719 research outputs found
Serum microRNA profiles in athyroid patients on and off levothyroxine therapy
Background Levothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone. Objective To study if serum miRNA profiles are changed in different thyroid states. Design and methods We studied 13 athyroid patients (6 males) during TSH suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic bead capture system was used to isolate 384 defined miRNAs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after individual target amplification. Results Mean age of the subjects was 44.0 years (range 20ā61 years). Median TSH levels were 88.9 mU/l during levothyroxine withdrawal and 0.006 mU/l during LT4 treatment with a median dosage of 2.1 Ī¼g/kg. After normalization to allow inter-sample analysis, a paired analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment
Serum microRNA profiles in athyroid patients on and off levothyroxine therapy
BackgroundLevothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone.ObjectiveTo study if serum miRNA profiles are changed in different thyroid states.Design and methodsWe studied 13 athyroid patients (6 males) during TSH suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic bead capture system was used to isolate 384 defined miRNAs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after individual target amplification.ResultsMean age of the subjects was 44.0 years (range 20-61 years). Median TSH levels were 88.9 mU/I during levothyroxine withdrawal and 0.006 mU/I during LT4 treatment with a median dosage of 2.1 fag/kg. After normalization to allow inter-sample analysis, a paired analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment.ConclusionAlthough we previously showed an up-regulation of pri-miRNAs 133b and 206 in hypothyroid state in skeletal muscle, the present study does not supply evidence that thyroid state also affects serum miRNAs in humans
Spin-orbit density wave induced hidden topological order in URu2Si2
The conventional order parameters in quantum matters are often characterized
by 'spontaneous' broken symmetries. However, sometimes the broken symmetries
may blend with the invariant symmetries to lead to mysterious emergent phases.
The heavy fermion metal URu2Si2 is one such example, where the order parameter
responsible for a second-order phase transition at Th = 17.5 K has remained a
long-standing mystery. Here we propose via ab-initio calculation and effective
model that a novel spin-orbit density wave in the f-states is responsible for
the hidden-order phase in URu2Si2. The staggered spin-orbit order 'spontaneous'
breaks rotational, and translational symmetries while time-reversal symmetry
remains intact. Thus it is immune to pressure, but can be destroyed by magnetic
field even at T = 0 K, that means at a quantum critical point. We compute
topological index of the order parameter to show that the hidden order is
topologically invariant. Finally, some verifiable predictions are presented.Comment: (v2) Substantially modified from v1, more calculation and comparison
with experiments are include
Different effects of continuous infusion of interleukin-1 and interleukin-6 on the hypothalamic-hypophysial-thyroid axis
The cytokines interleukin-1 (IL-1) and IL-6 are thought to be important
mediators in the suppression of thyroid function during nonthyroidal
illness. In this study we compared the effects of IL-1 and IL-6 infusion
on the hypothalamus-pituitary-thyroid axis in rats. Cytokines were
administered by continuous ip infusion of 4 micrograms IL-1 alpha/day for
1, 2, or 7 days or of 15 micrograms IL-6/day for 7 days. Body weight and
temperature, food and water intake, and plasma TSH, T4, free T4 (FT4), T3,
and corticosterone levels were measured daily, and hypothalamic pro-TRH
messenger RNA (mRNA) and hypophysial TSH beta mRNA were determined after
termination of the experiments. Compared with saline-treated controls,
infusion of IL-1, but not of IL-6, produced a transient decrease in food
and water intake, a transient increase in body temperature, and a
prolonged decrease in body weight. Both cytokines caused transient
decreases in plasma TSH and T4, which were greater and more prolonged with
IL-1 than with IL-6, whereas they effected similar transient increases in
the plasma FT4 fraction. Infusion with IL-1, but not IL-6, also induced
transient decreases in plasma FT4 and T3 and a transient increase in
plasma corticosterone. Hypothalamic pro-TRH mRNA was significantly
decreased (-73%) after 7 days, but not after 1 or 2 days, of IL-1 infusion
and was unaffected by IL-6 infusion. Hypophysial TSH beta mRNA was
significantly decreased after 2 (-62%) and 7 (-62%) days, but not after 1
day, of IL-1 infusion and was unaffected by IL-6 infusion. These results
are in agreement with previous findings that IL-1, more so than IL-6,
directly inhibits thyroid hormone production. They also indicate that IL-1
and IL-6 both decrease plasma T4 binding. Furthermore, both cytokines
induce an acute and dramatic decrease in plasma TSH before (IL-1) or even
without (IL-6) a decrease in hypothalamic pro-TRH mRNA or hypophysial TSH
beta mRNA, suggesting that the acute decrease in TSH secretion is not
caused by decreased pro-TRH and TSH beta gene expression. The
TSH-suppressive effect of IL-6, either administered as such or induced by
IL-1 infusion, may be due to a direct effect on the thyrotroph, whereas
additional effects of IL-1 may involve changes in the hypothalamic release
of somatostatin or TRH.(ABSTRACT TRUNCATED AT 400 WORDS
The impact of predation by marine mammals on Patagonian toothfish longline fisheries
