Measuring FOXO Nuclear Shuttling Dynamics by Fluorescence Microscopy.

FOXO transcription factors respond to a number of different stresses by shuttling from the cytoplasm to the nucleus where they upregulate hundreds of target genes with diverse cellular functions. The cellular consequences of FOXO activation are both stress and cell-type specific. Recent evidence suggests that one way in which FOXO dictates stress-specific outcomes is through distinct nuclear/cytoplasmic shuttling dynamics.

Nuclear EGFR in breast cancer suppresses NK cell recruitment and cytotoxicity.

Natural Killer (NK) cells can target and destroy cancer cells, yet tumor microenvironments typically suppress NK cell recruitment and cytotoxicity. The epidermal growth factor receptor (EGFR) is a potent oncogene that can activate survival, migration, and proliferation pathways, and clinical data suggests it may also play an immunomodulating role in cancers. Recent work has demonstrated a novel role for nuclear EGFR (nEGFR) in regulating transcriptional events unique from the kinase domain.

Cell-based high-content approach for SARS-CoV-2 neutralization identifies unique monoclonal antibodies and PI3K pathway inhibitors.

The sudden rise of the SARS-CoV-2 virus and the delay in the development of effective therapeutics to mitigate it made evident a need for ways to screen for compounds that can block infection and prevent further pathogenesis and spread. Yet, identifying effective drugs efficacious against viral infection and replication with minimal toxicity for the patient can be difficult. Monoclonal antibodies were shown to be effective, yet as the SARS-CoV-2 mutated, these antibodies became ineffective.

Entropy in Electroencephalographic Signals Modulates with Force Magnitude During Grasping - A Preliminary Report.

The ability to hold objects relies on neural processes underlying grip force control during grasping. Brain activity lateralized to contralateral hemisphere averaged over trials is associated with grip force applied on an object. However, the involvement of neural variability within-trial during grip force control remains unclear.

Characterization of Event Related Desynchronization in Chronic Stroke Using Motor Imagery Based Brain Computer Interface for Upper Limb Rehabilitation.

Objective: Motor imagery-based brain-computer interface (MI-BCI) is a promising novel mode of stroke rehabilitation. The current study aims to investigate the feasibility of MI-BCI in upper limb rehabilitation of chronic stroke survivors and also to study the early event-related desynchronization after MI-BCI intervention.

Methods: Changes in the characteristics of sensorimotor rhythm modulations in response to a short brain-computer interface (BCI) intervention for upper limb rehabilitation of stroke-disabled hand and normal hand were examined.

Temporal coordination of the transcription factor response to HO stress.

Oxidative stress from excess HO activates transcription factors that restore redox balance and repair oxidative damage. Although many transcription factors are activated by HO, it is unclear whether they are activated at the same HO concentration, or time. Dose-dependent activation is likely as oxidative stress is not a singular state and exhibits dose-dependent outcomes including cell-cycle arrest and cell death.

Lateralized Neural Entropy modulates with Grip Force during Precision Grasping.

When holding a coffee mug filled to the brim, we strive to avoid spilling the coffee. This ability relies on the neural processes underlying the control of finger forces on a moment-to-moment basis. The brain activity lateralized to the contralateral hemisphere averaged over a trial and across the trials is known to be associated with the magnitude of grip force applied on an object.

Temporal Coordination of the Transcription Factor Response to HO stress.

Oxidative stress from excess HO activates transcription factors (TFs) that restore redox balance and repair oxidative damage. Though many TFs are activated by HO, it is unknown whether they are activated at the same HO concentration or time after HO stress. We found TF activation is tightly coordinated over time and dose dependent.

Temporal Coordination of the Transcription Factor Response to HO stress.

The p53 and FOXO transcription factors (TFs) share many similarities despite their distinct evolutionary origins. Both TFs are activated by a variety of cellular stresses and upregulate genes in similar pathways including cell-cycle arrest and apoptosis. Oxidative stress from excess HO activates both FOXO1 and p53, yet whether they are activated at the same time is unclear.

FOXO nuclear shuttling dynamics are stimulus-dependent and correspond with cell fate.

FOXO transcription factors are regulators of cellular homeostasis linked to increased lifespan and tumor suppression. FOXOs are activated by diverse cell stresses including serum starvation and oxidative stress. FOXO activity is regulated through posttranslational modifications that control shuttling of FOXO proteins to the nucleus.

Feedback in the β-catenin destruction complex imparts bistability and cellular memory.

Wnt ligands are considered classical morphogens, for which the strength of the cellular response is proportional to the concentration of the ligand. Herein, we show an emergent property of bistability arising from feedback among the Wnt destruction complex proteins that target the key transcriptional co-activator β-catenin for degradation. Using biochemical reconstitution, we identified positive feedback between the scaffold protein Axin and the kinase glycogen synthase kinase 3 (GSK3).

Live-cell imaging in human colonic monolayers reveals ERK waves limit the stem cell compartment to maintain epithelial homeostasis.

The establishment and maintenance of different cellular compartments in tissues is a universal requirement across all metazoans. Maintaining the correct ratio of cell types in time and space allows tissues to form patterned compartments and perform complex functions. Patterning is especially evident in the human colon, where tissue homeostasis is maintained by stem cells in crypt structures that balance proliferation and differentiation.

