Active Segmentation Research Articles

Defective kinase activity of IKKα leads to combined immunodeficiency and disruption of immune tolerance in humans.

IKKα is a multifunctional serine/threonine kinase that controls various biological processes, either dependent on or independent of its kinase activity. However, the importance of the kinase function of IKKα in human physiology remains unknown since no biallelic variants disrupting its kinase activity have been reported. In this study, we present a homozygous germline missense variant in the kinase domain of IKKα, which is present in three children from two Turkish families. This variant, referred to as IKKαG167R, is in the activation segment of the kinase domain and affects the conserved (DF/LG) motif responsible for coordinating magnesium atoms for ATP binding. As a result, IKKαG167R abolishes the kinase activity of IKKα, leading to impaired activation of the non-canonical NF-κB pathway. Patients carrying IKKαG167R exhibit a range of immune system abnormalities, including the absence of secondary lymphoid organs, hypogammaglobulinemia and limited diversity of T and B cell receptors with evidence of autoreactivity. Overall, our findings indicate that, unlike a nonsense IKKα variant that results in early embryonic lethality in humans, the deficiency of IKKα's kinase activity is compatible with human life. However, it significantly disrupts the homeostasis of the immune system, underscoring the essential and non-redundant kinase function of IKKα in humans.

Abstract 4138237: Clinical Utility of T2 Mapping for the Assessment of Myocardial Inflammation in Patients With Cardiac Sarcoidosis

Introduction: 18 F-FDG PET has been used for the evaluation of active inflammatory lesions in cardiac sarcoidosis (CS), but it is burdensome for patients to perform as a routine follow-up. Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) that can detect myocardial fibrosis is limited in its ability to assess active inflammation. T2 mapping has been shown to detect myocardial inflammation in myocardial diseases without radiation exposure and contrast agents (Figure). However, the ability of T2 mapping for discriminating inflammatory myocardium has not been fully clarified in patients with CS. Hypothesis: We assessed the hypothesis that T2 mapping has potential for the discrimination of inflammatory myocardium in patients with CS. Methods: Twenty-seven subjects who underwent CMR at 3T and 18 F-FDG PET to diagnose CS were enrolled. Fourteen subjects were diagnosed as CS due to LGE and myocardial FDG uptake on 18 F-FDG PET (PET-positive group). Thirteen subjects showed no myocardial FDG uptake (PET-negative group). NativeT1, T2, and extracellular volume fraction (ECV) were measured using a 16-segment model. Receiver-operating characteristic (ROC) curve analysis was performed to evaluate T1 and T2 mapping in discriminating between active and inactive inflammatory segments in the PET-positive group. Results: Mean native T1, native T2 and ECV showed no significant differences between the PET-positive and the PET-negative groups. However, maximum T2 values, which were highest ones in the 16 segments, were significantly higher in the PET-positive group than the PET-negative group (51.3 ± 7.7 ms vs 45.7 ± 3.6 ms, p = 0.014). In the PET-positive group, ROC analysis showed AUC of 0.72 in native T2, 0.61 in native T1, and 0.68 in ECV for discriminating inflammatory myocardium. The optimal cutoff value of native T2 was 45.7 ms, and the diagnostic performance had a sensitivity of 44.4 %, specificity of 93.3 % , positive predictive value of 88.1 %, and negative predictive value of 60.1 %. Conclusion: T2 mapping is a promising approach for the discrimination of inflammatory myocardium without radiation exposure and contrast agents in patients with cardiac sarcoidosis.

