The authors successfully used a new approach that significantly minimized brain damage caused by stroke in mouse models, which works by targeting hemichannels that are expressed by astrocytes. When stroke occurs, these hemichannels open and can leak toxic molecules into the space outside the astrocytes, causing inflammation and damage to neurons.
The authors identified roles for a protein called EFHC1 at both the cilium and the neuronal synapse, which is involved in relaying information to other cells. EFHC1 was previously associated with the motility of cilia, but not sensory or signalling functions. Using the nematode Caenorhabditis elegans as a model system, they found that EFHC1 operates specifically in ciliated cells and regulates dopamine signalling. Accordingly, they discovered that disruption of EFHC1 leads to defects in dopamine-mediated behavioural phenotypes.
The authors created highly detailed functional and protein maps of the entire blood stem and progenitor populations that can be isolated from human cord blood. These maps showed that cell populations isolated by methods historically used to enrich for distinct outputs are much more heterogeneous in all their properties than had been previously assumed. This led them to develop new ways of isolating populations that are quite “pure” in terms of the cell types they can produce, which then made it possible to analyze some of their related molecular properties.
Huntington’s disease is caused by an abnormally expanded CAG repeat expansion in the HTT gene, which confers a predominant toxic gain of function in the mutant huntingtin (mHTT) protein. There are currently no disease-modifying therapies available, but approaches that target proximally in disease pathogenesis hold great promise. These include DNA-targeting techniques such as zinc-finger proteins, transcription activator-like effector nucleases, and CRISPR/Cas9; post-transcriptional huntingtin-lowering approaches such as…
Prostate cancer (PCa) is the most common malignant neoplasm among men in many countries. Since most precancerous and cancerous tissues show signs of inflammation, chronic bacterial prostatitis has been hypothesized to be a possible etiology. However, establishing a causal relationship between microbial inflammation and PCa requires a comprehensive analysis of the prostate microbiome. The aim of this study was to…
Background Acute chorioamnionitis (aCA), inflammation of the placenta and fetal membranes, is a frequently reported lesion in preterm deliveries. Genetic variants in innate immune system genes such as Interleukin-6 (IL6) may contribute to the placenta’s inflammatory response, thus predisposing some pregnancies to aCA. These genetic variants may modulate molecular processes such as DNA methylation and gene expression, and in turn…
The blood-brain barrier (BBB) separates the brain from circulating blood and it is essential for maintaining healthy brain function. Expression of podocalyxin on the inner “tube” of blood vessels (vascular endothelia) has been known for a long time. When the authors delete this protein from blood vessels in mice they develop normally and appeared to be perfectly healthy. However, they found that podocalyxin has an important role in maintaining BBB integrity during inflammation.
The authors conducted a gene expression screen to identify genes controlling innate and adaptive immunity, and ABCF1, an ATP-Binding Cassette gene, was identified as a potential regulator of immunity and inflammation. Their interest was further sparked because others had shown that ABCF1 expression is elevated in the synovial fluid of rheumatoid arthritis patients and the ABCF1 gene had also been mapped as a susceptibility risk gene for autoimmune pancreatitis.
In their most current integrative genomics studies the authors discovered the genetic and molecular features associated with MHC class I and II loss. They uncovered that MHC class II loss is most relevant in germinal center B (GCB) cell-type DLBCL as loss is associated with poor treatment outcome, a specific set of gene mutations characteristic of GCB-DLBCL, and an expression program that is associated with an immunologically “cold” microenvironment with a reduced T cell infiltrate.
Standard isolation of ctDNA involves the separation of plasma by centrifugation followed by column or magnetic bead-based purification of nucleic acids. While magnetic beads are more amenable to automation on liquid handlers, the upstream centrifugation remains largely manual and limits scalability. We present here a magnetic bead-based ctDNA isolation method that eliminates centrifugation steps to allow ctDNA purification directly from whole blood in 96-well plate format. Furthermore, this automated method minimizes manual handling of patient blood, lowering the risk of sample swaps and exposure to staff of blood borne infections.