Novel Far-Red Fluorescent 1,4-Dihydropyridines for L-Type Calcium Channel Imaging.

Upregulation of L-type calcium channels (LTCCs) is implicated in a range of cardiovascular and neurological disorders. Therefore, the development of toolboxes that unlock fast imaging protocols in live cells is coveted. Herein, we report a library of first-in-class far-red small-molecule-based fluorescent ligands (FluoDiPines), able to target LTCCs.

Subtle changes in plant diversity in the Bavarian Alps over the past eight decades.

Historical resurveys represent a unique opportunity to analyze vegetation dynamics over longer timescales than is typically achievable. Leveraging the oldest historical dataset of vegetation change in the Bavarian Alps, Germany, we address how environmental conditions, vegetation composition, and functional diversity in the calcareous grasslands of the Schachen region have changed across different elevational ranges over an 83-year timeframe. We document changes in regional average temperature and precipitation.

Rectal organoid morphology analysis (ROMA) as a novel physiological assay for diagnostic classification in cystic fibrosis.

Background: Diagnosing cystic fibrosis (CF) is not always straightforward, in particular when sweat chloride concentration (SCC) is intermediate and <2 CF-causing variants are identified. The physiological CFTR assays proposed in the guidelines, nasal potential difference and intestinal current measurement, are not readily available nor feasible at all ages. Rectal organoid morphology analysis (ROMA) was previously shown to discriminate between organoids from subjects with and without CF based on a distinct phenotypical difference: compared with non-CF organoids, CF organoids have an irregular shape and lack a visible lumen.

Innovating in a bioimaging core through instrument development.

Developing devices and instrumentation in a bioimaging core facility is an important part of the innovation mandate inherent in the core facility model but is a complex area due to the required skills and investments, and the impossibility of a universally applicable model. Here, we seek to define technological innovation in microscopy and situate it within the wider core facility innovation portfolio, highlighting how strategic development can accelerate access to innovative imaging modalities and increase service range, and thus maintain the cutting edge needed for sustainability. We consider technology development from the perspective of core facility staff and their stakeholders as well as their research environment and aim to present a practical guide to the 'Why, When, and How' of developing and integrating innovative technology in the core facility portfolio.

Staying on track - Keeping things running in a high-end scientific imaging core facility.

Modern life science research is a collaborative effort. Few research groups can single-handedly support the necessary equipment, expertise and personnel needed for the ever-expanding portfolio of technologies that are required across multiple disciplines in today's life science endeavours. Thus, research institutes are increasingly setting up scientific core facilities to provide access and specialised support for cutting-edge technologies.

What we can learn from deep space communication for reproducible bioimaging and data analysis.

Multiple initiatives have attempted to define and recommend the annotation of images with metadata. However, proper documentation of complex and evolving projects is a difficult task, and the variety of storage methods—electronic labnotebooks, metadata servers, repositories and manuscripts—along with data from different time points of a given project leads to either redundancy in annotation or omissions. In this Commentary, we discuss how to tackle this problem, taking inspiration from space communication which uses error-correction protocols based on redundancy for data transmission.

Heterozygous mutations in the C-terminal domain of COPA underlie a complex autoinflammatory syndrome.

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.

Early weight measures and long-term neuropsychological outcome of critically ill neonates and infants: a secondary analysis of the PEPaNIC trial.

Unlabelled: Neonates and infants surviving critical illness show impaired growth during critical illness and are at risk for later neuropsychological impairments. Early identification of individuals most at risk is needed to provide tailored long-term follow-up and care. The research question is whether early growth during hospitalization is associated with growth and neuropsychological outcomes in neonates and infants after pediatric intensive care unit admission (PICU).

A comparison of ultrafast and conventional spectral Doppler ultrasound to measure cerebral blood flow velocity during inguinal hernia repair in infants.

Background: Ultrafast cerebral Doppler ultrasound enables simultaneous quantification and visualization of cerebral blood flow velocity. The aim of this study is to compare the use of conventional and ultrafast spectral Doppler during anesthesia and their potential to show the effect of anesthesiologic procedures on cerebral blood flow velocities, in relation to blood pressure and cerebral oxygenation in infants undergoing inguinal hernia repair.

Methods: A single-center prospective observational cohort study in infants up to six months of age.

Novel non-HAP class A HBV capsid assembly modulators have distinct and profiles.

Chronic hepatitis B is the most important cause of liver cancer worldwide and affects more than 290 million people. Current treatments are mostly suppressive and rarely lead to a cure. Therefore, there is a need for novel and curative drugs that target the host or the causative agent, hepatitis B virus itself.

High-intensity interval training and thromboembolic events during chemotherapy for testicular cancer: a retrospective analysis from the cohort.

