Stem Cell Markers LGR5, LGR4 and Their Immediate Signalling Partners are Dysregulated in Preeclampsia.

Leucine-rich repeat-containing G protein-coupled receptors 5/4 (LGR5/LGR4) are critical stem cell markers in epithelial tissues including intestine. They agonise wingless-related integration site (WNT) signalling. Until now, LGR5/LGR4 were uncharacterised in placenta, where analogous functions may exist.

Lessons learned from the experiences of patients with long-term conditions: recommendations for enhancing the undergraduate medical curriculum.

The importance of involving patients in medical education is widely accepted, but their contribution to medical curriculum design is not well documented. Patients have the potential to bring a unique perspective and more refined experience to curriculum development. This applies particularly to those with long-term conditions (LTCs) who have multiple exposures to doctors throughout their healthcare journey.

Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) is reduced with preeclampsia and small for gestational aged fetuses.

Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) is an inhibitory receptor expressed on immune cells. We evaluated LAIR1 in placentas from preeclamptic or small for gestational age (SGA) pregnancies, and placental explant model (1 % O, IL6 and TNFα, or control). LAIR1 mRNA was reduced in placentas from preeclamptic (p < 0.

Reprogramming human B cells with custom heavy-chain antibodies.

The immunoglobulin locus of B cells can be reprogrammed by genome editing to produce custom or non-natural antibodies that are not induced by immunization. However, current strategies for antibody reprogramming require complex expression cassettes and do not allow for customization of the constant region of the antibody. Here we show that human B cells can be edited at the immunoglobulin heavy-chain locus to express heavy-chain-only antibodies that support alterations to both the fragment crystallizable domain and the antigen-binding domain, which can be based on both antibody and non-antibody components.

Trophoblast Side-Population Markers are Dysregulated in Preeclampsia and Fetal Growth Restriction.

Dysregulated progenitor cell populations may contribute to poor placental development and placental insufficiency pathogenesis. Side-population cells possess progenitor properties. Recent human trophoblast side-population isolation identified enrichment of 8 specific genes (CXCL8, ELL2, GATA6, HK2, HLA-DPB1, INTS6, SERPINE3 and UPP1) (Gamage et al.

Development and Evaluation of Real-Time Quantitative PCR Assays for Detection of Causing Brown Root Rot Disease.

Brown root rot disease (BRRD) is a highly destructive tree disease. Early diagnosis of BRRD has been challenging because the first symptoms and signs are often observed after extensive tissue colonization. Existing molecular detection methods, all based on the internal transcribed spacer (ITS) region, were developed without testing against global isolates, other wood-decay fungi, or host plant tissues.

Transcriptome analysis of cardiac endothelial cells after myocardial infarction reveals temporal changes and long-term deficits.

Endothelial cells (ECs) have essential roles in cardiac tissue repair after myocardial infarction (MI). To establish stage-specific and long-term effects of the ischemic injury on cardiac ECs, we analyzed their transcriptome at landmark time points after MI in mice. We found that early EC response at Day 2 post-MI centered on metabolic changes, acquisition of proinflammatory phenotypes, initiation of the S phase of cell cycle, and activation of stress-response pathways, followed by progression to mitosis (M/G2 phase) and acquisition of proangiogenic and mesenchymal properties during scar formation at Day 7.

A Safe Framework for Quantitative In Vivo Human Evaluation of Image Guidance.

We present a new framework for in vivo image guidance evaluation and provide a case study on robotic partial nephrectomy. This framework (called the "bystander protocol") involves two surgeons, one who solely performs the therapeutic process without image guidance, and another who solely periodically collects data to evaluate image guidance. This isolates the evaluation from the therapy, so that in-development image guidance systems can be tested without risk of negatively impacting the standard of care.

To burn or not to burn: governance of wildfires in Australia.

Globally, wildfires are increasing in extent, frequency, and severity. Although global climate change is a major driver and large-scale governance interventions are essential, focusing on governance at smaller scales is of great importance for fostering resilience to wildfires. Inherent tensions in managing wildfire risk are evident at such scales, as objectives and mandates may conflict, and trade-offs and impacts vary across ecosystems and communities.

3D convolutional neural networks uncover modality-specific brain-imaging predictors for Alzheimer's disease sub-scores.

Different aspects of cognitive functions are affected in patients with Alzheimer's disease. To date, little is known about the associations between features from brain-imaging and individual Alzheimer's disease (AD)-related cognitive functional changes. In addition, how these associations differ among different imaging modalities is unclear.

Are 3D Image Guidance Systems Ready for Use? A Comparative Analysis of 3D Image Guidance Implementations in Minimally Invasive Partial Nephrectomy.

Three-dimensional image-guided surgical (3D-IGS) systems for minimally invasive partial nephrectomy (MIPN) can potentially improve the efficiency and accuracy of intraoperative anatomical localization and tumor resection. This review seeks to analyze the current state of research regarding 3D-IGS, including the evaluation of clinical outcomes, system functionality, and qualitative insights regarding 3D-IGS's impact on surgical procedures. We have systematically reviewed the clinical literature pertaining to 3D-IGS deployed for MIPN.

Comparison of SARS-CoV-2 entry inhibitors based on ACE2 receptor or engineered Spike-binding peptides.

