Activity Patterns Research Articles

Altered spontaneous brain activity patterns in hypertensive retinopathy using fractional amplitude of low-frequency fluctuations: a functional magnetic resonance imaging study.

To study functional brain abnormalities in patients with hypertensive retinopathy (HR) and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations (fALFFs) method. Twenty HR patients and 20 healthy controls (HCs) were respectively recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the fALFF method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Further, we used Pearson's correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR. The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus (RO-MFG) and right lingual gyrus. In contrast, the values of fALFFs in the left middle temporal gyrus (MTG), left superior temporal pole (STP), left middle frontal gyrus (MFG), left superior marginal gyrus (SMG), left superior parietal lobule (SPL), and right supplementary motor area (SMA) were higher in the HR group. The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group (P<0.001). The fALFF values of the left middle frontal gyrus in HR patients were positively correlated with anxiety scores (r=0.9232; P<0.0001) and depression scores (r=0.9682; P<0.0001). fALFF values in multiple brain regions of HR patients are abnormal, suggesting that these brain regions in HR patients may be dysfunctional, which may help to reveal the pathophysiological mechanisms of HR.

Anatomy of a fumarole field: drone remote-sensing and petrological approaches reveal the degassing and alteration structure at La Fossa cone, Vulcano, Italy

Abstract. Hydrothermal alteration and mineralization processes can affect the physical and chemical properties of volcanic rocks. Aggressive acidic degassing and fluid flow often also lead to changes in the appearance of a rock, such as changes in surface coloration or intense bleaching. Although hydrothermal alteration can have far-reaching consequences for rock stability and permeability, limited knowledge exists on the detailed structures, extent, and dynamic changes that take place near the surface of hydrothermal venting systems. By integrating drone-based photogrammetry with mineralogical and chemical analyses of rock samples and surface gas flux, we investigate the structure of the evolving volcanic degassing and alteration system at the La Fossa cone on the island of Vulcano, Italy. Our image analysis combines principal component analysis (PCA) with image classification and thermal analysis through which we identify an area of approximately 70 000 m2 that outlines the maximum extent of hydrothermal alteration effects at the surface, represented by a shift in rock color from reddish to gray. Within this area, we identify distinct gradients of surface coloration and temperature that indicate a local variability in the degassing and alteration intensity and define several structural units within the fumarole field. At least seven such larger units of increased activity could be constrained. Through mineralogical and geochemical analysis of samples from the different alteration units, we define a relationship between surface appearance in drone imagery and the mineralogical and chemical composition. Gradients in surface color from reddish to gray correlate with a reduction in Fe2O3 from up to 3.2 % in the unaltered regime to 0.3 % in the altered regime, and the latter coincides with the area of increased diffuse acid gas flux. As the pixel brightness increases towards higher alteration gradients, we note a loss of the initial (igneous) mineral fraction and a change in the bulk chemical composition with a concomitant increase in sulfur content from close to 0 % in the unaltered samples to up to 60 % in samples from the altered domains. Using this approach of combined remote-sensing and in situ analyses, we define and spatially constrain several alteration units and compare them to the present-day thermally active surface and degassing pattern over the main crater area. The combined results permit us to present a detailed anatomy of the La Fossa fumarole field, including high-temperature fumaroles and seven larger units of increased alteration intensity, surface temperature, and variably intense surface degassing. Importantly, we also identify apparently sealed surface domains that prevent degassing, likely as a consequence of mineral precipitation from degassing and alteration processes. By assessing the thermal energy release of the identified spatial units quantitatively, we show that thermal radiation of high-temperature fumaroles accounts for &lt; 50 % of the total thermal energy release only and that the larger part is emitted by diffuse degassing units. The integrated use of methods presented here has proven to be a useful combination for a detailed characterization of alteration and activity patterns of volcanic degassing sites and has the potential for application in alteration research and for the monitoring of volcanic degassing systems.

Cortical mechanisms of across-ear speech integration investigated using functional near-infrared spectroscopy (fNIRS).

