Bridging Wright-Fisher and Moran models.

The Wright-Fisher model and the Moran model are both widely used in population genetics. They describe the time evolution of the frequency of an allele in a well-mixed population with fixed size. We propose a simple and tractable model which bridges the Wright-Fisher and the Moran descriptions.

Collagen signaling and matrix stiffness regulate multipotency in glandular epithelial stem cells in mice.

Glandular epithelia, including mammary gland (MG) and prostate, are composed of luminal and basal cells. During embryonic development, glandular epithelia arise from multipotent stem cells (SCs) that are replaced after birth by unipotent basal and unipotent luminal SCs. Different conditions, such as basal cell transplantation, luminal cell ablation, and oncogene expression can reinduce adult basal SC (BaSCs) multipotency in different glandular epithelia.

A modular toolbox for the optogenetic deactivation of transcription.

Light-controlled transcriptional activation is a commonly used optogenetic strategy that allows researchers to regulate gene expression with high spatiotemporal precision. The vast majority of existing tools are, however, limited to light-triggered induction of gene expression. Here, we inverted this mode of action and created optogenetic systems capable of efficiently terminating transcriptional activation in response to blue light.

Spotlight on cytochrome b561 and DOMON domain proteins.

Biotic and abiotic stresses constrain plant growth worldwide. Therefore, understanding the molecular mechanisms contributing to plant resilience is key to achieving food security. In recent years, proteins containing dopamine β-monooxygenase N-terminal (DOMON) and/or cytochrome b561 domains have been identified as important regulators of plant responses to multiple stress factors.

DiffPaSS-high-performance differentiable pairing of protein sequences using soft scores.

Motivation: Identifying interacting partners from two sets of protein sequences has important applications in computational biology. Interacting partners share similarities across species due to their common evolutionary history, and feature correlations in amino acid usage due to the need to maintain complementary interaction interfaces. Thus, the problem of finding interacting pairs can be formulated as searching for a pairing of sequences that maximizes a sequence similarity or a coevolution score.

Oscillatory traveling waves provide evidence for predictive coding abnormalities in schizophrenia.

Background: The computational mechanisms underlying psychiatric disorders are hotly debated. One hypothesis, grounded in the Bayesian predictive coding framework, proposes that schizophrenia patients have abnormalities in encoding prior beliefs about the environment, resulting in abnormal sensory inference, which can explain core aspects of the psychopathology, such as some of its symptoms.

Methods: Here, we tested this hypothesis by identifying oscillatory traveling waves as neural signatures of predictive coding.

Identification of methylation-sensitive human transcription factors using meSMiLE-seq.

Transcription factors (TFs) are key players in eukaryotic gene regulation, but the DNA binding specificity of many TFs remains unknown. Here, we assayed 284 mostly poorly characterized, putative human TFs using selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq), revealing 72 new DNA binding motifs. To investigate whether some of the 158 TFs for which we did not find motifs preferably bind epigenetically modified DNA (i.

Native learning ability and not age determines the effects of brain stimulation.

Healthy aging often entails a decline in cognitive and motor functions, affecting independence and quality of life in older adults. Brain stimulation shows potential to enhance these functions, but studies show variable effects. Previous studies have tried to identify responders and non-responders through correlations between behavioral change and baseline parameters, but results lack generalization to independent cohorts.

Symbiodiniaceae algal symbionts of Pocillopora damicornis larvae provide more carbon to their coral host under elevated levels of acidification and temperature.

Climate change destabilizes the symbiosis between corals and Symbiodiniaceae. The effects of ocean acidification and warming on critical aspects of coral survical such as symbiotic interactions (i.e.

A multicellular developmental program in a close animal relative.

All animals develop from a single-celled zygote into a complex multicellular organism through a series of precisely orchestrated processes. Despite the remarkable conservation of early embryogenesis across animals, the evolutionary origins of how and when this process first emerged remain elusive. Here, by combining time-resolved imaging and transcriptomic profiling, we show that single cells of the ichthyosporean Chromosphaera perkinsii-a close relative that diverged from animals about 1 billion years ago-undergo symmetry breaking and develop through cleavage divisions to produce a prolonged multicellular colony with distinct co-existing cell types.

The Emerging Role of Brain Mitochondria in Fear and Anxiety.

