Dark/Visible Parallel Universes and Big Bang Nucleosynthesis

We develop a model for visible matter-dark matter interaction based on the exchange of a massive gray boson called herein the Mulato. Our model hinges on the assumption that all known particles in the visible matter have their counterparts in the dark matter. We postulate six families of particles five of which are dark. This leads to the unavoidable postulation of six parallel worlds, the visible one and five invisible worlds. A close study of big bang nucleosynthesis (BBN), baryon asymmetries, cosmic microwave background (CMB) bounds, galaxy dynamics, together with the Standard Model assumptions, help us to set a limit on the mass and width of the new gauge boson. Modification of the statistics underlying the kinetic energy distribution of particles during the BBN is also discussed. The changes in reaction rates during the BBN due to a departure from the Debye-Hueckel electron screening model is also investigated.Comment: Invited talk at the Workshops "CompStar: the physics and astrophysics of compact stars", Tahiti, June 4-8, 2012, "New Directions in Nuclear Astrophysics", Castiglion Fiorentino, Italy, June 18-22, 2012, and "Carpathian Summer School of Physics", Sinaia, Romania, June 24 - July 7, 2012. To be published in AIP Proceeding

Evolution of the Insertion-Deletion Mutation Rate Across the Tree of Life

Citation: Sung, W., Ackerman, M. S., Dillon, M. M., Platt, T. G., Fuqua, C., Cooper, V. S., & Lynch, M. (2016). Evolution of the Insertion-Deletion Mutation Rate Across the Tree of Life. G3-Genes Genomes Genetics, 6(8), 2583-2591. doi:10.1534/g3.116.030890/-/DC1Mutations are the ultimate source of variation used for evolutionary adaptation, while also being predominantly deleterious and a source of genetic disorders. Understanding the rate of insertion-deletion mutations (indels) is essential to understanding evolutionary processes, especially in coding regions, where such mutations can disrupt production of essential proteins. Using direct estimates of indel rates from 14 phylogenetically diverse eukaryotic and bacterial species, along with measures of standing variation in such species, we obtain results that imply an inverse relationship of mutation rate and effective population size. These results, which corroborate earlier observations on the base-substitution mutation rate, appear most compatible with the hypothesis that natural selection reduces mutation rates per effective genome to the point at which the power of random genetic drift (approximated by the inverse of effective population size) becomes overwhelming. Given the substantial differences in DNA metabolism pathways that give rise to these two types of mutations, this consistency of results raises the possibility that refinement of other molecular and cellular traits may be inversely related to species-specific levels of random genetic drift

Evidence for Diversity in Transcriptional Profiles of Single Hematopoietic Stem Cells

Hematopoietic stem cells replenish all the cells of the blood throughout the lifetime of an animal. Although thousands of stem cells reside in the bone marrow, only a few contribute to blood production at any given time. Nothing is known about the differences between individual stem cells that dictate their particular state of activation readiness. To examine such differences between individual stem cells, we determined the global gene expression profile of 12 single stem cells using microarrays. We showed that at least half of the genetic expression variability between 12 single cells profiled was due to biological variation in 44% of the genes analyzed. We also identified specific genes with high biological variance that are candidates for influencing the state of readiness of individual hematopoietic stem cells, and confirmed the variability of a subset of these genes using single-cell real-time PCR. Because apparent variation of some genes is likely due to technical factors, we estimated the degree of biological versus technical variation for each gene using identical RNA samples containing an RNA amount equivalent to that of single cells. This enabled us to identify a large cohort of genes with low technical variability whose expression can be reliably measured on the arrays at the single-cell level. These data have established that gene expression of individual stem cells varies widely, despite extremely high phenotypic homogeneity. Some of this variation is in key regulators of stem cell activity, which could account for the differential responses of particular stem cells to exogenous stimuli. The capacity to accurately interrogate individual cells for global gene expression will facilitate a systems approach to biological processes at a single-cell level