Protracted magma evolution and transcrustal magmatic plumbing system architecture at Erta Ale volcano (Afar, Ethiopia)

Abstract The Afar region is one of the only places on Earth where magmatic continental rifting and associated ongoing break-up processes are exposed onshore. The several active magmatic segments there are characterized by contrasted morphologies, crustal thicknesses, magma production rates, and magma-tectonic styles. In the Erta Ale Range rift segment, extension is magmatically accommodated, making the range the ideal place to study the magmatic behavior of a mature rift segment. Erta Ale Range comprises sub-segments with magma compositions ranging from basalts to rhyolites, but only the Erta Ale Volcano (EAV) sub-segment is active, where only basaltic compositions have been reported so far. Here, we show for the first time protracted differentiation at EAV that is not expressed volcanically at the surface, but is rather accessible via unique cognate gabbroic and microgabbroic blocks, and recorded by mixing with erupted basaltic magmas. These cognate samples record previously unknown mushy and evolved parts of the EAV plumbing system. To constrain their origin and evolution, we measured the major and trace element compositions of the bulk rocks, interstitial glasses, and melt inclusions. We also measured the oxygen isotopic compositions of olivine crystals, interstitial glasses, and melt inclusions. By combining these results with textural relationships and oxy-thermo-barometry calculations, we discuss magma differentiation and storage conditions, as well as magmatic interactions during transport through the crust. Comparison of our results with rhyolite-MELTS thermodynamic models highlights that protracted fractional crystallization is the main process of magma evolution, and when associated with reactive porous flow is capable of forming the evolved compositions observed (up to 75 wt.% SiO2). We also use the model outputs to quantify distinct steps of igneous differentiation in both shallow and deep crustal reservoirs, and we highlight significant interactions with hydrothermally altered wall rocks. We discuss this model within the geological contexts of the Erta Ale Range rift segment and the larger Afar region, and highlight contrasts with mature oceanic systems to argue that the region is not in the final stages of continental break-up.

On the role of trans-lithospheric faults in the long-term seismotectonic segmentation of active margins: a case study in the Andes

Abstract. Plate coupling plays a fundamental role in the way in which seismic energy is released during the seismic cycle. This process includes quasi-instantaneous release during megathrust earthquakes and long-term creep. Both mechanisms can coexist in a given subduction margin, defining a seismotectonic segmentation in which seismically active segments are separated by zones where ruptures stop, classified for simplicity as asperities and barrier, respectively. The spatiotemporal stability of this segmentation has been a matter of debate in the seismological community for decades. In this regard, we explore in this paper the potential role of the interaction between geological heterogeneities in the overriding plate and fluids released from the subducting slab towards the subduction channel. As a case study, we take the convergence between the Nazca and South American plates between 18–40° S, given its relatively simple convergence style and the availability of a high-quality instrumental and historical record. We postulate that trans-lithospheric faults striking at a high angle with respect to the trench behave as large fluid sinks that create the appropriate conditions for the development of barriers and promote the growth of highly coupled asperity domains in their periphery. We tested this hypothesis against key short- and long-term observations in the study area (seismological, geodetic, and geological), obtaining consistent results. If the spatial distribution of asperities is controlled by the geology of the overriding plate, seismic risk assessment could be established with better confidence.

Relationship between physical activity, body posture and morbidity risk in the elderly population

Background Physical activity plays a crucial role in the health and well-being of older adults, positively influencing various aspects of their quality of life. This study aims to explore the relationship between physical activity and body segments, as well as the risk indices of non-communicable chronic diseases in healthy elderly individuals. Methods The analyzed variables include weekly physical activity, the Postural Correction Index (PCI), measured using the system developed by Portland State University (PSU), and predictors of non-communicable chronic diseases assessed through body mass index (BMI) and waist-to-hip ratio. Results The results reveal a moderate positive relationship between physical activity and the PCI (r=0.45; p≤0.05), with significant correlations in specific components of the PCI, such as thoracic depression (r=0.51; p<0.01), anteroposterior shoulder alignment (r=0.51; p<0.01), and upper back (r=0.53; p<0.001). Conclusions It is concluded that physical activity has a significant positive impact on the posture of older adults, particularly in the trunk, contributing 40% to the improvement of PCI components. The PCI values obtained, exceeding 84.67 in men and 82.67 in women according to the PSU evaluation, underscore the effectiveness of physical activity in postural correction and the prevention of issues associated with chronic diseases.

