Development of the preterm infant gut microbiome: a research priority.

The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role of the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. The paper concludes with speculation about how the VLBW infants' gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host

Energy-Related Indicators and Breast Cancer Risk among White and Black Women

Energy-related indicators, including physical activity, energy intake, body mass index (BMI) and adult weight change, have been linked to breast cancer risk. Very few studies of these associations have been conducted among black women, therefore we used the Nashville Breast Health Study (NBHS) to determine whether similar effects were seen in black and white women. The NBHS is a population-based case-control study of breast cancer among women age 25 to 75 years conducted between 2001 and 2010 in and around the Nashville Metropolitan area. Telephone interviews and self-administered food frequency questionnaires were completed with 2,614 incident breast cancer cases ascertained through hospitals and the statewide cancer registry, and 2,306 controls selected using random digit dialing. Among premenopausal white and black women, there was little effect of adult exercise or other energy-related indicators on breast cancer risk, regardless of tumor estrogen receptor (ER) status. The beneficial effect of adult exercise on postmenopausal breast cancer appeared to be comparable between white and black women (highest tertile relative to none - white odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6-1.0, p for trend=0.05; black OR 0.7, 95% CI 0.4-1.1, p for trend=0.07); however, among black women the reduction was limited to those with ER-positive disease. White and black women should be encouraged to engage in more physical activity to reduce their risk of postmenopausal breast cancer

Fast-evolving noncoding sequences in the human genome

BACKGROUND: Gene regulation is considered one of the driving forces of evolution. Although protein-coding DNA sequences and RNA genes have been subject to recent evolutionary events in the human lineage, it has been hypothesized that the large phenotypic divergence between humans and chimpanzees has been driven mainly by changes in gene regulation rather than altered protein-coding gene sequences. Comparative analysis of vertebrate genomes has revealed an abundance of evolutionarily conserved but noncoding sequences. These conserved noncoding (CNC) sequences may well harbor critical regulatory variants that have driven recent human evolution. RESULTS: Here we identify 1,356 CNC sequences that appear to have undergone dramatic human-specific changes in selective pressures, at least 15% of which have substitution rates significantly above that expected under neutrality. The 1,356 'accelerated CNC' (ANC) sequences are enriched in recent segmental duplications, suggesting a recent change in selective constraint following duplication. In addition, single nucleotide polymorphisms within ANC sequences have a significant excess of high frequency derived alleles and high F(ST)values relative to controls, indicating that acceleration and positive selection are recent in human populations. Finally, a significant number of single nucleotide polymorphisms within ANC sequences are associated with changes in gene expression. The probability of variation in an ANC sequence being associated with a gene expression phenotype is fivefold higher than variation in a control CNC sequence. CONCLUSION: Our analysis suggests that ANC sequences have until very recently played a role in human evolution, potentially through lineage-specific changes in gene regulation

Human feeder cell line for derivation and culture of hESc/hiPSc

AbstractWe have generated a human feeder cell line from early second trimester Placental Stromal Fibroblasts (ihPSF) stably over-expressing the polycomb protein BMI-1. These feeder cells retain the ability to maintain human Embryonic Stem cells (hESc) over long-term culture whereas hTERT or BMI-1/hTERT immortalised feeder cell lines do not. ihPSFs were able to support the derivation of a new hESc line in near xenofree (free of non-human animal components) conditions and support continued culture of newly derived hESc and human induced Pluripotent Stem (hiPS) cell lines in complete xenofree conditions necessary for clinical use

ConDeTri - A Content Dependent Read Trimmer for Illumina Data

During the last few years, DNA and RNA sequencing have started to play an increasingly important role in biological and medical applications, especially due to the greater amount of sequencing data yielded from the new sequencing machines and the enormous decrease in sequencing costs. Particularly, Illumina/Solexa sequencing has had an increasing impact on gathering data from model and non-model organisms. However, accurate and easy to use tools for quality filtering have not yet been established. We present ConDeTri, a method for content dependent read trimming for next generation sequencing data using quality scores of each individual base. The main focus of the method is to remove sequencing errors from reads so that sequencing reads can be standardized. Another aspect of the method is to incorporate read trimming in next-generation sequencing data processing and analysis pipelines. It can process single-end and paired-end sequence data of arbitrary length and it is independent from sequencing coverage and user interaction. ConDeTri is able to trim and remove reads with low quality scores to save computational time and memory usage during de novo assemblies. Low coverage or large genome sequencing projects will especially gain from trimming reads. The method can easily be incorporated into preprocessing and analysis pipelines for Illumina data

