Search bioRxiv⌕ Search

Biology subjects

Davis, R. J.

Publications and source records attributed to Davis, R. J..

12 recordsLinked to original sources

Using spatial prioritization to navigate current and future tradeoffs when controlling invaders

Controlling invasive species is a global conservation priority but is typically resource-limited, necessitating strategies to optimize control. Spatial prioritization methods can improve the efficiency of invader control by quantifying the benefits, costs, and risks of alternative intervention strategies. Yet prioritization designs are sensitive to the distinction between protecting native populations that are currently sympatric with invaders versus safeguarding presently allopatric native populations by preventing invader expansion. Gaining a better understanding of this distinction stands to improve our ability to prioritize the management of invaders whose distributions--and thus impacts on native species--are dynamic. We asked how prioritization designs addressing current versus future invader threats affected tradeoffs among focal species protection, biodiversity conservation, disturbance risk, and overlap with existing conservation infrastructure. As a case study, we spatially prioritized population control of invasive barred owls (Strix varia) in the northwestern US. We found that distinguishing between current versus future threats posed by barred owls to the native spotted owl (S. occidentalis) strongly mediated whether invader control stood to benefit native at-risk animal communities. Furthermore, this distinction also affected the degree to which population control would overlap with fire risk and federally protected forests, both of which plausibly affect the viability and success of conservation action. These results thus illustrate that deciding to prioritize the control of invaders based on their current versus future impacts on native species can dramatically affect the distribution and characteristics of high-priority areas for management. Our findings also directly inform control of barred owls in the northwestern US: we found that prioritizing future threats to spotted owls could protect at-risk amphibian communities from novel barred owl predation, but that high fire risk and minimal protected forest may complicate implementation. Thus, in both our system and more broadly, spatial prioritization methods are an important tool for quantitative, reproducible, and successful invader control.

ecology↗

Passive Acoustic Monitoring within the Northwest Forest Plan Area: 2025 Annual Report

The Northwest Forest Plan (NWFP) Passive Acoustic Monitoring (PAM) program is a large-scale interagency biodiversity monitoring framework designed to assess the status and trends of northern spotted owls (Strix occidentalis caurina), barred owls (Strix varia), marbled murrelets (Brachyramphus marmoratus), and broader forest biodiversity across federally administered lands in the Pacific Northwest. In 2025, we deployed autonomous recording units at 2,095 sampling stations within 532 5-km2 hexagons randomly selected across approximately 24 million acres of federal forest lands in Washington, Oregon, and California. These deployments generated 1.37 million hours of acoustic recordings that we processed using the convolutional neural network PNW-Cnet v5 for automated species identification and subsequent human validation of focal species detections. Northern spotted owls were detected in 28% of sampled hexagons range-wide, including 16% in Washington, 25% in Oregon, and 60% in California. Occupancy patterns remained consistent compared to previous years, with higher occupancy concentrated in southern portions of the geographic range and continued low occupancy across much of the Washington Cascades and Oregon Coast Range. Barred owls were detected in 86% of sampled hexagons and remained broadly distributed throughout most of the NWFP area. Marbled murrelets were detected in 50% of reviewed hexagons within NWFP marbled murrelet management zones, with highest occupancy occurring in coastal forests of Oregon and Washington. The 2025 field season occurred under substantial operational constraints that reduced sampling effort by approximately half relative to 2023 and 2024 because of staffing limitations affecting participating federal agencies. Despite these reductions, the NWFP-PAM framework continued to provide broad-scale, spatially representative ecological information across the NWFP area. Results highlight the growing importance of passive acoustic monitoring and machine learning approaches for long-term biodiversity monitoring under changing environmental and operational conditions.

ecology↗

A hypothalamus-liver-skeletal muscle axis controlled by JNK1 and FGF21 mediates olanzapine-induced insulin resistance in an intraperitoneal treatment in male mice

