Utility of Thyroid Function Testing in the Inpatient Setting

ObjectivePrevious studies have reported a low value of ordering inpatient thyroid function tests (TFTs), with few changes in clinical management resulting from these tests. This study was designed to evaluate how often testing the thyroid function during hospitalization leads to medication initiation or adjustment and to determine whether the frequency of medication initiation or adjustment differs based on the indication for testing.MethodsThis is a retrospective observational study of 2278 patients who underwent TFTs tested while admitted to an academic hospital during a 5-month period. The indications for ordering TFTs were determined by reviewing clinical documentation, and those with abnormal test results were reviewed to assess whether thyroid medication was initiated or adjusted.ResultsThe percentage of abnormal TFTs that led to medication initiation or adjustment was 15.1%, 12.2%, and 6.0%, for those tested based on a history of functional thyroid disease, suspicion of thyroid dysfunction, and reasons not directly related to thyroid dysfunction, respectively. Overall, 63 patients were started on thyroid medication or had their thyroid medication dose adjusted, which represented 10.1% of those with abnormal TFTs and only 2.8% of those tested.ConclusionAbnormal TFTs are common, but a disproportionate number of tests are needed to find a small percentage of clinically significant thyroid dysfunction, of which only a low percentage leads to changes in management. Education on this topic should be provided to inpatient providers to limit thyroid function testing to instances in which they are clinically indicated and abnormal results would lead to changes in management.     

Accounting for phenology in the analysis of animal movement

The analysis of animal tracking data provides important scientific understanding and discovery in ecology. Observations of animal trajectories using telemetry devices provide researchers with information about the way animals interact with their environment and each other. For many species, specific geographical features in the landscape can have a strong effect on behavior. Such features may correspond to a single point (eg, dens or kill sites), or to higher dimensional subspaces (eg, rivers or lakes). Features may be relatively static in time (eg, coastlines or home‐range centers), or may be dynamic (eg, sea ice extent or areas of high‐quality forage for herbivores). We introduce a novel model for animal movement that incorporates active selection for dynamic features in a landscape. Our approach is motivated by the study of polar bear (Ursus maritimus) movement. During the sea ice melt season, polar bears spend much of their time on sea ice above shallow, biologically productive water where they hunt seals. The changing distribution and characteristics of sea ice throughout the year mean that the location of valuable habitat is constantly shifting. We develop a model for the movement of polar bears that accounts for the effect of this important landscape feature. We introduce a two‐stage procedure for approximate Bayesian inference that allows us to analyze over 300 000 observed locations of 186 polar bears from 2012 to 2016. We use our model to estimate a spatial boundary of interest to wildlife managers that separates two subpopulations of polar bears from the Beaufort and Chukchi seas.     

幽门螺杆菌外膜囊泡研究进展

幽门螺杆菌(Helicobacter pylori)被认为是引起人类胃部疾病的元凶之一。外膜囊泡(Outer Membrane Vesicles,OMVs)是由细菌外膜自发脱落而形成的囊泡状结构,其具有细菌外膜多数成分,包括外膜蛋白、多糖、脂质以及其他蛋白组分。越来越多的研究正在关注外膜囊泡在幽门螺杆菌感染、发生、发展过程中的作用。同时,研究表明幽门螺杆菌外膜囊泡作为疫苗,在防治幽门螺杆菌感染中也展现了良好的应用潜力。因此,本综述总结了目前关于幽门螺杆菌外膜囊泡组成成分的研究,并讨论了外膜囊泡在幽门螺杆菌存活和致病机制中的作用,以及外膜囊泡在幽门螺杆菌感染治疗中发挥的作用。     

Function of a membrane-embedded domain evolutionarily multiplied in the GPI lipid anchor pathway proteins PIG-B,PIG-M,PIG-U,PIG-W,PIG-V,and PIG-Z

Distant homology relationships among proteins with many transmembrane regions (TMs) are difficult to detect as they are clouded by the TMs’ hydrophobic compositional bias and mutational divergence in connecting loops. In the case of several GPI lipid anchor biosynthesis pathway components, the hidden evolutionary signal can be revealed with dissectHMMER, a sequence similarity search tool focusing on fold-critical, high complexity sequence segments. We find that a sequence module with 10 TMs in PIG-W, described as acyl transferase, is homologous to PIG-U, a transamidase subunit without characterized molecular function, and to mannosyltransferases PIG-B, PIG-M, PIG-V and PIG-Z. We conclude that this new, membrane-embedded domain named BindGPILA functions as the unit for recognizing, binding and stabilizing the GPI lipid anchor in a modification-competent form as this appears the only functional aspect shared among all proteins. Thus, PIG-U's likely molecular function is shuttling/presenting the anchor in a productive conformation to the transamidase complex.     

