Adult-neurogenesis allows for representational stability and flexibility in early olfactory system.

In the early olfactory system, adult-neurogenesis, a process of neuronal replacement results in the continuous reorganization of synaptic connections and network architecture throughout the animal's life. This poses a critical challenge: How does the olfactory system maintain stable representations of odors and therefore allow for stable sensory perceptions amidst this ongoing circuit instability? Utilizing a detailed spiking network model of early olfactory circuits, we uncovered dual roles for adult-neurogenesis: one that both supports representational stability to faithfully encode odor information and also one that facilitates plasticity to allow for learning and adaptation. In the main olfactory bulb, adult-neurogenesis affects neural codes in individual mitral and tufted cells but preserves odor representations at the neuronal population level.

Impact of Laryngopharyngeal Reflux in Patients with Voice Disorders.

Objective: The aim of this study is to evaluate the presence of laryngopharyngeal reflux in patients with voice disorders thereby aiding in the early management and improving the quality of life.

Study Design: Cross Sectional study.

Methods: This cross sectional study was carried out in a tertiary care hospital, patients with history of voice change for more than 3 weeks were included, and divided into 4 groups depending upon the level of voice use.

Differential disruptions in population coding along the dorsal-ventral axis of CA1 in the APP/PS1 mouse model of Aβ pathology.

Alzheimer's Disease (AD) is characterized by a range of behavioral alterations, including memory loss and psychiatric symptoms. While there is evidence that molecular pathologies, such as amyloid beta (Aβ), contribute to AD, it remains unclear how this histopathology gives rise to such disparate behavioral deficits. One hypothesis is that Aβ exerts differential effects on neuronal circuits across brain regions, depending on the neurophysiology and connectivity of different areas.

Detecting abnormal cell behaviors from dry mass time series.

The prediction of pathological changes on single cell behaviour is a challenging task for deep learning models. Indeed, in self-supervised learning methods, no prior labels are used for the training and all of the information for event predictions are extracted from the data themselves. We present here a novel self-supervised learning model for the detection of anomalies in a given cell population, StArDusTS.

Spectrophotometric evaluation of color stability of composite resin after exposure to cold drinks: An study.

Objectives: The aim of this study was to evaluate the color stability of two composite resins after exposure to beverages such as Cola, Pepsi, Red Bull, and distilled water after 15 days.

Materials And Methods: The color stability of a microhybrid and nanohybrid composite was evaluated after storage in distilled water, Coca-Cola, Pepsi, and Red Bull for 15 days. Color measurement was done using a reflectance spectrophotometer based on the CIE L*a*b* color scale.

Touch receptor end-organ innervation and function require sensory neuron expression of the transcription factor Meis2.

Touch sensation is primarily encoded by mechanoreceptors, called low-threshold mechanoreceptors (LTMRs), with their cell bodies in the dorsal root ganglia. Because of their great diversity in terms of molecular signature, terminal endings morphology, and electrophysiological properties, mirroring the complexity of tactile experience, LTMRs are a model of choice to study the molecular cues differentially controlling neuronal diversification. While the transcriptional codes that define different LTMR subtypes have been extensively studied, the molecular players that participate in their late maturation and in particular in the striking diversity of their end-organ morphological specialization are largely unknown.

Algebraic approach to spike-time neural codes in the hippocampus.

Although temporal coding through spike-time patterns has long been of interest in neuroscience, the specific structures that could be useful for spike-time codes remain highly unclear. Here, we introduce an analytical approach, using techniques from discrete mathematics, to study spike-time codes. As an initial example, we focus on the phenomenon of "phase precession" in the rodent hippocampus.

Network size affects the complexity of activity in human iPSC-derived neuronal populations.

Multi-electrode recording of neural activity in cultures offer opportunities for understanding how the structure of a network gives rise to function. Although it is hypothesized that network size is critical for determining the dynamics of activity, this relationship in human neural cultures remains largely unexplored. By applying new methods for analyzing neural activity to human iPSC derived cultures at either low-densities or high-densities, we uncovered the significant impacts that neuron number has on the individual neurophysiological properties of cells (such as firing rates), the collective behavior of the networks these cultures formed (as measured by entropy), and the relationship between the two.

High-resolution structural and functional retinal imaging in the awake behaving mouse.

The laboratory mouse has provided tremendous insight to the underpinnings of mammalian central nervous system physiology. In recent years, it has become possible to image single neurons, glia and vascular cells in vivo by using head-fixed preparations combined with cranial windows to study local networks of activity in the living brain. Such approaches have also succeeded without the use of general anesthesia providing insights to the natural behaviors of the central nervous system.

Transient cell-in-cell formation underlies tumor relapse and resistance to immunotherapy.

Despite the remarkable successes of cancer immunotherapies, the majority of patients will experience only partial response followed by relapse of resistant tumors. While treatment resistance has frequently been attributed to clonal selection and immunoediting, comparisons of paired primary and relapsed tumors in melanoma and breast cancers indicate that they share the majority of clones. Here, we demonstrate in both mouse models and clinical human samples that tumor cells evade immunotherapy by generating unique transient cell-in-cell structures, which are resistant to killing by T cells and chemotherapies.

Macrophage TGF-β signaling is critical for wound healing with heterotopic ossification after trauma.

Transforming growth factor-β1 (TGF-β1) plays a central role in normal and aberrant wound healing, but the precise mechanism in the local environment remains elusive. Here, using a mouse model of aberrant wound healing resulting in heterotopic ossification (HO) after traumatic injury, we find autocrine TGF-β1 signaling in macrophages, and not mesenchymal stem/progenitor cells, is critical in HO formation. In-depth single-cell transcriptomic and epigenomic analyses in combination with immunostaining of cells from the injury site demonstrated increased TGF-β1 signaling in early infiltrating macrophages, with open chromatin regions in TGF-β1-stimulated genes at binding sites specific for transcription factors of activated TGF-β1 (SMAD2/3).

Apoptosis and tissue thinning contribute to symmetric cell division in the developing mouse epidermis in a nonautonomous way.

Mitotic spindle orientation (SO) is a conserved mechanism that governs cell fate and tissue morphogenesis. In the developing epidermis, a balance between self-renewing symmetric divisions and differentiative asymmetric divisions is necessary for normal development. While the cellular machinery that executes SO is well characterized, the extrinsic cues that guide it are poorly understood.

Anillin governs mitotic rounding during early epidermal development.

Background: The establishment of tissue architecture requires coordination between distinct processes including basement membrane assembly, cell adhesion, and polarity; however, the underlying mechanisms remain poorly understood. The actin cytoskeleton is ideally situated to orchestrate tissue morphogenesis due to its roles in mechanical, structural, and regulatory processes. However, the function of many pivotal actin-binding proteins in mammalian development is poorly understood.

Mammalian PERIOD2 regulates H2A.Z incorporation in chromatin to orchestrate circadian negative feedback.

Mammalian circadian oscillators are built on a feedback loop in which the activity of the transcription factor CLOCK-BMAL1 is repressed by the PER-CRY complex. Here, we show that murine Per fibroblasts display aberrant nucleosome occupancy around transcription start sites (TSSs) and at promoter-proximal and distal CTCF sites due to impaired histone H2A.Z deposition.

Top-down feedback enables flexible coding strategies in the olfactory cortex.

In chemical sensation, multiple models have been proposed to explain how odors are represented in the olfactory cortex. One hypothesis is that the combinatorial identity of active neurons within sniff-related time windows is critical, whereas another model proposes that it is the temporal structure of neural activity that is essential for encoding odor information. We find that top-down feedback to the main olfactory bulb dictates the information transmitted to the piriform cortex and switches between these coding strategies.

From synapses to circuits and back: Bridging levels of understanding in animal models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by behavioural changes that include memory loss and cognitive decline and is associated with the appearance of amyloid-β plaques and neurofibrillary tangles throughout the brain. Although aspects of the disease percolate across multiple levels of neuronal organization, from the cellular to the behavioural, it is increasingly clear that circuits are a critical junction between the cellular pathology and the behavioural phenotypes that bookend these levels of analyses. In this review, we discuss critical aspects of neural circuit research, beginning with synapses and progressing to network activity and how they influence our understanding of disease processed in AD.

Oppositional poly(A) tail length regulation by FMRP and CPEB1.

Poly(A) tail length is regulated in both the nucleus and cytoplasm. One factor that controls polyadenylation in the cytoplasm is CPEB1, an RNA binding protein that associates with specific mRNA 3'UTR sequences to tether enzymes that add and remove poly(A). Two of these enzymes, the noncanonical poly(A) polymerases GLD2 (TENT2, PAPD4, Wispy) and GLD4 (TENT4B, PAPD5, TRF4, TUT3), interact with CPEB1 to extend poly(A).

The Clock Takes Shape-24 h Dynamics in Genome Topology.

Circadian rhythms orchestrate organismal physiology and behavior in order to anticipate daily changes in the environment. Virtually all cells have an internal rhythm that is synchronized every day by Zeitgebers (environmental cues). The synchrony between clocks within the animal enables the fitness and the health of organisms.

The SEQC2 epigenomics quality control (EpiQC) study.

Background: Cytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify types of cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and cross-validated resource for epigenetics research from the FDA's Epigenomics Quality Control Group.

Safety and Efficacy of GFB-887, a TRPC5 Channel Inhibitor, in Patients With Focal Segmental Glomerulosclerosis, Treatment-Resistant Minimal Change Disease, or Diabetic Nephropathy: TRACTION-2 Trial Design.

Introduction: A critical unmet need exists for precision therapies for chronic kidney disease. GFB-887 is a podocyte-targeting, small molecule inhibitor of transient receptor potential canonical-5 (TRPC5) designed specifically to treat patients with glomerular kidney diseases characterized by an overactivation of the TRPC5-Rac1 pathway. In a first-in-human study, GFB-887 was found to be safe and well tolerated, had a pharmacokinetic (PK) profile allowing once-daily dosing, and dose dependently decreased urinary Rac1 in healthy adults.

Divergence in Population Coding for Space between Dorsal and Ventral CA1.

Molecular, anatomic, and behavioral studies show that the hippocampus is structurally and functionally heterogeneous, with dorsal hippocampus implicated in mnemonic processes and spatial navigation and ventral hippocampus involved in affective processes. By performing electrophysiological recordings of large neuronal populations in dorsal and ventral CA1 in head-fixed mice navigating a virtual environment, we found that this diversity resulted in different strategies for population coding of space. Populations of neurons in dorsal CA1 showed more complex patterns of activity, which resulted in a higher dimensionality of neural representations that translated to more information being encoded, as compared ensembles in vCA1.