This study aimed to investigate integration of alternating speech, a stimulus which classically produces a V-shaped speech intelligibility function with minimum at 2-6 Hz in typical-hearing (TH) listeners. We further studied how degraded speech impacts intelligibility across alternating rates (2, 4, 8, and 32 Hz) using vocoded speech, either in the right ear or bilaterally, to simulate single-sided deafness with a cochlear implant (SSD-CI) and bilateral CIs (BiCI), respectively. To assess potential cortical signatures of across-ear integration, we recorded activity in the bilateral auditory cortices (AC) and dorsolateral prefrontal cortices (DLPFC) during the task using functional near-infrared spectroscopy (fNIRS). For speech intelligibility, the V-shaped function was reproduced only in the BiCI condition; TH (with ceiling scores) and SSD-CI conditions had significantly higher scores across all alternating rates compared to the BiCI condition. For fNIRS, the AC and DLPFC exhibited significantly different activity across alternating rates in the TH condition, with altered activity patterns in both regions in the SSD-CI and BiCI conditions. Our results suggest that degraded speech inputs in one or both ears impact across-ear integration and that different listening strategies were employed for speech integration manifested as differences in cortical activity across conditions.

Spatiotemporal interactions between jaguars (Panthera onca) and their potential prey in Amazonian islands

AbstractAlthough large carnivores usually prefer large prey, in some situations, they may shift their predation patterns towards smaller but abundant prey. The jaguar (Panthera onca) is a large carnivore capable of changing its diet according to prey and habitat availability. Here, we assessed the temporal and spatiotemporal interactions between jaguars and their prey in the Maracá‐Jipioca Islands (Northeastern Amazon, Brazil) through camera traps. We assessed overlapping activity patterns and tested for spatiotemporal segregation/avoidance between jaguars and nine potential prey species. We used a time‐to‐encounter approach, which consists in calculating the minimum time between prey and jaguar's detections, and vice versa, for each record of preys' species at a specific camera trap station, which translates into aggregation or avoidance behaviors. We found that these insular jaguars are more active in daylight periods when most of their prey are active and in locations used by species that cannot become nocturnal to avoid predators due to morphology constraints. Four prey species (great egret, white‐tailed deer, muscovy duck, and black‐and‐white tegu) presented moderate activity overlapping with jaguars. Agoutis and white‐tailed deer seek to spatiotemporally segregate from jaguars, although jaguars did not show spatiotemporal aggregation with any of the evaluated prey. Understanding the spatiotemporal dynamics is essential to establish the islands' trophic network composition and structure. This is fundamental information to efficiently allocate efforts for reducing costs and maximizing benefits in managing this population aiming to protect and conserve it, and consequently, the related ecosystems.

Metabolic rate does not scale with body size or activity in some tick species.

Respiration in ticks is highly efficient and exceptionally low. Ticks can survive years between bloodmeals by having low activity and respiration to conserve energetic resources. Our objective was to compare metabolic (VCO2) and activity rates across 6 tick species. We predicted that VCO2 would be different among species and scale linearly with activity and body mass. Activity and CO2 production were measured for 32h in 6 tick species: Dermacentor andersoni, D. variabilis, Haemaphysalis longicornis, Rhipicephalus appendiculatus, R. microplus, and R. sanguineus. Individual ticks were measured for 30min three times to ensure breathing occurred. Absolute and mass-specific VCO2, total activity, body mass, and ventilation patterns were compared among species. As expected, ticks did not always breathe during the 30-minute measurements, especially R. sanguineus. Ventilation patterns differed among species with R. microplus having primarily cyclic patterns and R. appendiculatus having discontinuous gas exchange. VCO2 did not scale with body mass in most species. Haemaphysalis longicornis and R. sanguineus had the lowest VCO2; however, H. longicornis was the second most active species. Life history, including questing behavior and range expansion, could be contributing to differences between species. For instance, H. longicornis had exceptionally low metabolic rates despite above average activity levels, suggesting an energetic advantage which may underlie recently documented range expansions in North America. Our results demonstrate how ticks utilize energetic resources to maximize longevity. Future research describing questing behavior and distribution modeling may help explain differences in metabolic rates and activity and impacts on life history traits.

