Differential Abundance of DNA Damage Sensors and Innate Immune Signaling Proteins in Inositol Polyphosphate 4-Phosphatase Type II-Negative Triple-Negative Breast Cancer Classified by Immunotype.

The influence of neoplastic cells on the tumor microenvironment is poorly understood. In this study, eight patient samples representing two immunotypes of triple-negative breast cancer (TNBC), defined by quantitative histologic criteria as T-cell desert and T-cell infiltrated (TCI), were compared via label-free quantitative protein mass spectrometry of material extracted directly from targeted regions of formalin-fixed, paraffin-embedded tissue sections. Of 2934 proteins quantitated, 439 were significantly differentially abundant, among which 361 were overabundant in TCI-TNBC.

Characterization of a chromatin-associated TCF7L1 complex in human embryonic stem cells.

Human embryonic stem cells (hESCs) resemble the pluripotent epiblast cells found in the early postimplantation human embryo and represent the "primed" state of pluripotency. One factor that helps primed pluripotent cells retain pluripotency and prepare genes for differentiation is the transcription factor TCF7L1, a member of a small family of proteins known as T cell factors/Lymphoid enhancer factors (TCF/LEF) that act as downstream components of the WNT signaling pathway. Transcriptional output of the WNT pathway is regulated, in part, by the activity of TCF/LEFs in conjunction with another component of the WNT pathway, β-CATENIN.

Combination of deep XLMS with deep learning reveals an ordered rearrangement and assembly of a major protein component of the vaccinia virion.

An outstanding problem in the understanding of poxvirus biology is the molecular structure of the mature virion. Via deep learning methods combined with chemical cross-linking mass spectrometry, we have addressed the structure and assembly pathway of P4a, a key poxvirus virion core component.

Kinematic cues in driver-pedestrian communication to support safe road crossing.

Objective: Right-of-way negotiation between drivers and pedestrians often relies on explicit (e.g., waving) and implicit (e.

Driver response and recovery following automation initiated disengagement in real-world hands-free driving.

Objective: Advanced driver assistance systems are increasingly available in consumer vehicles, making the study of drivers' behavioral adaptation and the impact of automation beneficial for driving safety. Concerns over driver's being out-of-the-loop, coupled with known limitations of automation, has led research to focus on time-critical, system-initiated disengagements. This study used real-world data to assess drivers' response to, and recovery from, automation-initiated disengagements by quantifying changes in visual attention, vehicle control, and time to steady-state behaviors.

Deconstructing Allograft Adipose and Fascia Matrix: Fascia Matrix Improves Angiogenesis, Volume Retention, and Adipogenesis in a Rodent Model.

Background: Autologous fat grafting is commonly used for soft-tissue repair (approximately 90,000 cases per year in the United States), but outcomes are limited by volume loss (20% to 80%) over time. Human allograft adipose matrix (AAM) stimulates de novo adipogenesis in vivo, but retention requires optimization. The extracellular matrix derived from superficial fascia, interstitial within the adipose layer, is typically removed during AAM processing.

Interdependence of driver and pedestrian behavior in naturalistic roadway negotiations.

Objective: This paper characterizes the actions of pedestrian-driver dyads by examining their interdependence across intersection types (e.g., zebra crossings, stop signs).

Characterizing driver speeding behavior when using partial-automation in real-world driving.

Speeding is a prevalent and complex risky behavior that can be affected by many factors. Understanding how drivers speed is important for developing countermeasures, especially as new automation features emerge. The current study seeks to identify and describe types of real-world speeding behaviors with and without the use of partial-automation.

Non-Apoptotic Caspase Activity Preferentially Targets a Novel Consensus Sequence Associated With Cytoskeletal Proteins in the Developing Auditory Brainstem.

The auditory brainstem relies on precise circuitry to facilitate sound source localization. In the chick, the development of this specialized circuitry requires non-apoptotic activity of caspase-3, for which we previously identified several hundred proteolytic substrates. Here we tested whether the sequence of the caspase cleavage site differentially encodes proteolytic preference in apoptotic and non-apoptotic contexts.

Speeding behavior while using adaptive cruise control and lane centering in free flow traffic.

Objective: Adaptive cruise control (ACC) and lane centering are usually marketed as convenience features but may also serve a safety purpose. However, given that speeding is associated with increased crash risk and worse crash outcomes, the extent to which driver's speed using ACC may reduce the maximum safety benefit they can obtain from this system. The current study was conducted to characterize speeding behavior among drivers using adaptive cruise control and a similar system with added lane centering.

A model for naturalistic glance behavior around Tesla Autopilot disengagements.

Objective: We present a model for visual behavior that can simulate the glance pattern observed around driver-initiated, non-critical disengagements of Tesla's Autopilot (AP) in naturalistic highway driving.

Background: Drivers may become inattentive when using partially-automated driving systems. The safety effects associated with inattention are unknown until we have a quantitative reference on how visual behavior changes with automation.

Driver behavior and the use of automation in real-world driving.

Background: The emergence of partial-automation in consumer vehicles is reshaping the driving task, the driver role, and subsequent driver behavior. When using partial-automation, drivers delegate the operational control of the dynamic driving task to the automation system, while remaining responsible for monitoring, object/event detection, response selection, and execution. Hence, driving has become a collaboration between driver and automation systems that is characterized by dynamic Transfers of Control (TOC).

