Light-induced conformational switching and magnetic sensitivity of Drosophila cryptochrome.

Cryptochromes are light-sensitive flavoproteins with various biological roles, including a proposed function in magnetoreception. This mechanism rests on a magnetically sensitive photochemical reaction of the flavin chromophore with a chain of tryptophan residues within the protein scaffold. However, the protein-mediated mechanisms of magnetic signal transduction are unclear.

14-3-3ε UFMylation promotes RIG-I-mediated signaling.

Unlabelled: Post-translational modifications are critical for regulating the RIG-I signaling pathway. Previously, we identified a role for the post-translation modification UFM1 (UFMylation) in promoting RIG-I signaling by stimulating the interaction between RIG-I and its membrane-targeting protein 14-3-3ε. Here, we identify UFMylation of 14-3-3ε as a novel regulatory mechanism promoting RIG-I signaling.

The Exonuclease TREX1 Constitutes an Innate Immune Checkpoint Limiting cGAS/STING-Mediated Antitumor Immunity.

The DNA exonuclease three-prime repair exonuclease 1 (TREX1) is critical for preventing autoimmunity in mice and humans by degrading endogenous cytosolic DNA, which otherwise triggers activation of the innate cGAS/STING pathway leading to the production of type I IFNs. As tumor cells are prone to aberrant cytosolic DNA accumulation, we hypothesized that they are critically dependent on TREX1 activity to limit their immunogenicity. Here, we show that in tumor cells, TREX1 restricts spontaneous activation of the cGAS/STING pathway, and the subsequent induction of a type I IFN response.

Absolute Photoionization Cross Section and Dissociative Ionization Pathways of Alpha-Pinene.

The absolute photoionization cross section of the monoterpenoid, alpha-pinene (AP), is presented together with the relative photoionization cross sections of its dissociative fragments for the first time. Experiments are performed via multiplexed vacuum ultraviolet (VUV) synchrotron photoionization (PI) mass spectrometry in the 8.0-11.

Risk prediction models for antineoplastic-associated cardiotoxicity in treatment of breast cancer: A systematic review.

Purpose: The objective of this systematic review is to assess methodology of published models to predict the risk of antineoplastic-associated cardiotoxicity in patients with breast cancer.

Methods: We searched PubMed and Embase for studies that developed or validated a multivariable risk prediction model. Data extraction and quality assessments were performed according to the Prediction Model Risk of Bias Assessment Tool (PROBAST).

Predicting wildlife corridors for multiple species in an East African ungulate community.

Wildlife corridors are typically designed for single species, yet holistic conservation approaches require corridors suitable for multiple species. Modelling habitat linkages for wildlife is based on several modelling steps (each involving multiple choices), and in the case of multi-species corridors, an approach to optimize single species corridors to few or a single functional corridor for multiple species. To model robust corridors for multiple species and simultaneously evaluate the impact of methodological choices, we develop a multi-method approach to delineate corridors that effectively capture movement of multiple wildlife species, while limiting the area required.

PICC versus midlines: Comparison of peripherally inserted central catheters and midline catheters with respect to incidence of thromboembolic and infectious complications.

Introduction: To decrease the complications related to central catheters there has been an increasing utilization of peripherally inserted central catheters (PICC) and ultrasound-guided long peripheral intravenous catheters (i.e. midlines).

Strength of Recommendation and Quality of Evidence for Recommendations in Current Infectious Diseases Society of America Guidelines.

Background: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) is a systematic approach to grading strength of recommendation (SOR) and quality of evidence (QOE) for guideline recommendations. We aimed to assess the relationship between SOR and QOE in current Infectious Diseases Society of America (IDSA) guidelines.

Methods: In this cross-sectional analysis, we analyzed the frequency of SOR-QOE pairings, including discordance (defined as strong SOR based on expert opinion, very low, or low QOE) for GRADEd recommendations in IDSA guidelines published since 2010.

pH-dependence of signaling-state formation in Drosophila cryptochrome.

Cryptochromes, FAD-dependent blue light photoreceptors, undergo a series of electron transfer reactions after light excitation. Time-resolved optical spectroscopy was employed to investigate the pH dependence of all light-dependent reactions in the cryptochrome from fruit flies. Signal state formation experiments on a time scale of seconds were found to be strongly pH dependent, and formation of both anionic and neutral FAD radicals could be detected, with reaction rates increasing by a factor of ~2.

Why are they not accessing it? User barriers to clinical information access.

The Medical Library Association's InSight Initiative provides an open and collaborative environment for library and industry partners to discuss vexing problems and find solutions to better serve their users. The initiative's fifth summit, continuing work from the previous summit, focused on understanding how users discover and access information in the clinical environment. During the summit, participants were divided into working groups and encouraged to create a tangible product as a result of their discussions.

Autoimmunity linked protein phosphatase PTPN22 as a target for cancer immunotherapy.