Choosing where to work: an empirical study of collaborative activities’ impact on workspace choice behavior

Purpose In today’s rapidly evolving work landscape, the design of office spaces is a crucial concern for organizations. Companies are redefining offices as collaboration hubs to entice employees back to in-person work. However, the understanding of how employees choose their workspaces, especially for collaborative activities, and how this should inform office design is lacking. Workers’ collaborative activity patterns can help better understand workspace choice behavior (WCB). In two studies, this paper aims to explore which characteristics of collaborative activities to consider when reshaping offices. Design/methodology/approach Data collected in a cross-sectional study design at a research institution (n = 285) and a university (n = 352) were used for confirmatory factor analyses and regression analysis. Findings The first study shows that collaborative activities can be classified into three distinct types: coordinative activities (planned and formal), deep collaboration (planned and complex) and spontaneous communication (informal and short encounters). The second study revalidates this classification and reveals patterns impacting WCB. Frequency and location preference of spontaneous communication and work environment satisfaction are strong predictors of on-site work. Personal characteristics like gender, age, managerial position or commute time are less consequential than assumed. Practical implications The results pinpoint guidelines for office designers and leaders in shaping effective workspaces and policies. Originality/value This paper provides new insights into classifying collaborative activities and personal characteristics, activity characteristics and environmental factors influencing WCB.

Electrophysiological and Behavioral Markers of Hyperdopaminergia in DAT-KO Rats.

Background/Objectives: Dopamine dysfunction (DA) is a hallmark of many neurological disorders. In this case, the mechanism of changes in dopamine transmission on behavior remains unclear. This study is a look into the intricate link between disrupted DA signaling, neuronal activity patterns, and behavioral abnormalities in a hyperdopaminergic animal model. Methods: To study the relationship between altered DA levels, neuronal activity, and behavioral deficits, local field potentials (LFPs) were recorded during four different behaviors in dopamine transporter knockout rats (DAT-KO). At the same time, local field potentials were recorded in the striatum and prefrontal cortex. Correlates of LFP and accompanying behavioral patterns in genetically modified (DAT-KO) and control animals were studied. Results: DAT-KO rats exhibited desynchronization between LFPs of the striatum and prefrontal cortex, particularly during exploratory behavior. A suppressive effect of high dopamine levels on the striatum was also observed. Wild-type rats showed greater variability in LFP patterns across certain behaviors, while DAT-KO rats showed more uniform patterns. Conclusions: The decisive role of the synchrony of STR and PFC neurons in the organization of motor acts has been revealed. The greater variability of control animals in certain forms of behavior probably suggests greater adaptability. More uniform patterns in DAT-KO rats, indicating a loss of striatal flexibility when adapting to specific motor tasks. It is likely that hyperdopaminergy in the DAT-KO rat reduces the efficiency of information processing due to less synchronized activity during active behavior.

Multistability of bursting rhythms in a half-center oscillator and the protective effects of synaptic inhibition.

