461 research outputs found
A bacteriophage tubulin harnesses dynamic instability to center DNA in infected cells.
Dynamic instability, polarity, and spatiotemporal organization are hallmarks of the microtubule cytoskeleton that allow formation of complex structures such as the eukaryotic spindle. No similar structure has been identified in prokaryotes. The bacteriophage-encoded tubulin PhuZ is required to position DNA at mid-cell, without which infectivity is compromised. Here, we show that PhuZ filaments, like microtubules, stochastically switch from growing in a distinctly polar manner to catastrophic depolymerization (dynamic instability) both in vitro and in vivo. One end of each PhuZ filament is stably anchored near the cell pole to form a spindle-like array that orients the growing ends toward the phage nucleoid so as to position it near mid-cell. Our results demonstrate how a bacteriophage can harness the properties of a tubulin-like cytoskeleton for efficient propagation. This represents the first identification of a prokaryotic tubulin with the dynamic instability of microtubules and the ability to form a simplified bipolar spindle
Diagnostic Utility of the Impact of Event Scale-Revised in Two Samples of Survivors of War
The study aimed at examining the diagnostic utility of the Impact of Event Scale-Revised (IES-R) as a screening tool for post-traumatic stress disorder (PTSD) in survivors of war. The IES-R was completed by two independent samples that had survived the war in the Balkans: a sample of randomly selected people who had stayed in the area of former conflict (n = 3,313) and a sample of refugees to Western European countries (n = 854). PTSD was diagnosed using the MINI International Neuropsychiatric Interview. Prevalence of PTSD was 20.1% in the Balkan sample and 33.1% in the refugee sample. Results revealed that when considering a minimum value of specificity of 0.80, the optimally sensitive cut-off score for screening for PTSD in the Balkan sample was 34. In both the Balkan sample and the refugee sample, this cut-off score provided good values on sensitivity (0.86 and 0.89, respectively) and overall efficiency (0.81 and 0.79, respectively). Further, the kappa coefficients for sensitivity for the cut-off of 34 were 0.80 in both samples. Findings of this study support the clinical utility of the IES-R as a screening tool for PTSD in large-scale research studies and intervention studies if structured diagnostic interviews are regarded as too labor-intensive and too costly
Lycoris -- a large-area, high resolution beam telescope
A high-resolution beam telescope is one of the most important and demanding
infrastructure components at any test beam facility. Its main purpose is to
provide reference particle tracks from the incoming test beam particles to the
test beam users, which allows measurement of the performance of the
device-under-test (DUT). \LYCORIS, a six-plane compact beam telescope with an
active area of 10\SI{10}{\square\centi\metre} (extensible to
10\SI{20}{\square\centi\metre}) was installed at the \DIITBF in 2019,
to provide a precise momentum measurement in a \SI{1}{\tesla} solenoid magnet
or to provide tracking over a large area. The overall design of \LYCORIS will
be described as well as the performance of the chosen silicon sensor. The
\SI{25}{\micro\metre} pitch micro-strip sensor used for \LYCORIS was originally
designed for the \SID detector concept for the International Linear Collider.
It adopts a second metallization layer to route signals from strips to the
bump-bonded \KPIX ASIC and uses a wire-bonded flex cable for the connection to
the DAQ and the power supply system. This arrangement eliminates the need for a
dedicated hybrid PCB. Its performance was tested for the first time in this
project. The system has been evaluated at the \DIITBF in several test-beam
campaigns and has demonstrated an average single-point resolution of
\SI{7.07}{\micro\meter}.Comment: 43 pages, 37 figure
The tau tubulin kinases TTBK1/2 promote accumulation of pathological TDP-43
Pathological aggregates of phosphorylated TDP-43 characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), two devastating groups of neurodegenerative disease. Kinase hyperactivity may be a consistent feature of ALS and FTLD-TDP, as phosphorylated TDP-43 is not observed in the absence of neurodegeneration. By examining changes in TDP-43 phosphorylation state, we have identified kinases controlling TDP-43 phosphorylation in a C. elegans model of ALS. In this kinome-wide survey, we identified homologs of the tau tubulin kinases 1 and 2 (TTBK1 and TTBK2), which were also identified in a prior screen for kinase modifiers of TDP-43 behavioral phenotypes. Using refined methodology, we demonstrate TTBK1 and TTBK2 directly phosphorylate TDP-43 in vitro and promote TDP-43 phosphorylation in mammalian cultured cells. TTBK1/2 overexpression drives phosphorylation and relocalization of TDP-43 from the nucleus to cytoplasmic inclusions reminiscent of neuropathologic changes in disease states. Furthermore, protein levels of TTBK1 and TTBK2 are increased in frontal cortex of FTLD-TDP patients, and TTBK1 and TTBK2 co-localize with TDP-43 inclusions in ALS spinal cord. These kinases may represent attractive targets for therapeutic intervention for TDP-43 proteinopathies such as ALS and FTLD-TDP
Recurrent post-partum coronary artery dissection
Coronary artery dissection is a rare but well-described cause for myocardial infarction during the post-partum period. Dissection of multiple coronary arteries is even less frequent. Here we present a case of recurrent post-partum coronary artery dissections. This unusual presentation poses unique problems for management. A 35 year-old female, gravida 3 para 2, presented with myocardial infarction 9 weeks and 3 days post-partum. Cardiac catheterization demonstrated left anterior descending (LAD) dissection but an otherwise normal coronary anatomy. The lesion was treated with four everolimus eluting stents. Initially the patient made an unremarkable recovery until ventricular fibrillation arrest occurred on the following day. Unsynchronized cardioversion restored a normal sinus rhythm and repeat catheterization revealed new right coronary artery (RCA) dissection. A wire was passed distally, but it was unclear whether this was through the true or false lumen and no stents could be placed. However, improvement of distal RCA perfusion was noted on angiogram. Despite failure of interventional therapy the patient was therefore treated conservatively. Early operation after myocardial infarction has a significantly elevated risk of mortality and the initial dissection had occurred within 24 hours. This strategy proved successful as follow-up transthoracic echocardiography after four months demonstrated a preserved left ventricular ejection fraction of 55-60% without regional wall motion abnormalities. The patient remained asymptomatic from a cardiac point of view
The Balloon-Borne Large Aperture Submillimeter Telescope (BLAST) 2005: A 10 deg^2 Survey of Star Formation in Cygnus X
We present Cygnus X in a new multi-wavelength perspective based on an
unbiased BLAST survey at 250, 350, and 500 micron, combined with rich datasets
for this well-studied region. Our primary goal is to investigate the early
stages of high mass star formation. We have detected 184 compact sources in
various stages of evolution across all three BLAST bands. From their
well-constrained spectral energy distributions, we obtain the physical
properties mass, surface density, bolometric luminosity, and dust temperature.
