Microglia replacement by ER-Hoxb8 conditionally immortalized macrophages provides insight into Aicardi-Goutières Syndrome neuropathology.

Microglia, the brain's resident macrophages, can be reconstituted by surrogate cells - a process termed "microglia replacement." To expand the microglia replacement toolkit, we here introduce estrogen-regulated (ER) homeobox B8 (Hoxb8) conditionally immortalized macrophages, a cell model for generation of immune cells from murine bone marrow, as a versatile model for microglia replacement. We find that ER-Hoxb8 macrophages are highly comparable to primary bone marrow-derived (BMD) macrophages in vitro, and, when transplanted into a microglia-free brain, engraft the parenchyma and differentiate into microglia-like cells.

[Comparison of the Quality of the Most Commonly Used New UHMWPE Articulation Inserts of the Total Knee Replacement].

Purpose Of Study: Total joint replacements (TJR) have become the cornerstone of modern orthopedic surgery. A great majority of TJR employs ultrahigh molecular weight polyethylene (UHMWPE) liners. TJR manufacturers use many different types of UHMWPE, which are modified by various combinations of crosslinking, thermal treatment, sterilization and/or addition of biocompatible stabilizers.

Quality by design approach to improve quality and decrease cost of in vitro transcription of mRNA using design of experiments.

In vitro transcription (IVT) reaction is an RNA polymerase-catalyzed production of messenger RNA (mRNA) from DNA template, and the unit operation with highest cost of goods in the mRNA drug substance production process. To decrease the cost of mRNA production, reagents should be optimally utilized. Due to the catalytic, multicomponent nature of the IVT reaction, optimization is a multi-factorial problem, ideally suited to design-of-experiment approach for optimization and identification of design space.

ADAM19 cleaves the PTH receptor and associates with brachydactyly type E.

Brachydactyly type E (BDE), shortened metacarpals, metatarsals, cone-shaped epiphyses, and short stature commonly occurs as a sole phenotype. Parathyroid hormone-like protein (PTHrP) has been shown to be responsible in all forms to date, either directly or indirectly. We used linkage and then whole genome sequencing in a small pedigree, to elucidate BDE and identified a truncated disintegrin-and-metalloproteinase-19 (ADAM19) allele in all affected family members, but not in nonaffected persons.

The enteric nervous system relays psychological stress to intestinal inflammation.

Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation.

Ultrastructural effects of sleep and wake on the parallel fiber synapses of the cerebellum.

Multiple evidence in rodents shows that the strength of excitatory synapses in the cerebral cortex and hippocampus is greater after wake than after sleep. The widespread synaptic weakening afforded by sleep is believed to keep the cost of synaptic activity under control, promote memory consolidation, and prevent synaptic saturation, thus preserving the brain's ability to learn day after day. The cerebellum is highly plastic and the Purkinje cells, the sole output neurons of the cerebellar cortex, are endowed with a staggering number of excitatory parallel fiber synapses.

Increasing yield of in vitro transcription reaction with at-line high pressure liquid chromatography monitoring.

The COVID-19 pandemic triggered an unprecedented rate of development of messenger ribonucleic acid (mRNA) vaccines, which are produced by in vitro transcription reactions. The latter has been the focus of intense development to increase productivity and decrease cost. Optimization of in vitro transcription (IVT) depends on understanding the impact of individual reagents on the kinetics of mRNA production and the consumption of building blocks, which is hampered by slow, low-throughput, end-point analytics.

Patient Perception of Plant Based Diets for Kidney Disease.

Objective: Plant-based diets can delay the progression of chronic kidney disease (CKD) and help manage complications and comorbid conditions such as hypertension, acidosis, diabetes, and cardiovascular disease. The objective of this study was to understand nephrology patients' familiarity, perception, and use of plant-based diets.

Design & Methods: A survey was shared via the National Kidney Foundation's social media channels.

Functional modulation of PTH1R activation and signaling by RAMP2.

Receptor-activity-modifying proteins (RAMPs) are ubiquitously expressed membrane proteins that associate with different G protein-coupled receptors (GPCRs), including the parathyroid hormone 1 receptor (PTH1R), a class B GPCR and an important modulator of mineral ion homeostasis and bone metabolism. However, it is unknown whether and how RAMP proteins may affect PTH1R function. Using different optical biosensors to measure the activation of PTH1R and its downstream signaling, we describe here that RAMP2 acts as a specific allosteric modulator of PTH1R, shifting PTH1R to a unique preactivated state that permits faster activation in a ligand-specific manner.

How Engineers and Roadside Vegetation Managers Maintain Roadside Vegetation in Iowa, USA.

Recently the value of roadside vegetation as habitat for pollinators has gained increased attention, particularly in areas dominated by agriculture where there is little native vegetation available. However, many factors, including safety, cost, public perception, erosion control, and weedy plants must be considered when managing roadside vegetation. Although their decisions influence thousands of hectares of public rights-of-way, how engineers and roadside managers maintain roadside vegetation has been the subject of little research.

Receptor-associated independent cAMP nanodomains mediate spatiotemporal specificity of GPCR signaling.

G protein-coupled receptors (GPCRs) relay extracellular stimuli into specific cellular functions. Cells express many different GPCRs, but all these GPCRs signal to only a few second messengers such as cAMP. It is largely unknown how cells distinguish between signals triggered by different GPCRs to orchestrate their complex functions.

