Cancer Immunol Immunother
January 2022
B7H6, a stress-induced ligand which binds to the NK cell receptor NKp30, has recently emerged as a promising candidate for immunotherapy due to its tumor-specific expression on a broad array of human tumors. NKp30 can function as a chimeric antigen receptor (CAR) extracellular domain but exhibits weak binding with a fast on and off rate to B7H6 compared to the TZ47 anti-B7H6 single-chain variable fragment (scFv). Here, directed evolution using yeast display was employed to isolate novel NKp30 variants that bind to B7H6 with higher affinity compared to the native receptor but retain its fast association and dissociation profile.
View Article and Find Full Text PDFUnlabelled: This case series describes the effect of angiotensin II administration on hemodynamics in patients with parenchymal lung injury due to submersion injury.
Case Summary: A 33-year-old female and a 72-year-old female were both brought to the emergency department after incidents of near drowning. Upon arrival to the emergency department, both patients were hemodynamically unstable and were eventually intubated for airway protection.
We present here a series of thermoresponsive glycopolymers in the form of poly(-isopropylacrylamide)(2-[β-manno[oligo]syloxy] ethyl methacrylate)s. These copolymers were prepared from oligo-β-mannosyl ethyl methacrylates that were synthesized through enzymatic catalysis, and were subsequently investigated with respect to their aggregation and phase behavior in aqueous solution using a combination of H NMR spectroscopy, dynamic light scattering, cryogenic transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). The thermoresponsive glycopolymers were prepared by conventional free radical copolymerization of different mixtures of 2-(β-manno[oligo]syloxy)ethyl methacrylates (with either one or two saccharide units) and -isopropylacrylamide (NIPAm).
View Article and Find Full Text PDFAdeno-associated virus' (AAV) relatively simple structure makes it accommodating for engineering into controllable delivery platforms. Cancer, such as pancreatic ductal adenocarcinoma (PDAC), are often characterized by upregulation of membrane-bound proteins, such as MMP-14, that propagate survival integrin signaling. In order to target tumors, we have engineered an MMP-14 protease-activatable AAV vector that responds to both membrane-bound and extracellularly active MMPs.
View Article and Find Full Text PDFInvited for the cover of this issue are Dr. Stephen Butler, Dr. Hennie Valkenier and co-workers at Université Libre de Bruxelles, Loughborough University, Masaryk University, and the University of Bristol.
View Article and Find Full Text PDFAnion receptors can be used to transport ions across lipid bilayers, which has potential for therapeutic applications. Synthetic bicarbonate transporters are of particular interest, as defects in transmembrane transport of bicarbonate are associated with various diseases. However, no convenient method exists to directly observe bicarbonate transport and study the mechanisms involved.
View Article and Find Full Text PDFBackground: For men with radiation-managed prostate cancer, there is conflicting evidence regarding the association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM), particularly among those who have with preexisting comorbidities. The objective of this study was to analyze the association between ADT and CVM across patient comorbidity status using prospectively collected data from a large clinical trial.
Methods: In total, 1463 men were identified who were diagnosed with clinically localized, intermediate-risk/high-risk prostate cancer (T2b-T4, Gleason 7-10, or prostate-specific antigen >10 ng/mL) from 1993 to 2001 and managed with either radiation therapy (RT) alone or RT plus ADT during the randomized Prostate, Lung, Colon, and Ovarian (PLCO) Cancer Screening Trial.
Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but the antibody characteristics that contribute to efficacy remain poorly understood. This study analyzed plasma samples from 126 eligible convalescent blood donors in addition to 15 naive individuals, as well as an additional 20 convalescent individuals as a validation cohort. Multiplexed Fc Array binding assays and functional antibody response assays were utilized to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody composition and activity.
View Article and Find Full Text PDFLaser-induced refractive index change (LIRIC) is a new, non-incisional, non-ablative, femtosecond photo-modification technique being developed for vision correction in humans. Prior, exvivo studies showed intra-tissue refractive index change to induce minimal cell death, restricted to the laser focal zone in the corneal stroma, and with no observable damage to the epithelium or endothelium. Here, we used live rabbits to ascertain longer-term consequences of LIRIC in vivo.
View Article and Find Full Text PDFBackground And Aims: Social media use has become a ubiquitous part of society, with 3.8 billion users worldwide. While research has shown that there are positive aspects to social media engagement (e.
View Article and Find Full Text PDFAntibodies (Abs) recognizing the Dengue virus (DENV) E dimer epitope (EDE) that potently neutralize all DENV serotypes are promising templates for vaccine design. As an important feature for some Abs is their bivalency, we sought to define the role avidity plays in neutralization by EDE Abs. We compared neutralization activity between bivalent IgGs and monovalent Ab fragments (Fabs) for two EDE Abs, A11 and C10.
View Article and Find Full Text PDFAims And Method: This study evaluated a pilot psychiatry summer school for GCSE students in terms of participant experience, effects on attitudes to mental illness and perception of psychiatry as a career option. This was done using the Community Attitudes towards the Mentally Ill scale, career choice questionnaires and a discussion group following the week-long programme attended by 26 students.
Results: Students were significantly more likely to choose psychiatry after the summer school (P = 0.
Background: A growing proportion of cancer survivors experience financial toxicity. However, the psychological burden of cancer costs and associated mental health outcomes require further investigation. We assessed prevalence and predictors of self-reported financial worry and mental health outcomes among cancer survivors.
View Article and Find Full Text PDFCommissural axons have been a key model system for identifying axon guidance signals in vertebrates. This review summarizes the current thinking about the molecular and cellular mechanisms that establish a specific commissural neural circuit: the dI1 neurons in the developing spinal cord. We assess the contribution of long- and short-range signaling while sequentially following the developmental timeline from the birth of dI1 neurons, to the extension of commissural axons first circumferentially and then contralaterally into the ventral funiculus.
View Article and Find Full Text PDFBackground: As yet, there is limited research that can identify factors that differentiate between painful and nonpainful neuropathies after traumatic nerve injury. The aim of this study was to compare subjects with pain and without pain, all after operative nerve repair in the upper extremities.
Methods: Subjects in both groups (pain, n = 69; painless, n = 62) underwent clinical assessment of sensory nerve function and psychophysical tests: quantitative sensory testing and conditioned pain modulation (CPM).
We describe two differentiation protocols to derive sensory spinal interneurons (INs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). In protocol 1, we use retinoic acid (RA) to induce pain, itch, and heat mediating dI4/dI6 interneurons, and in protocol 2, RA with bone morphogenetic protein 4 (RA+BMP4) is used to induce proprioceptive dI1s and mechanosensory dI3s in hPSC cultures. These protocols provide an important step toward developing therapies for regaining sensation in spinal cord injury patients.
View Article and Find Full Text PDFWildlife conservation policies directed at common and widespread, but declining, species are difficult to design and implement effectively, as multiple environmental changes are likely to contribute to population declines. Conservation actions ultimately aim to influence demographic rates, but targeting actions towards feasible improvements in these is challenging in widespread species with ranges that encompass a wide range of environmental conditions. Across Europe, sharp declines in the abundance of migratory landbirds have driven international calls for action, but actions that could feasibly contribute to population recovery have yet to be identified.
View Article and Find Full Text PDFMouse handling and restraint affect behavior, physiology, and animal welfare, yet little information is available on how various mouse restraint methods affect cardiovascular parameters. We validated the use of a smartphone-based ECG sys- tem in mice by performing simultaneous smartphone and telemetry ECG recordings in conscious, restrained mice and in anesthetized mice. We observed that mice held in standard immobilizing restraint ("scruffing") experienced severe bradycardia.
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