Differential Effects of Confinement on the Dynamics of Normal and Tumor-Derived Pancreatic Ductal Organoids.

Pancreatic ductal adenocarcinoma (PDAC) is a cancer of the epithelia comprising the ductal network of the pancreas. During disease progression, PDAC tumors recruit fibroblasts that promote fibrosis, increasing local tissue stiffness and subjecting epithelial cells to increased compressive forces. Previous in vitro studies have documented cytoskeletal and nuclear adaptation following compressive stresses in two-dimensional (2D) and three-dimensional (3D) environments.

Site-Specific Histidine Aza-Michael Addition in Proteins Enabled by a Ferritin-Based Metalloenzyme.

Histidine modifications of proteins are broadly based on chemical methods triggering N-substitution reactions such as aza-Michael addition at histidine's moderately nucleophilic imidazole side chain. While recent studies have demonstrated chemoselective, histidine-specific modifications by further exploiting imidazole's electrophilic reactivity to overcome interference from the more nucleophilic lysine and cysteine, achieving site-specific histidine modifications remains a major challenge due to the absence of spatial control over chemical processes. Herein, through X-ray crystallography and cryo-electron microscopy structural studies, we describe the rational design of a nature-inspired, noncanonical amino-acid-incorporated, human ferritin-based metalloenzyme that is capable of introducing site-specific post-translational modifications (PTMs) to histidine in peptides and proteins.

Simulation of Polymer Fractal Formation Using a Triangular Network Growth Model.

Fractal formation in spin-coated thin-film polymers is of experimental and theoretical interest. Modeling the determinants and dynamics of this process will deepen our understanding of polymer aggregation and the predictability of thin-film structures. This is especially true if the model used has readily interpretable parameters and has been demonstrated to yield a close match to experimental processes under a variety of conditions.

A novel CPR-assist device vs. established chest compression techniques in infant CPR: A manikin study.

Introduction: Guidelines for infant CPR recommend the two-thumb encircling hands technique (TTT) and the two-finger technique (TFT) for chest compression. Some devices have been designed to assist with infant CPR, but are often not readily available. Syringe plungers may serve as an alternative infant CPR assist device given their availability in most hospitals.

Negative Emotions Recruit the Parabrachial Nucleus Efferent to the VTA to Disengage Instrumental Food Seeking.

The parabrachial nucleus (PBN) interfaces between taste and feeding systems and is also an important hub for relaying distress information and threats. Despite that the PBN sends projections to the ventral tegmental area (VTA), a heterogeneous brain region that regulates motivational behaviors, the function of the PBN-to-VTA connection remains elusive. Here, by using male mice in several behavioral paradigms, we discover that VTA-projecting PBN neurons are significantly engaged in contextual fear, restraint or mild stress but not palatable feeding, visceral malaise, or thermal pain.

Amine Adsorbents Stability for Post-Combustion CO Capture: Determination and Validation of Laboratory Degradation Rates in a Multi-staged Fluidized Bed Pilot Plant.

Alternative to current liquid amine technologies for post-combustion CO capture, new technologies such as adsorbent-based processes are developed, wherein material lifetime and degradation is important. Herein a robust method to determine degradation rates in a laboratory setup is developed, which was validated with a continuous multi-staged fluidized bed pilot plant designed to capture 1 ton CO per day. An amine functionalized polystyrene adsorbent showed very good agreement between the experimental 1000-hour laboratory degradation rates and 2200 hours of degradation in a pilot plant.

Utilizing MiSeq Sequencing to Detect Circulating microRNAs in Plasma for Improved Lung Cancer Diagnosis.

Non-small cell lung cancer (NSCLC) is a major contributor to cancer-related deaths, but early detection can reduce mortality. NSCLC comprises mainly adenocarcinoma (AC) and squamous cell carcinoma (SCC). Circulating microRNAs (miRNAs) in plasma have emerged as promising biomarkers for NSCLC.

Effect of thoracic stiffness on chest compression performance - A prospective randomized crossover observational manikin study.

Introduction: Human thoracic stiffness varies and may affect the performance during external chest compression (ECC). The Extra Compression Spring Resusci® QCPR Anne manikin is a high-fidelity training model developed for ECC training that can account for varying levels of thoracic stiffness. The aim of this study was to use this training model to investigate the effects of thoracic stiffness on ECC biomechanics and qualities.

Biomechanical analysis of force distribution in one-handed and two-handed child chest compression- a randomized crossover observational study.

Background: Even force distribution would generate efficient external chest compression (ECC). Little research has been done to compare force distribution between one-hand (OH) and two-handed (TH) during child ECC. Therefore, this study was to investigate force distribution, rescuer perceived fatigue and discomfort/pain when applying OH and TH ECC in children.

Ferritin Conjugates With Multiple Clickable Amino Acids Encoded by C-Terminal Engineered Pyrrolysyl-tRNA Synthetase.

This study reports the application of expanding genetic codes in developing protein cage-based delivery systems. The evolved Methanosarcina mazei pyrrolysyl-tRNA synthetase (PylRS)•tRNA pairs derived from directed evolution are examined to probe their recognition for para-substituted phenylalanine analogs. The evolved MmPylRS, AzFRS, harboring a wide range of substrates, is further engineered at the C-terminal region into another variant, AzFRS-MS.

Biomechanical analysis of force distribution in one-handed and two-handed adult chest compression: a randomised crossover observational study.

Introduction: The standard method of chest compression for adults is a two-handed procedure. One-handed external chest compression (ECC) is used in some situations such as during transport of patients who had an out-of-hospital cardiac arrest, but the quality of one-handed ECC is still not well known. The distribution of force is related to the quality of chest compression and may affect the risk of injury.

Detection and Differentiation of SARS-CoV-2, Influenza, and Respiratory Syncytial Viruses by CRISPR.

