Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2 inhibitor meloxicam alone and in combination with irradiation were investigated on human glioma cells in vitro. A panel of three glioma cell lines (D384, U87 and U251) was used in the experiments from which U87 cells expressed constitutive COX-2. The response to meloxicam and irradiation (dose-range of 0–6 Gy) was determined by the clonogenic assay, cell proliferation was evaluated by growth analysis and cell cycle distribution by FACS. 24–72 h exposure to 250–750 μM meloxicam resulted in a time and dose dependent growth inhibition with an almost complete inhibition after 24 h for all cell lines. Exposure to 750 μM meloxicam for 24 h increased the fraction of cells in the radiosensitive G2/M cell cycle phase in D384 (18–27%) and U251 (17–41%) cells. 750 μM meloxicam resulted in radiosensitization of D384 (DMF:2.19) and U87 (DMF:1.25) cells, but not U251 cells (DMF:1.08). The selective COX-2 inhibitor meloxicam exerted COX-2 independent growth inhibition and radiosensitization of human glioma cells

Acute Abdominal Pain Caused by an Infected Mesenteric Cyst in a 24-Year-Old Female

A mesenteric cyst is a rare cause for abdominal pain. This umbrella term includes cystic entities which reside in the mesentery. We present a case of an infected false mesenteric cyst in a 24-year-old female patient without prior surgery or known trauma. Mainstay of treatment involves surgical resection, although less invasive treatments have been described. Prognosis depends on the origin of the cyst

Early Switch in Glial Protein and Fibronectin Markers on Cells during the Culture of Human Gliomas

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75201/1/j.1749-6632.1984.tb13851.x.pd

The Connectome Visualization Utility: Software for Visualization of Human Brain Networks

In analysis of the human connectome, the connectivity of the human brain is collected from multiple imaging modalities and analyzed using graph theoretical techniques. The dimensionality of human connectivity data is high, and making sense of the complex networks in connectomics requires sophisticated visualization and analysis software. The current availability of software packages to analyze the human connectome is limited. The Connectome Visualization Utility (CVU) is a new software package designed for the visualization and network analysis of human brain networks. CVU complements existing software packages by offering expanded interactive analysis and advanced visualization features, including the automated visualization of networks in three different complementary styles and features the special visualization of scalar graph theoretical properties and modular structure. By decoupling the process of network creation from network visualization and analysis, we ensure that CVU can visualize networks from any imaging modality. CVU offers a graphical user interface, interactive scripting, and represents data uses transparent neuroimaging and matrix-based file types rather than opaque application-specific file formats

A consecutive series of 235 epigastric hernias

Abstract Background Epigastric herniation is a common, though not always symptomatic condition. It is likely, that in accordance to the tension-free principles for other hernias, epigastric hernia repair should be mesh based. Methods Patients from two large hospitals were investigated retrospectively if they were operated on an epigastric hernia for the past 6 years. Follow-up was completed with a postal questionnaire. Results A total of 235 patients (50 % male) were operated. Sixty-eight patients were operated with mesh and 167 patients with suture repair. Forty-six patients were loss-to follow-up (19.6 %). In the mesh operated patients the recurrence rate was 10.9 % (n = 6) compared to 14.9 % (n = 20) in the suture repair group. Cox-regression analysis showed an increased risk for recurrence in the suture repair group (odds ratio 1.43; 95 % CI 0.56-3.57; p = 0.44). Operation time for mesh repair (47 min) was significantly longer compared to suture repair (29 min) (p \ 0.0001). Thirty-seven patients had previous or other anterior wall hernias. A total of 51 patients smoked and 14 patients had diabetes mellitus. Fourteen patients used steroids and 22 patients suffered from a chronic lung disease. Subgroup analysis showed a significant difference for pain in patients in which re-operation for a recurrence occurred (p = 0.004). Conclusions This is one of the largest reported series on solely epigastric hernias. A recurrence occurred more often after sutured repair compared to mesh repair. No differences in chronic pain was seen between mesh and suture repaired patients. Male:female ratio of 1:1, which is different from the 3:1 ratio found in previous older smaller studies, could be more reliable