BackgroundOlanzapine (OLA), a widely prescribed second-generation antipsychotic, is associated with adverse metabolic effects. We recently showed that oral OLA treatment in male mice induces weight gain and hepatic steatosis, whereas intraperitoneal (i.p.) administration leads to weight loss due to higher hypothalamic OLA levels and activation of brown adipose tissue. Since clinical studies report insulin resistance in individuals treated with OLA, here we investigated the impact of OLA i.p. treatment on insulin sensitivity, focusing on the liver- skeletal muscle axis. Material and MethodsWild-type male mice were treated with OLA (10 mg/kg, i.p.) for 8 weeks or received a single intrahypothalamic injection (15 nmol). Glucose homeostasis parameters were assessed. Mechanistic studies were performed in vagotomized mice, mice lacking JNK in either the hypothalamus or liver, mice overexpressing hepatic FGF21, and PTP1B-deficient mice (PTP1B-KO). ResultsOLA i.p. treatment induced systemic insulin resistance, pyruvate intolerance, and reduced insulin signaling in both liver and skeletal muscle. These effects were accompanied by increased hepatic JNK phosphorylation and IRS1 serine phosphorylation. A single intrahypothalamic OLA injection similarly impaired peripheral insulin action and activated hepatic JNK. Deletion of hypothalamic or hepatic JNK1, as well as vagotomy, prevented these defects. OLA reduced hepatic Fgf21 expression, an effect reversed by hypothalamic JNK1 deletion or vagotomy. Hepatic FGF21 overexpression prevented OLA-induced insulin resistance in skeletal muscle but not in liver. PTP1B-KO mice were protected from all metabolic impairments. ConclusionAlthough OLA i.p. treatment prevents weight gain, it decreases peripheral insulin sensitivity through a hypothalamus-liver axis driven by hypothalamic JNK1, which activates hepatic JNK via the vagus nerve, suppresses hepatic FGF21 and ultimately impairs insulin signaling in skeletal muscle. Importantly, the protection conferred by PTP1B deficiency against OLA-induced insulin resistance strongly suggests that targeting PTP1B might prevent metabolic comorbidities in patients under OLA treatment in a personalized manner.

physiology↗

Passive Acoustic Monitoring within the Northwest Forest Plan Area: 2024 Annual Report

Passive acoustic monitoring (PAM) has become the primary framework for assessing the status, distribution, and habitat associations of forest-dependent wildlife under the Northwest Forest Plan (NWFP). In 2024, the NWFP PAM program continued to operate as a fully integrated, range-wide monitoring network, building on deployments initiated in 2018 and now conducting surveys across approximately 24 million acres of federal land. Using a randomized 2+20% sampling design, more than 4,000 autonomous recording units generated over 2 million hours of acoustic data analyzed with convolutional neural networks, enabling statistically rigorous inference at regional and range-wide scales. This report summarizes 2024 field efforts and analytical advancements in the context of recent peer-reviewed and in-progress studies. Updated analyses confirm persistent, low occupancy of northern spotted owls (Strix occidentalis caurina), with detections concentrated in the Klamath Mountains and southern Cascades, consistent with long-term demographic declines. Range-wide models of barred owl (Strix varia) landscape use continue to show high occupancy across much of the NWFP area, reinforcing competitive displacement as the dominant driver of spotted owl range contraction. The PAM network also advanced monitoring of marbled murrelets (Brachyramphus marmoratus), with 2024 results supporting PAM as a cost-efficient alternative to traditional audio-visual surveys for assessing inland nesting habitat use in coastal forests. Beyond focal species, the program increasingly supports multi-taxa biodiversity monitoring through bioacoustic bycatch and soundscape analyses, linking species occurrence, habitat condition, and disturbance dynamics. Collectively, 2024 results demonstrate that PAM has reached operational maturity as the cornerstone of Phase II NWFP effectiveness monitoring. Sustaining adequate sampling effort and field capacity remains a challenge but essential, as reduced deployment intensity would increase uncertainty and weaken inference. Continued investment in PAM infrastructure and expertise is critical for informing adaptive management, supporting sustainable timber harvest, and evaluating ecosystem resilience under changing disturbance regimes.

ecology↗

Passive Acoustic Monitoring within the Northwest Forest Plan Area: 2023 Annual Report

