Cross-Life Stage Effects of Aquatic Larval Density and Terrestrial Moisture on Growth and Corticosterone in the Spotted Salamander

For organisms with complex life cycles, conditions experienced during early life stages may constrain later growth and survival. Conversely, compensatory mechanisms may attenuate negative effects from early life stages. We used the spotted salamander, Ambystoma maculatum, to test how aquatic larval density and terrestrial moisture influence juvenile growth, food intake, evaporative water loss and water reuptake rates, and corticosterone levels. We conducted an outdoor mesocosm experiment to manipulate larval density and transferred metamorphosed salamanders into low and high terrestrial moisture treatments in laboratory terrariums. After the larval stage, high-density salamanders were significantly smaller and had higher corticosterone release rates than those from low-density treatments. Salamanders in the low terrestrial moisture treatment consumed fewer roaches, had lower mass-specific growth rates, higher water reuptake, and higher corticosterone release rates than salamanders in high terrestrial moisture treatments. Across moisture treatments, smaller salamanders had higher mass-specific growth rates than larger salamanders. Our results suggest that salamanders can partially compensate for competition in the larval aquatic habitat with increased growth as juveniles, but this response is dependent on terrestrial habitat quality. Thus, the persistence of early life stage effects can be an important, yet context-dependent, component of amphibian life cycles

Physiological Responses to Elevated Temperature across the Geographic Range of a Terrestrial Salamander

Widespread species often possess physiological mechanisms for coping with thermal heterogeneity, and uncovering these mechanisms provides insight into species responses to climate change. The emergence of non-invasive corticosterone (CORT) assays allows us to rapidly assess physiological responses to environmental change on a large scale. We lack, however, a basic understanding of how temperature affects CORT, and whether temperature and CORT interactively affect performance. Here, we examine the effects of elevated temperature on CORT and whole-organism performance in a terrestrial salamander, Plethodon cinereus, across a latitudinal gradient. Using water-borne hormone assays, we found that raising ambient temperature from 15 to 25°C increased CORT release at a similar rate for salamanders from all sites. However, CORT release rate was higher overall in the warmest, southernmost site. Elevated temperatures also affected physiological performance, but the effects differed among sites. Ingestion rate increased in salamanders from the warmer sites but remained the same for those from cooler sites. Mass gain was reduced for most individuals, though this reduction was more dramatic in salamanders from the cooler sites. We also found a temperature-dependent relationship between CORT and food conversion efficiency (i.e., the amount of mass gained per unit food ingested). CORT was negatively related to food conversion efficiency at 25°C but was unrelated at 15°C. Thus, the energetic gains of elevated ingestion rates may be counteracted by elevated CORT release rates experienced by salamanders in warmer environments. By integrating multiple physiological metrics, we highlight the complex relationships between temperature and individual responses to warming climates

Does The Glucocorticoid Stress Response Make Toads More Toxic? An Experimental Study on The Regulation of Bufadienolide Toxin Synthesis

Chemical defense is a crucial component of fitness in many organisms, yet the physiological regulation of defensive toxin synthesis is poorly understood, especially in vertebrates. Bufadienolides, the main defensive compounds of toads, are toxic to many predators and other natural enemies, and their synthesis can be upregulated by stressors, including predation risk, high conspecific density, and pollutants. Thus, higher toxin content may be the consequence of a general endocrine stress response in toads. Therefore, we hypothesized that bufadienolide synthesis may be stimulated by elevated levels of corticosterone (CORT), the main glucocorticoid hormone of amphibians, or by upstream regulators that stimulate CORT production. To test these alternatives, we treated common toad tadpoles with exogenous CORT (exoCORT) or metyrapone (MTP, a CORT-synthesis inhibitor that stimulates upstream regulators of CORT by negative feedback) in the presence or absence of predation cues for 2 or 6 days, and subsequently measured their CORT release rates and bufadienolide content. We found that CORT release rates were elevated by exoCORT, and to a lesser extent also by MTP, regardless of treatment length. Bufadienolide content was significantly decreased by treatment with exoCORT for 6 days but was unaffected by exposure to exoCORT for 2 days or to MTP for either 6 or 2 days. The presence or absence of predation cues affected neither CORT release rate nor bufadienolide content. Our results suggest that changes in bufadienolide synthesis in response to environmental challenges are not driven by CORT but may rather be regulated by upstream hormones of the stress response

Differences in resource assimilation between the unisexual Amazon molly, Poecilia formosa (Poeciliidae) and its sexual host (Poecilia latipinna)

Abstract Unisexual sperm-dependent species depend on a sexual host for reproduction, and must live in sympatry with their sperm donor. If niche overlap between the species is substantial, the intrinsic faster population growth of the unisexual over sexual species can cause competitive exclusion of the host from resources, causing the demise of the unisexual species. However, theoretical models predict that coexistence is possible, even without niche differentiation, if the unisexual species is a poorer competitor than the sexual host and if the effect of the unisexual species on the exploitative abilities of the sexual species is smaller than the effect that the sexually reproducing individuals have among themselves. We tested these predictions in the unisexualbisexual mating complex of Poecilia formosa, and one of its sexual hosts, P. latipinna. Fishes were housed from parturition for 76 days with both conspecific and heterospecific individuals under both limited and ad libitum food regimes. Only one of the predictions of the models was met: the effects of intraspecific competition for P. latipinna were stronger than the effects of interspecific competition. Poecilia latipinna raised with conspecifics with limited food stored fewer fats than both heterospecific P. formosa, and conspecifics raised in any other treatment

LATE-NC staging in routine neuropathologic diagnosis : an update

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer's disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.Peer reviewe

Frequency of LATE neuropathologic change across the spectrum of Alzheimer’s disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer’s disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese–American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia—broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with “frequent” neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer’s disease neuropathology

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Elevated Corticosterone Levels and Changes in Amphibian Behavior Are Associated with Batrachochytrium dendrobatidis (Bd) Infection and Bd Lineage

Received: January 21, 2015; Accepted: February 6, 2015; Published: April 20, 2015Few studies have examined the role hormones play in mediating clinical changes associated with infection by the parasite Batrachochytrium dendrobatidis (Bd). Glucocorticoid (GC) hormones such as corticosteroids (CORT) regulate homeostasis and likely play a key role in response to infection in amphibians. We explore the relationship between CORT release rates and Bd infection in tadpoles of the common midwife toad, Alytes obstetricians, using a non-invasive water-borne hormone collection method across seven populations. We further examined whether tadpoles of A. muletensis infected with a hypervirulent lineage of Bd, BdGPL, had greater CORT release rates than those infected with a hypovirulent lineage, BdCAPE. Finally, we examined the relationship between righting reflex and CORT release rates in infected metamorphic toads of A. obstetricans. We found an interaction between elevation and Bd infection status confirming that altitude is associated with the overall severity of infection. In tandem, increasing elevation was associated with increasing CORT release rates. Tadpoles infected with the hypervirulent BdGPL had significantly higher CORT release rates than tadpoles infected with BdCAPE showing that more aggressive infections lead to increased CORT release rates. Infected metamorphs with higher CORT levels had an impaired righting reflex, our defined experimental endpoint. These results provide evidence that CORT is associated with an amphibian's vulnerability to Bd infection, and that CORT is also affected by the aggressiveness of infection by Bd. Together these results indicate that CORT is a viable biomarker of amphibian stress.Peer reviewe