SARS-CoV-2, influenza, and respiratory syncytial viruses (RSVs) cause acute respiratory infections with similar symptoms. Since the treatments and outcomes of these infections are different, the early detection and accurate differentiation of the viruses are clinically important for the prevention and treatment of the diseases. We previously demonstrated that clustered regularly interspaced short palindromic repeats (CRISPR) could rapidly and precisely detect SARS-CoV-2.

How does the side of approach impact the force delivered during external chest compression?

Background: We investigated the biomechanics of four external chest compression (ECC) approaches involving different sides of approach and hand placement during cardiopulmonary resuscitation (CPR).

Methods: A total of 60 participants (30 women and 30 men) with CPR certification performed standard continuous 2-min ECC on a Resusci Anne manikin with real-time feedback in four scenarios: rescuer at the manikin's right side with right hand chest contact (RsRc), rescuer at the manikin's right side with left hand chest contact (RsLc), rescuer at the manikin's left side with left hand chest contact (LsLc), and rescuer at the manikin's left side with right hand chest contact (LsRc). Pressure distribution maps of the palm, peak compression pressure, and compression forces were analysed.

Rapid and Sensitive Detection of SARS-CoV-2 Using Clustered Regularly Interspaced Short Palindromic Repeats.

Rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for controlling the pandemic of coronavirus disease 2019. Polymerase chain reaction (PCR)-based technique is the standard test for detection of SARS-CoV-2, which, however, requires complicated sample manipulation (e.g.

Sensitive Detection of KRAS Mutations by Clustered Regularly Interspaced Short Palindromic Repeats.

Kirsten rat sarcoma viral oncogene (KRAS) is the isoform most frequently mutated in human tumors. Testing for activating KRAS mutations has important implications for diagnosis and the personalized medicine of cancers. The current techniques for detecting KRAS mutations have moderate sensitivity.

Linker and N-Terminal Domain Engineering of Pyrrolysyl-tRNA Synthetase for Substrate Range Shifting and Activity Enhancement.

The pyrrolysyl-tRNA synthetase (PylRS)⋅tRNA pair can be used to incorporate non-canonical amino acids (ncAAs) into proteins at installed amber stop codons. Although engineering of the PylRS active site generates diverse binding pockets, the substrate ranges are found similar in charging lysine and phenylalanine analogs. To expand the diversity of the ncAA side chains that can be incorporated the PylRS⋅tRNA pair, exploring remote interactions beyond the active site is an emerging approach in expanding the genetic code research.

A CRISPR Test for Rapidly and Sensitively Detecting Circulating EGFR Mutations.

The detection of EGFR mutations in circulating cell-free DNA can enable personalized therapy for cancer. The current techniques for detecting circulating EGFR mutations are expensive and time-consuming with moderate sensitivity. Emerging CRISPR is revolutionizing medical diagnostics and showing a great promise for nucleic acid detection.

A CRISPR Test for Detection of Circulating Nuclei Acids.

Emerging CRISPR-based nucleic acid detection shows great promise in molecular diagnosis of diseases. CRISPR-Cas12a can sensitively and specifically detect human papillomavirus (HPV) DNA in anal swabs. However, the current CRISPR-Cas12a system needs auxiliary and expensive equipment, which limit its application as a point-of-care (POC) diagnostic tool.

Biomechanics of two-thumb versus two-finger chest compression for cardiopulmonary resuscitation in an infant manikin model.

Objective: The loading force applied in infant external chest compression (ECC) has not been determined. The objective of this crossover study was to quantify the actual force involved in two-thumb (TT)-encircling hands and two-finger (TF) methods during infant cardiopulmonary resuscitation.

Methods: A total of 42 emergency medical professionals performed lone rescuer infant external chest compression (ECC) with TF and TT methods.

Fucosylation genes as circulating biomarkers for lung cancer.

Purpose: Fucosyltransferases (FUTs) catalyze fucosylation, which plays a central role in biological processes. Aberrant fucosylation is associated with malignant transformation. Here we investigated whether transcriptional levels of genes coding the FUTs in plasma could provide cell-free circulating biomarkers for lung cancer.

Effects of Kinesio taping and exercise on forward head posture.

Background: Little is known about the effects of Kinesio taping and therapeutic exercise on correcting forward head posture.

Objective: To compare Kinesio taping versus therapeutic exercise for forward head posture on static posture, dynamic mobility and functional outcomes.

Methods: Sixty subjects (31 women, 29 men) with forward head postures participated in this study.

Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4.

Autoantibodies against SCLC-associated neuronal antigen ELAVL4 (HuD) have been linked to smaller tumors and improved survival, but the antigenic epitope and mechanism of autoimmunity have never been solved. We report that recombinant human ELAVL4 protein incubated under physiological conditions acquires isoaspartylation, a type of immunogenic protein damage. Specifically, the N-terminal region of ELAVL4, previously implicated in SCLC-associated autoimmunity, undergoes isoaspartylation in vitro, is recognized by sera from anti-ELAVL4 positive SCLC patients and is highly immunogenic in subcutaneously injected mice and in vitro stimulated human lymphocytes.

Pontomesencephalic Tegmental Afferents to VTA Non-dopamine Neurons Are Necessary for Appetitive Pavlovian Learning.

The ventral tegmental area (VTA) receives phenotypically distinct innervations from the pedunculopontine tegmental nucleus (PPTg). While PPTg-to-VTA inputs are thought to play a critical role in stimulus-reward learning, direct evidence linking PPTg-to-VTA phenotypically distinct inputs in the learning process remains lacking. Here, we used optogenetic approaches to investigate the functional contribution of PPTg excitatory and inhibitory inputs to the VTA in appetitive Pavlovian conditioning.