Biology subjects

Jones, P. L.

Publications and source records attributed to Jones, P. L..

9 recordsLinked to original sources

bioRxiv2026

Burrow disturbance, renovation, and collapse in a cavity-nesting seabird

Researcher disturbance can alter the behavior, survival, and breeding success of wildlife, with effects that are especially well-documented in waterbirds. Anecdotal reports suggest that disturbance can even cause cavity-nesting species to alter the structure of their nests. We used a long-term study of a burrowing seabird, the Leach's Storm-Petrel (Hydrobates leucorhous), to ask whether storm-petrels renovate existing burrows and whether such renovation is related to a history of researcher disturbance. Our study was conducted at the Bowdoin Scientific Station on Kent Island, New Brunswick, Canada, where in 2024 we measured the burrow architecture of 363 burrows, including length and structure for occupied and unoccupied burrows both inside and outside a long-term study site with consistent research activity. Of these, 150 burrows had been measured in 2006, allowing for direct longitudinal comparison of burrow architecture. Nearly all burrows changed in length over the 18-year study period (mean absolute change = 20.8 cm +- 18.2 SD). A linear model revealed two contrasting processes of burrow length change: more frequently occupied burrows grew longer, whereas initially longer burrows shortened towards mean burrow length (~50 cm) through collapse. Occupied burrows inside the long-term study site were on average 34% longer and significantly more complex than burrows adjacent to the site, suggesting that researcher disturbance directly or indirectly reshapes burrows. Overall, these results show that storm-petrel burrows are shaped by cycles of renovation and subsequent collapse that may be exacerbated by human disturbance. Given ongoing population declines in storm-petrels and other cavity-nesting seabirds, this study emphasizes the need to balance scientific research with minimizing disturbance, particularly in long-term studies.

ecology↗

bioRxiv2026

Scheduling problems and the energetics of biparental care in a model of imperiled seabirds

For organisms with biparental care, successful reproduction hinges on coordination between partners. Seabirds face an extreme coordination challenge because parents must schedule nest attendance on land with long-distance foraging trips at sea. We present a computational model of incubation schedules for a vulnerable seabird, the Leachs Storm-Petrel (Hydrobates leucorhous). Using only simple energetic rules and parameters, the model recapitulates natural incubation rhythms, exposes a tradeoff between parent energy and egg attendance, and predicts severe reproductive failure in harsh environments. Incubation primarily fails through "schedule breakdown" -- a single point in the season when both parents spend too long foraging and the egg dies from cold. The resilience of the developing offspring to neglect is thus a fundamental adaptation to the uncertainties of biparental care. These results raise new alarms about the indirect causes of reproductive failure in sensitive marine species and provide theoretical foundations for the evolutionary ecology of scheduling behaviors.

ecology↗

bioRxiv2026

The D4Z4caster DNA methylation signature identifies individuals at epigenetic risk for developing facioscapulohumeral muscular dystrophy (FSHD)

