Holocentric Chromosomes of Luzula elegans Are Characterized by a Longitudinal Centromere Groove, Chromosome Bending, and a Terminal Nucleolus Organizer Region

The structure of holocentric chromosomes was analyzed in mitotic cells of Luzula elegans. Light and scanning electron microscopy observations provided evidence for the existence of a longitudinal groove along each sister chromatid. The centromere-specific histone H3 variant, CENH3, colocalized with this groove and with microtubule attachment sites. The terminal chromosomal regions were CENH3-negative. During metaphase to anaphase transition, L. elegans chromosomes typically curved to a sickle-like shape, a process that is likely to be influenced by the pulling forces of microtubules along the holocentric axis towards the corresponding microtubule organizing regions. A single pair of 45S rDNA sites, situated distal to Arabidopsis-telomere repeats, was observed at the terminal region of one chromosome pair. We suggest that the 45S rDNA position in distal centromere-free regions could be required to ensure chromosome stability. Copyright (C) 2011 S. Karger AG, Base

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Effects of autologous bone marrow stem cell transplantation on beta-adrenoceptor density and electrical activation pattern in a rabbit model of non-ischemic heart failure

BACKGROUND: Since only little is known on stem cell therapy in non-ischemic heart failure we wanted to know whether a long-term improvement of cardiac function in non-ischemic heart failure can be achieved by stem cell transplantation. METHODS: White male New Zealand rabbits were treated with doxorubicine (3 mg/kg/week; 6 weeks) to induce dilative non-ischemic cardiomyopathy. Thereafter, we obtained autologous bone marrow stem cells (BMSC) and injected 1.5–2.0 Mio cells in 1 ml medium by infiltrating the myocardium via a left anterolateral thoracotomy in comparison to sham-operated rabbits. 4 weeks later intracardiac contractility was determined in-vivo using a Millar catheter. Thereafter, the heart was excised and processed for radioligand binding assays to detect β(1)- and β(2)-adrenoceptor density. In addition, catecholamine plasma levels were determined via HPLC. In a subgroup we investigated cardiac electrophysiology by use of 256 channel mapping. RESULTS: In doxorubicine-treated animals β-adrenoceptor density was significantly down-regulated in left ventricle and septum, but not in right ventricle, thereby indicating a typical left ventricular heart failure. Sham-operated rabbits exhibited the same down-regulation. In contrast, BMSC transplantation led to significantly less β-adrenoceptor down-regulation in septum and left ventricle. Cardiac contractility was significantly decreased in heart failure and sham-operated rabbits, but was significantly higher in BMSC-transplanted hearts. Norepinephrine and epinephrine plasma levels were enhanced in heart failure and sham-operated animals, while these were not different from normal in BMSC-transplanted animals. Electrophysiological mapping revealed unaltered electrophysiology and did not show signs of arrhythmogeneity. CONCLUSION: BMSC transplantation improves sympathoadrenal dysregualtion in non-ischemic heart failure

Quantum Computing

Quantum mechanics---the theory describing the fundamental workings of nature---is famously counterintuitive: it predicts that a particle can be in two places at the same time, and that two remote particles can be inextricably and instantaneously linked. These predictions have been the topic of intense metaphysical debate ever since the theory's inception early last century. However, supreme predictive power combined with direct experimental observation of some of these unusual phenomena leave little doubt as to its fundamental correctness. In fact, without quantum mechanics we could not explain the workings of a laser, nor indeed how a fridge magnet operates. Over the last several decades quantum information science has emerged to seek answers to the question: can we gain some advantage by storing, transmitting and processing information encoded in systems that exhibit these unique quantum properties? Today it is understood that the answer is yes. Many research groups around the world are working towards one of the most ambitious goals humankind has ever embarked upon: a quantum computer that promises to exponentially improve computational power for particular tasks. A number of physical systems, spanning much of modern physics, are being developed for this task---ranging from single particles of light to superconducting circuits---and it is not yet clear which, if any, will ultimately prove successful. Here we describe the latest developments for each of the leading approaches and explain what the major challenges are for the future.Comment: 26 pages, 7 figures, 291 references. Early draft of Nature 464, 45-53 (4 March 2010). Published version is more up-to-date and has several corrections, but is half the length with far fewer reference

The Role of Anorexia in Resistance and Tolerance to Infections in Drosophila

Infections initiate a signaling loop in which sick animals become anorexic, and the resulting change in diet alters the body's ability to fight infections in good and bad ways

Resource-oriented music therapy for psychiatric patients with low therapy motivation: Protocol for a randomised controlled trial [NCT00137189]

BACKGROUND: Previous research has shown positive effects of music therapy for people with schizophrenia and other mental disorders. In clinical practice, music therapy is often offered to psychiatric patients with low therapy motivation, but little research exists about this population. The aim of this study is to examine whether resource-oriented music therapy helps psychiatric patients with low therapy motivation to improve negative symptoms and other health-related outcomes. An additional aim of the study is to examine the mechanisms of change through music therapy. METHODS: 144 adults with a non-organic mental disorder (ICD-10: F1 to F6) who have low therapy motivation and a willingness to work with music will be randomly assigned to an experimental or a control condition. All participants will receive standard care, and the experimental group will in addition be offered biweekly sessions of music therapy over a period of three months. Outcomes will be measured by a blind assessor before and 1, 3, and 9 months after randomisation. DISCUSSION: The findings to be expected from this study will fill an important gap in the knowledge of treatment effects for a patient group that does not easily benefit from treatment. The study's close link to clinical practice, as well as its size and comprehensiveness, will make its results well generalisable to clinical practice

Essential Functions of the Histone Demethylase Lid

Drosophila Little imaginal discs (Lid) is a recently described member of the JmjC domain class of histone demethylases that specifically targets trimethylated histone H3 lysine 4 (H3K4me3). To understand its biological function, we have utilized a series of Lid deletions and point mutations to assess the role that each domain plays in histone demethylation, in animal viability, and in cell growth mediated by the transcription factor dMyc. Strikingly, we find that lid mutants are rescued to adulthood by either wildtype or enzymatically inactive Lid expressed under the control of its endogenous promoter, demonstrating that Lid's demethylase activity is not essential for development. In contrast, ubiquitous expression of UAS-Lid transgenes lacking its JmjN, C-terminal PHD domain, and C5HC2 zinc finger were unable to rescue lid homozygous mutants, indicating that these domains carry out Lid's essential developmental functions. Although Lid-dependent demethylase activity is not essential, dynamic removal of H3K4me3 may still be an important component of development, as we have observed a genetic interaction between lid and another H3K4me3 demethylase, dKDM2. We also show that Lid's essential C-terminal PHD finger binds specifically to di- and trimethylated H3K4 and that this activity is required for Lid to function in dMyc-induced cell growth. Taken together, our findings highlight the importance of Lid function in the regulated removal and recognition of H3K4me3 during development