Thyroid hormones (THs) play key regulatory roles in growth, development and metabolism in vertebrates. Modulation of the cellular hormonal response is largely through the activity of two nuclear TH ...receptors, TRα and TRβ, which act as transcription factors and alter gene expression programs. Little information is available regarding their structure and regulation in reptiles. We have cloned the expressed sequences encoding these two receptors in the American alligator,
Alligator mississippiensis. The encoded putative proteins share a high degree of amino acid sequence conservation with other vertebrates, however, both alligator TRs contain putative N-terminal truncations. This phenomenon is shared with the chicken for TRβ, but not for TRα, making this the first demonstration of this type of TRα isoform. We measured the steady-state levels of TR transcripts in heart, lung, liver, thyroid, cliterophallus/phallus, and gonad of juvenile alligators 24 and 48
h after injection with thyroid stimulating hormone (TSH). TRα transcript levels were increased in the heart, decreased in the lung and cliterophallus/phallus, and unaffected in the liver, thyroid, and gonad. TRβ transcript levels were increased in the heart, lung, and gonad whereas estrogen receptor α transcript levels were elevated by TSH treatment only in the gonad. Modulation of these transcripts in the gonad is consistent with TH playing an important role in this tissue’s function since seasonal TH fluctuations coincide with reproductive events. These data demonstrate that alligator tissues are differentially responsive to TSH by regulation of TR expression and provide an important comparative framework among vertebrates.
Inhibitor of growth 2 (ING2) belongs to a family of tumor suppressors that are important regulators of a wide range of cellular processes including proliferation, apoptosis, and DNA repair. ING ...family members are found in yeast, plants, invertebrates and many vertebrate species. However, to date, ING has not been characterized in reptiles. Herein we describe the isolation of expressed ING2 sequence in the American alligator,
Alligator mississippiensis, and compare this sequence with that isolated in the chicken. We identify features that are unique to these two representatives of the Archosaurs including conservation of specific amino acid residues and the absence of an adenylate residue in the 5′ end of the nucleotide sequence relative to frogs and mammals. The latter feature results in an alteration of the coding potential leading to distinctive N-termini. Injection of juvenile alligators with thyroid stimulating hormone (TSH), which increases endogenous thyroid hormones, results in the modulation of ING2 transcript levels. Quantitative real time polymerase chain reaction analyses revealed a reduction in the steady-state levels of ING2 mRNA in the phallus/cliterophallus, lung, and liver by 48 h after TSH injection. ING2 expression in the thyroid gland, gonad, and heart was unaffected by TSH treatment. These data indicate that control of ING2 expression by the thyroid axis may be conserved among species and is tissue-dependent.
Two studies were undertaken to confirm the previous findings that homosexual men in general tend to have a later than expected birth order and that extremely feminine homosexual men also tend to have ...a higher than expected proportion of brothers (i.e., a higher sibling sex ratio). Subjects in Study 1 were Dutch, adult and adolescent, biological male patients with gender dysphoria (persistent and recurrent desires to belong to the opposite sex), who were undergoing treatment with feminizing hormones. These comprised 83 patients who reported sexual attraction to other males (the homosexual group) and 58 who reported sexual attraction to females or equal attraction to males and females (the non-homosexual group). Subjects in Study 2 were Dutch adolescent male patients at another hospital. The homosexual group consisted of 21 gender-dysphoric homosexual teenagers referred to a gender identity clinic for children and adolescents. The control group were 21 adolescent males referred to the child psychiatry department of the same hospital for reasons other than gender identity disorder, homosexuality, or transvestism. These were individually matched to the homosexual subjects on age and sibship size. In both studies, the homosexual group had a significantly later average birth order than the comparison group. In Study 1, the homosexual group had a significantly elevated sibling sex ratio; this was not tested in Study 2 because of its small sample size. These studies add to the mounting evidence that late birth orders are common to all homosexual samples and that elevated sibling sex ratios are an additional characteristic of extremely feminine ones.
