Variation in season length and development time is sufficient to drive the emergence and coexistence of social and solitary behavioural strategies.

Season length and its associated variables can influence the expression of social behaviours, including the occurrence of eusociality in insects. Eusociality can vary widely across environmental gradients, both within and between different species. Numerous theoretical models have been developed to examine the life history traits that underlie the emergence and maintenance of eusociality, yet the impact of seasonality on this process is largely uncharacterized.

Nuclear instance segmentation and tracking for preimplantation mouse embryos.

For investigations into fate specification and morphogenesis in time-lapse images of preimplantation embryos, automated 3D instance segmentation and tracking of nuclei are invaluable. Low signal-to-noise ratio, high voxel anisotropy, high nuclear density, and variable nuclear shapes can limit the performance of segmentation methods, while tracking is complicated by cell divisions, low frame rates, and sample movements. Supervised machine learning approaches can radically improve segmentation accuracy and enable easier tracking, but they often require large amounts of annotated 3D data.

Emergency department utilization among children with Long COVID symptoms: a COVID-19 research consortium study.

Background And Objectives: Long COVID, characterized by persistent symptoms beyond the acute infection phase, remains poorly characterized in children. Our study aim is to determine if children who exhibit any symptoms/conditions associated with Long COVID after acute COVID-19 infection have higher Emergency Department (ED) utilization compared to those who do not exhibit these symptoms.

Methods: Data from the HealthJump ambulatory database from the COVID-19 Research Database Consortium was utilized to identify pediatric COVID-19 cases from March 2020 to May 2023.

Minimal motifs for habituating systems.

Habituation-a phenomenon in which a dynamical system exhibits a diminishing response to repeated stimulations that eventually recovers when the stimulus is withheld-is universally observed in living systems from animals to unicellular organisms. Despite its prevalence, generic mechanisms for this fundamental form of learning remain poorly defined. Drawing inspiration from prior work on systems that respond adaptively to step inputs, we study habituation from a nonlinear dynamics perspective.

Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking.

Aggregates of stem cells can break symmetry and self-organize into embryo-like structures with complex morphologies and gene expression patterns. Mechanisms including reaction-diffusion Turing patterns and cell sorting have been proposed to explain symmetry breaking but distinguishing between these candidate mechanisms of self-organization requires identifying which early asymmetries evolve into subsequent tissue patterns and cell fates. Here we use synthetic 'signal-recording' gene circuits to trace the evolution of signalling patterns in gastruloids, three-dimensional stem cell aggregates that form an anterior-posterior axis and structures resembling the mammalian primitive streak and tailbud.

The tracheal terminal cell as a model for branching morphogenesis.

The terminal cells of the larval tracheal system are perhaps the simplest delivery networks, providing an analogue for mammalian vascular growth and function in a system with many fewer components. These cells are a prime example of single-cell morphogenesis, branching significantly over time to adapt to the needs of the growing tissue they supply. While the genetic mechanisms governing local branching decisions have been studied extensively, an understanding of the emergence of a global network architecture is still lacking.

The exchange dynamics of biomolecular condensates.

A hallmark of biomolecular condensates formed via liquid-liquid phase separation is that they dynamically exchange material with their surroundings, and this process can be crucial to condensate function. Intuitively, the rate of exchange can be limited by the flux from the dilute phase or by the mixing speed in the dense phase. Surprisingly, a recent experiment suggests that exchange can also be limited by the dynamics at the droplet interface, implying the existence of an 'interface resistance'.

General control nonderepressible 2 (GCN2) as a therapeutic target in age-related diseases.

The function of General Control Nonderepressible 2 (GCN2), an evolutionary-conserved component of the integrated stress response (ISR), has been well-documented across organisms from yeast to mammals. Recently GCN2 has also gained attention for its role in health and disease states. In this review, we provide a brief overview of GCN2, including its structure, activation mechanisms and interacting partners, and explore its potential significance as a therapeutic target in various age-related diseases including neurodegeneration, inflammatory disorders and cancer.

