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101.
Kaitlyn M. Price Karen G. Wigg Yu Feng Kirsten Blokland Margaret Wilkinson Gengming He Elizabeth N. Kerr Tasha‐Cate Carter Sharon L. Guger Maureen W. Lovett Lisa J. Strug Cathy L. Barr 《Genes, Brain & Behavior》2020,19(6)
Reading disabilities (RD) are the most common neurocognitive disorder, affecting 5% to 17% of children in North America. These children often have comorbid neurodevelopmental/psychiatric disorders, such as attention deficit/hyperactivity disorder (ADHD). The genetics of RD and their overlap with other disorders is incompletely understood. To contribute to this, we performed a genome‐wide association study (GWAS) for word reading. Then, using summary statistics from neurodevelopmental/psychiatric disorders, we computed polygenic risk scores (PRS) and used them to predict reading ability in our samples. This enabled us to test the shared aetiology between RD and other disorders. The GWAS consisted of 5.3 million single nucleotide polymorphisms (SNPs) and two samples; a family‐based sample recruited for reading difficulties in Toronto (n = 624) and a population‐based sample recruited in Philadelphia [Philadelphia Neurodevelopmental Cohort (PNC)] (n = 4430). The Toronto sample SNP‐based analysis identified suggestive SNPs (P ~ 5 × 10?7) in the ARHGAP23 gene, which is implicated in neuronal migration/axon pathfinding. The PNC gene‐based analysis identified significant associations (P < 2.72 × 10?6) for LINC00935 and CCNT1, located in the region of the KANSL2/CCNT1/LINC00935/SNORA2B/SNORA34/MIR4701/ADCY6 genes on chromosome 12q, with near significant SNP‐based analysis. PRS identified significant overlap between word reading and intelligence (R2 = 0.18, P = 7.25 × 10?181), word reading and educational attainment (R2 = 0.07, P = 4.91 × 10?48) and word reading and ADHD (R2 = 0.02, P = 8.70 × 10?6; threshold for significance = 7.14 × 10?3). Overlap was also found between RD and autism spectrum disorder (ASD) as top‐ranked genes were previously implicated in autism by rare and copy number variant analyses. These findings support shared risk between word reading, cognitive measures, educational outcomes and neurodevelopmental disorders, including ASD. 相似文献
102.
Patricia Geesink Carl-Eric Wegner Alexander J. Probst Martina Herrmann Hang T. Dam Anne-Kristin Kaster Kirsten Küsel 《Environmental microbiology》2020,22(2):726-737
Subsurface ecosystems like groundwater harbour diverse microbial communities, including small-sized, putatively symbiotic organisms of the Candidate Phyla Radiation, yet little is known about their ecological preferences and potential microbial partners. Here, we investigated a member of the superphylum Microgenomates (Cand. Roizmanbacterium ADI133) from oligotrophic groundwater using mini-metagenomics and monitored its spatio-temporal distribution using 16S rRNA gene analyses. A Roizmanbacteria-specific quantitative PCR assay allowed us to track its abundance over the course of 1 year within eight groundwater wells along a 5.4 km hillslope transect, where Roizmanbacteria reached maximum relative abundances of 2.3%. In-depth genomic analyses suggested that Cand. Roizmanbacterium ADI133 is a lactic acid fermenter, potentially able to utilize a range of complex carbon substrates, including cellulose. We hypothesize that it attaches to host cells using a trimeric autotransporter adhesin and inhibits their cell wall biosynthesis using a toxin–antitoxin system. Network analyses based on correlating Cand. Roizmanbacterium ADI133 abundances with amplicon sequencing-derived microbial community profiles suggested one potential host organism, classified as a member of the class Thermodesulfovibrionia (Nitrospirae). By providing lactate as an electron donor Cand. Roizmanbacterium ADI133 potentially mediates the transfer of carbon to other microorganisms and thereby is an important connector in the microbial community. 相似文献
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106.
Persson Joel Ford Scott Keophoxay Anousith Mertz Ole Nielsen Jonas Østergaard Vongvisouk Thoumthone Zörner Michael 《Human ecology: an interdisciplinary journal》2021,49(5):597-616
Human Ecology - Despite the popularity of integrated conservation and development approaches to protected area management, adjacent communities increasingly face livelihood dilemmas. Yet... 相似文献
107.
Jonathan C. Guito Joseph B. Prescott Catherine E. Arnold Brian R. Amman Amy J. Schuh Jessica R. Spengler Tara K. Sealy Jessica R. Harmon JoAnn D. Coleman-McCray Kirsten A. Kulcsar Elyse R. Nagle Raina Kumar Gustavo F. Palacios Mariano Sanchez-Lockhart Jonathan S. Towner 《Current biology : CB》2021,31(2):257-270.e5
108.
Kirsten S. Koretz Claire E. McGraw Steven Stradley Ahmed Elbaradei Noah Malmstadt Anne S. Robinson 《Biophysical journal》2021,120(9):1641-1649
Because of their surface localization, G protein-coupled receptors (GPCRs) are often pharmaceutical targets as they respond to a variety of extracellular stimuli (e.g., light, hormones, small molecules) that may activate or inhibit a downstream signaling response. The adenosine A2A receptor (A2AR) is a well-characterized GPCR that is expressed widely throughout the human body, with over 10 crystal structures determined. Truncation of the A2AR C-terminus is necessary for crystallization as this portion of the receptor is long and unstructured; however, previous work suggests shortening of the A2AR C-terminus from 412 to 316 amino acids (A2AΔ316R) ablates downstream signaling, as measured by cAMP production, to below that of constitutive full-length A2AR levels. As cAMP production is downstream of the first activation event—coupling of G protein to its receptor—investigating that first step in activation is important in understanding how the truncation effects native GPCR function. Here, using purified receptor and Gαs proteins, we characterize the association of A2AR and A2AΔ316R to Gαs with and without GDP or GTPγs using surface plasmon resonance (SPR). Gαs affinity for A2AR was greatest for apo-Gαs, moderately affected in the presence of GDP and nearly completely ablated by the addition of GTPγs. Truncation of the A2AR C-terminus (A2AΔ316R) decreased the affinity of the unliganded receptor for Gαs by ~20%, suggesting small changes to binding can greatly impact downstream signaling. 相似文献
109.
Kefei Chen Christoph Knorr Kirsten Bornemann-Kolatzki LuSheng Huang Gary A. Rohrer 《Animal biotechnology》2013,24(1):43-49
We isolated and characterized the highly polymorphic tetra-nucleotide microsatellite S0719 on SSC7q14-q15 adjacent to the porcine testis-specific phosphoglycerate kinase 2 (PGK2) gene and assigned it to the USDA-MARC linkage map on SSC7 position 77.5 cM closely linked to markers SW859 (76.3 cM) and SWR2036 (79.0 cM). In a panel of 344 individuals representing 11 pig breeds (European, Chinese, and North American), a total of 32 alleles were observed, and the overall breeds' calculated PIC (polymorphism information content), HE (heterozygosity), and NE (effective allele number) were 0.94, 0.94, and 16.41. Breed-specific PIC and HE ranged from 0.66 to 0.87, whereas NE was as low as 2.95 and as high as 7.96. Considering the high allelic variation of S0719 within and among pig breeds (79% of the genotyped animals were heterozygous), the marker is useful for individual animal identification and parentage determination. Finally, S0719 is also a valuable STS marker for fine-mapping QTL on SSC7 as position 77.5 cM is located in 25 QTL intervals (http://www.animalgenome.org/QTLdb/). 相似文献
110.
Bertil Persson Anders Andersson Björn Hultberg Christer Hansson 《Free radical research》2013,47(2):151-156
Glutathione, the most abundant low-molecular weight thiol in the skin, has been shown to protect the skin from both photobiological and chemical injury. The thiols, glutathione in particular, have also been shown to be crucially involved in defence against contact allergens. Since the levels of extracellular thiol concentrations are important determinants of intracellular thiol status, we have compared the normal concentrations and the redox status of the main low-molecular weight thiol components in the extracellular fluid at the dermo-epidermal junction with the corresponding plasma levels. In their sulfhydryl form, all three thiols, i.e. glutathione, cysteine and homocysteine, were more abundant in experimental skin blister fluid than in plasma, as were the free disulfides of glutathione and homocysteine, whereas the free disulfides of cysteine were about the same in blister fluid and in plasma. Protein mixed disulfide levels were higher in plasma than in blister fluid. The present results provide information concerning the extracellular defence in the skin. 相似文献