CRB1 is required for recycling by RAB11A+ vesicles in human retinal organoids.

CRB1 gene mutations can cause early- or late-onset retinitis pigmentosa, Leber congenital amaurosis, or maculopathy. Recapitulating human CRB1 phenotypes in animal models has proven challenging, necessitating the development of alternatives. We generated human induced pluripotent stem cell (iPSC)-derived retinal organoids of patients with retinitis pigmentosa caused by biallelic CRB1 mutations and evaluated them against autologous gene-corrected hiPSCs and hiPSCs from healthy individuals.

Quantification of Movement Characteristics in Women's English Premier Elite Domestic Rugby Union.

This study aims were to determine the positional physical requirements of English domestic women's rugby union match-play. Global positioning system data (Catapult Minimax S4) were collected at 10 Hz of 129 competitive player games from the Tyrrells Premier15 league. Players were classified according to broad (Forwards, Backs) and specific positions (front-, second-, back-row, scrum-half, inside-, and outside-backs).

Analysis of the association of EPHB6, EFNB1 and EFNB3 variants with hypertension risks in males with hypogonadism.

Several members of the EPH kinase family and their ligands are involved in blood pressure regulation, and such regulation is often sex- or sex hormone-dependent, based on animal and human genetic studies. EPHB6 gene knockout (KO) in mice leads to hypertension in castrated males but not in un-manipulated KO males or females. To assess whether this finding in mice is relevant to human hypertension, we conducted a human genetic study for the association of EPHB6 and its two ligands, EFNB1 and EFNB3, with hypertension in hypogonadic patients.

Effect of the PreBind Engagement Process on Scrum Timing and Stability in the 2013-16 Six Nations.

This study examined whether changes in scrum engagement laws from the "crouch-touch-set" in 2013 to the "PreBind" engagement from 2014 onward have led to changes in scrum characteristics, specifically timing, in international rugby union. Duration and outcomes were identified for all scrums occurring in the 2013-16 Six Nations (N = 60 games) using video analysis. Scrum duration increased after the introduction of the PreBind engagement from 59 s in 2013 to 69 s in 2016 (P = .

Evidence from single nucleotide polymorphism analyses of ADVANCE study demonstrates EFNB3 as a hypertension risk gene.

EPH kinases and their ligands, ephrins (EFNs), have vital and diverse biological functions. We recently reported that Efnb3 gene deletion results in hypertension in female but not male mice. These data suggest that EFNB3 regulates blood pressure in a sex- and sex hormone-dependent way.

The role of GRIP1 and ephrin B3 in blood pressure control and vascular smooth muscle cell contractility.

Several erythropoietin-producing hepatocellular receptor B family (EPHB) and their ligands, ephrinBs (EFNBs), are involved in blood pressure regulation in animal models. We selected 528 single nucleotide polymorphisms (SNPs) within the genes of EPHB6, EFNB2, EFNB3 and GRIP1 in the EPH/EFN signalling system to query the International Blood Pressure Consortium dataset. A SNP within the glutamate receptor interacting protein 1 (GRIP1) gene presented a p-value of 0.

Primary Pancreatic Secretinoma: Further Evidence Supporting Secretin as a Diarrheogenic Hormone.

Objectives: To document the existence of primary pancreatic secretinoma in patients with watery diarrhea syndrome (WDS) and achlorhydria and establish secretin as a diarrheogenic hormone.

Background: Vasoactive intestinal peptide (VIP) has been widely accepted as the main mediator of WDS. However, in 1968, Zollinger et al reported 2 female patients with pancreatic neuroendocrine tumors, WDS, and achlorhydria.

Effect of Hyperglycemia on Gene Expression during Early Organogenesis in Mice.

Background: Cardiovascular and neural malformations are common sequels of diabetic pregnancies, but the underlying molecular mechanisms remain unknown. We hypothesized that maternal hyperglycemia would affect the embryos most shortly after the glucose-sensitive time window at embryonic day (ED) 7.5 in mice.

Differentiating technical skill and motor abilities in selected and non-selected 3-5 year old team-sports players.

This study examined the difference in 22 3-5year old boys selected to an advanced or non-advanced group on an English community-based professional club training program. Time to complete 15m linear sprint and 15m zig-zag agility tests, with and without a ball, were used to assess the children's technical skill and motor ability. Age and body mass of both groups were the same, whereas height was greater and BMI was lower in the selected group (p<0.

Next-generation sequencing of microRNAs in primary human polarized macrophages.

