49 research outputs found
A 4-Selenocysteine, 2-Selenocysteine Insertion Sequence (SECIS) Element Methionine Sulfoxide Reductase from \u3ci\u3eMetridium senile\u3c/i\u3e Reveals a Non-catalytic Function of Selenocysteines
Selenocysteine (Sec) residues occur in thiol oxidoreductase families, and functionally characterized selenoenzymes typically have a single Sec residue used directly for redox catalysis. However, how new Sec residues evolve and whether non-catalytic Sec residues exist in proteins is not known. Here, we computationally identified several genes with multiple Sec insertion sequence (SECIS) elements, one of which was a methionine-Rsulfoxide reductase (MsrB) homolog from Metridium senile that has four in-frame UGA codons and two nearly identical SECIS elements. One of the UGA codons corresponded to the conserved catalytic Sec or Cys in MsrBs, whereas the three other UGA codons evolved recently and had no homologs with Sec or Cys in these positions. Metabolic 75Se labeling showed that all four in-frame UGA codons supported Sec insertion and that both SECIS elements were functional and collaborated in Sec insertion at each UGA codon. Interestingly, recombinant M. senile MsrB bound iron, and further analyses suggested the possibility of binding an iron-sulfur cluster by the protein. These data show that Sec residues may appear transiently in genes containing SECIS elements and be adapted for non-catalytic functions
Thrombotic Thrombocytopenic Purpura Associated with Clopidogrel
BACKGROUND: The antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice. More than 3 million patients have received clopidogrel. We report the clinical and laboratory findings in 11 patients in whom thrombotic thrombocytopenic purpura developed during or soon after treatment with clopidogrel. METHODS: The 11 patients were identified by active surveillance by the medical directors of blood banks (3 patients), hematologists (6), and the manufacturer of clopidogrel (2). RESULTS: Ten of the 11 patients received clopidogrel for 14 days or less before the onset of thrombotic thrombocytopenic purpura. Although 10 of the 11 patients had a response to plasma exchange, 2 required 20 or more exchanges before clinical improvement occurred, and 2 had relapses while not receiving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis. CONCLUSIONS: Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment
Rubin-Euclid Derived Data Products:Initial Recommendations
This report is the result of a joint discussion between the Rubin and Euclid scientific communities. The work presented in this report was focused on designing and recommending an initial set of Derived Data products (DDPs) that could realize the science goals enabled by joint processing. All interested Rubin and Euclid data rights holders were invited to contribute via an online discussion forum and a series of virtual meetings. Strong interest in enhancing science with joint DDPs emerged from across a wide range of astrophysical domains: Solar System, the Galaxy, the Local Volume, from the nearby to the primaeval Universe, and cosmology
Genetic mixed-stock analysis of Atlantic herring populations in a mixed feeding area
Determining spatio-temporal distributions of fish populations is of interest to marine
ecology, in general, and to fisheries science in particular. Genetic mixed-stock analysis is routinely
applied in several anadromous fishes for determining migratory routes and timing but has rarely
been used for marine fishes, for which population differentiation is commonly weak and the
method presumably less powerful. We used microsatellite information for Northeast Atlantic herring
Clupea harengus L. populations and mixed stocks to address 2 questions. We used simulated
mixture samples and 3 different statistical approaches to determine whether mixed stock composition
could be determined with accuracy. Simulations showed that the applied approaches and
mixture samples of 100 individuals enabled detailed composition analyses on a regional level,
with resolution for tracing the ecologically dominant Rügen (Greifswalder Bodden) herring population.
We then estimated spatio-temporal variation in herring migratory behaviour in the Skagerrak
from 17 mixed samples collected over 2 seasons and 2 yr, and identified hitherto undescribed
differences in distributions among populations that feed and winter in the area
Genetic mixed-stock analysis of Atlantic herring populations in a mixed feeding area
Determining spatio-temporal distributions of fish populations is of interest to marine
ecology, in general, and to fisheries science in particular. Genetic mixed-stock analysis is routinely
applied in several anadromous fishes for determining migratory routes and timing but has rarely
been used for marine fishes, for which population differentiation is commonly weak and the
method presumably less powerful. We used microsatellite information for Northeast Atlantic herring
Clupea harengus L. populations and mixed stocks to address 2 questions. We used simulated
mixture samples and 3 different statistical approaches to determine whether mixed stock composition
could be determined with accuracy. Simulations showed that the applied approaches and
mixture samples of 100 individuals enabled detailed composition analyses on a regional level,
with resolution for tracing the ecologically dominant Rügen (Greifswalder Bodden) herring population.
We then estimated spatio-temporal variation in herring migratory behaviour in the Skagerrak
from 17 mixed samples collected over 2 seasons and 2 yr, and identified hitherto undescribed
differences in distributions among populations that feed and winter in the area.2016-12-0
North Sea herring population structure revealed by microsatellite analysis
The Atlantic herring Clupea harengus has played a pivotal role in the formulation of
ideas relating to population structuring in marine fishes, yet considerable uncertainty remains as to
the extent to which phenotypic and genetic differentiation coincide in such a highly mobile species.
In this study, we examined genetic population structure across the major herring spawning aggregations
in the North Sea and adjacent waters over 2 years, 2002 and 2003. We analysed 1660 spawning
individuals across 9 microsatellite loci. Data were analysed using several approaches, taking into
account the effect of location, year-class and sex, as well as pooling all individuals together, making
no assumption as to the number of populations present in the data set. The results suggest the presence
of a genetically homogeneous unit off Northern Scotland, and a temporally stable pattern of isolation
by distance determined predominantly by the divergence of the English Channel samples and,
in 2003, by the Norwegian spring spawners. Our data suggest that the current view of North Sea
herring as a unit-stock might be adequate, but confirm the considerable degree of demographic
independence of the herring populations in the English Channel. Despite major recent population
collapses, genetic data indicated no evidence of bottlenecks affecting the genetic diversity of extant
North Sea herring populations. Finally, despite evidence of weak population structuring, we discuss
the risks of underestimating population differentiation in marine fish of large population sizes, and
with reference to herring population history and dynamics, we attempt to reconcile the existing
theories on herring population structure
Benefits of Sports Participation for Executive Function in Disabled Athletes
We investigated the effect of sports activity on physically-disabled individuals using behavioral and electrophysiological techniques. Visual go/no-go discriminative and simple response tasks were used. Participants included 17 disabled athletes, 9 from open-skill (wheelchair basketball) and eight from closed-skill (swimming) sports, and 18 healthy non-athletes. Reaction times of the disabled athletes were slower than those of healthy non-athletes on both tasks (7% and 13% difference, respectively). Intra-individual variations in reaction times, switch cost, and number of false alarms, were higher in the swimmers, but comparable to healthy non-athletes, in the basketball group. Event-related potentials (ERPs) early components P1, N1, and P2 had longer latencies in the disabled athletes. The late P3 component had longer latency and smaller amplitude in the disabled athletes only in the discriminative response task. The N2 component, which reflected inhibition/execution processing in the discriminative response task, was delayed and reduced in the swimmer group, but was comparable to healthy subjects in the basketball group. Our results show that (1) the ERP components related to perceptual processing, and late components related to executive processing, were impaired in disabled subjects; and (2) open-skill sports such as basketball may partially compensate for executive control impairment by fostering the stability of motor responses and favoring response flexibility