Evaluating models for lithospheric loss and intraplate volcanism beneath the Central Appalachian Mountains

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Long, M. D., Wagner, L. S., King, S. D., Evans, R. L., Mazza, S. E., Byrnes, J. S., Johnson, E. A., Kirby, E., Bezada, M. J., Gazel, E., Miller, S. R., Aragon, J. C., & Liu, S. Evaluating models for lithospheric loss and intraplate volcanism beneath the Central Appalachian Mountains. Journal of Geophysical Research: Solid Earth, 126(10), (2021): e2021JB022571, https://doi.org/10.1029/2021JB022571.The eastern margin of North America has been shaped by a series of tectonic events including the Paleozoic Appalachian Orogeny and the breakup of Pangea during the Mesozoic. For the past ∼200 Ma, eastern North America has been a passive continental margin; however, there is evidence in the Central Appalachian Mountains for post-rifting modification of lithospheric structure. This evidence includes two co-located pulses of magmatism that post-date the rifting event (at 152 and 47 Ma) along with low seismic velocities, high seismic attenuation, and high electrical conductivity in the upper mantle. Here, we synthesize and evaluate constraints on the lithospheric evolution of the Central Appalachian Mountains. These include tomographic imaging of seismic velocities, seismic and electrical conductivity imaging along the Mid-Atlantic Geophysical Integrative Collaboration array, gravity and heat flow measurements, geochemical and petrological examination of Jurassic and Eocene magmatic rocks, and estimates of erosion rates from geomorphological data. We discuss and evaluate a set of possible mechanisms for lithospheric loss and intraplate volcanism beneath the region. Taken together, recent observations provide compelling evidence for lithospheric loss beneath the Central Appalachians; while they cannot uniquely identify the processes associated with this loss, they narrow the range of plausible models, with important implications for our understanding of intraplate volcanism and the evolution of continental lithosphere. Our preferred models invoke a combination of (perhaps episodic) lithospheric loss via Rayleigh-Taylor instabilities and subsequent small-scale mantle flow in combination with shear-driven upwelling that maintains the region of thin lithosphere and causes partial melting in the asthenosphere.The authors acknowledge support from the U.S. National Science Foundation EarthScope and GeoPRISMS programs via grants EAR-1460257 (R. L. Evans), EAR-1249412 (E. Gazel), EAR-1249438 (E. A. Johnson), EAR-1250988 (S. D. King), EAR-1251538 (E. Kirby), and EAR-1251515 (M. D. Long). The collection and dissemination of most of the geophysical data and models discussed in this study were facilitated by the Incorporated Research Institutions for Seismology (IRIS). The facilities of the IRIS Consortium are supported by the United States National Science Foundation under Cooperative Agreement EAR-1261681

Treatment of fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurological disorder that affects older adult carriers, predominantly males, of premutation alleles (55 to 200 CGG repeats) of the fragile X (FMR1) gene. Principal features of FXTAS are intention tremor, ataxia, parkinsonism, cognitive decline, and peripheral neuropathy; ancillary features include, autonomic dysfunction, and psychiatric symptoms of anxiety, depression, and disinhibition. Although controlled trials have not been carried out in individuals with FXTAS, there is a significant amount of anecdotal information regarding various treatment modalities. Moreover, there exists a great deal of evidence regarding the efficacy of various medications for treatment of other disorders (eg, Alzheimer disease) that have substantial phenotypic overlap with FXTAS. The current review summarizes what is currently known regarding the symptomatic treatment, or potential for treatment, of FXTAS