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Evolvable traits of organisms can alter the environment those organisms experience. While it is well appreciated that those modified environments can influence natural selection to which organisms are exposed, they can also influence the expression of genetic variances and covariances of traits under selection. When genetic variance and covariance change in response to changes in the evolving, modified environment, rates and outcomes of evolution also change. Here we discuss the basic mechanisms whereby organisms modify their environments, review how those modified environments have been shown to alter genetic variance and covariance, and discuss potential evolutionary consequences of such dynamics. With these dynamics, responses to selection can be more rapid and sustained, leading to more extreme phenotypes, or they can be slower and truncated, leading to more conserved phenotypes. Patterns of correlated selection can also change, leading to greater or less evolutionary independence of traits, or even causing convergence or divergence of traits, even when selection on them is consistent across environments. Developing evolutionary models that incorporate changes in genetic variances and covariances when environments themselves evolve requires developing methods to predict how genetic parameters respond to environments-frequently multifactorial environments. It also requires a population-level analysis of how traits of collections of individuals modify environments for themselves and/or others in a population, possibly in spatially explicit ways. Despite the challenges of elucidating the mechanisms and nuances of these processes, even qualitative predictions of how environment-modifying traits alter evolutionary potential are likely to improve projections of evolutionary outcomes., (© The American Genetic Association. 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Exomoons represent a crucial missing puzzle piece in our efforts to understand extrasolar planetary systems. To address this deficiency, we here describe an exomoon survey of 70 cool, giant transiting exoplanet candidates found by Kepler. We identify only one exhibiting a moon-like signal that passes a battery of vetting tests: Kepler-1708 b. We show that Kepler-1708 b is a statistically validated Jupiter-sized planet orbiting a Sun-like quiescent star at 1.6 au. The signal of the exomoon candidate, Kepler-1708 b-i, is a 4.8 σ effect and is persistent across different instrumental detrending methods, with a 1% false-positive probability via injection-recovery. Kepler-1708 b-i is ~2.6 Earth radii and is located in an approximately coplanar orbit at ~12 planetary radii from its ~1.6 au Jupiter-sized host. Future observations will be necessary to validate or reject the candidate., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2021.)

Background and Objective: Primary lateral sclerosis (PLS) is a neurodegenerative disease characterized by progressive upper motor neuron dysfunction. Because PLS patients represent only 1 to 4% of patients with adult motor neuron diseases, there is limited information about the disease's natural history. The objective of this study was to establish a large multicenter retrospective longitudinal registry of PLS patients seen at Northeast ALS Consortium (NEALS) sites to better characterize the natural progression of PLS. Methods: Clinical characteristics, electrophysiological findings, laboratory values, disease-related symptoms, and medications for symptom management were collected from PLS patients seen between 2000 and 2015. Results: The NEALS registry included data from 250 PLS patients. Median follow-up time was 3 years. The mean rate of functional decline measured by ALSFRS-R total score was -1.6 points/year (SE:0.24, n  = 124); the mean annual decline in vital capacity was -3%/year (SE:0.55, n  = 126). During the observational period, 18 patients died, 17 patients had a feeding tube placed and 7 required permanent assistive ventilation. Conclusions: The NEALS PLS Registry represents the largest available aggregation of longitudinal clinical data from PLS patients and provides a description of expected natural disease progression. Data from the registry will be available to the PLS community and can be leveraged to plan future clinical trials in this rare disease.

Variations in the axial tilt, or obliquity, of terrestrial planets can affect their climates and therefore their habitability. Kepler-62f is a 1.4 R ⊕ planet orbiting within the habitable zone of its K2 dwarf host star. We perform N-body simulations that monitor the evolution of obliquity of Kepler-62f for 10-million-year timescales to explore the effects on model assumptions, such as the masses of the Kepler-62 planets and the possibility of outer bodies. Significant obliquity variation occurs when the rotational precession frequency overlaps with one or more of the secular orbital frequencies, but most variations are limited to ≲10°. Moderate variations (∼10-20°) can occur over a broader range of initial obliquities when the relative nodal longitude (ΔΩ) overlaps with the frequency and phase of a given secular mode. However, we find that adding outer gas giants on long-period orbits (∼1000 days) can produce large (∼60°) variations in obliquity if Kepler-62f has a very rapid (4 h) rotation period. The possibility of giant planets on long-period orbits impacts the climate and habitability of Kepler-62f through variations in the latitudinal surface flux, where large variations can occur on million year timescales.

Introduction: The prevalence and characteristics of agrin and low-density lipoprotein-related receptor protein 4 (LRP4) antibody-positive amyotrophic lateral sclerosis (ALS) patients were studied., Methods: We tested 82 ALS patients and 59 controls for agrin and LRP4 antibodies using enzyme-linked immunoassay (ELISA)., Results: We found that 13.8% of ALS patients had agrin antibodies, and 9.8% had LRP4 antibodies. Women with ALS are twice as likely as men to have antibodies. Agrin-positive ALS patients are younger than agrin-negative ALS patients., Conclusions: Antibodies to agrin and LRP4 are found in ALS patients. It must be determined whether these antibodies are pathogenic. Because antibody-positive patients have upper as well as lower motor neuron findings, the antibodies' effects cannot be explained solely by their actions at the neuromuscular junction. A breakdown in interneuronal signaling may be the cause of ALS. Further research is needed to resolve this question. Muscle Nerve, 2016 Muscle Nerve 55: 430-432, 2017., (© 2016 Wiley Periodicals, Inc.)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. Although the etiology of ALS is obscure, genetic studies of familiar ALS suggest a multifactorial etiology for this condition. Similarly, there probably are multiple causes for sporadic ALS. Autoimmune-mediated motor neuron dysfunction is one proposed etiology for sporadic ALS. In the present study, anti-glycolipid antibodies including GM1, GD1b, GD3, and sulfoglucuronosyl paragloboside (SGPG) were investigated in the sera of a large number of patient samples, including 113 ALS patients and 50 healthy controls, by means of enzyme-linked immunosorbent assay with affinity parametric complex criterion evaluation and thin-layer chromatography immunooverlay (immuno-TLC). Anti-SGPG antibodies were found in the sera of 13.3% ALS patients (15 out of 113). The highest titer reached 1:1600. The presence of anti-SGPG antibodies in the serum samples was also confirmed by immuno-TLC. Importantly, a multiple logistic regression analysis showed that the presence of anti-SGPG antibody was positively correlated with age (p < .01) and negatively correlated with ALS Functional Rating Scale score (p < .05). Moreover, the localization of SGPG-immunoreactivity on the motor neurons of rat spinal cord and a mouse motor neuronal cell line, NSC-34 was observed by an immunofluorescence method. These data suggest that SGPG could represent a specific pathogenic antigen in those ALS patients. The presence of anti-SGPG antibodies in the serum of ALS patients should represent a diagnostic biomarker of ALS, and it could reflect the severity of the disease., (© The Author(s) 2016.)