Caspase-3 Cleaves Extracellular Vesicle Proteins During Auditory Brainstem Development.

Sound localization requires extremely precise development of auditory brainstem circuits, the molecular mechanisms of which are largely unknown. We previously demonstrated a novel requirement for non-apoptotic activity of the protease caspase-3 in chick auditory brainstem development. Here, we used mass spectrometry to identify proteolytic substrates of caspase-3 during chick auditory brainstem development.

Induction of protection in mice against a respiratory challenge by a vaccine formulated with exosomes isolated from infected cells.

The goal of this study was to determine if exosomes, isolated from infected HeLa cells (-exosomes), induce protective immune responses in mice following vaccination using CpG plus Montanide as adjuvants. Exosomes, collected from uninfected HeLa cells and PBS, formulated with the same adjuvants, were used as negative controls. Mass spectrometry analyses identified 113 proteins in the -exosome preparation including the major outer membrane protein and the polymorphic membrane proteins.

Structure-Based Deep Mining Reveals First-Time Annotations for 46 Percent of the Dark Annotation Space of the 9,671-Member Superproteome of the Nucleocytoplasmic Large DNA Viruses.

We conducted an exhaustive search for three-dimensional structural homologs to the proteins of 20 key phylogenetically distinct nucleocytoplasmic DNA viruses (NCLDV). Structural matches covered 429 known protein domain superfamilies, with the most highly represented being ankyrin repeat, P-loop NTPase, F-box, protein kinase, and membrane occupation and recognition nexus (MORN) repeat. Domain superfamily diversity correlated with genome size, but a diversity of around 200 superfamilies appeared to correlate with an abrupt switch to paralogization.

Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair.

C1q plays a key role as a recognition molecule in the immune system, driving autocatalytic complement cascade activation and acting as an opsonin. We have previously reported a non-immune role of complement C1q modulating the migration and fate of human neural stem cells (hNSC); however, the mechanism underlying these effects has not yet been identified. Here, we show for the first time that C1q acts as a functional hNSC ligand, inducing intracellular signaling to control cell behavior.

Crash rates over time among younger and older drivers in the SHRP 2 naturalistic driving study.

Objective: To examine crash rates over time among 16-17-year-old drivers compared to older drivers.

Methods: Data were from a random sample of 854 of the 3,500 study participants in SHRP 2, a U.S.

Learner Driver Experience and Teenagers' Crash Risk During the First Year of Independent Driving.

Importance: One mechanism for teenagers' elevated crash risk during independent driving may be inadequate learner driving experience.

Objective: To determine how learner driver experience was associated with crash risk during the first year of independent driving.

Design, Setting, And Participants: Youth aged 15.

Vaccinia Virus Ankyrin-Repeat/F-Box Protein Targets Interferon-Induced IFITs for Proteasomal Degradation.

IFITs are interferon-induced proteins that can bind 5'-triphosphate or ribose-unmethylated capped ends of mRNA to inhibit translation. Although some viruses avoid IFITs by synthesizing RNAs with eukaryotic-like caps, no viral proteins were known to antagonize IFITs. We show that the N- and C-terminal portions of C9, a protein required for vaccinia virus to resist the human type I interferon-induced state, bind IFITs and ubiquitin regulatory complexes, respectively.

Kinematic risky driving behavior among younger and older drivers: Differences over time by age group and sex.

This research examined the incidence rates of elevated gravitational force events (kinematic risky driving, KRD) among 16- to 17-year-old drivers compared to those of 18- to 20-year-old, 21- to 25-year-old, and 35- to 55-year-old drivers over a 12-month period. Data were sampled from the Strategic Highway Research Program 2 (SHRP2) naturalistic driving study that recruited a U.S.

Stable native RIP9 complexes associate with C-to-U RNA editing activity, PPRs, RIPs, OZ1, ORRM1 and ISE2.

The mitochondrial and chloroplast mRNAs of the majority of land plants are modified through cytidine to uridine (C-to-U) RNA editing. Previously, forward and reverse genetic screens demonstrated a requirement for pentatricopeptide repeat (PPR) proteins for RNA editing. Moreover, chloroplast editing factors OZ1, RIP2, RIP9 and ORRM1 were identified in co-immunoprecipitation (co-IP) experiments, albeit the minimal complex sufficient for editing activity was never deduced.

Distracted Driving, Visual Inattention, and Crash Risk Among Teenage Drivers.

Introduction: Distracted driving resulting from secondary task engagement is a major contributing factor to teenage drivers' crash risk. This study aims to determine the extent to which visual inattention while engaging in distracting secondary tasks contributes to teenage drivers' crash risk.

Methods: Real-world driving data were collected from a cohort of 82 newly licensed teenagers (average age 16.

The Vaccinia virion: Filling the gap between atomic and ultrastructure.

We have investigated the molecular-level structure of the Vaccinia virion in situ by protein-protein chemical crosslinking, identifying 4609 unique-mass crosslink ions at an effective FDR of 0.33%, covering 2534 unique pairs of crosslinked protein positions, 625 of which were inter-protein. The data were statistically non-random and rational in the context of known structures, and showed biological rationality.