Here we document progress in implementing large-scale passive acoustic monitoring across the Northwest Forest Plan area to track population trends of northern spotted owls (Strix occidentalis caurina), barred owls (S. varia), marbled murrelets (Brachyramphus marmoratus), and a broad array of forest-adapted wildlife. In 2023, we deployed 4,012 autonomous recording units across 1,009 randomly selected 5-km{superscript 2} hexagons, generating nearly 2.2 million hours of recordings, representing approximately 1 petabyte of acoustic data. These data were processed with PNW-Cnet v5, the latest version of our convolutional neural network model, trained on 135 sound classes representing over 80 species and environmental sounds. Model performance demonstrated high precision for focal species and many additional taxa, substantially reducing manual review effort while enabling broad-scale biodiversity assessments. Results confirmed northern spotted owl detections in all 20% sample areas, with occupancy varying geographically and declining notably in the Tyee study area. Barred owls were widely detected, with the highest prevalence in Oregon and Washington and comparatively lower occupancy in California. Marbled murrelets were consistently detected in coastal areas, particularly the Olympic Peninsula and Oregon Coast Range. Beyond these focal species, PAM and PNW-Cnet generated robust datasets for a wide range of birds, mammals, and disturbance indicators, underscoring the value of random-site, multi-species monitoring. The 2023 field season marked the first full implementation of the 2% + 20% NWFP sampling design, expanding monitoring coverage while strengthening collaborations with federal and state partners. These efforts provide the foundation for long-term, cost-effective wildlife monitoring and inform conservation strategies in dynamic forest ecosystems.

ecology↗

Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity

Coordination of adaptive metabolism through cellular signaling networks and metabolic response is essential for balanced flow of energy and homeostasis. Post-translational modifications such as phosphorylation offer a rapid, efficient, and dynamic mechanism to regulate metabolic networks. Although numerous phosphorylation sites have been identified on metabolic enzymes, much remains unknown about their contribution to enzyme function and systemic metabolism. In this study, we stratify phosphorylation sites on metabolic enzymes based on their location with respect to functional and dimerization domains. Our analysis reveals that the majority of published phosphosites are on oxidoreductases, with particular enrichment of phosphotyrosine (pY) sites in proximity to binding domains for substrates, cofactors, active sites, or dimer interfaces. We identify phosphosites altered in obesity using a high fat diet (HFD) induced obesity model coupled to multiomics, and interrogate the functional impact of pY on hepatic metabolism. HFD induced dysregulation of redox homeostasis and reductive metabolism at the phosphoproteome and metabolome level in a sex-specific manner, which was reversed by supplementing with the antioxidant butylated hydroxyanisole (BHA). Partial least squares regression (PLSR) analysis identified pY sites that predict HFD or BHA induced changes of redox metabolites. We characterize predictive pY sites on glutathione S-transferase pi 1 (GSTP1), isocitrate dehydrogenase 1 (IDH1), and uridine monophosphate synthase (UMPS) using CRISPRi-rescue and stable isotope tracing. Our analysis revealed that sites on GSTP1 and UMPS inhibit enzyme activity while the pY site on IDH1 induces activity to promote reductive carboxylation. Overall, our approach provides insight into the convergence points where cellular signaling fine-tunes metabolism. Summary StatementBy employing a multi-disciplinary approach we stratify structural features of phosphorylation sites on metabolic enzymes, map the systems level changes induced by obesity, identify key pathways with sex specific phosphoproteomic responses, and validate the functional role of phosphorylation sites for select enzymes.

biochemistry↗

c-Jun N-terminal kinase (JNK) signaling contributes to cystic burden in polycystic kidney disease

