The Written, Spoken, and Signed Word

0ur title points us to the Word of God. It tells us that God speaks to us in three different ways. But it is the same Word that He speaks in all three. There is only one Word of God. The Word, whether written, spoken, or signed, is the same Word. It is the same message from God. It is the same Gospel, proclaiming God\u27s salvation to lost sinners. It is what Luther calls die ewige Wahrheit Gottes, God\u27s own revelation of eternal truth

Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation

© 2018 by The American Society of Hematology Although survival outcomes have significantly improved, up to 40% of patients die within 1 year of HLA-matched unrelated-donor blood and marrow transplantation (BMT). To identify non-HLA genetic contributors to mortality after BMT, we performed the first exome-wide association study in the DISCOVeRY-BMT cohorts using the Illumina HumanExome BeadChip. This study includes 2473 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome and 2221 10/10 HLA-matched donors treated from 2000 to 2011. Single-variant and gene-level analyses were performed on overall survival (OS), transplantation-related mortality (TRM), and disease-related mortality (DRM). Genotype mismatches between recipients and donors in a rare nonsynonymous variant of testis-expressed gene TEX38 significantly increased risk of TRM, which was more dramatic when either the recipient or donor was female. Using the SKAT-O test to evaluate gene-level effects, variant genotypes of OR51D1 in recipients were significantly associated with OS and TRM. In donors, 4 (ALPP, EMID1, SLC44A5, LRP1), 1 (HHAT), and 2 genes (LYZL4, NT5E) were significantly associated with OS, TRM, and DRM, respectively. Inspection of NT5E crystal structures showed 4 of the associated variants affected the enzyme structure and likely decreased the catalytic efficiency of the enzyme. Further confirmation of these findings and additional functional studies may provide individualized risk prediction and prognosis, as well as alternative donor selection strategies

Visuo-spatial cognition in Williams syndrome: Reviewing and accounting for the strengths and weaknesses in performance

Individuals with Williams syndrome typically show relatively poor visuo-spatial abilities in comparison to stronger verbal skills. However, individuals' level of performance is not consistent across all visuo-spatial tasks. The studies assessing visuo-spatial functioning in Williams syndrome are critically reviewed, in order to provide a clear pattern of the relative difficulty of these tasks. This prompts a possible explanation of the variability in performance seen which focuses on the processing demands of some of these tasks. Individuals with Williams syndrome show an atypical processing style on tests of construction, which does not affect tests of perception

Fluorescent RNA cytosine analogue - an internal probe for detailed structure and dynamics investigations

The bright fluorescent cytosine analogue tCO stands out among fluorescent bases due to its virtually unquenched fluorescence emission in duplex DNA. However, like most reported base analogues, it has not been thoroughly characterized in RNA. We here report on the first synthesis and RNA-incorporation of tCO, and characterize its base-mimicking and fluorescence properties in RNA. As in DNA, we find a high quantum yield inside RNA duplexes (<?F> = 0.22) that is virtually unaffected by the neighbouring bases (?F = 0.20-0.25), resulting in an average brightness of 1900 M-1 cm-1. The average fluorescence lifetime in RNA duplexes is 4.3 ns and generally two lifetimes are required to fit the exponential decays. Fluorescence properties in ssRNA are defined by a small increase in average quantum yield (<?F > = 0.24) compared to dsRNA, with a broader distribution (?F = 0.17-0.34) and slightly shorter average lifetimes. Using circular dichroism, we find that the tCO-modified RNA duplexes form regular A-form helices and in UV-melting experiments the stability of the duplexes is only slightly higher than that of the corresponding natural RNA (<?T m> = + 2.3 °C). These properties make tCO a highly interesting fluorescent RNA base analogue for detailed FRET-based structural measurements, as a bright internal label in microscopy, and for fluorescence anisotropy measurements of RNA dynamics

A newborn with Cornelia de Lange syndrome: a case report

Cornelia de Lange syndrome (CdLS) is a rarely seen multisystem developmental disorder syndrome characterized by facial dysmorphia (arched eyebrows, synophrys, depressed nasal bridge, long philtrum, down-turned angles of the mouth), upper-extremity malformations, hirsutism, cardiac defects, growth and cognitive retardation, and gastrointestinal abnormalities. The features of this disorder vary widely among affected individuals and range from relatively mild to severe. Early in life, the distinctive craniofacial features in mild de Lange syndrome may be indistinguishable from the severe (classical) phenotype. We present here a case of newborn with CdLs

A case of Cornelia de Lange syndrome from Sudan

BACKGROUND: Brachmann de Lange syndrome (BDLS) is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, prenatal and postnatal growth deficiency, psychomotor delay, behavioral problems, and malformations of the upper extremities. CASE PRESENTATION: Here we present for the first time a case of BDLS from Sudan, a 7-month-old female infant, who was referred as a case of malnutrition. The patient was from a Sudanese western tribe. Clinical investigation showed that the child was a classical case of BDLS, but with some additional clinical findings not previously reported including crowded ribs and tied tongue. CONCLUSION: Reporting BDLS cases of different ethnic backgrounds could add nuances to the phenotypic description of the syndrome and be helpful in diagnosis

Inherited variants in regulatory T cell genes and outcome of ovarian cancer.

Although ovarian cancer is the most lethal of gynecologic malignancies, wide variation in outcome following conventional therapy continues to exist. The presence of tumor-infiltrating regulatory T cells (Tregs) has a role in outcome of this disease, and a growing body of data supports the existence of inherited prognostic factors. However, the role of inherited variants in genes encoding Treg-related immune molecules has not been fully explored. We analyzed expression quantitative trait loci (eQTL) and sequence-based tagging single nucleotide polymorphisms (tagSNPs) for 54 genes associated with Tregs in 3,662 invasive ovarian cancer cases. With adjustment for known prognostic factors, suggestive results were observed among rarer histological subtypes; poorer survival was associated with minor alleles at SNPs in RGS1 (clear cell, rs10921202, p = 2.7×10(-5)), LRRC32 and TNFRSF18/TNFRSF4 (mucinous, rs3781699, p = 4.5×10(-4), and rs3753348, p = 9.0×10(-4), respectively), and CD80 (endometrioid, rs13071247, p = 8.0×10(-4)). Fo0r the latter, correlative data support a CD80 rs13071247 genotype association with CD80 tumor RNA expression (p = 0.006). An additional eQTL SNP in CD80 was associated with shorter survival (rs7804190, p = 8.1×10(-4)) among all cases combined. As the products of these genes are known to affect induction, trafficking, or immunosuppressive function of Tregs, these results suggest the need for follow-up phenotypic studies

Genetic Ancestry, Self-Reported Race and Ethnicity in African Americans and European Americans in the PCaP Cohort

Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP