Identification and characterization of OSTL (RNF217) encoding a RING-IBR-RING protein adjacent to a translocation breakpoint involving ETV6 in childhood ALL

Genomic aberrations involving ETV6 on band 12p13 are amongst the most common chromosomal abnormalities in human leukemia. The translocation t(6;12)(q23;13) in a childhood B-cell acute lymphoblastic leukemia (ALL) cell line fuses ETV6 with the putative long non-coding RNA gene STL. Linking STL properties to leukemia has so far been difficult. Here, we describe a novel gene, OSTL (annotated as RNF217 in Genbank), which shares the first exon and a CpG island with STL but is transcribed in the opposite direction. Human RNF217 codes for a highly conserved RING finger protein and is mainly expressed in testis and skeletal muscle with different splice variants. RNF217 shows regulated splicing in B cell development, and is expressed in a number of human B cell leukemia cell lines, primary human chronic myeloid leukemia, acute myeloid leukemia with normal karyotype and acute T-ALL samples. Using a yeast two-hybrid screen, we identified the anti-apoptotic protein HAX1 to interact with RNF217. This interaction could be mapped to the C-terminal RING finger motif of RNF217. We propose that some of the recurring aberrations involving 6q might deregulate the expression of RNF217 and result in imbalanced apoptosis signalling via HAX1, promoting leukemia development

The usefulness of a free self-test for screening albuminuria in the general population: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>In this study we evaluated the usefulness of a free self-test for screening albuminuria in the general population.</p> <p>Methods</p> <p>Dutch adults were invited by the Dutch Kidney Foundation to order a free albuminuria self-test, consisting of three semi quantitative dipstick tests, via the Internet. Results were classified in negative, low-positive and high-positive. In case of a positive test result, the tester was recommended to visit a GP for supplementary examination and/or treatment. Participants of the programme were sent a questionnaire for evaluation by e-mail eight weeks after receiving the self-test.</p> <p>Results</p> <p>During the first 30 days of the self-test programme, 996,927 self-tests were ordered. In total, 71,714 participants completed the questionnaire: 79% had a negative test result and 21% had a positive test result (20% low-positive and 1% high-positive). Of the positive testers, 25% visited a GP after testing for albuminuria. Among the 3,983 participants who visited a GP, 193 new diseases were detected: 25 chronic renal failure, 152 hypertension and 31 diabetes mellitus.</p> <p>Conclusion</p> <p>Using a free self-test for screening albuminuria in the general population resulted in a large response and a number of newly detected diseases. However, we found a very high percentage of positive testers of which probably a large part is false positive. Furthermore, only a small part of the positive testers visited a GP for additional examination and/or treatment. The efficiency of such a campaign could be increased by embedding the testing in health care to reduce the number of false-positive results and to ensure follow-up and treatment in case of a positive test result.</p

On the Mechanistic Origins of Toughness in Bone

One of the most intriguing protein materials found in nature is bone, a material composed of assemblies of tropocollagen molecules and tiny hydroxyapatite mineral crystals that form an extremely tough, yet lightweight, adaptive and multifunctional material. Bone has evolved to provide structural support to organisms, and therefore its mechanical properties are of great physiological relevance. In this article, we review the structure and properties of bone, focusing on mechanical deformation and fracture behavior from the perspective of the multidimensional hierarchical nature of its structure. In fact, bone derives its resistance to fracture with a multitude of deformation and toughening mechanisms at many size scales ranging from the nanoscale structure of its protein molecules to the macroscopic physiological scale.United States. Army Research Office (contract number W911NF-06-1-0291)National Science Foundation (U.S.) (CAREER award (contract number 0642545))Lawrence Berkeley National Laboratory (Laboratory Directed Research and Development Program)United States. Dept. of Energy (Office of Science, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering, contract number DE-AC02-05CH11231

Stability study of a model for the Klein-Gordon equation in Kerr spacetime

The current early stage in the investigation of the stability of the Kerr metric is characterized by the study of appropriate model problems. Particularly interesting is the problem of the stability of the solutions of the Klein-Gordon equation, describing the propagation of a scalar field of mass $\mu$ in the background of a rotating black hole. Rigorous results proof the stability of the reduced, by separation in the azimuth angle in Boyer-Lindquist coordinates, field for sufficiently large masses. Some, but not all, numerical investigations find instability of the reduced field for rotational parameters $a$ extremely close to 1. Among others, the paper derives a model problem for the equation which supports the instability of the field down to $a/M \approx 0.97$.Comment: Updated version, after minor change

Musculoskeletal injuries in real tennis.