BackgroundFacioscapulohumeral muscular dystrophy (FSHD) is caused by epigenetic dysregulation at the chromosome 4q35 D4Z4 repeat array under specific permissive genetic conditions. Due to the complexity, expense, and general inaccessibility of FSHD genetic testing, many individuals displaying characteristic muscle weakness are never genetically confirmed and at-risk relatives cannot get screened. We previously developed a targeted bisulfite sequencing (BSS) protocol using the Sanger method to determine DNA methylation levels at specific D4Z4 loci relevant to distinguishing forms of FSHD from non-FSHD that can be used with DNA isolated from saliva, thereby reducing cost and increasing accessibility compared to traditional D4Z4 deletion testing that uses DNA isolated from blood. MethodsHere, we adapt the D4Z4 BSS protocol to next-generation sequencing (NGS) to increase sequencing depth and further reduce cost, validate both sequencing technologies against several cohorts of genetically defined samples, and introduce the D4Z4caster software for computing DNA methylation signatures with diagnostic utility from raw sequencing data. ResultsBoth Sanger and NGS BSS methods using D4Z4caster were validated as providing high sensitivity and specificity, with geometric mean of sensitivity and specificity (G-mean) >95% and area-under-the ROC curve (AUC) of 0.99. The NGS method allows for higher throughput and increased read depth, while the Sanger method allows faster processing of individual samples. Importantly, the NGS method could identify FSHD1 cases that are likely mosaic and would otherwise be missed. ConclusionsD4Z4caster methylation signatures can accurately detect contracted FSHD1-permissive chromosome 4q35 alleles, hypomethylation of D4Z4 arrays indicative of FSHD2, and SNPs that are important for diagnostic use. This workflow is amenable to transitioning to clinical settings for an accurate, low-cost FSHD molecular diagnostic test that could be accessible worldwide. What is already known on this topicCurrently accepted genetic diagnostics for FSHD1 are complex and expensive and can mischaracterize certain complex genetic cases. These diagnostics all require high molecular weight genomic DNA typically freshly isolated from blood, highly specialized equipment, and additional testing for FSHD2, making FSHD diagnostics the most expensive among neuromuscular diseases and inaccessible to much of the world. However, the epigenetic status of the 4q35 and 10q26 D4Z4 repeat arrays, as determined by DNA methylation status using our bisulfite sequencing-based protocol, distinguishes genetically FSHD1, FSHD2, and non-FSHD samples. Additionally, since our protocol is PCR-based, it can utilize DNA isolated from multiple sources, including saliva and buccal swabs. What this study addsThis study validates the relevant DNA methylation signatures against several large cohorts of genetically-confirmed FSHD and non-FSHD samples and optimizes the DNA methylation data analysis for the greater accuracy required for diagnostic utility, including the exclusion of nonpathogenic chromosome 10q or 4A166 contractions. In addition, we introduce the D4Z4caster analysis software, which runs in a portable and scalable Docker container, and provides increased quantitative accuracy important for: 1) confirming likely clinical cases of FSHD that do not meet the currently accepted genetic definition of FSHD1 or FSHD2, 2) identifying FSHD1 somatic mosaicism, and 3) potential prognostic applications. How this study might affect research, practice or policyFSHD1 is genetically defined by a D4Z4 array at the 4q35 locus that is contracted to 1-10 repeat units. However, disease penetrance is influenced by repeat number, epigenetic modifications, and genetic background, causing a misalignment of current genetic diagnosis with clinical diagnosis. This study will improve the accuracy of epigenetic analysis for determining cases of genetic FSHD, help broaden the definition of genetic FSHD to more accurately correspond to clinical FSHD, and allow identification of those at risk for developing clinical FSHD in affected families and in large population studies now being performed and proposed. In addition, it will better inform how an individuals epigenetic status is interpreted for potential prognostic value. Overall, this methodology is: 1) significantly less expensive than current clinically-approved FSHD diagnostic technologies, 2) more accessible due to compatibility with DNA isolated from multiple sources including saliva, and 3) compatible with the current sequencing equipment and workflow for DNA isolation used in commercial clinical laboratories. Together, these advantages will help move the technology toward becoming an approved molecular diagnostic test for FSHD in the USA, Europe, and countries currently lacking clear access to testing.

genetics↗

bioRxiv2026

Identification of compounds that repress DUX4 expression in facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is caused by epigenetic dysregulation of the disease locus, leading to pathogenic misexpression of DUX4 in skeletal muscle. Thus, most FSHD therapeutic approaches target DUX4. Our previous study identified the chromatin remodeling factor BAZ1A (bromodomain adjacent to zinc finger domain protein 1A) as a promising target for therapeutic development. Here we used an artificial intelligence-based screening pipeline to identify molecules predicted to bind the BAZ1A bromodomain, and validated hit compounds using FSHD-specific assays in FSHD myocytes. One compound, termed C06, emerged as a potent and specific repressor of DUX4 and DUX4 target gene expression. Interestingly, while C06 exhibited binding to BAZ1A in vitro, it can also inhibit multiple kinases, including p38, an upstream activator of DUX4. Despite this, at low doses C06 was an equally effective and more specific repressor of DUX4 than losmapimod, which is a robust and specific p38 inhibitor. Thus, C06 is a useful tool for potent and specific DUX4 suppression, and a viable candidate for further development. Our results highlight both the utility and limitations of AI for targeted drug discovery, and the importance of using an FSHD-specific functional screening strategy for selecting relevant candidates.

