Gene loss and relaxed selection of plaat1 in vertebrates adapted to low-light environments.

Gene loss is an important mechanism for evolution in low-light or cave environments where visual adaptations often involve a reduction or loss of eyesight. The plaat gene family encodes phospholipases essential for the degradation of organelles in the lens of the eye. These phospholipases translocate to damaged organelle membranes, inducing them to rupture. This rupture is required for lens transparency and is essential for developing a functioning eye. Plaat3 is thought to be responsible for this role in mammals, while plaat1 is thought to be responsible in other vertebrates. We used a macroevolutionary approach and comparative genomics to examine the origin, loss, synteny and selection of plaat1 across bony fishes and tetrapods. We showed that plaat1 (probably ancestral to all bony fish + tetrapods) has been lost in squamates and is significantly degraded in lineages of low-visual-acuity and blind mammals and fishes. Our findings suggest that plaat1 is important for visual acuity across bony vertebrates, and that its loss through relaxed selection and pseudogenization may have played a role in the repeated evolution of visual systems in low-light environments. Our study sheds light on the importance of gene-loss in trait evolution and provides insights into the mechanisms underlying visual acuity in low-light environments.

Digest: Pelagic habitats promote speciation but constrain morphological evolution.

What happens when ecological factors predicted to promote evolutionary change coincide with factors predicted to constrain it? A recent study by Burress and Hart (2024) shows that the transition of North American minnows from a competitive and complex benthic habitat to a noncompetitive and homogeneous pelagic habitat is associated with an increase in speciation rates but a decrease in rates of morphological evolution. These results demonstrate that different dimensions of evolutionary change may respond to different ecological factors.

Loci associated with cave-derived traits concentrate in specific regions of the Mexican cavefish genome.

A major goal of modern evolutionary biology is connecting phenotypic evolution with its underlying genetic basis. The Mexican cavefish (Astyanax mexicanus), a characin fish species comprised of a surface ecotype and a cave-derived ecotype, is well suited as a model to study the genetic mechanisms underlying adaptation to extreme environments. Here we map 206 previously published quantitative trait loci (QTL) for cave-derived traits in A. mexicanus to the newest version of the surface fish genome assembly, AstMex3. This analysis revealed that QTL cluster in the genome more than expected by chance, and this clustering is not explained by the distribution of genes in the genome. To investigate whether certain characteristics of the genome facilitate phenotypic evolution, we tested whether genomic characteristics, such as highly mutagenic CpG sites, are reliable predictors of the sites of trait evolution but did not find any significant trends. Finally, we combined the QTL map with previously collected expression and selection data to identify a list of 36 candidate genes that may underlie the repeated evolution of cave phenotypes, including rgrb which is predicted to be involved in phototransduction. We found this gene has disrupted exons in all non-hybrid cave populations but intact reading frames in surface fish. Overall, our results suggest specific "evolutionary hotspots" in the genome may play significant roles in driving adaptation to the cave environment in Astyanax mexicanus and demonstrate how this compiled dataset can facilitate our understanding of the genetic basis of repeated evolution in the Mexican cavefish.

Gene loss and relaxed selection of plaat1 in vertebrates adapted to low-light environments.

Gene loss is an important mechanism for evolution in low-light or cave environments where visual adaptations often involve a reduction or loss of eyesight. The plaat gene family are phospholipases essential for the degradation of organelles in the lens of the eye. They translocate to damaged organelle membranes, inducing them to rupture. This rupture is required for lens transparency and is essential for developing a functioning eye. Plaat3 is thought to be responsible for this role in mammals, while plaat1 is thought to be responsible in other vertebrates. We used a macroevolutionary approach and comparative genomics to examine the origin, loss, synteny, and selection of plaat1 across bony fishes and tetrapods. We show that plaat1 (likely ancestral to all bony fish + tetrapods) has been lost in squamates and is significantly degraded in lineages of low-visual acuity and blind mammals and fish. Our findings suggest that plaat1 is important for visual acuity across bony vertebrates, and that its loss through relaxed selection and pseudogenization may have played a role in the repeated evolution of visual systems in low-light-environments. Our study sheds light on the importance of gene-loss in trait evolution and provides insights into the mechanisms underlying visual acuity in low-light environments.

Selection-driven trait loss in independently evolved cavefish populations.

Laboratory studies have demonstrated that a single phenotype can be produced by many different genotypes; however, in natural systems, it is frequently found that phenotypic convergence is due to parallel genetic changes. This suggests a substantial role for constraint and determinism in evolution and indicates that certain mutations are more likely to contribute to phenotypic evolution. Here we use whole genome resequencing in the Mexican tetra, Astyanax mexicanus, to investigate how selection has shaped the repeated evolution of both trait loss and enhancement across independent cavefish lineages. We show that selection on standing genetic variation and de novo mutations both contribute substantially to repeated adaptation. Our findings provide empirical support for the hypothesis that genes with larger mutational targets are more likely to be the substrate of repeated evolution and indicate that features of the cave environment may impact the rate at which mutations occur.

Alterations to the gut microbiome after sport-related concussion in a collegiate football players cohort: A pilot study.