长链非编码RNA及其与疾病相关性的研究进展*

人类基因组中,用于蛋白质编码的核酸序列约占1.5%,另外98.5%的非蛋白编码基因被视为"噪音"序列,并未引起人们的注意。随着测序技术的发展,人们发现大部分的基因被转录成RNA,其中多数为长度大于200nt且不编码蛋白质的长链非编码RNA(Long non-coding RNA, lncRNA),其作用机制包括支架分子、引导分子等,广泛参与细胞发育、增殖及迁移过程,且其水平的改变又与肿瘤、代谢性疾病等相关。本文主要对lncRNA的分类、作用机制及涉及的疾病等进行综述,为进一步研究lncRNA的功能机制奠定基础。     

Evolutionary analysis of the multigene pregnancy-specific β1-Glycoprotein family: Separation of historical and nonhistorical signals

The pregnancy-specific ₁-glycoproteins (PSG) form a large family of closely related proteins. Using newly developed methods of sequence analysis, in combination with protein modeling, we provide a framework for investigating the evolution and biological function of genes like the PSG. Evolutionary trees, based on C-terminal sequence, group PSG genes in a manner consistent with their genomic organization. Trees constructed using the N-terminal domain sequences are unreliable as an indicator of phylogeny because of non-neutral processes of sequence change. During duplication of the PSG genes, evolutionary pressures have resulted in a gradient of constrained change across each gene. The N-terminal domains show a nonrandom pattern of amino acid substitutions clustered in the immunoglobulin complementarity-determining region (CDR)-like regions, which appear to be important in the function of the protein.     

Radial glial cell development and transformation are disturbed in reeler forebrain

Radial glia are among the earliest cell types to differentiate in the developing mammalian forebrain. Glial fibers span the early cortical wall, forming a dense scaffold; this persists throughout corticogenesis, providing a cellular substrate which supports and directs the migration of young neurons. Although the mechanisms regulating radial glial cell development are poorly understood, a secreted cortical radial glial differentiation signal was recently identified in the embryonic mouse forebrain. This signal is abundant at the time radial glia function to support neuronal migration, and down-regulated perinatally, when radial glia are known to undergo transformation into astrocytes. Therefore, it seems that this signal functions as a radial glial maintenance factor, the availability of which regulates the phenotype of cortical astroglia. Here the differentiation signal is further characterized as RF60, a protein with a molecular weight of approximately 60 kD. In addition, the neurologic mutant mouse reeler provides a genetic model for analysis of RF60 function. Radial glia in reeler cortex are shown to be poorly differentiated and the radial scaffold is shown to be maintained for a shorter time than normal. Furthermore, although astroglial cells from normal cortex are induced to elaborate a radial phenotype by RF60, reeler astroglia show an impaired differentiation response to this. These findings suggest that an intrinsic defect in glial differentiation contributes to the phenotype of abnormal cortical lamination seen in reeler mouse, and indicate that RF60 may play a critical role in normal cortical patterning. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 459–472, 1997     

The plant homeodomain finger protein MESR4 is essential for embryonic development in Drosophila

Misexpression Suppressor of Ras 4 (MESR4), a plant homeodomain (PHD) finger protein with nine zinc‐finger motifs has been implicated in various biological processes including the regulation of fat storage and innate immunity in Drosophila. However, the role of MESR4 in the context of development remains unclear. Here it is shown that MESR4 is a nuclear protein essential for embryonic development. Immunostaining of polytene chromosomes using anti‐MESR4 antibody revealed that MESR4 binds to numerous bands along the chromosome arms. The most intense signal was detected at the 39E‐F region, which is known to contain the histone gene cluster. P‐element insertions in the MESR4 locus, which were homozygous lethal during embryogenesis with defects in ventral ectoderm formation and head encapsulation was identified. In the mutant embryos, expression of Fasciclin 3 (Fas3), an EGFR signal target gene was greatly reduced, and the level of EGFR signal‐dependent double phosphorylated ERK (dp‐ERK) remained low. However, in the context of wing vein formation, genetic interaction experiments suggested that MESR4 is involved in the EGFR signaling as a negative regulator. These results suggested that MESR4 is a novel chromatin‐binding protein required for proper expression of genes including those regulated by the EGFR signaling pathway during development. genesis 53:701–708, 2015. © 2015 Wiley Periodicals, Inc.