SGR 0418+5729: a low-magnetic-field magnetar

Soft gamma-ray repeaters and anomalous X-ray pulsars are a small (but growing) group of X-ray sources characterized by the emission of short bursts and by a large variability in their persistent flux. They are believed to be magnetars, i.e. neutron stars powered by extreme magnetic fields 1E14-1E15 G). We found evidence for a magnetar with a low magnetic field, SGR 0418+5729, recently detected after it emitted bursts similar to those of soft gamma-ray repeaters. New X-ray observations show that its dipolar magnetic field cannot be greater than 8E12 G, well in the range of ordinary radio pulsars, implying that a high surface dipolar magnetic field is not necessarily required for magnetar-like activity. The magnetar population may thus include objects with a wider range of magnetic-field strengths, ages and evolutionary stages than observed so far.Comment: 4 pages, 2 figures; to appear in the Proceedings of the Pulsar Conference 2010, Chia, Sardinia (Italy), 10-15 October 201

A method for sensitivity analysis to assess the effects of measurement error in multiple exposure variables using external validation data

Measurement error in self-reported dietary intakes is known to bias the association between dietary intake and a health outcome of interest such as risk of a disease. The association can be distorted further by mismeasured confounders, leading to invalid results and conclusions. It is, however, difficult to adjust for the bias in the association when there is no internal validation data

Unstable particles as open quantum systems

We present the probability preserving description of the decaying particle within the framework of quantum mechanics of open systems taking into account the superselection rule prohibiting the superposition of the particle and vacuum. In our approach the evolution of the system is given by a family of completely positive trace preserving maps forming one-parameter dynamical semigroup. We give the Kraus representation for the general evolution of such systems which allows one to write the evolution for systems with two or more particles. Moreover, we show that the decay of the particle can be regarded as a Markov process by finding explicitly the master equation in the Lindblad form. We also show that there are remarkable restrictions on the possible strength of decoherence.Comment: 11 pp, 2 figs (published version

RNA secondary structure formation: a solvable model of heteropolymer folding

The statistical mechanics of heteropolymer structure formation is studied in the context of RNA secondary structures. A designed RNA sequence biased energetically towards a particular native structure (a hairpin) is used to study the transition between the native and molten phase of the RNA as a function of temperature. The transition is driven by a competition between the energy gained from the polymer's overlap with the native structure and the entropic gain of forming random contacts. A simplified Go-like model is proposed and solved exactly. The predicted critical behavior is verified via exact numerical enumeration of a large ensemble of similarly designed sequences.Comment: 4 pages including 2 figure

Mechanistic Insights into Hsp104 Potentiation

Potentiated variants of Hsp104, a protein disaggregase from yeast, can dissolve protein aggregates connected to neurodegenerative diseases such as Parkinson disease and amyotrophic lateral sclerosis. However, the mechanisms underlying Hsp104 potentiation remain incompletely defined. Here, we establish that 2–3 subunits of the Hsp104 hexamer must bear an A503V potentiating mutation to elicit enhanced disaggregase activity in the absence of Hsp70. We also define the ATPase and substrate-binding modalities needed for potentiated Hsp104A503V activity in vitro and in vivo. Hsp104A503V disaggregase activity is strongly inhibited by the Y257A mutation that disrupts substrate binding to the nucleotide-binding domain 1 (NBD1) pore loop and is abolished by the Y662A mutation that disrupts substrate binding to the NBD2 pore loop. Intriguingly, Hsp104A503V disaggregase activity responds to mixtures of ATP and adenosine 5′-(γ-thio)-triphosphate (a slowly hydrolyzable ATP analogue) differently from Hsp104. Indeed, an altered pattern of ATP hydrolysis and altered allosteric signaling between NBD1 and NBD2 are likely critical for potentiation. Hsp104A503V variants bearing inactivating Walker A or Walker B mutations in both NBDs are inoperative. Unexpectedly, however, Hsp104A503V retains potentiated activity upon introduction of sensor-1 mutations that reduce ATP hydrolysis at NBD1 (T317A) or NBD2 (N728A). Hsp104T317A/A503V and Hsp104A503V/N728A rescue TDP-43 (TAR DNA-binding protein 43), FUS (fused in sarcoma), and α-synuclein toxicity in yeast. Thus, Hsp104A503V displays a more robust activity that is unperturbed by sensor-1 mutations that greatly reduce Hsp104 activity in vivo. Indeed, ATPase activity at NBD1 or NBD2 is sufficient for Hsp104 potentiation. Our findings will empower design of ameliorated therapeutic disaggregases for various neurodegenerative diseases

Lutzomyia adiketis sp. n. (Diptera: Phlebotomidae), a vector of Paleoleishmania neotropicum sp. n. (Kinetoplastida: Trypanosomatidae) in Dominican amber