For animals to meet environmental challenges, the activity patterns of specialized oscillatory neural circuits, central pattern generators (CPGs), controlling rhythmic movements like breathing and locomotion, are adjusted by neuromodulation. As a representative example, the leech heartbeat is controlled by a CPG driven by two pairs of mutually inhibitory interneurons, heart interneuron (HN) half-center oscillators (HCO). Experiments and modeling indicate that neuromodulation of HCO navigates this CPG between dysfunctional regimes by employing a co-regulating inverted relation; reducing Na+/K+ pump current and increasing hyperpolarization-activated (h-) current. Simply reducing pump activity or increasing h-current leads to either seizure-like bursting or an asymmetric bursting dysfunctional regime, respectively. Here, we demonstrate through modeling that, alongside this coregulation path, a new bursting regime emerges. Both regimes fulfill the criteria for functional bursting activity. Although the cycle periods and burst durations of these patterns are roughly the same, the new one exhibits an intra-burst spike frequency that is twice as high as the other. This finding suggests that neuromodulation could introduce additional functional regimes with higher spike frequency, and thus more effective synaptic transmission to motor neurons. We found that this new regime co-exists with the original bursting. The HCO can be switched between them by a short pulse of excitatory or inhibitory conductance. In this domain of coexisting functional patterns, an isolated cell model exhibits only one regime, a severely dysfunctional plateau-containing, seizure-like activity. This aligns with widely reported notion that deficiency of inhibition can cause seizures and other dysfunctional neural activities. We show that along the coregulation path of neuromodulation, the high excitability of the single HNs induced by myomodulin is harnessed by mutually inhibitory synaptic interactions of the HCO into the functional bursting pattern.

Lower extremity muscle activity during reactive balance differs between adults with chronic traumatic brain injury and controls.

Control of reactive balance is key to achieving safe independent walking and engagement in life activities. After traumatic brain injury (TBI), motor impairments and mobility challenges are persistent sequelae. To date, no studies have explored muscle activity of individuals with chronic TBI during a task that requires reactive control of balance. To investigate lower extremity muscle activity during a reactive balance test performed by adults with chronic severe TBI and matched controls. We hypothesized that abnormal activity of lower extremity muscles would be related with poorer reactive balance performance. Also, we performed an exploratory analysis for those with TBI investigating the impact of unilateral versus bilateral lower extremity involvement in the control of reactive balance. Ten adults with chronic severe TBI who were independent community ambulators and ten matched controls performed the computerized reactive balance test (Propriotest®) while lower extremity muscle activity was recorded. Electromyographic (EMG) activity was contrasted (Mann-Whitney U Test) between groups across each 10 s epoch of the 120 s test. Additionally, test scores were correlated (Spearman) with lower extremity composite EMG activity to distinguish muscle activity patterns related with reactive balance performance. Lastly, reactive balance test scores were correlated with reactive balance test scores and clinical functional measures only for the TBI group. Although the TBI group exhibited greater EMG activity across the entire test compared with the control group, significant differences were not observed. Greater composite EMG activity correlated significantly with poorer reactive balance performance across most of the 10 s windows of the test. Greater muscle activity exhibited during the reactive balance test by individuals with chronic severe TBI compared to those without disabilities, particularly at small unexpected perturbations, highlights the greater physiologic effort required to control reactive balance even after independent ambulation is achieved.

Alzheimer's pathology disrupts flexible place cell coding and hippocampal-prefrontal neural dynamics during risky foraging decisions in mice.

This study investigates the neural activity patterns associated with impaired decision-making in Alzheimer's disease (AD) by examining the effects of amyloid pathology on prefrontal-hippocampal circuit dynamics in 5XFAD mice, a model system known for its pronounced early amyloid pathology. Using ecologically relevant "approach food-avoid predator" paradigms, we revealed that 5XFAD mice display impaired decision strategies in risky foraging tasks, characterized by rigid hippocampal place fields and diminished sharp-wave ripple (SWR) frequencies, accompanied by disrupted prefrontal-hippocampal connectivity. These neural deficits align with behavioral inflexibility in dynamic threat scenarios. Our findings indicate that disrupted SWR dynamics and corticolimbic connectivity contribute to decision-making deficits in AD, emphasizing the potential of targeting these specific neural mechanisms to ameliorate cognitive impairments. This research contributes significantly to our understanding of AD's impact on cognition, providing insights that could lead to more targeted therapeutic strategies.