Inferring cell differentiation maps from lineage tracing data.

During development, mulitpotent cells differentiate through a hierarchy of increasingly restricted progenitor cell types until they realize specialized cell types. A cell differentiation map describes this hierarchy, and inferring these maps is an active area of research spanning traditional single marker lineage studies to data-driven trajectory inference methods on single-cell RNA-seq data. Recent high-throughput lineage tracing technologies profile lineages and cell types at scale, but current methods to infer cell differentiation maps from these data rely on simple models with restrictive assumptions about the developmental process.

Cardiac NAD depletion in mice promotes hypertrophic cardiomyopathy and arrhythmias prior to impaired bioenergetics.

Nicotinamide adenine dinucleotide (NAD) is an essential co-factor in metabolic reactions and co-substrate for signaling enzymes. Failing human hearts display decreased expression of the major NAD biosynthetic enzyme nicotinamide phosphoribosyltransferase (Nampt) and lower NAD levels, and supplementation with NAD precursors is protective in preclinical models. Here we show that Nampt loss in adult cardiomyocytes caused depletion of NAD along with marked metabolic derangements, hypertrophic remodeling and sudden cardiac deaths, despite unchanged ejection fraction, endurance and mitochondrial respiratory capacity.

Engineered chimeric receptors for dissecting interferon signaling.

Though interferons (IFNs) were once heralded as panaceas to numerous diseases, how cells decode varying IFN stimuli and subsequently produce (in)appropriate signaling remain unclear. Our labs recently engineered novel erythropoietin receptor-IFN chimeric receptors, and we highlight their utility in two cases uncovering differential genetic determinants of type I (IFN-α/β) and type III (IFN-λ) IFN signaling. These and other types of synthetic (cytokine) receptors could be expanded to real-time signaling dynamics and studies.

neuron-specific expression of reprogramming factor orthologs does not alleviate age-related cognitive decline.

Overexpression of the OSK(M) (Oct4, Sox2, Klf4, with or without cMyc) pluripotency factors have shown promise in rejuvenating the function of aged neurons. To test whether this intervention could also ameliorate age-associated cognitive decline, we used a doxycycline inducible system to overexpress the OSK orthologs specifically in aging neurons. We find that OSK does not improve short-term associative memory or extend lifespan and can further disrupt chemotaxis behavior.

Treatment of Plagiocephaly With Orthotic Helmets: Prevalence, Costs, and Inequities in Massachusetts.

Positional plagiocephaly is a craniofacial condition resulting from infant positioning that applies pressure consistently to a part of the skull. This study analyzed the prevalence of, and costs associated with orthotic helmet treatment for positional plagiocephaly and assessed inequities in treatment between medically underserved areas (MUAs) and non-MUAs using health insurance claims data from the Center for Health Information and Analysis (CHIA) in Massachusetts for the years 2016-2021. The mean percentage of patients receiving orthotic helmet therapy was 4.

The built environment is more predictive of cardiometabolic health than other aspects of lifestyle in two rapidly transitioning Indigenous populations.

Background: Many subsistence-level and Indigenous societies around the world are rapidly experiencing urbanization, nutrition transition, and integration into market-economies, resulting in marked increases in cardiometabolic diseases. Determining the most potent and generalized drivers of changing health is essential for identifying vulnerable communities and creating effective policies to combat increased chronic disease risk across socio-environmental contexts. However, comparative tests of how different lifestyle features affect the health of populations undergoing lifestyle transitions remain rare, and require comparable, integrated anthropological and health data collected in diverse contexts.

Integrating computer vision and molecular neurobiology to bridge the gap between behavior and the brain.

The past decade of social insect research has seen rapid development in automated behavioral tracking and molecular profiling of the nervous system, two distinct but complementary lines of inquiry into phenotypic variation across individuals, colonies, populations, and species. These experimental strategies have developed largely in parallel, as automated tracking generates a continuous stream of behavioral data, while, in contrast, 'omics-based profiling provides a single 'snapshot' of the brain. Better integration of these approaches applied to studying variation in social behavior will reveal the underlying genetic and neurobiological mechanisms that shape the evolution and diversification of social life.