The functional complexity of brain circuits underlies the broad spectrum of behaviors, cognitive functions, and their associated disorders. Mitochondria, traditionally known for their role in cellular energy metabolism, are increasingly recognized as central to brain function and behavior. This review examines how mitochondria are pivotal in linking cellular energy processes with the functioning of neural circuits that govern fear and anxiety.

Community-based reconstruction and simulation of a full-scale model of the rat hippocampus CA1 region.

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system.

Intestinal commensal bacteria promote Bactrocera dorsalis larval development through the vitamin B6 synthesis pathway.

Background: The gut microbiota can facilitate host growth under nutrient-constrained conditions. However, whether this effect is limited to certain bacterial species remains largely unclear, and the relevant underlying mechanisms remain to be thoroughly investigated.

Results: We found that the microbiota was required for Bactrocera dorsalis larval growth under poor dietary conditions.

Cation reactivity inhibits perovskite degradation in efficient and stable solar modules.

Perovskite solar modules (PSMs) show outstanding power conversion efficiencies (PCEs), but long-term operational stability remains problematic. We show that incorporating -dimethylmethyleneiminium chloride into the perovskite precursor solution formed dimethylammonium cation and that previously unobserved methyl tetrahydrotriazinium ([MTTZ]) cation effectively improved perovskite film. The in situ formation of [MTTZ] cation increased the formation energy of iodine vacancies and enhanced the migration energy barrier of iodide and cesium ions, which suppressed nonradiative recombination, thermal decomposition, and phase segregation processes.

Statistical inference with a manifold-constrained RNA velocity model uncovers cell cycle speed modulations.

Across biological systems, cells undergo coordinated changes in gene expression, resulting in transcriptome dynamics that unfold within a low-dimensional manifold. While low-dimensional dynamics can be extracted using RNA velocity, these algorithms can be fragile and rely on heuristics lacking statistical control. Moreover, the estimated vector field is not dynamically consistent with the traversed gene expression manifold.

Reciprocal inhibition of NOTCH and SOX2 shapes tumor cell plasticity and therapeutic escape in triple-negative breast cancer.

Cancer cell plasticity contributes significantly to the failure of chemo- and targeted therapies in triple-negative breast cancer (TNBC). Molecular mechanisms of therapy-induced tumor cell plasticity and associated resistance are largely unknown. Using a genome-wide CRISPR-Cas9 screen, we investigated escape mechanisms of NOTCH-driven TNBC treated with a gamma-secretase inhibitor (GSI) and identified SOX2 as a target of resistance to Notch inhibition.

Transcriptomic and proteomic changes associated with cobalamin-dependent propionate production by the rumen bacterium .

Unlabelled: is an abundant rumen bacterium that produces propionate in a cobalamin (vitamin B)-dependent manner via the succinate pathway. However, the extent to which this occurs across ruminal and closely related bacteria, and the effect of cobalamin supplementation on the expression of propionate pathway genes and enzymes has yet to be investigated. To assess this, we screened 14 strains and found that almost all strains produced propionate when supplemented with cobalamin.

Dissecting the Membrane Association Mechanism of Aerolysin Pores at Femtomolar Concentrations Using Water as a Probe.

Aerolysin is a bacterial toxin that forms transmembrane pores at the host plasma membrane and has a narrow internal diameter and great stability. These assets make it a highly promising nanopore for detecting biopolymers such as nucleic acids and peptides. Although much is known about aerolysin from a microbiological and structural perspective, its membrane association and pore-formation mechanism are not yet fully understood.

Gentle Rhodamines for Live-Cell Fluorescence Microscopy.

Rhodamines have been continuously optimized in brightness, biocompatibility, and color to fulfill the demands of modern bioimaging. However, the problem of phototoxicity caused by the excited fluorophore under long-term illumination has been largely neglected, hampering their use in time-lapse imaging. Here we introduce cyclooctatetraene (COT) conjugated rhodamines that span the visible spectrum and exhibit significantly reduced phototoxicity.

Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infection.

Pseudomonas aeruginosa frequently causes antibiotic-recalcitrant pneumonia, but the mechanisms driving its adaptation during human infections remain unclear. To reveal the selective pressures and adaptation strategies at the mucosal surface, here we investigated P. aeruginosa growth and antibiotic tolerance in tissue-engineered airways by transposon insertion sequencing (Tn-seq).