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"Clinton, J. Robert"
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Chronic anthropogenic noise disrupts glucocorticoid signaling and has multiple effects on fitness in an avian community
Anthropogenic noise is a pervasive pollutant that decreases environmental quality by disrupting a suite of behaviors vital to perception and communication. However, even within populations of noise-sensitive species, individuals still select breeding sites located within areas exposed to high noise levels, with largely unknown physiological and fitness consequences. We use a study system in the natural gas fields of northern New Mexico to test the prediction that exposure to noise causes glucocorticoid-signaling dysfunction and decreases fitness in a community of secondary cavity-nesting birds. In accordance with these predictions, and across all species, we find strong support for noise exposure decreasing baseline corticosterone in adults and nestlings and, conversely, increasing acute stressor-induced corticosterone in nestlings. We also document fitness consequences with increased noise in the form of reduced hatching success in the western bluebird (Sialia mexicana), the species most likely to nest in noisiest environments. Nestlings of all three species exhibited accelerated growth of both feathers and body size at intermediate noise amplitudes compared with lower or higher amplitudes. Our results are consistent with recent experimental laboratory studies and show that noise functions as a chronic, inescapable stressor. Anthropogenic noise likely impairs environmental risk perception by species relying on acoustic cues and ultimately leads to impacts on fitness. Our work, when taken together with recent efforts to document noise across the landscape, implies potential wide-spread, noise-induced chronic stress coupled with reduced fitness for many species reliant on acoustic cues.
Journal Article
Direct replication of Gervais & Norenzayan (2012): No evidence that analytic thinking decreases religious belief
Gervais & Norenzayan (2012) reported in Science a series of 4 experiments in which manipulations intended to foster analytic thinking decreased religious belief. We conducted a precise, large, multi-site pre-registered replication of one of these experiments. We observed little to no effect of the experimental manipulation on religious belief (d = 0.07 in the wrong direction, 95% CI[-0.12, 0.25], N = 941). The original finding does not seem to provide reliable or valid evidence that analytic thinking causes a decrease in religious belief.
Journal Article
HSP72 protects against obesity-induced insulin resistance
Patients with type 2 diabetes have reduced gene expression of heat shock protein (HSP) 72, which correlates with reduced insulin sensitivity. Heat therapy, which activates HSP72, improves clinical parameters in these patients. Activation of several inflammatory signaling proteins such as c-jun amino terminal kinase (JNK), inhibitor of κB kinase, and tumor necrosis factor-α, can induce insulin resistance, but HSP 72 can block the induction of these molecules in vitro. Accordingly, we examined whether activation of HSP72 can protect against the development of insulin resistance. First, we show that obese, insulin resistant humans have reduced HSP72 protein expression and increased JNK phosphorylation in skeletal muscle. We next used heat shock therapy, transgenic overexpression, and pharmacologic means to overexpress HSP72 either specifically in skeletal muscle or globally in mice. Herein, we show that regardless of the means used to achieve an elevation in HSP72 protein, protection against diet- or obesity-induced hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance was observed. This protection was tightly associated with the prevention of JNK phosphorylation. These findings identify an essential role for HSP72 in blocking inflammation and preventing insulin resistance in the context of genetic obesity or high-fat feeding.
Journal Article
Treatment of type 2 diabetes with the designer cytokine IC7Fc
The gp130 receptor cytokines IL-6 and CNTF improve metabolic homeostasis but have limited therapeutic use for the treatment of type 2 diabetes. Accordingly, we engineered the gp130 ligand IC7Fc, in which one gp130-binding site is removed from IL-6 and replaced with the LIF-receptor-binding site from CNTF, fused with the Fc domain of immunoglobulin G, creating a cytokine with CNTF-like, but IL-6-receptor-dependent, signalling. Here we show that IC7Fc improves glucose tolerance and hyperglycaemia and prevents weight gain and liver steatosis in mice. In addition, IC7Fc either increases, or prevents the loss of, skeletal muscle mass by activation of the transcriptional regulator YAP1. In human-cell-based assays, and in non-human primates, IC7Fc treatment results in no signs of inflammation or immunogenicity. Thus, IC7Fc is a realistic next-generation biological agent for the treatment of type 2 diabetes and muscle atrophy, disorders that are currently pandemic.
The chimeric cytokine IC7Fc combines the beneficial effects of the cytokines IL-6 and CNTF on weight loss and metabolism in mice, with no obvious side effects in mice and non-human primates.
Journal Article
grassy tillers1 promotes apical dominance in maize and responds to shade signals in the grasses
The shape of a plant is largely determined by regulation of lateral branching. Branching architecture can vary widely in response to both genotype and environment, suggesting regulation by a complex interaction of autonomous genetic factors and external signals. Tillers, branches initiated at the base of grass plants, are suppressed in response to shade conditions. This suppression of tiller and lateral branch growth is an important trait selected by early agriculturalists during maize domestication and crop improvement. To understand how plants integrate external environmental cues with endogenous signals to control their architecture, we have begun a functional characterization of the maize mutant grassy tillers1 (gt1). We isolated the gt1 gene using positional cloning and found that it encodes a class I homeodomain leucine zipper gene that promotes lateral bud dormancy and suppresses elongation of lateral ear branches. The gt1 expression is induced by shading and is dependent on the activity of teosinte branched1 (tb1), a major domestication locus controlling tillering and lateral branching. Interestingly, like tb1, gt1 maps to a quantitative trait locus that regulates tillering and lateral branching in maize and shows evidence of selection during maize domestication. Branching and shade avoidance are both of critical agronomic importance, but little is known about how these processes are integrated. Our results indicate that gt1 mediates the reduced branching associated with the shade avoidance response in the grasses. Furthermore, selection at the gt1 locus suggests that it was involved in improving plant architecture during the domestication of maize.
