnostic test (RDT) results on decisions to seek healthcare. To investigate magnitude of potential bias, we constructed decision trees with input probabilities obtained from longitudinal surveys of U.

Evaluation of machine learning models for predicting xerostomia in adults with head and neck cancer during proton and heavy ion radiotherapy.

Background And Purpose: Few studies have examined the factors associated with xerostomia during proton and carbon ion radiotherapy for head and neck cancer (HNC), which are reported to have fewer toxic effects compared to traditional photon-based radiotherapy. This study aims to evaluate the performance of machine learning approaches in predicting grade 2 + xerostomia in adults with HNC receiving proton and carbon ion radiotherapy.

Materials And Methods: A retrospective study involving 1,769 adults with HNC who completed proton or carbon ion radiotherapy was conducted.

RBBP6 anchors pre-mRNA 3' end processing to nuclear speckles for efficient gene expression.

Pre-mRNA 3' processing is an integral step in mRNA biogenesis. However, where this process occurs in the nucleus remains unknown. Here, we demonstrate that nuclear speckles (NSs), membraneless organelles enriched with splicing factors, are major sites for pre-mRNA 3' processing in human cells.

Fighting Fire with Fire: Impact of Sugary Diets on Metabolically Deranged Mice.

There is controversy about the health risks of sugary diets. A recent study reported that chronic consumption of 11% sugar solutions improved glycemic control in lean mice. Based on this finding, we hypothesized that chronic consumption of the same 11% sugar solutions would also improve glycemic control in metabolically deranged mice.

Expanding perspectives and understanding relational potential: Are mutually beneficial human-animal relationships compatible with current animal agricultural practices?

Animal agriculture employs approximately one-eighth of world's human population and results in the slaughter of over 160 billion animals annually, representing perhaps the most extensive intertwining of human and animal lives on the planet. In principle, close, intersubjective relationships (involving shared attention and mental states) between humans and the animals in agriculture are possible, though these are infrequently studied and are unlikely to be achieved in farming, given systemic constraints (e.g.

AI as an intervention: improving clinical outcomes relies on a causal approach to AI development and validation.

The primary practice of healthcare artificial intelligence (AI) starts with model development, often using state-of-the-art AI, retrospectively evaluated using metrics lifted from the AI literature like AUROC and DICE score. However, good performance on these metrics may not translate to improved clinical outcomes. Instead, we argue for a better development pipeline constructed by working backward from the end goal of positively impacting clinically relevant outcomes using AI, leading to considerations of causality in model development and validation, and subsequently a better development pipeline.

Low-Dose Oral Ginger Improves Daily Symptom Scores in Asthma.

A significant number of individuals with asthma have poorly controlled daily symptoms and utilize dietary supplements such as ginger in a quest for improved symptom control; however, its effectiveness at improving the control of symptoms is unproven. We questioned whether low-dose oral ginger would improve subjective and objective measurements of asthma control in mild-to-moderate asthmatics. We performed a randomized, placebo-controlled, double-blinded study of a low dose (1 g twice daily) of a dietary supplement of ginger in 32 mild-to-moderate uncontrolled asthmatics over a 2-month trial period while maintaining daily conventional asthma therapies.