Biology subjects

Block, G. D.

Publications and source records attributed to Block, G. D..

5 recordsLinked to original sources

bioRxiv2026

Detection of Pancreatic Cancer Using a Methylation-Specific PCR-Based Multi-Cancer Early Detection Test

ContextPancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy often diagnosed at advanced stages due to the lack of early clinical symptoms. DNA methylation alterations arise early in PDAC tumorigenesis and may serve as promising biomarkers for blood-based cancer detection. ObjectiveTo evaluate the performance of EPISEEK, a laboratory-developed blood-based multi-cancer early detection (MCED) assay, for detecting PDAC across disease stages. DesignA retrospective cohort study included 97 patients with stage I-IV PDAC and 201 asymptomatic healthy controls. Sensitivity, specificity, area under the curve (AUC), and stage-specific performance were assessed. EPISEEK-MCED performance was also compared with CA 19-9 alone and in combination with CA 19-9. ResultsEPISEEK-MCED classified 65 of 97 PDAC cases as positive, corresponding to an observed sensitivity of 70.1% (95% CI, 60.3% - 78.3%) at 99.5% specificity. The assay demonstrated strong discrimination between PDAC cases and healthy controls, with an AUC of 0.916 (95% CI, 0.88 - 0.952). Sensitivity increased with advancing stage while remaining substantial in early-stage disease, measuring 53.6% for stage I and 65.1% for stage II PDAC, 100% for stage III and 94.7% for stage IV. Across stages, EPISEEK-MCED outperformed CA 19-9 alone, particularly in early-stage disease. Combined analysis of EPISEEK-MCED and CA 19-9 further improved detection performance, achieving sensitivity of 57.1% and 81.4% for stage I and II, respectively. ConclusionsEPISEEK-MCED demonstrated high specificity and sensitivity for PDAC detection across disease stages, including early-stage disease. Combining EPISEEK-MCED with CA19-9 further improved performance, supporting its clinical utility for PDAC detection.

molecular biology↗

bioRxiv2026

Bright Days Buffer Nighttime Light: Daytime Illumination Shapes Sex Differences in Sleep and Circadian Regulation

Sex differences in sleep and wakefulness are well documented in humans but remain inconsistent in rodent studies, suggesting strong sensitivity to experimental context. In prior work, we observed no sex differences in sleep-wake architecture under relatively bright daytime light, raising the possibility that daytime illumination is a critical but underappreciated variable shaping sex-dependent sleep regulation. Here, we tested the hypothesis that daytime light intensity modulates sex differences in sleep-wake architecture and vulnerability to dim light at night (DLaN). Male and female C57BL/6J mice were exposed to acute (one night) or chronic (two weeks) DLaN (10 lux) under three daytime light intensities (50, 100, 300 lux). Sleep was assessed using electroencephalographic-based measures of vigilance states and slow wave activity (SWA). Dim daytime light (50 lux) unmasked robust sex differences in dark-phase sleep-wake architecture that were absent under brighter daytime light (300 lux). Acute DLaN reduced early-night wakefulness in both sexes under low daytime light but had minimal effect under bright daytime conditions. Following chronic DLaN, males exhibited reduced dim light-phase wakefulness and dampened rhythm amplitude, whereas females showed pronounced phase shifts, rhythm attenuation, and altered timing of SWA under 50 and 100 lux. These changes were largely prevented under bright daytime light. Together, these findings identify daytime light intensity as a critical contextual factor governing sex-specific regulation of sleep and vulnerability to nighttime light, providing a unifying framework to reconcile inconsistencies in the rodent sleep literature. HighlightsO_LIDaytime light intensity shapes sex differences in sleep-wake architecture C_LIO_LIAcute and chronic nighttime light elicit distinct sex-specific sleep responses C_LIO_LIFemales exhibit greater circadian and slow-wave vulnerability to nighttime light C_LIO_LIBrighter daytime light buffers sleep and circadian disruption C_LI

animal behavior and cognition↗

bioRxiv2025

Dissociating the Effects of Light at Night from Circadian Misalignment in a Neurodevelopmental Disorder Mouse Model Using Ultradian Light-Dark Cycles.