A draft genome sequence of the elusive giant squid, Architeuthis dux

Background: The giant squid (Architeuthis dux; Steenstrup, 1857) is an enigmatic giant mollusc with a circumglobal distribution in the deep ocean, except in the high Arctic and Antarctic waters. The elusiveness of the species makes it difficult to study. Thus, having a genome assembled for this deep-sea-dwelling species will allow several pending evolutionary questions to be unlocked. Findings: We present a draft genome assembly that includes 200 Gb of Illumina reads, 4 Gb of Moleculo synthetic long reads, and 108 Gb of Chicago libraries, with a final size matching the estimated genome size of 2.7 Gb, and a scaffold N50 of 4.8 Mb. We also present an alternative assembly including 27 Gb raw reads generated using the Pacific Biosciences platform. In addition, we sequenced the proteome of the same individual and RNA from 3 different tissue types from 3 other species of squid (Onychoteuthis banksii, Dosidicus gigas, and Sthenoteuthis oualaniensis) to assist genome annotation. We annotated 33,406 protein-coding genes supported by evidence, and the genome completeness estimated by BUSCO reached 92%. Repetitive regions cover 49.17% of the genome. Conclusions: This annotated draft genome of A. dux provides a critical resource to investigate the unique traits of this species, including its gigantism and key adaptations to deep-sea environments

HIV's evasion of the cellular immune response

Despite a strong cytotoxic T-lymphocyte (CTL) response directed against viral antigens, untreated individuals infected with the human immunodeficiency virus (HIV-1) develop AIDS, We have found that primary T cells infected with HIV-1 downregulate surface MHC class I antigens and are resistant to lysis by HLA-A2-restricted CTL clones. In contrast, cells infected with an HIV-1 in which the nef gene is disrupted are sensitive to CTLs in an MHC and peptide-specific manner. In primary T cells HLA-A2 antigens are downmodulated more dramatically than total MHC class I antigens, suggesting that nef selectively downmodulates certain MHC class I antigens. In support of this, studies on ceils expressing individual MHC class I alietes have revealed that nef does not downmodulate HLA-C and HLA-E antigens, This selective downmodulation allows Infected cells to maintain resistance to certain natural killer cells that lyse infected cells expressing low levels of MHC class I antigens. Downmodulation of MHC class I HLA-A2 antigens occurs not only in primary T cells, but also in B and astrocytoma cell lines. No effect of other HIV-1 accessory proteins such as vpu and vpr was observed. Thus Nef is a protein that may promote escape of HIV-1 from immune surveillance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75570/1/j.1600-065X.1999.tb01283.x.pd

Glioblastoma—a moving target

The slow development of effective treatment of glioblastoma is contrasted by the rapidly advancing research on the molecular mechanisms underlying the disease. Amplification and overexpression of receptor tyrosine kinases, particularly EGFR and PDGFRA, are complemented by mutations in the PI3K, RB1, and p53 signaling pathways. In addition to finding effective means to target these pathways, we may take advantage of the recent understanding of the hierarchical structure of tumor cell populations, where the progressive expansion of the tumor relies on a minor subpopulation of glioma stem cells, or glioma-initiating cells. Finding ways to reprogram these cells and block their self-renewal is one of the most important topics for future research

Antibiotic prophylaxis for acute cholecystectomy: PEANUTS II multicentre randomized non-inferiority clinical trial

BACKGROUND\nMETHODS\nRESULTS\nCONCLUSION\nGuidelines recommending antibiotic prophylaxis at emergency cholecystectomy for cholecystitis were based on low-quality evidence. The aim of this trial was to demonstrate that omitting antibiotics is not inferior to their prophylactic use.\nThis multicentre, randomized, open-label, non-inferiority clinical trial randomly assigned adults with mild-to-moderate acute calculous cholecystitis (immediate cholecystectomy indicated) to 2 g cefazolin administered before incision or no antibiotic prophylaxis. The primary endpoint was a composite of all postoperative infectious complications in the first 30 days after surgery. Secondary endpoints included all individual components of the primary endpoint, other morbidity, and duration of hospital stay.\nSixteen of 226 patients (7.1 per cent) in the single-dose prophylaxis group and 29 of 231 (12.6 per cent) in the no-prophylaxis group developed postoperative infectious complications (absolute difference 5.5 (95 per cent c.i. -0.4 to 11.3) per cent). With a non-inferiority margin of 10 per cent, non-inferiority of no prophylaxis was not proven. The number of surgical-site infections was significantly higher in the no-prophylaxis group (5.3 versus 12.1 per cent; P = 0.010). No differences were observed in the number of other complications, or duration of hospital stay.\nOmitting antibiotic prophylaxis is not recommended.Pharmacolog