Thermal constraints and gender-related differences in the activity patterns of the monomorphic rodent Clyomys laticeps

Abstract The daily activity pattern of animals can be classified as diurnal, nocturnal, crepuscular, and cathemeral reflecting strategic decisions to maximize mating and foraging while reducing predation risks and thermal constraints. Among monomorphic mammals, competition for resources and gender-related differences in physiology and reproductive strategies may translate into different activity patterns of males and females. Therefore, to understand the daily activity pattern both aboveground and belowground of the semifossorial rodent Clyomys laticeps, we tested the following hypotheses: (1) males and females differ in their diel activity patterns; (2) males are active for longer periods than females due to a promiscuous mating system and female site fidelity; and (3) higher maximum temperatures restrain C. laticeps activity. The study was carried out in the Serra de Caldas Novas State Park (Goiás, Brazil) in the Cerrado biome. The activity of C. laticeps was recorded using the telemetry technique over 5 days and nights (twice in each season, rainy and dry, between 2019 and 2021). Clyomys laticeps activity was bimodal, with 2 peaks around dawn and dusk, resembling a crepuscular pattern. Temporal segregation in male and female activity patterns was restricted to the dry season, when female activity was more diurnal than males who were mainly nocturnal. Intersexual competition for resources or male-avoidance behavior by females during the dry food scarcity season could contribute to this pattern, although it may also be explained by gender-related differences in thermal tolerances. Overall, males were active for longer periods than females, probably as a strategy to increase mating opportunities among the former and site fidelity in the latter. Finally, temperature imposed major constraints on C. laticeps activities who preferred milder temperatures and avoided being active in temperatures above their thermoneutral zone.

Heritability of movie-evoked brain activity and connectivity.

The neural bases of sensory processing are conserved across people, but no two individuals experience the same stimulus in exactly the same way. Recent work has established that the idiosyncratic nature of subjective experience is underpinned by individual variability in brain responses to sensory information. However, the fundamental origins of this individual variability have yet to be systematically investigated. Here, we establish a genetic basis for individual differences in sensory processing by quantifying (1) the heritability of high-dimensional brain responses to movies and (2) the extent to which this heritability is grounded in lower-level aspects of brain function. Specifically, we leverage 7T fMRI data collected from a twin sample to first show that movie-evoked brain activity and connectivity patterns are heritable across the cortex. Next, we use hyperalignment to decompose this heritability into genetic similarity in where vs. how sensory information is processed. Finally, we show that the heritability of brain activity patterns can be partially explained by the heritability of the neural timescale, a one-dimensional measure of local circuit functioning. These results demonstrate that brain responses to complex stimuli are heritable, and that this heritability is due, in part, to genetic control over stable aspects of brain function.

Distinct brain-wide presynaptic networks underlie the functional identity of individual cortical neurons.

Neuronal connections provide the scaffolding for neuronal function. Revealing the connectivity of functionally identified individual neurons is necessary to understand how activity patterns emerge and support behavior. Yet, the brain-wide presynaptic wiring rules that lay the foundation for the functional selectivity of individual neurons remain largely unexplored. Cortical neurons, even in primary sensory cortex, are heterogeneous in their selectivity, not only to sensory stimuli but also to multiple aspects of behavior. Here, to investigate presynaptic connectivity rules underlying the selectivity of pyramidal neurons to behavioral state 1-12 in primary somatosensory cortex (S1), we used two-photon calcium imaging, neuropharmacology, single-cell based monosynaptic input tracing, and optogenetics. We show that behavioral state-dependent neuronal activity patterns are stable over time. These are minimally affected by neuromodulatory inputs and are instead driven by glutamatergic inputs. Analysis of brain-wide presynaptic networks of individual neurons with distinct behavioral state-dependent activity profiles revealed characteristic patterns of anatomical input. While both behavioral state-related and unrelated neurons had a similar pattern of local inputs within S1, their long-range glutamatergic inputs differed. Individual cortical neurons, irrespective of their functional properties, received converging inputs from the main S1-projecting areas. Yet, neurons that tracked behavioral state received a smaller proportion of motor cortical inputs and a larger proportion of thalamic inputs. Optogenetic suppression of thalamic inputs reduced behavioral state-dependent activity in S1, but this activity was not externally driven. Our results revealed distinct long-range glutamatergic inputs as a substrate for preconfigured network dynamics associated with behavioral state.

