High-throughput characterisation of bull semen motility using differential dynamic microscopy

<div><p>We report a high-throughput technique for characterising the motility of spermatozoa using differential dynamic microscopy. A movie with large field of view (∼10mm²) records thousands of cells (e.g. ≈ 5000 cells even at a low cell density of 20 × 10⁶ cells/ml) at once and yields averaged measurements of the mean () and standard deviation (<i>σ</i>) of the swimming speed, head oscillation amplitude (<i>A</i>₀) and frequency (<i>f</i>₀), and the fraction of motile spermatozoa (<i>α</i>). Interestingly, we found that the measurement of <i>α</i> is facilitated because the swimming spermatozoa enhance the motion of the non-swimming population. We demonstrate the ease and rapidity of our method by performing on-farm characterisation of bull spermatozoa motility, and validate the technique by comparing laboratory measurements with tracking. Our results confirm the long-standing theoretical prediction that for swimming spermatozoa.</p></div

Dose-dependent effects of Allopurinol on human foreskin fibroblast cell and human umbilical vein endothelial cell under hypoxia

Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1α protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1α mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells

Water interaction differences determine the relative energetic stability of the polyproline II conformation of the alanine dipeptide in aqueous environments

Although subsequent studies have provided extensive support for the 1968 Tiffany and Krimm proposal (Biopolymers 6, 1379) that the polyproline II (PPII) conformation is a significant component of the structure of unordered polypeptide chains, two issues are still not fully resolved: the PPII persistence length in a chain and the source of its relative stability with respect to the β‐conformation. We examine the latter question by studying the B97‐D/6‐31++G ** energy, in the absence and presence of a reaction field, of the alanine dipeptide hydrated by various amounts of explicit waters and resolving this into its three components: the energies of the individual solvated peptides and water structures plus the interaction energy involving them. We find that the relative stability of the PPII conformation is determined mainly by the difference in the interaction energies of the water structures in the near‐peptide layers. © 2012 Wiley Periodicals, Inc. Biopolymers 97: 789–794, 2012.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92429/1/22064_ftp.pd

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases

The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids

Rationale: Evidence suggests that the gut microbiome is involved in the development of cardiovascular disease, with the host–microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for cardiovascular disease from large-scale studies in humans. In particular, there was no strong evidence for association between cardiovascular disease and aberrant blood lipid levels. Objectives: To identify intestinal bacteria taxa, whose proportions correlate with body mass index and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, sex, and host genetics. Methods and Results: We studied 893 subjects from the LifeLines-DEEP population cohort. After correcting for age and sex, we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in body mass index, 6% in triglycerides, and 4% in high-density lipoproteins, independent of age, sex, and genetic risk factors. A novel risk model, including the gut microbiome explained ≤25.9% of high-density lipoprotein variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol. Conclusions: Our studies suggest that the gut microbiome may play an important role in the variation in body mass index and blood lipid levels, independent of age, sex, and host genetics. Our findings support the potential of therapies altering the gut microbiome to control body mass, triglycerides, and high-density lipoproteins

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

The ability of the mature mammalian nervous system to continually produce neuronal precursors is of considerable importance, as manipulation of this process might one day permit the replacement of cells lost as a result of injury or disease. In mammals, the anterior subventricular zone (SVZa) region is one of the primary sites of adult neurogenesis. Here we show that doublecortin (DCX), a widely used marker for newly generated neurons, when deleted in mice results in a severe morphological defect in the rostral migratory stream and delayed neuronal migration that is independent of direction or responsiveness to Slit chemorepulsion. DCX is required for nuclear translocation and maintenance of bipolar morphology during migration of these cells. Our data identifies a critical function for DCX in the movement of newly generated neurons in the adult brain

Prospective, multicentre study of screening, investigation and management of hyponatraemia after subarachnoid haemorrhage in the UK and Ireland

Background: Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH. Methods: We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (&lt;135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration &gt;10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression. Results: 175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was &gt;3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I–III, modified Fisher 2–4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia. Conclusions: In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care

Hormone Delivery System: The Contraceptive Ring

Many women use contraceptive methods that involve the hormones estrogen and progestin, which prevent the ovaries from developing and releasing mature eggs. This, therefore, prevents conception. Currently there are two well established types of birth control on the market. These possibilities are the pill form where the user ingests a large dose once a day for 21 days or the birth control patch is placed on the skin every week for three weeks out of the month. Women can also receive hormone shots or implants that last for four months. However, these methods only allow a menstrual cycle every four months, so they are difficult to compare to the other methods. All of these other methods can cause side effects such as headaches, blood clots, nausea, and breakthrough bleeding. However, there is a new form of birth control that comes in a flexible thin ring that is inserted into the vagina below the cervix. This ring is designed to releases a continuous low dose of hormone that is absorbed by the vagina and distributed into the blood stream. The ring actually releases two derivatives of estrogen and progestin known as etonogestrel and ethinyl estradiol (Organon USA Inc. 2005). See Figure 1 for the chemical structures of both of these compounds. Because the ring is only changed once a month, it ceases the fluctuation of hormone levels that is normal in the other birth control methods

High definition i-SCAN endoscopy with water immersion technique accurately reflects histological severity of celiac disease

Background and aims: Severe villous atrophy can be revealed with conventional white light endoscopy (WLE), however, milder grades or patchy villous atrophy are more difficult to detect. Novel endoscopic techniques such as high definition i-SCAN endoscopy with the water immersion technique (i-SCAN-HDWI) may provide the ability to visualize duodenal villi more accurately. We aimed to determine the performance of i-SCAN-HDWI in evaluating the severity of histological damage in the duodenum of patients with celiac disease. Patients and methods: A retrospective cohort study was performed in a single tertiary academic endoscopic center. We studied 58 patients (46 women; median age 36.5 years, range 18 – 72 years) with positive anti-TTG IgA antibody. The villous pattern of the second part of the duodenum was assessed by WLE and i-SCAN-HDWI. The endoscopic grades in both techniques were correlated using Marsh histologic grades by Spearman correlation coefficient. The diagnostic accuracy of i-SCAN-HDWI for detection of patchy or complete atrophy of the villi was evaluated. Results: A significant correlation was demonstrated between endoscopic grade using i-SCAN-HDWI and Marsh histologic grade (r = 0.732; P < 0.00001). The correlation between WLE grade and Marsh histologic grade was inferior to i-SCAN-HDWI (r = 0.31; P = 0.01). The sensitivity of i-SCAN-HDWI was 96 % (95 %CI: 85 – 99 %) and the specificity was 63 % (95 %CI: 26 – 90 %) in diagnosing abnormal biopsy consistent with celiac disease. Conclusion: i-SCAN-HDWI endoscopy can reflect the histological severity of celiac disease more accurately than conventional WLE alone. This novel endoscopic imaging can improve the diagnostic yield of duodenal biopsies in celiac patients, especially for those with a patchy distribution of villous damage