Covalent hitchhikers guide proteins to the nucleus.

In this issue of Cell Chemical Biology, Peng and Weerapana report the combination of chemoproteomic and proximity-based labeling approaches to identify cysteines in nuclear proteins that are reactive toward electrophilic probe compounds. They apply this novel technology to identify proteins that are localized to the nucleus and chromatin upon probe labeling.

ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging.

The ribotoxic stress response (RSR) is a signaling pathway in which the p38- and c-Jun N-terminal kinase (JNK)-activating mitogen-activated protein kinase kinase kinase (MAP3K) ZAKα senses stalling and/or collision of ribosomes. Here, we show that reactive oxygen species (ROS)-generating agents trigger ribosomal impairment and ZAKα activation. Conversely, zebrafish larvae deficient for ZAKα are protected from ROS-induced pathology.

Stimulus-Induced Relief of Intentionally Incorporated Frustration Drives Refolding of a Water-Soluble Biomimetic Foldamer.

Frustrated, or nonoptimal, interactions have been proposed to be essential to a protein's ability to display responsive behavior such as allostery, conformational signaling, and signal transduction. However, the intentional incorporation of frustrated noncovalent interactions has not been explored as a design element in the field of dynamic foldamers. Here, we report the design, synthesis, characterization, and molecular dynamics simulations of the first dynamic water-soluble foldamer that, in response to a stimulus, exploits relief of frustration in its noncovalent network to structurally rearrange from a pleated to an intercalated columnar structure.

The Presence of Two Genes in a Subset of Acanthopterygii Fish Is Associated with a Polyserine Insert in MyoD1.

The gene was duplicated during the teleost whole genome duplication and, while a second gene () was subsequently lost from the genomes of some lineages (including zebrafish), many fish lineages (including species) have retained both paralogues. Here we reveal the expression patterns of the two genes in ( using in situ hybridisation. We report our analysis of MyoD1 and MyoD2 protein sequences from 54 teleost species, and show that , along with some other teleosts, include a polyserine repeat between the amino terminal transactivation domains (TAD) and the cysteine-histidine rich region (H/C) in MyoD1.

Domestic violence and abuse in local child safeguarding policy: How is the problem represented?

Within the United Kingdom, domestic violence and abuse (DVA) is the most commonly identified factor within child in need assessments, with rates increasing in recent years in addition to 'lockdown'-related spikes. This article examines the representation of DVA in local child safeguarding policies using Bacchi's (2009) 'What is the problem represented to be?' approach. Policies were collected from the websites of all the child safeguarding partnerships of England in July 2021.

Genomic Characterization of the Cluster CZ4 Gordonia terrae Phage Oregano.

Oregano is a novel cluster CZ4 bacteriophage isolated from the soil using the bacterial host Gordonia terrae. The Oregano genome is 47,575 bp long and encodes two tyrosine integrases and a toxin/antitoxin system. It shares an immunity repressor with both and Mycobacterium phages that spans 7 clusters.

Fusing Location Data for Depression Prediction.

Recent studies have demonstrated that geographic location features collected using smartphones can be a powerful predictor for depression. While location information can be conveniently gathered by GPS, typical datasets suffer from significant periods of missing data due to various factors (e.g.

Direct Compaction Drug Product Process Modeling.

Most challenges during the development of solid dosage forms are related to the impact of any variations in raw material properties, batch size, or equipment scales on the product quality and the control of the manufacturing process. With the ever pertinent restrictions on time and resource availability versus heightened expectations to develop, optimize, and troubleshoot manufacturing processes, targeted and robust science-based process modeling platforms are essential. This review focuses on the modeling of unit operations and practices involved in batch manufacturing of solid dosage forms by direct compaction.

Highlighting DEM's Potential to Gauge Mechanistic Attributes of MUPS Tablet and Capsule Formulations.

Simulation of pharmaceutical unit operations by the discrete element method (DEM) has elevated our understanding of the impact of single-particle interactions on themselves, and on the entire tablets/powder. Studies in the past have shown how this knowledge helps to mitigate/solve multiple challenges during conventional formulation and process development/modernization/troubleshooting, with minimal use of active drug material. This communication adds to this- highlighting the tool's potential for a rapid preliminary assessment of the mechanistic attributes of multiple unit particle system (MUPS) based tablet and capsule drug products.

Automatic Depression Prediction Using Internet Traffic Characteristics on Smartphones.

Depression is a serious mental health problem. Recently, researchers have proposed novel approaches that use sensing data collected passively on smartphones for automatic depression screening. While these studies have explored several types of sensing data (e.

The Death of Freddie Gray and Its Impact on Homicides in Baltimore and Maryland.