A Phase 1a/1b Clinical Trial Design to Assess Safety, Acceptability, Pharmacokinetics and Tolerability of Intranasal Q-Griffithsin for COVID-19 Prophylaxis

Background: The COVID-19 pandemic remains an ongoing threat to global public health. Q-Griffithsin (Q-GRFT) is a lectin that has demonstrated potent broad-spectrum inhibitory activity in preclinical studies in models of Nipah virus and the beta coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2. Methods: Here, we propose a clinical trial design to test the safety, pharmacokinetics (PK), and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection as a prophylaxis strategy. The initial Phase 1a study will assess the safety and PK of a single dose of intranasally administered Q-GRFT. If found safe, the safety, PK, and tolerability of multiple doses of intranasal Q-GRFT will be assessed in a Phase 1b study. Group 1 participants will receive 3 mg of intranasal Q-GRFT (200 μL/nostril) once daily for 7 days. If this dose is tolerated, participants will be enrolled in Group 2 to receive 3 mg twice daily for 7 days. Secondary endpoints of the study will be user perceptions, acceptability, and the impact of product use on participants’ olfactory sensation and quality of life. Discussion: Results from this study will support further development of Q-GRFT as a prophylactic against respiratory viral infections in future clinical trials

A pilot study comparing the metabolic profiles of elite-level athletes from different sporting disciplines

Background: The outstanding performance of an elite athlete might be associated with changes in their blood metabolic profile. The aims of this study were to compare the blood metabolic profiles between moderate- and high-power and endurance elite athletes and to identify the potential metabolic pathways underlying these differences. Methods: Metabolic profiling of serum samples from 191 elite athletes from different sports disciplines (121 high- and 70 moderate-endurance athletes, including 44 high- and 144 moderate-power athletes), who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between high- and moderate-power and endurance sports were assessed by univariate linear models. Results: Out of 743 analyzed metabolites, gamma-glutamyl amino acids were significantly reduced in both high-power and high-endurance athletes compared to moderate counterparts, indicating active glutathione cycle. High-endurance athletes exhibited significant increases in the levels of several sex hormone steroids involved in testosterone and progesterone synthesis, but decreases in diacylglycerols and ecosanoids. High-power athletes had increased levels of phospholipids and xanthine metabolites compared to moderate-power counterparts. Conclusions: This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites. Replication studies are warranted to confirm differences in the metabolic profiles associated with athletes’ elite performance in independent data sets, aiming ultimately for deeper understanding of the underlying biochemical processes that could be utilized as biomarkers with potential therapeutic implications

Missing lithotroph identified as new planctomycete

With the increased use of chemical fertilizers in agriculture, many densely populated countries face environmental problems associated with high ammonia emissions. The process of anaerobic ammonia oxidation ('anammox') is one of the most innovative technological advances in the removal of ammonia nitrogen from waste water. This new process combines ammonia and nitrite directly into dinitrogen gas. Until now, bacteria capable of anaerobically oxidizing ammonia had never been found and were known as "lithotrophs missing from nature". Here we report the discovery of this missing lithotroph and its identification as a new, autotrophic member of the order Planctomycetales, one of the major distinct divisions of the Bacteria. The new planctomycete grows extremely slowly, dividing only once every two weeks. At present, it cannot be cultivated by conventional microbiological techniques. The identification of this bacterium as the one responsible for anaerobic oxidation of ammonia makes an important contribution to the problem of unculturability