Journal Article
Patterns and controls of reef-scale production of dissolved organic carbon by giant kelp Macrocystis pyrifera
We investigated the patterns and controls of dissolved organic carbon (DOC) production by the giant kelp (Macrocystis pyrifera) using data from short-term in situ incubations of entire blades and portions of stipes. These data were incorporated into an empirical model of reef-scale net primary production (NPP) at Mohawk Reef in southern California, U.S.A. for an 8-yr period. Rates of DOC release of incubated blades varied unpredictably with time of year, but were significantly related to the irradiance at the sea surface during the incubations. The growth stage, C/N ratio, and epiphyte load of the blades and the temperature of the ocean during the incubations had no discernable effect on rates of DOC release. Blades produced on average 2–3 timesmore DOC than stipes, and stipes and blades produced on average 30% and 80% more DOC respectively during the day compared to the night. Modeled DOC NPP at the reef scale was on average highest in summer and spring (~0.5 g C m−2 d−1) and lowest in winter and autumn (~0.31 g C m−2 d−1), but it varied greatly among years for any given season as large oscillations in standing biomass led to corresponding fluctuations in reef-scale DOC NPP. The fraction of NPP released as DOC was highly variable when examined at the monthly time scale, but became much more stable at seasonal and annual time scales averaging 14% of total NPP.
Journal Article
Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study
Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer’s dementia, while the APOE2 allele is associated with a lower risk of Alzheimer’s dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer’s dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer’s dementia cases and controls. APOE2/2 was associated with a low Alzheimer’s dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer’s disease could have a major impact on the understanding, treatment and prevention of the disease.
APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk.
Journal Article
Association between spinal manipulative therapy and lumbar spine reoperation after discectomy: a retrospective cohort study
Background
Patients who undergo lumbar discectomy may experience ongoing lumbosacral radiculopathy (LSR) and seek spinal manipulative therapy (SMT) to manage these symptoms. We hypothesized that adults receiving SMT for LSR at least one year following lumbar discectomy would be less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT, over two years’ follow-up.
Methods
We searched a United States network of health records (TriNetX, Inc.) for adults aged ≥ 18 years with LSR and lumbar discectomy ≥ 1 year previous, without lumbar fusion or instrumentation, from 2003 to 2023. We divided patients into two cohorts: (1) chiropractic SMT, and (2) usual care without chiropractic SMT. We used propensity matching to adjust for confounding variables associated with lumbar spine reoperation (e.g., age, body mass index, nicotine dependence), calculated risk ratios (RR), with 95% confidence intervals (CIs), and explored cumulative incidence of reoperation and the number of SMT follow-up visits.
Results
Following propensity matching there were 378 patients per cohort (mean age 61 years). Lumbar spine reoperation was less frequent in the SMT cohort compared to the usual care cohort (SMT: 7%; usual care: 13%), yielding an RR (95% CIs) of 0.55 (0.35–0.85;
P
= 0.0062). In the SMT cohort, 72% of patients had ≥ 1 follow-up SMT visit (median = 6).
Conclusions
This study found that adults experiencing LSR at least one year after lumbar discectomy who received SMT were less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT. While these findings hold promise for clinical implications, they should be corroborated by a prospective study including measures of pain, disability, and safety to confirm their relevance. We cannot exclude the possibility that our results stem from a generalized effect of engaging with a non-surgical clinician, a factor that may extend to related contexts such as physical therapy or acupuncture.
Registration
Open Science Framework (
https://osf.io/vgrwz
).
Journal Article
Critical limitations compromise the conclusions of a recent meta-analysis regarding spinal manipulation and migraine: a commentary
Background
A recent meta-analysis by Posadzki et al. synthesized randomized controlled trials to evaluate the effectiveness and safety of spinal manipulative therapy (SMT) for migraines. Considering
Systematic Reviews
recognizes several methodological guidelines and reporting standards, our Letter highlights deviations from best practice methodologies.
Main findings
We detail issues with the search strategy, application of selection criteria, inclusion of data, and outcome reporting and analysis. We partially replicated the authors’ search across three of their seven databases, which identified 1845 more articles than they reported. Finally, the authors’ interpretations appear to conflate mild and transient adverse effects with serious ones and minimize potentially meaningful benefits of SMT.
Conclusion
The methodological limitations in the meta-analysis by Posadzki et al. raise concerns about its reliability and reproducibility. Accordingly, we advise against relying on this study to guide clinical decision-making. Clinicians, patients, and stakeholders should interpret its conclusions cautiously when evaluating the appropriateness of SMT for migraine management.
Journal Article