Site fidelity trumps disturbance: aerial shooting does not cause surviving fallow deer (Dama dama) to disperse

Context Aerial shooting is an important tool for managing the economic and environmental impacts of widespread wild fallow deer populations in eastern Australia and could be crucial for mounting an effective response to an emergency animal disease incursion. However, there is a concern that the disturbance caused by aerial shooting could cause infected animals to disperse, thereby transmitting pathogens to previously uninfected areas. Aims We sought to describe the nature and extent of spatial behavioural changes in fallow deer exposed to aerial shooting to: (1) assess the risk that aerial shooting poses to disease spread, and (2) better understand how aerial shooting can contribute to routine deer management programs. Methods We contrasted movement rates, activity range areas, and daily activity patterns of 48 GPS-collared fallow deer before, during and after exposure to aerial shooting at three sites in New South Wales. Key results No collared deer left its pre-shoot activity range area during shooting or within 30 days after shooting finished. Observed behaviour changes included increased daily and hourly distance travelled by female deer during and after shooting, increased activity range areas for female deer after shooting, and increased nocturnal activity in female and male deer during shooting. However, observed changes were minor, temporary, localised, and variable among sites. Conclusions Collared deer showed strong site fidelity despite repeated intense disturbance and substantial population reductions. We found no evidence to support concerns that aerial shooting poses a hazard of disease spread. Implications Aerial shooting should be retained as a key control tool for managing wild fallow deer populations in Australia, including for reducing disease host population densities in the event of an emergency animal disease incursion.

Ipsilateral stimulation shows somatotopy of thumb and shoulder auricular points on the left primary somatosensory cortex using high-density fNIRS.

Auriculotherapy is a technique based on stimulation applied to specific ear points. Its mechanism of active and clinical efficacy remain to be established. This study aims to assess the role that primary somatosensory cortex may play to validate auriculotherapy mechanisms. This study examined whether tactile stimulation at specific auricular points is correlated with distinct cortical activation in the primary somatosensory cortex. Seventeen healthy adults participated in the study. Tactile stimuli were delivered to the thumb, shoulder, and skin master points on the ear using von Frey filaments. Functional near-infrared spectroscopy was used to measure and spatially map cortical responses. This study revealed distinct hemodynamic activity patterns in response to ear point stimulation, consistent with the classic homunculus model of somatotopic organization. Ipsilateral stimulation showed specific cortical activations for the thumb and shoulder points, while contralateral stimulation showed less significant activity. Functional near-infrared spectroscopy effectively captured localized cortical responses to ear tactile stimuli, supporting the somatotopic mapping hypothesis. These findings enhance the understanding of sensory processing with auricular stimulation and supports the concepts of auricular cartography that underpins some schools of auriculotherapy practice. Future research should explore bilateral cortical mapping and the integration of other neuroimaging techniques.

Spike Count Analysis for MultiPlexing Inference (SCAMPI).

Understanding how neurons encode multiple simultaneous stimuli is a fundamental question in neuroscience. We have previously introduced a novel theory of stochastic encoding patterns wherein a neuron's spiking activity dynamically switches among its constituent single-stimulus activity patterns when presented with multiple stimuli (Groh et al., 2024). Here, we present an enhanced, comprehensive statistical testing framework for such " multiplexing " or " code juggling ". Our new approach evaluates whether dual-stimulus responses can be accounted for as mixtures of Poissons either anchored to or bounded by single-stimulus benchmarks. Our enhanced framework improves upon previous methods in two key ways. First, it introduces a stronger set of foils for multiplexing, including an "overreaching" category that captures overdispersed activity patterns unrelated to the single-stimulus benchmarks, reducing false detection of multiplexing/code-juggling. Second, it detects faster fluctuations - i.e. at sub-trial timescales - that would have been overlooked before. We utilize a Bayesian inference framework, considering the hypothesis with the highest posterior probability as the winner, and employ predictive recursion marginal likelihood method for the involving nonparametric density estimation. Reanalysis of previous findings confirms the general observation of "code juggling" and indicates that such juggling may well occur on faster timescales than previously suggested. We further confirm that juggling is more prevalent in (a) the inferotemporal face patch system for combinations of face stimuli than for faces and non-face objects; and (b) the primary visual cortex for distinct vs fused objects.