pharmacology and toxicology↗

bioRxiv2025

Divergent climate impacts despite similar response to temperature in a widespread aerial insectivore

Climate change is shifting when animals breed1,2, but it is still not clear why some populations keep pace with warming while others fall behind3,4. Differences could arise from variation in sensitivity to temperature3 or constraints on the ability to respond to temperature. Without knowing whether populations differ in sensitivity--or in their ability to act on that sensitivity--we cannot identify which are most at risk. Using 1,555 population-years from 123 populations of tree swallows (Tachycineta bicolor), we show that populations have similar sensitivity to local temperature, advancing breeding by about one day per degree of warming. However, northern populations face tighter time constraints and greater exposure to recent warming. Northern populations have advanced laying dates the most, but still experience stronger selection for earlier breeding, especially in warm years; they have also declined most in breeding abundance. These findings show that vulnerability to climate change can arise not just from different sensitivity to warming, but from when and where populations can respond effectively. By disentangling sensitivity from timing constraints, our results support a general mechanism by which even uniformly responsive species can show uneven impacts of climate change across their ranges.

ecology↗

bioRxiv2025

Transgenic mouse models for investigating human DUX4 expression during development and its roles in FSHD pathophysiology

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy caused by aberrant expression of the DUX4 retrogene, and it affects skeletal muscles primarily in the face, shoulder, and limbs. In healthy individuals, DUX4 is expressed in early development and is subsequently silenced in most somatic tissues. The spatiotemporal pattern of DUX4 mis-expression beyond the cleavage stage in FSHD is poorly understood because DUX4 is not well conserved beyond primates. Here, we generated Cre reporter mouse lines with human DUX4 regulatory elements to investigate the cell lineages derived from DUX4-expressing cells in embryos and adults. Intriguingly, we found that DUX4-expressing cell lineages were present in embryonic forelimb, hindlimb, and face. In adults, the reporter was expressed strongly in testis and to a lesser extent in other tissues, including weak, sporadic expression in skeletal muscles, reminiscent of mosaic DUX4 expression in FSHD. Within skeletal muscles, DUX4 lineage cells include pericytes, an interstitial cell that contributes to muscle regeneration and repair. Overall, this study introduces a new research tool for the field, and provides new insight into potential developmental mechanisms underlying FSHD pathophysiology. Summary statementCre reporter mouse lines with human DUX4 regulatory elements are discovery tools for developmental processes and mechanisms underlying FSHD pathophysiology.

developmental biology↗

bioRxiv2023

Validation of the association between MRI and gene signatures in facioscapulohumeral dystrophy muscle: implications for clinical trial design

Identifying the aberrant expression of DUX4 in skeletal muscle as the cause of facioscapulohumeral dystrophy (FSHD) has led to rational therapeutic development and clinical trials. Several studies support the use of MRI characteristics and the expression of DUX4-regulated genes in muscle biopsies as biomarkers of FSHD disease activity and progression, but reproducibility across studies needs further validation. We performed lower-extremity MRI and muscle biopsies in the mid-portion of the tibialis anterior (TA) muscles bilaterally in FSHD subjects and validated our prior reports of the strong association between MRI characteristics and expression of genes regulated by DUX4 and other gene categories associated with FSHD disease activity. We further show that measurements of normalized fat content in the entire TA muscle strongly predict molecular signatures in the mid-portion of the TA. Together with moderate-to-strong correlations of gene signatures and MRI characteristics between the TA muscles bilaterally, these results suggest a whole muscle model of disease progression and provide a strong basis for inclusion of MRI and molecular biomarkers in clinical trial design.