Individuals with neurodevelopmental disorders (NDDs) often experience sleep disturbances and are frequently exposed to light during nighttime hours. Our previous studies using the Cntnap2 knockout (KO) mouse model of NDDs demonstrated that nighttime light exposure increases behaviors such as excessive grooming, reduces social interactions, and disrupts daily locomotor rhythms. To further evaluate the effects of nighttime light exposure, we exposed wild-type (WT) and Cntnap2 KO mice to an ultradian lighting cycle (T7), which alternates 3.5 hours of light and 3.5 hours of darkness. Circadian rhythms in activity, corticosterone levels, and clock gene expression are maintained under T7 lighting despite the presence of light during the usual night phase, whilst animals display increased depressive-like behaviors and reduce performance on the novel object recognition test. Based on these observations, we hypothesized that T7 lighting would mimic the impact of nighttime light exposure seen in standard light-dark cycles with dim light at night (DLaN). However, in this study, adult WT and Cntnap2 KO mice held under the T7 cycle did not show the increased grooming behavior or reduced social interaction observed in Cntnap2 KO mice exposed to DLaN. Regarding locomotor activity rhythms, the T7 cycle lengthened the circadian period and weakened the rhythm amplitude but did not abolish rhythmicity in either genotype. Finally, opposite to DLaN, neither the T7 cycle nor constant darkness (DD) elicited an increase in cFos expression in the basolateral amygdala in WT and KO mice. These results demonstrate that the adverse behavioral and neurobiological effects of nighttime light exposure in a model of a neurodevelopmental disorder depend on circadian disruption rather than light exposure alone, highlighting the importance of circadian stability as a protective factor in NDDS.

neuroscience↗

bioRxiv2025

Dim Light at Night Disrupts the Sleep-Wake Cycle and Exacerbates Seizure Activity in Cntnap2 Knockout Mice: Implications for Autism Spectrum Disorders

Epilepsy is one of the most common comorbidities in individuals with autism spectrum disorders (ASDs). Many patients with epilepsy as well as ASD experience disruptions in their sleep-wake cycle and exhibit daily rhythms in expression of symptoms. Chronic exposure to light at nighttime can disrupt sleep and circadian rhythms. Contactin associated protein-like 2 knockout (Cntnap2 KO) mice, a model for autism spectrum disorder (ASD) and epilepsy, exhibit sleep and circadian disturbances and seizure-like events. This study examines how chronic dim light at night (DLaN) exposure affects sleep architecture, EEG power spectra, and seizure activity in Cntnap2 KO and wildtype (WT) mice. Using electroencephalography (EEG) recordings, male and female Cntnap2 KO and WT mice were exposed to DLaN (5 lux) for 2 or 6 weeks. EEG recordings were analyzed to assess sleep architecture, power spectrum, and seizure-like events. DLaN exposure delays the wake onset and disrupts sleep patterns in a sex-dependent manner, with females being more affected. DLaN significantly increased slow-wave activity (SWA, 0.5-4 Hz) in both WT and KO mice, indicating increased sleep pressure. Finally, we found that DLaN dramatically increased the frequency of seizure-like events in the Cntnap2 KO mice and even increased the occurrence rate in the WT mice. Spectral analysis of seizure-like events revealed increased theta power, suggesting the involvement of hippocampus. Chronic DLaN exposure disrupts sleep and increases seizure-like events in Cntnap2 KO mice, with sex-specific differences. These findings emphasize the potential risks of nighttime light exposure for individuals with ASD and epilepsy, reinforcing the need to manage light exposure to improve sleep quality and reduce seizure risk.

neuroscience↗

bioRxiv2022

Long wavelength light reduces the negative consequences of dim light at night in the Cntnap2 mouse model of autism.

Many patients with autism spectrum disorders (ASD) show disturbances in their sleep/wake cycles, and may be particularly vulnerable to the impact of circadian disruptors. We have previously shown that exposure to dim light at night (DLaN) in contactin associated protein-like 2 knock out (Cntnap2 KO) mice disrupts diurnal rhythms, increases repetitive behaviors while reducing social interactions. These negative effects of DLaN may be mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin, which is maximally sensitive to blue light (480nm). In this study, we used a light-emitting diode (LED) array that enabled us to shift the spectral properties of the DLaN while keeping the intensity at 10 lx. First, using wild-type (WT) mice, we confirmed that the short-wavelength enriched lighting produced strong acute suppression of locomotor activity (masking), robust light-induced phase shifts, and c-Fos expression in the suprachiasmatic nucleus, while the long-wavelength enriched lighting evoked much weaker responses. Furthermore, exposure of WT mice to the short-wavelength light at night reduced the amplitude of locomotor activity rhythms and impaired social interactions. Mice lacking the melanopsin expressing ipRGCs (Opn4DTA mice) were resistant to these negative effects of DLaN. Importantly, the shift of the DLaN stimulus to longer wavelengths ameliorated the negative impact on the activity rhythms and autistic behaviors (i.e. reciprocal social interactions, repetitive grooming) of the Cntnap2 KO model. The short-, but not the long-wavelength enriched, DLaN triggered cFos expression in the peri-habenula region as well as in the basolateral amygdala (BLA). Finally, DLaN-driven c-Fos induction in BLA glutamatergic neurons was about 3-fold higher in the Cntnap2 KO mice, suggesting that these cells may be particularly vulnerable to the effects of photic disruption. Broadly, our findings suggest that the spectral properties of light at night should be considered in the management of ASD and other neurodevelopmental disorders.

neuroscience↗