Some of the bright sources reaching 40 K contain well-known compact H II
regions. We relate these to other sources at earlier stages of evolution via
the energetics as deduced from their position in the luminosity-mass (L-M)
diagram. The BLAST spectral coverage, near the peak of the spectral energy
distribution of the dust, reveals fainter sources too cool (~ 10 K) to be seen
by earlier shorter-wavelength surveys like IRAS. We detect thermal emission
from infrared dark clouds and investigate the phenomenon of cold ``starless
cores" more generally. Spitzer images of these cold sources often show stellar
nurseries, but these potential sites for massive star formation are ``starless"
in the sense that to date there is no massive protostar in a vigorous accretion
phase. We discuss evolution in the context of the L-M diagram. Theory raises
some interesting possibilities: some cold massive compact sources might never
form a cluster containing massive stars; and clusters with massive stars might
not have an identifiable compact cold massive precursor.Comment: 42 pages, 31 Figures, 6 table
The BLAST View of the Star Forming Region in Aquila (ell=45deg,b=0deg)
We have carried out the first general submillimeter analysis of the field
towards GRSMC 45.46+0.05, a massive star forming region in Aquila. The
deconvolved 6 deg^2 (3\degree X 2\degree) maps provided by BLAST in 2005 at
250, 350, and 500 micron were used to perform a preliminary characterization of
the clump population previously investigated in the infrared, radio, and
molecular maps. Interferometric CORNISH data at 4.8 GHz have also been used to
characterize the Ultracompact HII regions (UCHIIRs) within the main clumps. By
means of the BLAST maps we have produced an initial census of the submillimeter
structures that will be observed by Herschel, several of which are known
Infrared Dark Clouds (IRDCs). Our spectral energy distributions of the main
clumps in the field, located at ~7 kpc, reveal an active population with
temperatures of T~35-40 K and masses of ~10^3 Msun for a dust emissivity index
beta=1.5. The clump evolutionary stages range from evolved sources, with
extended HII regions and prominent IR stellar population, to massive young
stellar objects, prior to the formation of an UCHIIR.The CORNISH data have
revealed the details of the stellar content and structure of the UCHIIRs. In
most cases, the ionizing stars corresponding to the brightest radio detections
are capable of accounting for the clump bolometric luminosity, in most cases
powered by embedded OB stellar clusters
Moderators, Mediators, and Other Predictors of Risperidone Response in Children with Autistic Disorder and Irritability
Objective/Background:
The National Institute of Mental Health (NIMH) Research Units on Pediatric Psychopharmacology
(RUPP) Autism Network found an effect size of d = 1.2 in favor of risperidone on the main outcome measure
in an 8-week double-blind, placebo-controlled trial for irritabilityin autistic disorder. This paper explores
moderators and mediators of this effect.
Method:
Intention-to-treat (ITT) analyses were conducted with suspected moderators and mediators entered
into the regression equations. MacArthur Foundation Network subgroup guidelines were followed in the
evaluation of the results.
Results:
Only baseline severity moderated treatment response: Higher severity showed greater improvement
for risperidone but not for placebo. Weight gain mediated treatment response negatively: Those who gained
more weight improved less with risperidone and more with placebo. Compliance correlated with outcome for
risperidone but not placebo. Higher dose correlated with worse outcome for placebo, but not risperidone. Of
nonspecific predictors, parent education, family income, and low baseline prolactin positively predicted
outcome; anxiety, bipolar symptoms, oppositional-defiant symptoms, stereotypy, and hyperactivity
negatively predicted outcome. Risperidone moderated the effect of change in 5'-nucleotidase, a marker of
zinc status, for which decrease was associated with improvement only with risperidone, not with placebo.
Conclusion:
The benefit–risk ratio of risperidone is better with greater symptom severity. Risperidone can be
individually titrated to optimal dosage for excellent response in the majority of children. Weight gain is not
necessary for risperidone benefit and may even detract from it. Socioeconomic advantage, low prolactin, and
absence of co-morbid problems non-specifically predict better outcome. Mineral interactions with
risperidone deserve further study
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