Is the diel cycle of routine metabolic rate in mummichog (Fundulus heteroclitus) affected by near-infrared lighting used for visualizing behavior of fishes at night?

The metabolic rate of a freely moving fish (routine metabolic rate) is tightly coupled with volitional movement (spontaneous activity), both of which commonly show strong daily cycles linked to the species-specific diel activity pattern. Mummichog (Fundulus heteroclitus), an important estuarine fish in the north western Atlantic Ocean, are historically reported as diurnal (i.e., more active during daylight). Our recent laboratory studies on a Bay of Fundy population, however, showed a free-running (i.e., similarly active daytime and night-time) or even nocturnal (i.e., more active at night-time) diel activity pattern. In the laboratory, near-infrared (NIR) illumination is commonly used with a NIR-sensitive camera to visualize fish activity across the light-dark periods of the day. Because NIR light is close to the visible light spectrum and certain fishes show sensitivity to NIR, the use of NIR with mummichog possibly could disturb the animals and obscure the identification of their true diel activity pattern. We aimed to determine if NIR illumination (940 nm wavelength) influences the diel activity pattern of mummichog. We used measurements of routine metabolic rate (oxygen consumption rate, MO2) as a proxy for activity, as evaluating the effect of NIR requires treatments where NIR lights are off, which precludes visualization and direct assessment of fish activity at night-time. We measured routine MO2 of mummichogs over 6 days, exposed to either NIR off-on-off (2 days for each off or on period) or the opposite sequence of NIR on-off-on (to control for time-dependent effects). NIR lights did not influence the diel cycle of routine MO2, and activity by proxy, in mummichog. Thus, NIR illumination is a suitable method to visualize mummichog during light-dark diel cycles. Routine MO2, and presumably activity, was similar or higher during night-time periods compared to daytime periods, confirming a free-running or nocturnal activity pattern for at least certain populations of mummichog.

Decreased GABA levels during development result in increased connectivity in the larval zebrafish tectum.

γ-aminobutyric acid (GABA) is an abundant neurotransmitter that plays multiple roles in the vertebrate central nervous system (CNS). In the early developing CNS, GABAergic signaling acts to depolarize cells. It mediates several aspects of neural development, including cell proliferation, neuronal migration, neurite growth, and synapse formation, as well as the development of critical periods. Later in CNS development, GABAergic signaling acts in an inhibitory manner when it becomes the predominant inhibitory neurotransmitter in the brain. This behavior switch occurs due to changes in chloride/cation transporter expression. Abnormalities of GABAergic signaling appear to underlie several human neurological conditions, including seizure disorders. However, the impact of reduced GABAergic signaling on brain development has been challenging to study in mammals. Here we take advantage of zebrafish and light sheet imaging to assess the impact of reduced GABAergic signaling on the functional circuitry in the larval zebrafish optic tectum. Zebrafish have three gad genes: two gad1 paralogs known as gad1a and gad1b, and gad2. The gad1b and gad2 genes are expressed in the developing optic tectum. Null mutations in gad1b significantly reduce GABA levels in the brain and increase electrophysiological activity in the optic tectum. Fast light sheet imaging of genetically encoded calcium indicator (GCaMP)-expressing gab1b null larval zebrafish revealed patterns of neural activity that were different than either gad1b-normal larvae or gad1b-normal larvae acutely exposed to pentylenetetrazole (PTZ). These results demonstrate that reduced GABAergic signaling during development increases functional connectivity and concomitantly hyper-synchronization of neuronal networks.

