Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts; the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems

Devotions for Advent 2022 Canticles of Luke

Each week of this Advent devotional will focus on one of the four Lukan canticles, putting it in its context as well as making connections to other portions of Scripture. At the end of this Advent season, may we, like those who have gone before us, “sing to the Lord, bless his name; tell of his salvation from day to day” (Ps. 96:2). Many thanks to all the CSL and CTSFW students who contributed devotional reflections. A special note of thanks to my counterpart, Zachary Roll, who organized this effort at Concordia Seminary, St. Louis who has been a joy to work with and to get to know. A final note of thanks to Kim Hosier in the print shop and Rev. Dr. Paul Grime for their aid in completing this devotional booklet.https://scholar.csl.edu/osp/1021/thumbnail.jp

Beyond the Global Brain Differences:Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and globalbrain differences compared with noncarriers. However, interpreting regional differences is challenging if a globaldifference drives the regional brain differences. Intraindividual variability measures can be used to test for regionaldifferences beyond global differences in brain structure.METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n =30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matchednoncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual’sregional difference and global difference, were used to test for regional differences that diverge from the globaldifference.RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differedmore than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thicknessin regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal andsomatosensory cortex differed more than the global difference in cortical thickness.CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanismsinvolved in altered neurodevelopment

Assignment of Vicarages and Internships for Specific Ministry (SMP), Cross-Cultural Ministry Center (CMC) and Deaconess Internships. February 9, 2023.

Assignment of Vicarages and Internships for Specific Ministry (SMP), Cross-Cultural Ministry Center (CMC) and Deaconess Internships.https://scholar.csl.edu/smpvideos/1017/thumbnail.jp

Chicken or egg? : outcomes of experimental manipulations of maternally transmitted hormones depend on administration method : a meta‐analysis

Steroid hormones are important mediators of prenatal maternal effects in animals. Despite a growing number of studies involving experimental manipulation of these hormones, little is known about the impact of methodological differences among experiments on the final results expressed as offspring traits. Using ameta-analytical approach and a representative sample of experimental studies performed on birds, we tested the effect of two types of direct hormonal manipulations: manipulation of females (either by implantation of hormone pellets or injection of hormonal solutions) andmanipulation of eggs by injection. In both types ofmanipulation we looked at the effects of two groups of hormones: corticosterone and androgens in the form of testosterone and androstenedione. We found that the average effect on offspring traits differed between the manipulation types, with a well-supported positive effect of egg manipulation and lack of a significant effect of maternal manipulation. The observed average positive effect for egg manipulation was driven mainly by androgen manipulations, while corticosterone manipulations exerted no overall effect, regardless of manipulation type. Detailed analyses revealed effects of varying size and direction depending on the specific offspring traits; e.g., egg manipulation positively affected physiology and behaviour (androgens), and negatively affected future reproduction (corticosterone). Effect size was negatively related to the dose of androgen injected into the eggs, but unrelated to timing of manipulation, offspring developmental stage at the time of measuring their traits, solvent type, the site of egg injection and maternal hormone delivery method. Despite the generally acknowledged importance of maternal hormones for offspring development in birds, the overall effect of their experimental elevation is rather weak, significantly heterogeneous and dependent on the hormone and type of manipulation. We conclude by providing general recommendations as to how hormonalmanipulations should be performed in order to standardize their impact and the results achieved. We also emphasize the need for research on free-living birds with a focus on fitness-related and other long-term effects of maternal hormones

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function