Mesenchymal Vangl1 and Vangl2 facilitate airway elongation and widening independently of the planar cell polarity complex.

Adult mammalian lungs exhibit a fractal pattern, as each successive generation of airways is a fraction of the size of the parental branch. Achieving this structure likely requires precise control of airway length and diameter, as the embryonic airways initially lack the fractal scaling observed in the adult. In monolayers and tubes, directional growth can be regulated by the planar cell polarity (PCP) complex.

ERK synchronizes embryonic cleavages in Drosophila.

Extracellular-signal-regulated kinase (ERK) signaling controls development and homeostasis and is genetically deregulated in human diseases, including neurocognitive disorders and cancers. Although the list of ERK functions is vast and steadily growing, the full spectrum of processes controlled by any specific ERK activation event remains unknown. Here, we show how ERK functions can be systematically identified using targeted perturbations and global readouts of ERK activation.

Decomposition of phenotypic heterogeneity in autism reveals distinct and coherent genetic programs.

Unraveling the phenotypic and genetic complexity of autism is extremely challenging yet critical for understanding the biology, inheritance, trajectory, and clinical manifestations of the many forms of the condition. Here, we leveraged broad phenotypic data from a large cohort with matched genetics to characterize classes of autism and their patterns of core, associated, and co-occurring traits, ultimately demonstrating that phenotypic patterns are associated with distinct genetic and molecular programs. We used a generative mixture modeling approach to identify robust, clinically-relevant classes of autism which we validate and replicate in a large independent cohort.

Both the transcriptional activator, Bcd, and repressor, Cic, form small mobile oligomeric clusters.

Transcription factors play an essential role in pattern formation during early embryo development, generating a strikingly fast and precise transcriptional response that results in sharp gene expression boundaries. To characterize the steps leading up to transcription, we performed a side-by-side comparison of the nuclear dynamics of two morphogens, a transcriptional activator, Bicoid (Bcd), and a transcriptional repressor, Capicua (Cic), both involved in body patterning along the anterior-posterior axis of the early Drosophila embryo. We used a combination of fluorescence recovery after photobleaching, fluorescence correlation spectroscopy, and single-particle tracking to access a wide range of dynamical timescales.

Reassessing the modularity of gene co-expression networks using the Stochastic Block Model.

Finding communities in gene co-expression networks is a common first step toward extracting biological insight from these complex datasets. Most community detection algorithms expect genes to be organized into assortative modules, that is, groups of genes that are more associated with each other than with genes in other groups. While it is reasonable to expect that these modules exist, using methods that assume they exist a priori is risky, as it guarantees that alternative organizations of gene interactions will be ignored.

Single-cell gene-expression measurements in biofilms reveal spatiotemporal patterns underlying development.

Bacteria commonly exist in multicellular, surface-attached communities called biofilms. Biofilms are central to ecology, medicine, and industry. The pathogen forms biofilms from single founder cells that, via cell division, mature into three-dimensional structures with distinct, yet reproducible, regional architectures.

How Transcription Factor Clusters Shape the Transcriptional Landscape.

In eukaryotic cells, gene transcription typically occurs in discrete periods of promoter activity, interspersed with intervals of inactivity. This pattern deviates from simple stochastic events and warrants a closer examination of the molecular interactions that activate the promoter. Recent studies have identified transcription factor (TF) clusters as key precursors to transcriptional bursting.

Clusters of long COVID among patients hospitalized for COVID-19 in New York City.

Background: Recent studies have demonstrated that individuals hospitalized due to COVID-19 can be affected by "long-COVID" symptoms for as long as one year after discharge.

Objectives: Our study objective is to identify data-driven clusters of patients using a novel, unsupervised machine learning technique.

Methods: The study uses data from 437 patients hospitalized in New York City between March 3rd and May 15th of 2020.