Gross Alpha/Beta Radioactivity of Drinking Water and Relationships with Quality Parameters of Water from Alba County, Romania

Drinking-water is considered one of the existing exposure situations to radiation, which involves a level of risk for human health. Thus, its radioactivity is evaluated to keep exposure “as low as reasonably achievable”. Based on monitoring data sets (2017–2023) for six physical-chemical indicators of drinking water quality and total radioactivity expressed by gross alpha activity, gross beta activity and Radon222 content, we evaluated the correlations, relationships, predictors (water source, locality, year), regional variations and potential baseline patterns using statistical analysis and models. The obtained model shows that drinking water sources and localities are factors with significant effect on nitrates concentration and total hardness, ranking sources in the order: well &gt; spring &gt; municipal distribution system; the rank order of drinking water sources based on the concentration of Radon-222 is spring &gt; well &gt; municipal distribution system; locality was found the best predictor for radioactivity; significant correlations were found between gross alpha and gross beta, between gross beta and Radon-222, and between ammonia, nitrates, nitrites and total hardness. The establishment of a baseline pattern for gross alpha activity is a public health goal that can be achieved through performance monitoring of natural radioactivity in water, useful for preparedness in case of a nuclear event

Abstract B054: Protease activity as a biomarker and potential target among pancreatic cancer patients

Abstract Background: The pancreas produces digestive proteases, which are often elevated in diseased states and capable of indiscriminate cell surface receptor cleavage. High levels of digestive protease activity have been implicated in the pathophysiology of pancreatic ductal adenocarcinoma (PDAC). We hypothesize that elevated digestive protease activity might downregulate or cleave immune cell receptors from the surface of cancer cells and contribute to the resistance of PDAC to immunotherapy. We have focused initially on major histocompatibility complex (MHC)-1, a ubiquitous receptor essential for antigen presentation, and CD155, an adhesion molecule over-expressed on cancer cells that regulates immune surveillance through binding to the TIGIT and CD226 receptors on leukocytes. Methods: The Rapid Assay for Protease Detection (RAPD) assay is a novel assay developed at our institution that utilizes fluorescent charge-changing peptide substrates to produce a positively charged fluorescent product fragment upon cleavage by the target protease. The RAPD assay was used to analyze protease activity levels in PDAC patients (N=50) and healthy (N=25) plasma samples. We also analyzed plasma samples obtained from an orthotopic KPC-derived mouse model for PDAC. We investigated the effects of specific proteases as well as plasma samples from PDAC and healthy subjects on MHC-1 and CD-155 receptor cleavage in cultured cells in vitro. Utilizing flow cytometry and immunofluorescent imaging, receptor loss was quantified for different proteases and plasma samples. Results: We observed elevated activity levels of digestive protease chymotrypsin as well as cathepsin-S and MMP-2 in the plasma of PDAC patients compared to healthy subjects. Similar patterns of protease activity were seen in plasma from tumor-bearing mice compared to non-tumor-bearing mice. Additionally, our results suggest loss of CD155 and MHC-1 from pancreatic cancer cells when incubated with trypsin and cathepsin-S. Incubation of cells with PDAC plasma also decreases the number of cells expressing MHC-1 and CD155 compared to control plasma, with greater differences observed in plasma with higher protease levels. Higher levels of cleaved CD155 are also detectable by ELISA in human and mouse PDAC plasma than in control plasma. Also, the protease activity (MMP2 and trypsin) correlates with plasma levels of CD155 and PD-L1. Conclusions: These studies begin to elucidate a possible role of digestive proteases in the ability of PDAC to evade the immune system. Ongoing experiments are exploring other immune receptors (including checkpoints) and whether specific protease inhibitors can block immune receptor cleavage. These experiments will inform subsequent experiments combining protease inhibitors with immunotherapy in mouse models. Citation Format: Utsav Joshi, Heather Farris, Jorge De La Torre De La Torre, kim Nguyen-Ta1, Michael Heller, Geert Schmid-Schonbein, Rebekah White. Protease activity as a biomarker and potential target among pancreatic cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B054.