Men with testicular cancer receiving platinum-based chemotherapy have an increased risk of thromboembolic events, with incidence rates between 8-24%. A recent trial evaluating the effect of high-intensity interval training (HIIT) prematurely closed as three out of nine participants (33%) in the intervention group developed a thromboembolic event. The purpose of this retrospective cohort study was: 1) (primary) to evaluate the incidence of thromboembolic events in men receiving chemotherapy for testicular cancer who had participated in HIIT during a 6-week exercise program ( 2) to describe the feasibility of this program.

Improving de novo protein binder design with deep learning.

Recently it has become possible to de novo design high affinity protein binding proteins from target structural information alone. There is, however, considerable room for improvement as the overall design success rate is low. Here, we explore the augmentation of energy-based protein binder design using deep learning.

Class A capsid assembly modulator RG7907 clears HBV-infected hepatocytes through core-dependent hepatocyte death and proliferation.

Background And Aims: Effective therapies leading to a functional cure for chronic hepatitis B are still lacking. Class A capsid assembly modulators (CAM-As) are an attractive modality to address this unmet medical need. CAM-As induce aggregation of the HBV core protein (HBc) and lead to sustained HBsAg reductions in a chronic hepatitis B mouse model.

Early brain magnetic resonance imaging findings and neurodevelopmental outcome in children with congenital heart disease: A systematic review.

Aim: To investigate the association between early brain magnetic resonance imaging (MRI) findings and neurodevelopmental outcome (NDO) in children with congenital heart disease (CHD).

Method: A search for studies was conducted in Embase, Medline, Web of Science, Cochrane Central, PsycINFO, and Google Scholar. Observational and interventional studies were included, in which patients with CHD underwent surgery before 2 months of age, a brain MRI scan in the first year of life, and neurodevelopmental assessment beyond the age of 1 year.

French national diagnosis and care protocol (PNDS, protocole national de diagnostic et de soins): cystic lymphatic malformations.

Cystic lymphatic malformations (LMs) are rare chronic conditions which management differs according to the type (macrocystic LMs, microcystic LMs or both). Studies are lacking due to rarity of the pathology. We aimed to establish a French National Diagnosis and Care Protocol (PNDS: Protocole National de Diagnostic et de Soins), to provide health professionals with free open access synthesis on optimal management and care of patients with LMs ( https://www.

Neuropsychological outcome in survivors of congenital diaphragmatic hernia at 5 years of age, what does it tell?

Previous studies have frequently reported neurocognitive deficits in children born with congenital diaphragmatic hernia (CDH) at school age, which may contribute to academic difficulties. Yet, age at onset of these deficits is currently unknown. We evaluated neurocognitive skills with possible determinants in preschool children born with CDH.

How tech-savvy employees make the difference in core facilities: Recognizing core facility expertise with dedicated career tracks: Recognizing core facility expertise with dedicated career tracks.

Core facilities have a different mission than academic research labs. Accordingly, they require different career paths and structures.

Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation.

The ability of immune-modulating biologics to prevent and reverse pathology has transformed recent clinical practice. Full utility in the neuroinflammation space, however, requires identification of both effective targets for local immune modulation and a delivery system capable of crossing the blood-brain barrier. The recent identification and characterization of a small population of regulatory T (T) cells resident in the brain presents one such potential therapeutic target.

Preservation of Fluorescence Signal and Imaging Optimization for Integrated Light and Electron Microscopy.

Life science research often needs to define where molecules are located within the complex environment of a cell or tissue. Genetically encoded fluorescent proteins and or fluorescence affinity-labeling are the go-to methods. Although recent fluorescent microscopy methods can provide localization of fluorescent molecules with relatively high resolution, an ultrastructural context is missing.

Persisting Motor Function Problems in School-Aged Survivors of Congenital Diaphragmatic Hernia.

Children born with congenital diaphragmatic hernia (CDH) and treated with extracorporeal membrane oxygenation (ECMO), are at risk for motor function impairment during childhood. We hypothesized that all children born with CDH are at risk for persistent motor function impairment, irrespective of ECMO-treatment. We longitudinally assessed these children's motor function.

Structural basis of cytokine-mediated activation of ALK family receptors.

Anaplastic lymphoma kinase (ALK) and the related leukocyte tyrosine kinase (LTK) are recently deorphanized receptor tyrosine kinases. Together with their activating cytokines, ALKAL1 and ALKAL2 (also called FAM150A and FAM150B or AUGβ and AUGα, respectively), they are involved in neural development, cancer and autoimmune diseases. Furthermore, mammalian ALK recently emerged as a key regulator of energy expenditure and weight gain, consistent with a metabolic role for Drosophila ALK.