Background: Cancer immunotherapy has evolved from interferon-alpha (IFNα) and interleukin-2 in the 1980s to CTLA-4 and PD-1/PD-L1 checkpoint inhibitors (CPIs), the latter highlighting the importance of enhancing T-cell functions. While the search for novel immunomodulatory pathways continues, combination therapies augmenting multiple pathways can also increase efficacy. The association of autoimmune-related adverse events with clinical efficacy following CPI treatment has been inferred and suggests that breaking tolerance thresholds associated with autoimmunity may affect host immune responses for effective cancer immunotherapy.

COLD REGULATED 27 and 28 are targets of CONSTITUTIVELY PHOTOMORPHOGENIC 1 and negatively affect phytochrome B signalling.

Phytochromes are red/far-red light receptors in plants involved in the regulation of growth and development. Phytochromes can sense the light environment and contribute to measuring day length; thereby, they allow plants to respond and adapt to changes in the ambient environment. Two well-characterized signalling pathways act downstream of phytochromes and link light perception to the regulation of gene expression.

Role of angiotensin II in treatment of refractory distributive shock.

Objective: Clinical data and gaps in knowledge regarding angiotensin II (AT2), which was approved by the Food and Drug Administration in December 2017 via priority review for treatment of septic and other vasodilatory shock, is discussed.

Summary: AT2 is an endogenous peptide that raises blood pressure via vasoconstriction and increased aldosterone release. It was previously available but withdrawn from the US market; previous low-quality research describes increases in mean arterial pressure (MAP).

Photoactivation of cryptochrome through sequential conformational transitions.

Cryptochromes are blue-light photoreceptor proteins, which provide input to circadian clocks. The cryptochrome from (Cry) modulates the degradation of Timeless and itself. It is unclear how light absorption by the chromophore and the subsequent redox reactions trigger these events.

Ultrasonography for Dorsal-Sided Wrist Pain in a Combat Environment: Technique, Pearls, and a Case Report of Dynamic Evaluation of the Scapholunate Ligament.

Ultrasonography is a commonly utilized tool in orthopedic surgery for the diagnosis and treatment of a variety of musculoskeletal conditions, including pathology about the wrist. Its value should not be underestimated when other diagnostic resources are unavailable - such as in a combat setting where ultrasounds, but not X-ray, are a standard equipment item. An active duty soldier presented to an orthopedic provider in an austere environment with chronic dorsal wrist pain due to a previous fall.

Coexpression of Inhibitory Receptors Enriches for Activated and Functional CD8 T Cells in Murine Syngeneic Tumor Models.

Exhausted T cells have been described in cancer patients and murine tumor models largely based on their expression of various inhibitory receptors. Understanding of the functional attributes of these cells is limited. Here, we report that among CD8 T cells in commonly used syngeneic tumor models, the coexpression of inhibitory receptors PD-1, LAG3, and TIM3 defined a group of highly activated and functional effector cells.

Anti-PD-L1 Treatment Results in Functional Remodeling of the Macrophage Compartment.

Checkpoint inhibitors like anti-PD1/PD-L1 have demonstrated significant therapeutic efficacy in a subset of patients partly through reinvigoration of CD8 T cells. However, their impact on myeloid cells remains largely unknown. Here, we report that anti-PD-L1 treatment favorably impacts the phenotype and function of tumor macrophages by polarizing the macrophage compartment toward a more proinflammatory phenotype.

Novel Vasopressors in the Treatment of Vasodilatory Shock: A Systematic Review of Angiotensin II, Selepressin, and Terlipressin.

Study Objective: Vasodilatory shock is the most common type of shock. Catecholamine vasopressors are the cornerstone of hemodynamic therapy but carry risks. Angiotensin II (AT) was recently approved, and other novel agents (selepressin and terlipressin) are under investigation and used outside the United States (terlipressin).

The Safety of Intravenous Drug Delivery Systems: Update on Current Issues Since the 2009 Consensus Development Conference.

This review was prepared in advance of the Third Consensus Development Conference on the Safety of Intravenous Drug Delivery Systems that was held at the W Hotel in Chicago, Illinois, from November 1 through 3, 2018. The purpose of this conference was to evaluate the safety of intravenous (IV) infusion systems used for medication administration. The expert panel of pharmacists, physicians, and nurses updated the findings of the Second Consensus Development Conference in 2009 that reviewed 5 IV drug delivery systems (manufacturer ready to use, outsourced ready to use, point-of-care activated, pharmacy compounded, and nonpharmacy compounded at point of care) with regard to applicability, ease of use, regulatory compliance, cost, safety, and implementation.

The Natural History of Gastrointestinal Bleeding in Patients without an Obvious Source.

With the advent of proton pump inhibitors and H. Pylori treatment, the old dogma "the most common cause of lower GI bleeding is upper GI bleeding" may no longer be valid. We sought to determine the most common causes of GI bleeding in patients without an obvious source and their clinical outcomes.