Plant-based Diets in Kidney Disease: Nephrology Professionals' Perspective.

Objective: Plant-based diets can delay the progression of chronic kidney disease (CKD) and help manage complications and co-morbid conditions such as hypertension, acidosis, diabetes, and cardiovascular disease. However, it is unclear how often plant-based diets are recommended to patients with kidney disease. The objective of this study was to understand nephrology professionals' familiarity, perception, and recommendation of plant-based diets to people with kidney disease.

Using codesign to develop a mobile application for pelvic floor muscle training with an intravaginal device (femfit®).

Aims: The aim of this project was to use codesign to develop a mobile application (app) for pelvic floor muscle training, with an intravaginal device (femfit®). The objective was to obtain user feedback to guide the design and development of a mobile app, consistent with the Mobile Application Rating Scale (MARS) framework.

Methods: Twenty-six women (22-62 years) provided mobile app feedback using a Design Thinking framework and grounded theory approach.

Bioluminescence in G Protein-Coupled Receptors Drug Screening Using Nanoluciferase and Halo-Tag Technology.

Here we describe the stepwise application of bioluminescence resonance energy transfer (BRET)-based conformational receptor biosensors to study GPCR activation in intact cells. This technology can be easily adopted to various plate reader devices and microtiter plate formats. Due to the high sensitivity of these BRET-based receptor biosensors and their ability to quantify simultaneously receptor activation/de-activation kinetics as well as compound efficacy and potency, these optical tools provide the most direct and unbiased approach to monitor GPCR activity in a high-throughput-compatible assay format, representing a novel promising tool for the discovery of potential GPCR therapeutics.

Local Decision-makers' Perspectives on Roadside Revegetation and Management in Iowa, USA.

Environmental practitioners must understand those they collaborate with to implement programs that are both socially and ecologically effective. Practitioners who understand decision-makers' perspectives are better able to collaborate to lower political, financial, and cultural obstacles. In this study, we surveyed decision-makers involved with a voluntary environmental program in Iowa, USA.

Inflammation Drives MicroRNAs to Limit Hepatocyte Bile Acid Transport in Murine Biliary Atresia.

Background: Biliary atresia (BA) is an inflammatory pediatric cholangiopathy with only surgical means for treatment. Many contributors to bile acid synthesis and transport have previously been reported to be downregulated in patients with BA; yet, the driving factors of the abnormal bile acid synthesis and transport in regard to BA have not been previously studied.

Materials And Methods: Wild type or Ig-α mice were injected with salt solution (control) or rotavirus on day of life 0, and analyses were performed on day of life 14.

[Rotational Laxity of the Knee Joint - In Vivo MRI Study].

PURPOSE OF THE STUDY The purpose of the study was to evaluate tibio-femoral rotation during a simulated squat and to investigate the relationship between the rotational position of the femur in full extension and the amount of external rotation of the femur on the tibia during flexion. MATERIAL AND METHODS Part 1: MRIs of volunteers Data on healthy knees of 10 volunteers were obtained using 2D MRI measurements. The foot and the ankle were fixed to prevent rotation and adduction/abduction movements.

Evidence for sleep-dependent synaptic renormalization in mouse pups.

In adolescent and adult brains several molecular, electrophysiological, and ultrastructural measures of synaptic strength are higher after wake than after sleep [1, 2]. These results support the proposal that a core function of sleep is to renormalize the increase in synaptic strength associated with ongoing learning during wake, to reestablish cellular homeostasis and avoid runaway potentiation, synaptic saturation, and memory interference [2, 3]. Before adolescence however, when the brain is still growing and many new synapses are forming, sleep is widely believed to promote synapse formation and growth.

[Two-Stage Revision for Periprosthetic Infection of the Total Hip Arthroplasty: a Comparison of Two Methods].

PURPOSE OF THE STUDY The purpose of the study is a retrospective comparison of results of the two-stage revision total hip arthroplasty using a non-articulating and an articulating spacer to treat periprosthetic joint infection (PJI). Two basic hypotheses are evaluated: (1) the clinical outcomes of the patients treated with "hand made" articulating cement spacer are better than in non-articulating patient's group in two-stage revision for PJI of the total hip arthroplasty and (2) PJI recurrence is higher in the group of patients treated with an articulating spacer group. MATERIAL AND METHODS The evaluated group consists of a total of 57 patients (23 women, 34 men) with the mean age of 61.

[Anterior Cruciate Ligament Tears - Influence on Terminal Extension].

PURPOSE OF THE STUDY The aim of this paper was to compare terminal extension in normal and anterior cruciate ligament (ACL) deficient knees, and therefore to determine the role of the ACL during this motion. MATERIAL AND METHODS Ten knees with ACL tears (7 knees with recent ACL tears, 3 knees with long-standing tears) and 10 normal contralateral knees have been examined using MRI in passive hyperextension, 20° flexion and 20° flexion with a 9 kg posteriorly directed load on the femur. Movements of the femoral condyles on the tibia were calculated using previously described methods.

Risk factors for football injuries in young players aged 7 to 12 years.

Football (soccer) is very popular among children. Little is known about risk factors for football injuries in children. The aim was to analyze potential injury risk factors in 7- to 12-year-old players.