molecular biology↗

bioRxiv2022

Long-term memory in frog-eating bats

Long-term memory has clear advantages but also has neurological and behavioral costs1-3. Given these opposing selection pressures, understanding how long memories last can shed light on how memory enhances or constrains animals abilities to exploit their niches. Although testing memory retention in wild animals is difficult, it is important because captive conditions do not reflect the complex cognitive demands of wild environments, and long-term captivity changes the brain4 (past studies on nonhuman long-term memory are reviewed in Table S1). Here, we trained wild-caught frog-eating bats (Trachops cirrhosus) to find prey by flying to a novel acoustic cue, released them back into the wild, and then re-captured some of them 1-4 years later. When re-tested, all eight experienced bats that previously learned the novel prey sounds flew to those sounds within seconds, whereas 17 naive bats tested with the same sounds showed weak responses. Experienced bats also showed behavior indicating generalization of memories between novel sounds and rewards over time. The frog-eating bats remarkably long memory for novel acoustic cues indicates that an ability to remember rarely encountered prey may be advantageous for this predator, and suggests hitherto unknown cognitive abilities in bats. O_TBL View this table: org.highwire.dtl.DTLVardef@15a8294org.highwire.dtl.DTLVardef@132eb3forg.highwire.dtl.DTLVardef@1f29583org.highwire.dtl.DTLVardef@135dff2org.highwire.dtl.DTLVardef@19cfa_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable S1:C_FLOATNO O_TABLECAPTIONStudies of animal memory durations documenting memories of months or years. Memory duration = the longest duration demonstrated in the study. Wild or captive = where animals spent the time of memory retention; some "captive" animals were originally wild caught. Context = the ecological context and memory task being tested. 2-AFC = Two-alternative forced choice. C_TABLECAPTION C_TBL

animal behavior and cognition↗

bioRxiv2018

Transgenic mice expressing tunable levels of DUX4 develop characteristic facioscapulohumeral muscular dystrophy-like pathophysiology ranging in severity

BackgroundAll types of facioscapulohumeral muscular dystrophy (FSHD) are caused by the aberrant myogenic activation of the somatically silent DUX4 gene, which initiates a cascade of cellular events ultimately leading to FSHD pathophysiology. Therefore, FSHD is a dominant gain-of-function disease that is amenable to modeling by DUX4 overexpression. However, there is large variability in the patient population. Typically, progressive skeletal muscle weakness becomes noticeable in the second or third decade of life, yet there are many genetically FSHD individuals who develop symptoms much later in life or remain relatively asymptomatic throughout their lives. Conversely, in rare cases, FSHD may present clinically prior to 5-10 yrs of age, ultimately manifesting as a very severe early onset form of the disease. Thus, there is a need to control the timing and severity of pathology in FSHD-like models.\n\nMethodsWe have recently described a line of conditional DUX4 transgenic mice, FLExDUX4, that develop a myopathy upon induction of human DUX4-fl expression in skeletal muscle. Here, we use the FLExDUX4 mouse crossed with the skeletal muscle-specific and tamoxifen inducible line ACTAl-MerCreMer to generate a highly versatile bi-transgenic mouse model with chronic, low-level DUX4-fl expression and mild pathology, that can be induced to develop more severe FSHD-like pathology in a dose-dependent response to tamoxifen. We identified conditions to reproducibly generate models exhibiting mild, moderate, or severe DUX4-dependent pathophysiology, and characterized their progression.\n\nResultsWe assayed DUX4-fl mRNA and protein levels, fitness, strength, global gene expression, histopathology, and immune response, all of which are consistent with an FSHD-like myopathic phenotype. Importantly, we identified sex-specific and muscle-specific differences that should be considered when using these models for preclinical studies.\n\nConclusionsThe ACTA1-MCM;FLExDUX4 bi-transgenic mouse model expresses a chronic low level of DUX4-fl and has mild pathology and detectable muscle weakness. The onset and progression of moderate to severe pathology can be controlled via tamoxifen injection to provide consistent and readily screenable phenotypes for assessing therapies targeting DUX4-fl mRNA and protein. Thus, these FSHD-like mouse models can be used to study a range of DUX4-fl expression and pathology dependent upon investigator need, through controlled mosaic expression of DUX4.

cell biology↗