Predatory interaction of marine mammals with longline fisheries is observed globally, leading to partial or complete loss of the catch and in some parts of the world to considerable financial loss. Depredation can also create additional unrecorded fishing mortality of a stock and has the potential to introduce bias to stock assessments. Here we aim to characterise depredation in the Patagonian toothfish (Dissostichus eleginoides) fishery around South Georgia focusing on the spatio-temporal component of these interactions. Antarctic fur seals (Arctocephalus gazella), sperm whales (Physeter macrocephalus), and orcas (Orcinus orca) frequently feed on fish hooked on longlines around South Georgia. A third of longlines encounter sperm whales, but loss of catch due to sperm whales is insignificant when compared to that due to orcas, which interact with only 5% of longlines but can take more than half of the catch in some cases. Orca depredation around South Georgia is spatially limited and focused in areas of putative migration routes, and the impact is compounded as a result of the fishery also concentrating in those areas at those times. Understanding the seasonal behaviour of orcas and the spatial and temporal distribution of ādepredation hot spotsā can reduce marine mammal interactions, will improve assessment and management of the stock and contribute to increased operational efficiency of the fishery. Such information is valuable in the effort to resolve the human-mammal conflict for resources
Reliable identification at the species level of Brucella isolates with MALDI-TOF-MS
<p>Abstract</p> <p>Background</p> <p>The genus <it>Brucella </it>contains highly infectious species that are classified as biological threat agents. The timely detection and identification of the microorganism involved is essential for an effective response not only to biological warfare attacks but also to natural outbreaks. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is a rapid method for the analysis of biological samples. The advantages of this method, compared to conventional techniques, are rapidity, cost-effectiveness, accuracy and suitability for the high-throughput identification of bacteria. Discrepancies between taxonomy and genetic relatedness on the species and biovar level complicate the development of detection and identification assays.</p> <p>Results</p> <p>In this study, the accurate identification of <it>Brucella </it>species using MALDI-TOF-MS was achieved by constructing a <it>Brucella </it>reference library based on multilocus variable-number tandem repeat analysis (MLVA) data. By comparing MS-spectra from <it>Brucella </it>species against a custom-made MALDI-TOF-MS reference library, MALDI-TOF-MS could be used as a rapid identification method for <it>Brucella </it>species. In this way, 99.3% of the 152 isolates tested were identified at the species level, and <it>B. suis </it>biovar 1 and 2 were identified at the level of their biovar. This result demonstrates that for <it>Brucella</it>, even minimal genomic differences between these serovars translate to specific proteomic differences.</p> <p>Conclusions</p> <p>MALDI-TOF-MS can be developed into a fast and reliable identification method for genetically highly related species when potential taxonomic and genetic inconsistencies are taken into consideration during the generation of the reference library.</p
Tau PET and relative cerebral blood flow in Dementia with Lewy bodies: A PET study
Purpose: Alpha-synuclein often co-occurs with Alzheimerās disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB. /
Methods: Eighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology(DLB-AD+). Receptor parametric mapping(cerebellar gray matter reference region) was used to extract regional binding potential (BPND) and R1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [18F]flortaucipir BPND and R1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [18F]flortaucipir BPND, R1 and performance on ten neuropsychological tests. /
Results: Regional [18F]flortaucipir BPND in DLB was comparable with tau binding in controls (p>0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p<0.05). Occipital and lateral parietal R1 was lower in DLB compared to AD and controls (all p<0.01). Lower frontal R1 was associated with impaired performance on digit span forward (standardized beta, stĪ²=0.72) and category fluency (stĪ²=0.69) tests. Lower parietal R1 was related to lower delayed (stĪ²=0.50) and immediate (stĪ²=0.48) recall, VOSP number location (stĪ²=0.70) and fragmented letters (stĪ²=0.59) scores. Lower occipital R1 was associated to worse performance on VOSP fragmented letters (stĪ²=0.61), all p<0.05. /
Conclusion: The amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET
White matter microstructure disruption in early stage amyloid pathology.
Introduction: Amyloid beta (AĪ²) accumulation is the first pathological hallmark of Alzheimer's disease (AD), and it is associated with altered white matter (WM) microstructure. We aimed to investigate this relationship at a regional level in a cognitively unimpaired cohort. Methods: We included 179 individuals from the European Medical Information Framework for AD (EMIFāAD) preclinAD study, who underwent diffusion magnetic resonance (MR) to determine tractālevel fractional anisotropy (FA); mean, radial, and axial diffusivity (MD/RD/AxD); and dynamic [18F]flutemetamol) positron emission tomography (PET) imaging to assess amyloid burden. Results: Regression analyses showed a nonālinear relationship between regional amyloid burden and WM microstructure. Low amyloid burden was associated with increased FA and decreased MD/RD/AxD, followed by decreased FA and increased MD/RD/AxD upon higher amyloid burden. The strongest association was observed between amyloid burden in the precuneus and body of the corpus callosum (CC) FA and diffusivity (MD/RD) measures. In addition, amyloid burden in the anterior cingulate cortex strongly related to AxD and RD measures in the genu CC. Discussion: Early amyloid deposition is associated with changes in WM microstructure. The nonālinear relationship might reflect multiple stages of axonal damage
- ā¦