This study evaluated the impact that Freddie Gray's death on April, 19, 2015, had on homicides within Baltimore, Prince George's County, and the rest of Maryland. The numbers of these deaths were compared in the 2 years prior and after his death. The average number of homicide per month in Baltimore and Prince George's County, but not the rest of Maryland, showed a statistically significant increase in the 2 years after his death, with a sudden spike in homicides in Baltimore immediately following his death.

Grant Report on SCH: Personalized Depression Treatment Supported by Mobile Sensor Analytics.

We report on the newly started project "SCH: Personalized Depression Treatment Supported by Mobile Sensor Analytics". The current best practice guidelines for treating depression call for close monitoring of patients, and periodically adjusting treatment as needed. This project will advance personalized depression treatment by developing a system, DepWatch, that leverages mobile health technologies and machine learning tools.

Mechanics of Pharmaceutical Pellets-Constitutive Properties, Deformation, and Breakage Behavior.

To ensure robust manufacturing of unit-based oral solid dosage forms with minimal structural imperfections and high mechanical reliability across subsequent processing unit operations (e.g., withstanding mechanical stresses during coating, optional axial compression, handling, packaging, storage, and transport conditions), process design should include consideration of precise limits of accurate micro, macro, and bulk properties of the constituent pellets.

Modeling the Distribution of Scald Type Burns in a Child.

Splash or spill scald burns may be seen by medical examiners in the setting of intentional trauma or accidental injury. In order to model various scald burn scenarios, an 8-year-old subject dressed in white had colored water spilled or dropped onto her. The results were recorded by video and still photography.

Epidemic Fentanyl Deaths in Maryland: A Public Health Intervention Involving Geographic Information Systems and Collaboration with the Drug Enforcement Administration.

An ongoing epidemic of illicit fentanyl overdose deaths started in Maryland in July 2013. The records of the Office of the Chief Medical Examiner for the state of Maryland were searched to identify these deaths from July 2013 to February 2015. A geographic information system was used to map and analyze the spatial and temporal distribution of the deaths in Maryland.

Single cell analysis reveals the stochastic phase of reprogramming to pluripotency is an ordered probabilistic process.

Despite years of research, the reprogramming of human somatic cells to pluripotency remains a slow, inefficient process, and a detailed mechanistic understanding of reprogramming remains elusive. Current models suggest reprogramming to pluripotency occurs in two-phases: a prolonged stochastic phase followed by a rapid deterministic phase. In this paradigm, the early stochastic phase is marked by the random and gradual expression of pluripotency genes and is thought to be a major rate-limiting step in the successful generation of induced Pluripotent Stem Cells (iPSCs).

A model of proto-object based saliency.

Organisms use the process of selective attention to optimally allocate their computational resources to the instantaneously most relevant subsets of a visual scene, ensuring that they can parse the scene in real time. Many models of bottom-up attentional selection assume that elementary image features, like intensity, color and orientation, attract attention. Gestalt psychologists, however, argue that humans perceive whole objects before they analyze individual features.

Separation behavior of short single- and double-stranded DNA in 1 micron and 100 nm glass channels.

Micro- and nanofluidic lab-on-chip technology offers the unique capability of high-resolution separation, identification, and manipulation of biomolecules with broad applications in chemistry, biology, and medicine. In this work, we probe the effects of ionic strength on separation of ss- and dsDNA within 1 micron and 100 nm-deep glass channels. Separation behavior of DNA is influenced by a number of parameters, including ionic strength, melting temperature, strand length, strand conformation, and channel size.

Parameter estimation of a spiking silicon neuron.

Spiking neuron models are used in a multitude of tasks ranging from understanding neural behavior at its most basic level to neuroprosthetics. Parameter estimation of a single neuron model, such that the model's output matches that of a biological neuron is an extremely important task. Hand tuning of parameters to obtain such behaviors is a difficult and time consuming process.

Photorelease of tyrosine from α-carboxy-6-nitroveratryl (αCNV) derivatives.

The synthesis of photolabile tyrosine derivatives protected on the phenolic oxygen by the α-carboxy-6-nitroveratryl (αCNV) protecting group is described. The compounds undergo rapid photolysis at wavelengths longer than 300 nm to liberate the corresponding phenol in excellent yield (quantum yield for the deprotection of tyrosine = 0.19).

Estimating parameters of generalized integrate-and-fire neurons from the maximum likelihood of spike trains.

When a neuronal spike train is observed, what can we deduce from it about the properties of the neuron that generated it? A natural way to answer this question is to make an assumption about the type of neuron, select an appropriate model for this type, and then choose the model parameters as those that are most likely to generate the observed spike train. This is the maximum likelihood method. If the neuron obeys simple integrate-and-fire dynamics, Paninski, Pillow, and Simoncelli (2004) showed that its negative log-likelihood function is convex and that, at least in principle, its unique global minimum can thus be found by gradient descent techniques.