Peaks and Troughs of Three-Dimensional Vestibulo-ocular Reflex in Humans

The three-dimensional vestibulo-ocular reflex (3D VOR) ideally generates compensatory ocular rotations not only with a magnitude equal and opposite to the head rotation but also about an axis that is collinear with the head rotation axis. Vestibulo-ocular responses only partially fulfill this ideal behavior. Because animal studies have shown that vestibular stimulation about particular axes may lead to suboptimal compensatory responses, we investigated in healthy subjects the peaks and troughs in 3D VOR stabilization in terms of gain and alignment of the 3D vestibulo-ocular response. Six healthy upright sitting subjects underwent whole body small amplitude sinusoidal and constant acceleration transients delivered by a six-degree-of-freedom motion platform. Subjects were oscillated about the vertical axis and about axes in the horizontal plane varying between roll and pitch at increments of 22.5° in azimuth. Transients were delivered in yaw, roll, and pitch and in the vertical canal planes. Eye movements were recorded in with 3D search coils. Eye coil signals were converted to rotation vectors, from which we calculated gain and misalignment. During horizontal axis stimulation, systematic deviations were found. In the light, misalignment of the 3D VOR had a maximum misalignment at about 45°. These deviations in misalignment can be explained by vector summation of the eye rotation components with a low gain for torsion and high gain for vertical. In the dark and in response to transients, gain of all components had lower values. Misalignment in darkness and for transients had different peaks and troughs than in the light: its minimum was during pitch axis stimulation and its maximum during roll axis stimulation. We show that the relatively large misalignment for roll in darkness is due to a horizontal eye movement component that is only present in darkness. In combination with the relatively low torsion gain, this horizontal component has a relative large effect on the alignment of the eye rotation axis with respect to the head rotation axis

Telomere Length and Mental Well-Being in Elderly Men from the Netherlands and Greece

Telomeres, repetitive DNA sequences that promote chromosomal stability, have been related to different measures of mental well-being and self-rated health, but mainly in women during adulthood. We aimed to investigate whether accelerated telomere shortening is associated with poor mental well-being and poor self-rated health in community-dwelling elderly men. Leukocyte telomere length was measured using quantitative PCR in two different samples of 203 elderly men (mean age 78 years) from the Netherlands in 1993, and 123 elderly men (mean age 84 years) from Greece in 2000. We also obtained follow-up data in 2000 from 144 Dutch subjects, of whom 75 had paired telomere length data in 1993 and 2000. Mental well-being was conceptualized as dispositional optimism, depressive symptoms, cognitive functioning, and loneliness. Linear regression analyses were used to study the association between telomere length, measures of mental well being, and self-rated health, while adjusting for potential confounders. In cross-sectional analyses, leukocyte telomere length was not associated with measures of mental well-being and self-rated health, neither in the Netherlands nor in Greece. Also, the rate of leukocyte telomere shortening (mean decrease: 0.28 kbp over 7 years) in the 75 Dutch participants with longitudinal data was not associated with changes in different measures of mental well-being and self-rated health. Thus, our results provide no support for a relationship between leukocyte telomere length and mental well-being in elderly community-dwelling men

Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1

Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose) polymerase-1 (PARP-1) and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κb and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline) in human fibroblasts (HF) cultured under normal conditions and under conditions of chronic oxidative stress, induced by tert-butyl hydroperoxide (t-BHP). Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions

Patients with Crohn's disease have longer post-operative in-hospital stay than patients with colon cancer but no difference in complications' rate

BACKGROUNDRight hemicolectomy or ileocecal resection are used to treat benign conditions like Crohn's disease (CD) and malignant ones like colon cancer (CC).AIMTo investigate differences in pre- and peri-operative factors and their impact on post-operative outcome in patients with CC and CD.METHODSThis is a sub-group analysis of the European Society of Coloproctology's prospective, multi-centre snapshot audit. Adult patients with CC and CD undergoing right hemicolectomy or ileocecal resection were included. Primary outcome measure was 30-d post-operative complications. Secondary outcome measures were post-operative length of stay (LOS) at and readmission.RESULTSThree hundred and seventy-five patients with CD and 2,515 patients with CC were included. Patients with CD were younger (median = 37 years for CD and 71 years for CC (P < 0.01), had lower American Society of Anesthesiology score (ASA) grade (P < 0.01) and less comorbidity (P < 0.01), but were more likely to be current smokers (P < 0.01). Patients with CD were more frequently operated on by colorectal surgeons (P < 0.01) and frequently underwent ileocecal resection (P < 0.01) with higher rate of de-functioning/primary stoma construction (P < 0.01). Thirty-day post-operative mortality occurred exclusively in the CC group (66/2515, 2.3%). In multivariate analyses, the risk of post-operative complications was similar in the two groups (OR 0.80, 95%CI: 0.54-1.17; P = 0.25). Patients with CD had a significantly longer LOS (Geometric mean 0.87, 95%CI: 0.79-0.95; P < 0.01). There was no difference in re-admission rates. The audit did not collect data on post-operative enhanced recovery protocols that are implemented in the different participating centers.CONCLUSIONPatients with CD were younger, with lower ASA grade, less comorbidity, operated on by experienced surgeons and underwent less radical resection but had a longer LOS than patients with CC although complication's rate was not different between the two groups

Preferential retention of genes from one parental genome after polyploidy illustrates the nature and scope of the genomic conflicts induced by hybridization

<div><p>Polyploidy is increasingly seen as a driver of both evolutionary innovation and ecological success. One source of polyploid organisms’ successes may be their origins in the merging and mixing of genomes from two different species (e.g., allopolyploidy). Using POInT (the <u>P</u>olyploid <u>O</u>rthology <u>In</u>ference <u>T</u>ool), we model the resolution of three allopolyploidy events, one from the bakers’ yeast (<i>Saccharomyces cerevisiae</i>), one from the thale cress (<i>Arabidopsis thaliana)</i> and one from grasses including <i>Sorghum bicolor</i>. Analyzing a total of 21 genomes, we assign to every gene a probability for having come from each parental subgenome (i.e., derived from the diploid progenitor species), yielding orthologous segments across all genomes. Our model detects statistically robust evidence for the existence of <i>biased fractionation</i> in all three lineages, whereby genes from one of the two subgenomes were more likely to be lost than those from the other subgenome. We further find that a driver of this pattern of biased losses is the co-retention of genes from the same parental genome that share functional interactions. The pattern of biased fractionation after the <i>Arabidopsis</i> and grass allopolyploid events was surprisingly constant in time, with the same parental genome favored throughout the lineages’ history. In strong contrast, the yeast allopolyploid event shows evidence of biased fractionation only immediately after the event, with balanced gene losses more recently. The rapid loss of functionally associated genes from a single subgenome is difficult to reconcile with the action of genetic drift and suggests that selection may favor the removal of specific duplicates. Coupled to the evidence for continuing, functionally-associated biased fractionation after the <i>A</i>. <i>thaliana</i> At-α event, we suggest that, after allopolyploidy, there are functional conflicts between interacting genes encoded in different subgenomes that are ultimately resolved through preferential duplicate loss.</p></div