Concerns in the Blurred Divisions between Medical and Consumer Neurotechnology.

Neurotechnology has traditionally been central to the diagnosis and treatment of neurological disorders. While these devices have initially been utilized in clinical and research settings, recent advancements in neurotechnology have yielded devices that are more portable, user-friendly, and less expensive. These improvements allow laypeople to monitor their brain waves and interface their brains with external devices.

A Roadmap Towards Standards for Neurally Controlled End Effectors.

The control and manipulation of various types of end effectors such as powered exoskeletons, prostheses, and 'neural' cursors by brain-machine interface (BMI) systems has been the target of many research projects. A seamless "plug and play" interface between any BMI and end effector is desired, wherein similar user's intent cause similar end effectors to behave identically. This report is based on the outcomes of an IEEE Standards Association Industry Connections working group on End Effectors for Brain-Machine Interfacing that convened to identify and address gaps in the existing standards for BMI-based solutions with a focus on the end-effector component.

Towards a Portable Magnetoencephalography Based Brain Computer Interface with Optically-Pumped Magnetometers.

Brain Computer Interfaces (BCIs) allow individuals to control devices, machines and prostheses with their thoughts. Most feasibility studies with BCIs have utilized scalp electroencephalography (EEG), due to it being accessible, noninvasive, and portable. While BCIs have been studied with magnetoencephalography (MEG), the modality has limited applications due to the large immobile hardware.

Designing combination therapies with modeling chaperoned machine learning.

Chemotherapy resistance is a major challenge to the effective treatment of cancer. Thus, a systematic pipeline for the efficient identification of effective combination treatments could bring huge biomedical benefit. In order to facilitate rational design of combination therapies, we developed a comprehensive computational model that incorporates the available biological knowledge and relevant experimental data on the life-and-death response of individual cancer cells to cisplatin or cisplatin combined with the TNF-related apoptosis-inducing ligand (TRAIL).

Regression-based reconstruction of human grip force trajectories with noninvasive scalp electroencephalography.

Objective: Robotic devices show promise in restoring motor abilities to individuals with upper limb paresis or amputations. However, these systems are still limited in obtaining reliable signals from the human body to effectively control them. We propose that these robotic devices can be controlled through scalp electroencephalography (EEG), a neuroimaging technique that can capture motor commands through brain rhythms.

Hidden heterogeneity and circadian-controlled cell fate inferred from single cell lineages.

The origin of lineage correlations among single cells and the extent of heterogeneity in their intermitotic times (IMT) and apoptosis times (AT) remain incompletely understood. Here we developed single cell lineage-tracking experiments and computational algorithms to uncover correlations and heterogeneity in the IMT and AT of a colon cancer cell line before and during cisplatin treatment. These correlations could not be explained using simple protein production/degradation models.

Drug-induced aneuploidy and polyploidy is a mechanism of disease relapse in MYC/BCL2-addicted diffuse large B-cell lymphoma.

Unlabelled: Double-hit (DH) or double-expresser (DE) lymphomas are high-grade diffuse large B-cell lymphomas (DLBCL) that are mostly incurable with standard chemo-immunotherapy due to treatment resistance. The generation of drug-induced aneuploid/polyploid (DIAP) cells is a common effect of anti-DLBCL therapies (e.g.

A dynamical framework for complex fractional killing.

When chemotherapy drugs are applied to tumor cells with the same or similar genotypes, some cells are killed, while others survive. This fractional killing contributes to drug resistance in cancer. Through an incoherent feedforward loop, chemotherapy drugs not only activate p53 to induce cell death, but also promote the expression of apoptosis inhibitors which inhibit cell death.

Cell-to-Cell Variation in p53 Dynamics Leads to Fractional Killing.

Many chemotherapeutic drugs kill only a fraction of cancer cells, limiting their efficacy. We used live-cell imaging to investigate the role of p53 dynamics in fractional killing of colon cancer cells in response to chemotherapy. We found that both surviving and dying cells reach similar levels of p53, indicating that cell death is not determined by a fixed p53 threshold.

Predicting hand forces from scalp electroencephalography during isometric force production and object grasping.

In this study, we demonstrate the feasibility of predicting hand forces from brain activity recorded with scalp electroencephalography (EEG). Ten able-bodied subjects participated in two tasks: an isometric force production task and a grasp-and-lift task using unconstrained and constrained grasps. We found that EEG electrodes spanning central areas of the scalp were highly correlated to force rate trajectories.

An exploration of grip force regulation with a low-impedance myoelectric prosthesis featuring referred haptic feedback.

Background: Haptic display technologies are well suited to relay proprioceptive, force, and contact cues from a prosthetic terminal device back to the residual limb and thereby reduce reliance on visual feedback. The ease with which an amputee interprets these haptic cues, however, likely depends on whether their dynamic signal behavior corresponds to expected behaviors-behaviors consonant with a natural limb coupled to the environment. A highly geared motor in a terminal device along with the associated high back-drive impedance influences dynamic interactions with the environment, creating effects not encountered with a natural limb.

Draft Genome Sequence of the Ale-Fermenting Saccharomyces cerevisiae Strain GSY2239.

Saccharomyces cerevisiae strain GSY2239 is derived from an industrial yeast strain used to ferment ale-style beer. We present here the 11.5-Mb draft genome sequence for this organism.