<p>Abstract</p> <p>Background</p> <p>Amber fossils can be used to trace the history of disease-vector associations because microorganisms are preserved "in situ" inside the alimentary tract and body cavity of blood-sucking insects.</p> <p>Results</p> <p><it>Lutzomyia adiketis </it>sp. n. (Phlebotomidae: Diptera) is described from Dominican amber as a vector of <it>Paleoleishmania neotropicum </it>sp. n. (Kinetoplastida: Trypanosomatidae). The fossil sand fly differs from all previously described extinct and extant members of the genus by the following combination of characters: Sc forked with the branches meeting the costa and radius veins; wing L/W value of 4.1; a δ value of 18; a ratio β/α value of 0.86, and the shape and size of the spatulate rods on the ninth sternite. The trypanosomatid is characterized by the structure of its promastigotes, amastigotes and paramastigotes and its transmission by an extinct species of sand fly.</p> <p>Conclusion</p> <p>Morphological characters show that the fossil sand fly is a new extinct species and that it is host to a digenetic species of trypanosomatid. This study provides the first fossil evidence that Neotropical sand flies were vectors of trypanosomatids in the mid-Tertiary (20–30 mya).</p

Induction of annexin-1 at transcriptional and post-transcriptional level in rat brain by methylprednisolone and the 21-aminosteroid U74389F

Brain tissue of rats pretreated with methylprednisolone or with the 21-aminosteroid U74389F, and that of untreated control rats, was assessed for the expression of annexin-1 (Anx-1) and the transcription of its mRNA. For this purpose Anx-1 cDNA was amplified and simultaneously a T7-RNA-polymerase promoter was incorporated into the cDNA using a polymerase chain reaction (PCR). Then digoxigenin-11-UTP was incorporated into the transcribed cRNA with T7-RNA-polymerase. With this probe in situ hybridization was carried out on sections of the brain. The probe was visualized by an immunoassay using an antidigoxigenin antibody conjugate. Anx-1 protein was assessed by means of immunohistochemistry using a polyclonal antibody. The various brain areas of the control animals showed an appreciable amount of Anx-1 at mRNA or protein level; on the other hand, the animals which had been pretreated with either steroid, showed a more intense Anx-1 mRNA signal than the controls in many areas. In the pretreated animals Anx-1 immunostaining was unchanged in cortex, basal ganglia, amygdala and septum, but more intense in hippocampus, hypothalamus and thalamus. In ependyma, choroid plexus, meninges, and vascular walls there was no Anx-1 mRNA transcription detectable. An opposite profile was shown by the Anx-1 immunoreactivity, the protein was present in control animals as well as the steroid-pretreated animals, suggesting that here the protein was either from systemic origin, or has diffused from adjacent structures. The results indicated that Anx-1 mRNA transcription is upregulated by either steroid, and that in the untreated animals there is a resting level of Anx-1 mRNA transcription, presumably reflecting physiological influences on Anx-1 expression

Proteinlike behavior of a spin system near the transition between ferromagnet and spin glass

A simple spin system is studied as an analog for proteins. We investigate how the introduction of randomness and frustration into the system effects the designability and stability of ground state configurations. We observe that the spin system exhibits protein-like behavior in the vicinity of the transition between ferromagnet and spin glass. Our results illuminate some guiding principles in protein evolution.Comment: 12 pages, 4 figure

Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?

Objectives To give an overview of the genetic and structural abnormalities occurring in fetuses with nuchal translucency (NT) measurement exceeding the 95th percentile at first-trimester screening and to investigate which of these abnormalities would be missed if cell-free fetal DNA (cfDNA) were used as a first-tier screening test for chromosomal abnormalities. Methods This is a national study including 1901 pregnancies with NT &gt;= 95th percentile referred to seven university hospitals in the Netherlands between 1 January 2010 and 1 January 2016. All cases with unknown pregnancy outcome were excluded. Results of detailed ultrasound examinations, karyotyping, genotyping, pregnancy and neonatal outcomes, investigation by a clinical geneticist and post-mortem investigations were collected. Results In total, 821 (43%) pregnancies had at least one abnormality. The rate of abnormalities was 21% for fetuses with NT between 95(th) and 99(th) percentile and 62% for fetuses with NT &gt;= 99(th) percentile. Prevalence of single-gene disorders, submicroscopic, chromosomal and structural abnormalities was 2%, 2%, 30% and 9%, respectively. Conclusion Although cfDNA is superior to the combined test, especially for the detection of trisomy 21, 34% of the congenital abnormalities occurring in fetuses with increased NT may remain undetected in the first trimester of pregnancy, unless cfDNA is used in combination with fetal sonographic assessment, including NT measurement.</p