The MiMeS (Magnetism in Massive Stars) project is a large-scale, high-resolution, sensitive spectropolarimetric investigation of the magnetic properties of O- and early B-type stars. Initiated in ...2008 and completed in 2013, the project was supported by three Large Program allocations, as well as various programmes initiated by independent principal investigators, and archival resources. Ultimately, over 4800 circularly polarized spectra of 560 O and B stars were collected with the instruments ESPaDOnS (Echelle SpectroPolarimetric Device for the Observation of Stars) at the Canada–France–Hawaii Telescope, Narval at the Télescope Bernard Lyot and HARPSpol at the European Southern Observatory La Silla 3.6 m telescope, making MiMeS by far the largest systematic investigation of massive star magnetism ever undertaken. In this paper, the first in a series reporting the general results of the survey, we introduce the scientific motivation and goals, describe the sample of targets, review the instrumentation and observational techniques used, explain the exposure time calculation designed to provide sensitivity to surface dipole fields above approximately 100 G, discuss the polarimetric performance, stability and uncertainty of the instrumentation, and summarize the previous and forthcoming publications.
Glaucoma is the leading cause of irreversible blindness globally
. Despite its gravity, the disease is frequently undiagnosed in the community
. Raised intraocular pressure (IOP) is the most ...important risk factor for primary open-angle glaucoma (POAG)
. Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were nominally associated with glaucoma in an independent cohort, 14 of which were significant at a Bonferroni-corrected threshold. Regression-based glaucoma-prediction models had an area under the receiver operating characteristic curve (AUROC) of 0.76 in US NEIGHBORHOOD study participants and 0.74 in independent glaucoma cases from the UK Biobank. Genetic-prediction models for POAG offer an opportunity to target screening and timely therapy to individuals most at risk.
Fragile X syndrome (FXS) is the leading inherited form of intellectual disability and autism spectrum disorder, and patients can present with severe behavioural alterations, including hyperactivity, ...impulsivity and anxiety, in addition to poor language development and seizures. FXS is a trinucleotide repeat disorder, in which >200 repeats of the CGG motif in FMR1 leads to silencing of the gene and the consequent loss of its product, fragile X mental retardation 1 protein (FMRP). FMRP has a central role in gene expression and regulates the translation of potentially hundreds of mRNAs, many of which are involved in the development and maintenance of neuronal synaptic connections. Indeed, disturbances in neuroplasticity is a key finding in FXS animal models, and an imbalance in inhibitory and excitatory neuronal circuits is believed to underlie many of the clinical manifestations of this disorder. Our knowledge of the proteins that are regulated by FMRP is rapidly growing, and this has led to the identification of multiple targets for therapeutic intervention, some of which have already moved into clinical trials or clinical practice.
Abstract
Background: This is the 30th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of July 1, 2012, 57 of the nation's poison ...centers (PCs) uploaded case data automatically to NPDS. The upload interval was 7.58 6.30, 11.22 (median 25%, 75%) min, creating a near real-time national exposure and information database and surveillance system.
Methodology: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of 34 medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure to the death.
Results: In 2012, 3,373,025 closed encounters were logged by NPDS: 2,275,141 human exposures, 66,440 animal exposures, 1,025,547 information calls, 5,679 human confirmed nonexposures, and 218 animal confirmed nonexposures. Total encounters showed a 6.9% decline from 2011, while healthcare facility (HCF) exposure calls increased by 1.2%. All information calls decreased by 14.8% and HCF information calls decreased by 1.7%, medication identification requests (Drug ID) decreased by 22.0%, and human exposures reported to US PCs decreased by 2.5%. Human exposures with less serious outcomes have decreased by 3.7% per year since 2008, while those with more serious outcomes (moderate, major, or death) have increased by 4.6% per year since 2000.
The top five substance classes most frequently involved in all human exposures were analgesics (11.6%), cosmetics/personal care products (7.9%), household cleaning substances (7.2%), sedatives/hypnotics/antipsychotics (6.1%), and foreign bodies/toys/miscellaneous (4.1%). Analgesic exposures as a class increased the most rapidly (8,780 calls/year) over the last 12 years. The top five most common exposures in children aged 5 years or less were cosmetics/ personal care products (13.9%), analgesics (9.9%), household cleaning substances (9.7%), foreign bodies/toys/ miscellaneous (7.0%), and topical preparations (6.3%). Drug identification requests comprised 54.4% of all information calls. NPDS documented 2,937 human exposures resulting in death with 2,576 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory).
Conclusions: These data support the continued value of PC expertise and need for specialized medical toxicology information to manage the more severe exposures, despite a decrease in calls involving less severe exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for public health surveillance for all types of exposures, public health event identification, resilience response, and situational awareness tracking. NPDS is a model system for the nation and global public health.
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