Polycystic kidney disease is an inherited degenerative disease in which the uriniferous tubules are replaced by expanding fluid-filled cysts that ultimately destroy organ function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, afflicting approximately 1 in 1,000 people. It primarily is caused by mutations in the transmembrane proteins polycystin-1 (Pkd1) and polycystin-2 (Pkd2). The most proximal effects of Pkd mutations leading to cyst formation are not known, but pro-proliferative signaling must be involved for the tubule epithelial cells to increase in number over time. The c-Jun N-terminal kinase (JNK) pathway promotes proliferation and is activated in acute and chronic kidney diseases. Using a mouse model of cystic kidney disease caused by Pkd2 loss, we observe JNK activation in cystic kidneys and observe increased nuclear phospho c-Jun in cystic epithelium. Genetic removal of Jnk1 and Jnk2 suppresses the nuclear accumulation of phospho c-Jun, reduces proliferation and reduces the severity of cystic disease. While Jnk1 and Jnk2 are thought to have largely overlapping functions, we find that Jnk1 loss is nearly as effective as the double loss of Jnk1 and Jnk2. Jnk pathway inhibitors are in development for neurodegeneration, cancer, and fibrotic diseases. Our work suggests that the JNK pathway should be explored as a therapeutic target for ADPKD. Author SummaryAutosomal dominant polycystic kidney disease is a leading cause of end stage renal disease requiring dialysis or kidney transplant. During disease development, the cells lining the kidney tubules proliferate. This proliferation transforms normally small diameter tubules into fluid-filled cysts that enlarge with time, eventually destroying all kidney function. Despite decades of research, polycystic kidney disease remains incurable. Furthermore, the precise signaling events involved in cyst initiation and growth remain unclear. The c-Jun N-terminal kinase (JNK), is a major pathway regulating cellular proliferation and differentiation but its importance to polycystic kidney disease was not known. We show that JNK activity is elevated in cystic kidneys and that reducing JNK activity decreases cyst growth pointing to JNK inhibition as a therapeutic strategy for treating polycystic kidney disease.

genetics↗

Mitogen Kinase Kinase (MKK7) controls cytokine production in vitro and in vivo in mice

Mitogen kinase kinase 4 (MKK4) and Mitogen kinase kinase 7 (MKK7) are members of the MAP2K family which can activate downstream mitogen-activated protein kinases (MAPKs). MKK4 has been implicated in the activation of both, c-Jun N-terminal Kinase (JNK) and p38 MAPK, whereas MKK7 only activates JNK in response to different stimuli. The stimuli as well as cell type determine the choice of MAP2K member that mediates the response. In a variety of cell types, the MKK7 contributes to the activation of downstream MAPKs, JNK, which is known to regulate essential cellular processes, such as cell death, differentiation, stress response, and cytokine secretion. Previous studies have implicated the role of MKK7 in stress signaling pathways and cytokine production. However, little is known about the degree to which MKK7 and MKK4 contributes to innate immune response in macrophages as well as during inflammation in vivo. To address this question and elucidate the role of MKK7 and MKK4 in macrophage and in vivo, we developed MKK7- and MKK4-deficient mouse models with tamoxifen-inducible Rosa26 CreERT. This study reports that MKK7 is required for JNK activation both in vitro and in vivo. Additionally, we demonstrated that MKK7 in macrophages is necessary for LPS induced cytokine production and migration which appears to be a major contributor to the inflammatory response in vivo. Whereas MKK4 plays a significant but minor role in cytokine production in vivo.

biochemistry↗

Historical disturbances to rivers appear to constrain contemporary distribution of a river-dependent frog,

Frogs dependent on lotic environments are sensitive to disturbances that alter the hydrology (e.g., water impoundments), substrate (e.g., debris torrents), and riparian vegetation (e.g., wildfires) of river ecosystems. Although rivers are often very dynamic, disturbances can push environmental baselines outside of narrowly defined ecological tolerances under which a species evolved. Short-lived lotic-dependent organisms, restricted to movements within the water or the riparian corridor, are at risk of local extirpations owing to such disturbances if they fragment and isolate affected populations from recolonizing source populations. In Oregon, USA, the foothill yellow-legged frog (Rana boylii) is at its northernmost range margin and has experienced an approximately 41% range contraction compared to their historical distribution. To inform conservation and management, we used species distribution models to identify environmentally suitable watersheds based on intrinsic baseline environmental variables, and then examined potential effects of human-caused alterations to rivers, including splash dams used to ferry timber downstream prior to 1957, large water impoundments, and adjacency to agricultural croplands. We used machine-learning in program Maxent and three different river layers that varied in extent and location of mapped rivers but contained distinct information to produce species distribution models which we then combined into a single ensemble model. Stream order, annual precipitation, and precipitation frequency were the highest ranked baseline environmental variables in most models. Watersheds with highly suitable baseline conditions in our ensemble model were negatively correlated with anthropogenic disturbances to rivers. Foothill yellow-legged frogs appeared to be sensitive to human-caused disturbances to rivers, perhaps indicative of their narrow ecological tolerance to in-river conditions. We do not anticipate variables in our model to change much through time. Rather, for conservation we identified potential legacy (spash dams) and ongoing human-caused disturbances that are more likely to change conditions for the species in the short- and long-term.