Concussions, both single and repetitive, cause brain and body alterations in athletes during contact sports. The role of the brain-gut connection and changes in the microbiota have not been well established after sports-related concussions or repetitive subconcussive impacts. We recruited 33 Division I Collegiate football players and collected blood, stool, and saliva samples at three time points throughout the athletic season: mid-season, following the last competitive game (post-season), and after a resting period in the off-season. Additional samples were collected from four athletes that suffered from a concussion. 16S rRNA sequencing of the gut microbiome revealed a decrease in abundance for two bacterial species, Eubacterium rectale, and Anaerostipes hadrus, after a diagnosed concussion. No significant differences were found regarding the salivary microbiome. Serum biomarker analysis shows an increase in GFAP blood levels in athletes during the competitive season. Additionally, S100ß and SAA blood levels were positively correlated with the abundance of Eubacterium rectale species among the group of athletes that did not suffer a diagnosed concussion during the sports season. These findings provide initial evidence that detecting changes in the gut microbiome may help to improve concussion diagnosis following head injury.

Changes in Transcranial Sonographic Measurement of the Optic Nerve Sheath Diameter in Non-concussed Collegiate Soccer Players Across a Single Season.

Introduction Bedside ultrasound measurement of the optic nerve sheath diameter (ONSD) is emerging as a non-invasive technique to evaluate and predict raised intracranial pressure (ICP) in both children and adults. The prognostic value of increased ONSD on brain computed tomography (CT) scan has previously been correlated with increased intensive care unit (ICU) mortality in patients with severe traumatic brain injury (TBI). Previous studies have also evaluated the association between high-contact sports, such as soccer, and TBI; however, the related changes in ONSD are still unknown. The aim of this study was to evaluate for the natural evolution of changes in ONSD in athletes who participate in high-contact sports. Methods In this prospective observational study, volunteers from a collegiate women's soccer team underwent the measurement of ONSD with transcranial Doppler (TCD). ONSDs were measured during the initial visit during the pre-season period and again at the three-month follow-up. A single experienced neuro-sonographer performed all measurements to eliminate any operator bias. Results Twenty-four female college soccer players between the ages of 18 and 23 were included in this analysis. Mean ONSD during the initial pre-season clinic visit and the three-month follow-up were 4.14±0.6 mm and 5.02±0.72 mm, respectively (P < 0.0001). A two-tailed t-test analysis was performed, which resulted in a t-value of 4.76 and P < 0.00001. The average ONSD measured during the post-season follow-up showed a 21.3% increase compared to the baseline. Conclusion The evaluation of high-contact sports athletes is limited due to the lack of objective radiologic and diagnostic tools. Moreover, in an athlete suffering a concussion, return-to-play decisions are heavily dependent on the symptoms reported by the athletes. In our analysis of collegiate women's soccer players, active participation in soccer competitions and practice may be associated with an increase in ONSD, independent of concussions. Further studies are underway to evaluate the clinical significance of these findings as well as possible correlations between concussions and changes in ONSD.

Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study.

Stroke is a major cause of death and long-term disability, affecting one in six people worldwide. The only currently available approved pharmacological treatment for ischemic stroke is tissue plasminogen activator; however, relatively few patients are eligible for this therapy. We hypothesized that intravenous (IV) infusion of banked unrelated allogeneic umbilical cord blood (UCB) would improve functional outcomes in patients with ischemic stroke. To investigate this, we conducted a phase I open-label trial to assess the safety and feasibility of a single IV infusion of non-human leukocyte antigen (HLA) matched, ABO matched, unrelated allogeneic UCB into adult stroke patients. Ten participants with acute middle cerebral artery ischemic stroke were enrolled. UCB units were matched for blood group antigens and race but not HLA, and infused 3-9 days post-stroke. The adverse event (AE) profile over a 12 month postinfusion period indicated that the treatment was well-tolerated in these stroke patients, with no serious AEs directly related to the study product. Study participants were also assessed using neurological and functional evaluations, including the modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS). At 3 months post-treatment, all participants had improved by at least one grade in mRS (mean 2.8 ± 0.9) and by at least 4 points in NIHSS (mean 5.9 ± 1.4), relative to baseline. Together, these data suggest that a single i.v. dose of allogeneic non-HLA matched human UCB cells is safe in adults with ischemic stroke, and support the conduct of a randomized, placebo-controlled phase 2 study. Stem Cells Translational Medicine 2018;7:521-529.

Prehospital Administration of Tranexamic Acid by Ground Forces in Afghanistan: The Prehospital Trauma Registry Experience.

BACKGROUND: Tranexamic acid (TXA) was shown to reduce overall mortality and death secondary to hemorrhage in a large prospective study. This intervention is time sensitive. As such, the Tactical Combat Casualty Care (TCCC) guidelines recommend use of this low-cost, safe intervention among patients with possible hemorrhagic shock, penetrating trauma to the thorax or trunk, or extremity amputation. OBJECTIVE: Prehospital administration of TXA by ground forces in the Afghanistan combat theater is described. METHODS: We obtained data from the Prehospital Trauma Registry. We searched for all patients with documented hypotension, amputation, or penetrating trauma to the torso. RESULTS: From January 2013 to September 2014, there were 272 patients who met inclusion criteria. Most injuries (97.8%; n = 266) were battle injuries. Of the 272 patients who met criteria to receive prehospital TXA, 51 (18.8%) received TXA, whereas the remaining 221 (81.2%) did not. Higher proportions of patients receiving TXA versus patients not receiving TXA received hemostatic dressings, pressure dressings, and tourniquet placement. Conversely, the proportion of patients receiving intravenous fluids was higher in the no-TXA group. CONCLUSION: Overall, proportions of eligible patients receiving TXA were low despite emphasis in the guidelines. The reasons for this low adherence to TCCC guidelines are likely multifactorial. Future research should seek to identify reasons TXA is not given when indicated and to develop training and technology to increase prehospital TXA administration.