With increasing resistance of SARS-CoV-2 variants to antibodies, there is interest in developing entry inhibitors that target essential receptor-binding regions of the viral Spike protein and thereby present a high bar for viral resistance. Such inhibitors could be derivatives of the viral receptor, ACE2, or peptides engineered to interact specifically with the Spike receptor-binding pocket. We compared the efficacy of a series of both types of entry inhibitors, constructed as fusions to an antibody Fc domain.

Cell surface associated protein mucin 15 (MUC15) is elevated in preeclampsia.

Background: Mucins are a family of proteins that protect the epithelium. A particular type of mucin, MUC15 is highly expressed in the placenta. This study aimed to characterise MUC15 in preeclampsia and investigate its role in placental stem cell biology.

Reprogramming human B cells with custom heavy chain antibodies.

We describe a genome editing strategy to reprogram the immunoglobulin heavy chain (IgH) locus of human B cells to express custom molecules that respond to immunization. These heavy chain antibodies (HCAbs) comprise a custom antigen-recognition domain linked to an Fc domain derived from the IgH locus and can be differentially spliced to express either B cell receptor (BCR) or secreted antibody isoforms. The HCAb editing platform is highly flexible, supporting antigen-binding domains based on both antibody and non-antibody components, and also allowing alterations in the Fc domain.

Paternal Expressed Gene 10 (PEG10) is decreased in early-onset preeclampsia.

Background: Preeclampsia is a severe complication of pregnancy which is attributed to placental dysfunction. The retrotransposon, Paternal Expressed Gene 10 (PEG10) harbours critical placental functions pertaining to placental trophoblast cells. Limited evidence exists on whether PEG10 is involved in preeclampsia pathogenesis.

Exercise knowledge, barriers and motivators among LRRK2 G2019S mutation carriers.

Introduction: People with a Gly2019Ser mutation in the leucine-rich repeat kinase 2 (LRRK2 G2019S) are at increased risk of developing Parkinson's disease (PD). Recent evidence suggests that exercise may delay or prevent the development of clinically overt symptoms of PD in people at risk of PD. We determined whether LRRK2 G2019S mutation carriers with and without manifest PD are aware of the relationship between exercise and PD and how they differ in awareness, barriers and motivators to exercise.

Reprogramming human B cells with custom heavy chain antibodies.

We describe a genome editing strategy to reprogram the immunoglobulin heavy chain (IgH) locus of human B cells to express custom molecules that respond to immunization. These heavy chain antibodies (HCAbs) comprise a custom antigen-recognition domain linked to an Fc domain derived from the IgH locus and can be differentially spliced to express either B cell receptor (BCR) or secreted antibody isoforms. The HCAb editing platform is highly flexible, supporting antigen-binding domains based on both antibody and non-antibody components, and also allowing alterations in the Fc domain.

Submandibular sialolith migration.

A middle-aged male Caucasian had rejected previous offers of surgery for submandibular gland removal in the past due to concerns about surgical complications. He presented with a month's history of submandibular swelling and severe pain, which impeded his ability to eat. Prior to admission, he had been experiencing intermittent sialadenitis for several months.

SARS-CoV-2 Enters Human Leydig Cells and Affects Testosterone Production In Vitro.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a SARS-like coronavirus, continues to produce mounting infections and fatalities all over the world. Recent data point to SARS-CoV-2 viral infections in the human testis. As low testosterone levels are associated with SARS-CoV-2 viral infections in males and human Leydig cells are the main source of testosterone, we hypothesized that SARS-CoV-2 could infect human Leydig cells and impair their function.

Occurrence of emerging contaminants in biosolids in northern Queensland, Australia.

This study aims to identify and quantify different classes of emerging contaminants (ECs), such as pharmaceutical and personal care products (PPCPs), per-and polyfluoroalkyl substances (PFAS), heavy metals (HMs), polycyclic musks (PMs) in biosolids from different sewage treatment plants (STPs) from regional councils across Northern Queensland, Australia. Biosolids samples were named BS1 to BS7 for each council. The results revealed significant variations in the concentrations of different ECs in biosolids which could be explained in some instances by the characteristics of the upstream sewage network.

Challenge GP: using gamification to bring the reality and uncertainty of a duty doctor's surgery to early year medical students.

Exposing medical student cohorts to the lived reality of uncertainty and complexity experienced by GPs is challenging to achieve. We present a novel teaching concept: 'Challenge GP' designed for early years students. Gamification methodology is used to reproduce key elements of the 'duty GP' experience in a classroom setting where working in teams, students play a competitive card game.

Microbial and thermal treatment techniques for degradation of PFAS in biosolids: A focus on degradation mechanisms and pathways.

Per- and polyfluoroalkyl substances (PFAS) are persistent organic chemicals detected in biosolids worldwide, which have become a significant concern for biosolids applications due to their increasing environmental risks. Hence, it is pivotal to understand the magnitude of PFAS contamination in biosolids and implement effective technologies to reduce their contamination and prevent hazardous aftermaths. Thermal techniques such as pyrolysis, incineration and gasification, and biodegradation have been regarded as impactful solutions to degrade PFAS and transform biosolids into value-added products like biochar.

Circulating Chemerin Is Elevated in Women With Preeclampsia.

Background: Preeclampsia is a severe complication of pregnancy. Chemerin is an adipokine secreted from adipose tissue and highly expressed in placenta. This study evaluated the biomarker potential of circulating chemerin to predict preeclampsia.