ecology↗

Aberrant Ca2+ homeostasis in adipocytes links inflammation to metabolic dysregulation in obesity

Chronic metabolic inflammation is a key feature of obesity, insulin resistance and diabetes, although the initiation and propagation mechanisms of metaflammation are not fully established, particularly in the adipose tissue. Here we show that in adipocytes, altered regulation of the Ca2+ channel inositol triphosphate receptor (IP3Rs) is a key, adipocyte-intrinsic, event involved in the emergence and propagation of inflammatory signaling and the resulting insulin resistance. Inflammation, either induced by cytokine exposure in vitro or by obesity in vivo lead to increased expression and activity of IP3Rs in adipocytes in a JNK-dependent manner. This results in increased cytosolic Ca2+ and impaired insulin action. In mice, adipocyte-specific loss of IP3R1/2 protected against adipose tissue inflammation and insulin resistance despite significant diet-induced weight gain. Thus, this work reveals that IP3R over-activation and the resulting increase in cytosolic Ca2+ is a key link between obesity, inflammation and insulin resistance, and suggests that approaches to target adipocyte Ca2+ homeostasis may offer new therapeutic opportunities against metabolic diseases, especially since GWAS studies also implicate this locus in human obesity.

physiology↗

Evidence of Presence and Activation of the two Cell Cycle Kinases Nek6 and Nek7 in the ciliated Neuroretina

The serine/threonine NIMA kinases are widely found in eukaryotes. They are cell-cycle kinases that are associated with centrosomes and spindle apparatus and cilia. In cilia, NIMA kinases are reported to play a role in cilia length maintenance and deflagelation. Here we focus on the two Nek homologs, Nek6 and Nek7, and their potential role in retina. We report for the first-time expression of nek6 and nek7 mRNA and protein in retinal tissue. In particular, we detect localisation of these kinases to photoreceptors outer segments. Moreover, we are able to show a light-dependent phosphorylation of the activation loop (serine 206) of Nek6/7 in rod outer segments, suggesting activation of these kinases is downstream of the phototransduction pathway. Indeed, we demonstrate that Nek6/7 phosphorylation in the retina is dependent on Grk1 function. Furthermore, Nek6/7 phosphorylation can be stimulated in the brain by opiate drugs, suggesting that activation of Nek6/7 lies downstream of G protein coupled receptors activation, in general. Nek6/7 may couple photoreception with outer segment biogenesis through phosphorylation of downstream substrates, which may affect the microtubules of the axoneme.

biochemistry↗

Analysis and Correction of Inappropriate Image Duplication: The Molecular and Cellular Biology Experience

The present study analyzed 960 papers published in Molecular and Cellular Biology (MCB) from 2009-2016 and found 59 (6.1%) to contain inappropriately duplicated images. The 59 instances of inappropriate image duplication led to 42 corrections, 5 retractions and 12 instances in which no action was taken. Our experience suggests that the majority of inappropriate image duplications result from errors during figure preparation that can be remedied by correction. Nevertheless, ~10% of papers with inappropriate image duplications in MCB were retracted. If this proportion is representative, then as many as 35,000 papers in the literature are candidates for retraction due to image duplication. The resolution of inappropriate image duplication concerns after publication required an average of 6 h of journal staff time per published paper. MCB instituted a pilot program to screen images of accepted papers prior to publication that identified 12 manuscripts (14.5% out of 83) with image concerns in two months. The screening and correction of papers before publication required an average of 30 min of staff time per problematic paper. Image screening can identify papers with problematic images prior to publication, reduces post-publication problems and requires significantly less staff time than the correction of problems after publication.

scientific communication and education↗