Macrophages are important for mounting inflammatory responses to tissue damage or infection by invading pathogens, and therefore modulation of their cellular functions is essential for the success of the immune system as well as for maintaining tissue homeostasis. Small non-coding RNAs are important regulatory elements of gene expression and microRNAs are the most widely known to be fundamental for the proper development of cells of the immune system. Macrophages can exhibit different phenotypes, depending on the cytokine environment they encounter in the affected tissues.

Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia.

Dienoyl-CoA reductase (DECR) deficiency with hyperlysinemia is a rare disorder affecting the metabolism of polyunsaturated fatty acids and lysine. The molecular basis of this condition is currently unknown. We describe a new case with failure to thrive, developmental delay, lactic acidosis and severe encephalopathy suggestive of a mitochondrial disorder.

Next-generation sequencing of microRNAs uncovers expression signatures in polarized macrophages.

microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at a posttranscriptional level and play a crucial role in the development of cells of the immune system. Macrophages are essential for generating inflammatory reactions upon tissue damage and encountering of invading pathogens, yet modulation of their immune responses is critical for maintaining tissue homeostasis. Macrophages can present different phenotypes, depending on the cytokine environment they encounter in the affected tissues.

Monoallelic chromatin conformation flanking long-range silenced domains in cancer-derived and normal cells.

Epigenetic inactivation of chromatin plays an important role in determining cell phenotype in both normal and cancer cells, but our knowledge is still incomplete with respect to any potential monoallelic nature of the phenomenon. We have genotyped DNA isolated from chromatin of two colorectal cancer-derived lines and a culture of normal human intestinal epithelial cells (HIEC), which was immunoprecipitated with antibodies to acetylated vs. methylated histone H3K9, and presented the data as B allele frequency differences over multiple single-nucleotide polymorphism (SNP) moving window averages.

Recessive MYL2 mutations cause infantile type I muscle fibre disease and cardiomyopathy.

A cardioskeletal myopathy with onset and death in infancy, morphological features of muscle type I hypotrophy with myofibrillar disorganization and dilated cardiomyopathy was previously reported in three Dutch families. Here we report the genetic cause of this disorder. Multipoint parametric linkage analysis of six Dutch patients identified a homozygous region of 2.

Lack of association between cancer history and PARKIN genotype: a family based study in PARKIN/Parkinson's families.

A number of publications have attributed a tumor suppressive (TS) function to PARKIN, a gene associated with recessive familial early onset Parkinson's disease (EOPD). Discoveries of PARKIN deletions and point mutations in tumors, functional studies, and data from mouse models have been presented to support the hypothesis. We have asked whether PARKIN mutations are associated with history of cancer in humans.

The surgical clerkship: a contemporary paradigm.

Background: Traditional surgical clerkships have been composed of hospitalized patients, usually in academic centers, daily resident interaction, periodic attending rounds, assigned texts, and a lecture format. However, traditional clerkships do not reflect the current changes in learning theory nor the economic realities of today's surgical practice. Initiated in 2001, the allopathic Florida State University College of Medicine provided an opportunity to create a contemporary surgical clerkship.

Deep sequencing whole transcriptome exploration of the σE regulon in Neisseria meningitidis.

Bacteria live in an ever-changing environment and must alter protein expression promptly to adapt to these changes and survive. Specific response genes that are regulated by a subset of alternative σ(70)-like transcription factors have evolved in order to respond to this changing environment. Recently, we have described the existence of a σ(E) regulon including the anti-σ-factor MseR in the obligate human bacterial pathogen Neisseria meningitidis.

Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis.

Background: Myelofibrosis is a Philadelphia chromosome–negative myeloproliferative neoplasm associated with cytopenias, splenomegaly, poor quality of life, and shortened survival. About half of patients with myelofibrosis carry a gain-of-function mutation in the Janus kinase 2 gene (JAK2 V617F) that contributes to the pathophysiology of the disease. INCB018424 is a potent and selective Janus kinase 1 (JAK1) and JAK2 inhibitor.

More is less: inactivation and deletion events and the search for tumor suppressor genes.

Tumor suppressor genes are frequently inactivated in cancer by large-scale deletion events or epigenetic silencing, and experimental demonstration of such inactivation has historically been considered as support for assigning tumor suppressive function to a given gene. However, the discovery of a number of chromosomal domains wherein large deletions naturally occur at frequencies up to 100 times the average for the genome as a whole leads us to reevaluate the significance of sporadic deletions found within genes associated with these hotspots. Similarly, our recent demonstration that epigenetic chromatin silencing frequently spreads in cancer cells from gene-poor into gene-rich regions with apparent indifference to the gene content of the affected domain raises questions about the pertinence of inactivation as a criterion for ascribing tumor suppressor function to a given gene.