Unlabelled: Venus currently rotates slowly, with its spin controlled by solid-body and atmospheric thermal tides. However, conditions may have been far different 4 billion years ago, when the Sun was fainter and most of the carbon within Venus could have been in solid form, implying a low-mass atmosphere. We investigate how the obliquity would have varied for a hypothetical rapidly rotating Early Venus. The obliquity variation structure of an ensemble of hypothetical Early Venuses is simpler than that Earth would have if it lacked its large moon (Lissauer et al., 2012 ), having just one primary chaotic regime at high prograde obliquities. We note an unexpected long-term variability of up to ±7° for retrograde Venuses. Low-obliquity Venuses show very low total obliquity variability over billion-year timescales-comparable to that of the real Moon-influenced Earth., Key Words: Planets and satellites-Venus. Astrobiology 16, 487-499.

Objective: To assess prevention of bone mineral density (BMD) loss and durability of the response during treatment with prasterone in women with systemic lupus erythematosus (SLE) receiving chronic glucocorticoids., Methods: 155 patients with SLE received 200 mg/day prasterone or placebo for 6 months in a double-blind phase. Subsequently, 114 patients were re-randomized to receive 200 or 100 mg/day prasterone for 12 months in an open-label phase. Primary efficacy endpoints were changes in BMD at the lumbar spine (L-spine) from baseline to Month 6 and maintenance of BMD from Month 6 to 18 for patients who received prasterone during the double-blind phase., Results: In the double-blind phase, there was a trend for a small gain in BMD at the L-spine for patients who received 200 mg/day prasterone for 6 months versus a loss in the placebo group (mean +/- SD, 0.003 +/- 0.035 vs -0.005 +/- 0.053 g/cm(2), respectively; p = 0.293 between groups). In the open-label phase, there was dose-dependent increase in BMD at the L-spine at Month 18 between patients who received 200 versus 100 mg/day prasterone (p = 0.021). For patients who received 200 mg/day prasterone for 18 months, the L-spine BMD gain was 1.083 +/- 0.512% (p = 0.042). There was no overall change in BMD at the total hip over 18 months with 200 mg/day prasterone treatment. The safety profile reflected the weak androgenic properties of prasterone., Conclusion: This study suggests prasterone 200 mg/day may offer mild protection against bone loss in women with SLE receiving glucocorticoids. (ClinicalTrials.gov Identifiers NCT00053560 and NCT00082511).

Many descriptions of yeast species are based on a limited number of strains collected at one time from a single locale. Often, little is known of phenotypic or genotypic variation and covariation within species. We compare 36 strains of an asexual cactophilic yeast, Candida sonorensis, collected from Opuntia cacti. Comparisons were based on geographical distances between collection locales, responses to physiological assimilation and stress tests, random amplified polymorphic DNA (RAPD) profiles, partial Lage Subunit (LSU) rDNA sequences, relative DNA-DNA hybridization values, and electrokaryotypes. There was significant variation among strains in all types of data collected. Comparisons among the different data types found significant positive associations between RAPD profiles, geographical distances, physiologies, reassociation values, and electrokaryotypes. No significant associations were found between rDNA sequences and any other type of variation measured. Based on RAPD, reassociation, electrokaryotype, and physiological data, the 36 strains could be divided into two groups: those collected in West Texas (nine strains) and all others. RAPD data indicated that 10 (of 12) Australian strains also formed a distinct clade. The taxonomic and phylogenetic status of these clades is discussed. Evidence that new genotypes can sweep through large geographic areas is also discussed.

DNAs from 40 strains of Pichia cactophila and Pichia norvegensis, yeasts characteristic of cactus necroses, were compared using randomly amplified polymorphic DNA (RAPD) banding patterns and killer/sensitive phenotypes. Both species belong to the same species complex within the genus. The levels of between-strain RAPD variation were high in both species (higher in the automictic P. cactophila than in the heterothallic P. norvegensis), although there is little variation in physiological abilities within either species. Although each species was a separate lineage, RAPD analysis confirms that the species are related. Within each species, RAPD variation was related to the geographic origin of the strains. Pichia cactophila strains from southern Florida were more related to those from Antigua than to those from northern Florida. These results correlated well with the differences among killer/sensitive phenotypes of strains. Principal component analysis indicated that the phenotypes of each species differ. Here too, strains from southern Florida were more similar to those from Antigua than to those from northern Florida. Previous work had identified differences in the cactophilic yeast communities from southern and northern Florida, and these results indicate that the differences are detectable at the population levels as well.