Introduction: Real tennis is a growing, unique, and well-established sport. To date, there has been no epidemiological data on real tennis injuries. The primary aim of this retrospective study is to record the incidence and document any trends in real tennis musculoskeletal injuries, so as to improve injury awareness of common and possibly preventable injuries. Methods: A surveillance questionnaire e-mailed to 2,036 Tennis & Rackets Association members to retrospectively capture injuries sustained by amateur and professional real tennis players over their playing careers. Results: A total of 485 (438 males and 47 females) questionnaires were fully completed over 4 weeks. A total of 662 musculoskeletal injuries were recorded with a mean of 1.4 injuries per player (range 0-7). The incidence of sustaining an acute real tennis musculoskeletal injury is 0.4/1000 hrs. The three main anatomical locations reported injured were elbow 15.6% (103/662), knee 11.6% (77/662), and face 10.0% (66/662). The most common structures reported injured were muscle 24% (161/661), tendon 23.4% (155/661), ligament 7.0% (46/661), soft tissue bruising 6.5% (43/661), and eye 6.2% (41/661). The majority of the upper limb injuries were gradual onset (64.7%, 143/221), and the lower limb injuries were sudden onset (72.0%, 188/261). Conclusion: This study uniquely provides valuable preliminary data on the incidence and patterns of musculoskeletal injuries in real tennis players. In addition, it highlights a number of reported eye injuries. The study is also a benchmark for future prospective studies on academy and professional real tennis players

Desynchronizing effect of high-frequency stimulation in a generic cortical network model

Transcranial Electrical Stimulation (TCES) and Deep Brain Stimulation (DBS) are two different applications of electrical current to the brain used in different areas of medicine. Both have a similar frequency dependence of their efficiency, with the most pronounced effects around 100Hz. We apply superthreshold electrical stimulation, specifically depolarizing DC current, interrupted at different frequencies, to a simple model of a population of cortical neurons which uses phenomenological descriptions of neurons by Izhikevich and synaptic connections on a similar level of sophistication. With this model, we are able to reproduce the optimal desynchronization around 100Hz, as well as to predict the full frequency dependence of the efficiency of desynchronization, and thereby to give a possible explanation for the action mechanism of TCES.Comment: 9 pages, figs included. Accepted for publication in Cognitive Neurodynamic

Controlled mixing of lanthanide(III) ions in coacervate core micelles

This article presents a facile strategy to combine Eu3+ and Gd3+ ions into coacervate core micelles in a controlled way with a statistical distribution of the ions. Consequently, the formed micelles show a high tunability between luminescence and relaxivity. These highly stable micelles present great potential for new materials, e.g. as bimodal imaging probes

Quantum Simulation of Antiferromagnetic Spin Chains in an Optical Lattice

Understanding exotic forms of magnetism in quantum mechanical systems is a central goal of modern condensed matter physics, with implications from high temperature superconductors to spintronic devices. Simulating magnetic materials in the vicinity of a quantum phase transition is computationally intractable on classical computers due to the extreme complexity arising from quantum entanglement between the constituent magnetic spins. Here we employ a degenerate Bose gas confined in an optical lattice to simulate a chain of interacting quantum Ising spins as they undergo a phase transition. Strong spin interactions are achieved through a site-occupation to pseudo-spin mapping. As we vary an applied field, quantum fluctuations drive a phase transition from a paramagnetic phase into an antiferromagnetic phase. In the paramagnetic phase the interaction between the spins is overwhelmed by the applied field which aligns the spins. In the antiferromagnetic phase the interaction dominates and produces staggered magnetic ordering. Magnetic domain formation is observed through both in-situ site-resolved imaging and noise correlation measurements. By demonstrating a route to quantum magnetism in an optical lattice, this work should facilitate further investigations of magnetic models using ultracold atoms, improving our understanding of real magnetic materials.Comment: 12 pages, 9 figure

Synthetic organisms and living machines: Positioning the products of synthetic biology at the borderline between living and non-living matter

The difference between a non-living machine such as a vacuum cleaner and a living organism as a lion seems to be obvious. The two types of entities differ in their material consistence, their origin, their development and their purpose. This apparently clear-cut borderline has previously been challenged by fictitious ideas of “artificial organism” and “living machines” as well as by progress in technology and breeding. The emergence of novel technologies such as artificial life, nanobiotechnology and synthetic biology are definitely blurring the boundary between our understanding of living and non-living matter. This essay discusses where, at the borderline between living and non-living matter, we can position the future products of synthetic biology that belong to the two hybrid entities “synthetic organisms” and “living machines” and how the approaching realization of such hybrid entities affects our understanding of organisms and machines. For this purpose we focus on the description of three different types of synthetic biology products and the aims assigned to their realization: (1) synthetic minimal cells aimed at by protocell synthetic biology, (2) chassis organisms strived for by synthetic genomics and (3) genetically engineered machines produced by bioengineering. We argue that in the case of synthetic biology the purpose is more decisive for the categorization of a product as an organism or a machine than its origin and development. This has certain ethical implications because the definition of an entity as machine seems to allow bypassing the discussion about the assignment and evaluation of instrumental and intrinsic values, which can be raised in the case of organisms