Kinases and protein phosphorylation as regulators of steroid hormone action

Although the primary signal for the activation of steroid hormone receptors is binding of hormone, there is increasing evidence that the activities of cell signaling pathways and the phosphorylation status of these transcription factors and their coregulators determine the overall response to the hormone. In some cases, enhanced cell signaling is sufficient to cause activation of receptors in medium depleted of steroids. Steroid receptors are targets for multiple kinases. Many of the phosphorylation sites contain Ser/Thr-Pro motifs implicating proline-directed kinases such as the cyclin-dependent kinases and the mitogen-activated kinases (MAPK) in receptor phosphorylation. Although some sites are constitutively phosphorylated, others are phosphorylated in response to hormone. Still others are only phosphorylated in response to specific cell signaling pathways. Phosphorylation of specific sites has been implicated not only in overall transcriptional activity, but also in nuclear localization, protein stability, and DNA binding. The studies of the roles of phosphorylation in coregulator function are more limited, but it is now well established that many of them are highly phosphorylated and that phosphorylation regulates their function. There is good evidence that some of the phosphorylation sites in the receptors and coregulators are targets of multiple signaling pathways. Individual sites have been associated both with functions that enhance the activity of the receptor, as well as with functions that inhibit activity. Thus, the specific combinations of phosphorylations of the steroid receptor combined with the expression levels and phosphorylation status of coregulators will determine the genes regulated and the biological response

Swarming populations of Salmonella represent a unique physiological state coupled to multiple mechanisms of antibiotic resistance

Salmonella enterica serovar Typhimurium is capable of swarming over semi-solid surfaces. Although its swarming behavior shares many readily observable similarities with other swarming bacteria, the phenomenon remains somewhat of an enigma in this bacterium since some attributes skew away from the better characterized systems. Swarming is quite distinct from the classic swimming motility, as there is a prerequisite for cells to first undergo a morphological transformation into swarmer cells. In some organisms, swarming is controlled by quorum sensing, and in others, swarming has been shown to be coupled to increased expression of important virulence factors. Swarming in serovar Typhimurium is coupled to elevated resistance to a wide variety of structurally and functionally distinct classes of antimicrobial compounds. As serovar Typhimurium differentiates into swarm cells, the pmrHFIJKLM operon is up-regulated, resulting in a more positively charged LPS core. Furthermore, as swarm cells begin to de-differentiate, the pmr operon expression is down-regulated, rapidly reaching the levels observed in swim cells. This is one potential mechanism which confers swarm cells increased resistance to antibiotics such as the cationic antimicrobial peptides. However, additional mechanisms are likely associated with the cells in the swarm state that confer elevated resistance to such a broad spectrum of antimicrobial agents

Characteristics of Sexual Abuse in Childhood and Adolescence Influence Sexual Risk Behavior in Adulthood

Childhood and adolescent sexual abuse has been associated with subsequent (adult) sexual risk behavior, but the effects of force and type of sexual abuse on sexual behavior outcomes have been less well-studied. The present study investigated the associations between sexual abuse characteristics and later sexual risk behavior, and explored whether gender of the child/adolescent moderated these relations. Patients attending an STD clinic completed a computerized survey that assessed history of sexual abuse as well as lifetime and current sexual behavior. Participants were considered sexually abused if they reported a sexual experience (1) before age 13 with someone 5 or more years older, (2) between the ages of 13 and 16 with someone 10 or more years older, or (3) before the age of 17 involving force or coercion. Participants who were sexually abused were further categorized based on two abuse characteristics, namely, use of penetration and force. Analyses included 1177 participants (n=534 women; n=643 men). Those who reported sexual abuse involving penetration and/or force reported more adult sexual risk behavior, including the number of lifetime partners and number of previous STD diagnoses, than those who were not sexually abused and those who were abused without force or penetration. There were no significant differences in sexual risk behavior between nonabused participants and those who reported sexual abuse without force and without penetration. Gender of the child/adolescent moderated the association between sexual abuse characteristics and adult sexual risk behavior; for men, sexual abuse with force and penetration was associated with the greatest number of episodes of sex trading, whereas for women, those who were abused with penetration, regardless of whether the abuse involved force, reported the most episodes of sex trading. These findings indicate that more severe sexual abuse is associated with riskier adult sexual behavior