Seismotectonic Map of The Sinai Triple Junction

The geodynamic evolution of the Sinai Triple Junction, a highly deformed and seismically active area, is controlled by the Red Sea rift, Gulf of Suez and Aqaba-Dead Sea conjunctions. However, the driving forces for the focusing deformation at crustal depths beneath this area are still ambiguous. Here, we provide an updated seismotectonic map of the area relying on updated seismological and geodetic datasets. A homogenized earthquake catalog has been compiled from well-located earthquakes (> Mw 2.0) by the Egyptian Seismic Network and International Seismological Center in the period between 1990 and 2020.We calculated the average b-value along three seismogenic zones including Gulf of Aqaba, northern Red Sea and Gulf of Suez that amount to 1.1, 0.99 and 0.97, respectively. Additionally, we complied and updated a comprehensive P-wave-based database for the fault plane solutions in the area for events with Mw> 3.5 till 2023. Furthermore, a unified velocity field for the region as well as slip-rate and locking-depth at the active fault segments were estimated from a consistent geodetic dataset from peer-reviewed GPS velocities between 1999 and 2018. Results indicate a dominant NNE left-lateral strike-slip fault with normal component along the Gulf of Aqaba. Pure NW-SE to WNW-ESE dip-slip normal faulting, associated with a strike-slip component in some cases, is dominating the northern and central parts of the Gulf of Suez, whereas pure normal dip-slip movement with an NNE–SSW extension in a horizontal direction is observed in the southern part of the gulf. The estimated slip-rate and locking-depths at the Aqaba fault segments falls between 4.8-4.9 mm/yr and 8-12 km, respectively.

Segment-Based Unsupervised Deep Learning for Human Activity Recognition using Accelerometer Data and SBOA based Channel Attention Networks

The deep learning community has increasingly focused on the critical challenges of human activity segmentation and detection based on sensors, which have numerous real-world applications. In most prior efforts, activity segmentation and recognition have been treated as separate processes, relying on pre-segmented sensor streams. This research proposes an unsupervised deep learning approach for Human Activity Recognition (HAR) that is segment-based, with an emphasis on activity continuity. The approach integrates segment-based SimCLR with Segment Feature Decorrelation (SDFD) and a new framework that leverages pairs of segment data for contrastive learning of visual representations. Furthermore, the Secretary Bird Optimization Algorithm (SBOA) and Channel Attention with Spatial Attention Network (CASANet) are utilized to enhance the performance of sensor-based human activity detection. CASANet effectively extracts key features and spatial dependencies in sensor data, while SBOA optimizes the model for greater accuracy and generalization. Evaluations on two publicly available datasets—Mhealth and PAMAP2—demonstrated an average F1 score of 98%, highlighting the approach’s efficacy in improving activity recognition performance.

Quantitative chemical proteomics reveals that phenethyl isothiocyanate covalently targets BID to promote apoptosis

Naturally occurring isothiocyanates (ITCs) found in cruciferous vegetables, such as benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), and sulforaphane (SFN), have attracted significant research interest for their promising anti-cancer activity in vitro and in vivo. While the induction of apoptosis is recognized to play a key role in the anti-cancer effects of ITCs, the specific protein targets and associated upstream events underlying ITC-induced apoptosis remain unknown. In this study, we present a set of chemical probes that are derived from BITC, PEITC, and SFN and equipped with bioorthogonal alkynyl handles to systematically profile the target proteins of ITCs in live cancer cells. Using a competition-based quantitative chemical proteomics approach, we identify a range of candidate target proteins of ITCs enriched in biological processes such as apoptosis. We show that BID, an apoptosis regulator of the Bcl-2 family, is covalently modified by ITCs on its N-terminal cysteines. Functional characterization demonstrates that covalent binding to N-terminal cysteines of BID by PEITC results in conformational changes of the protein and disruption of the self-inhibitory interaction between N- and C-terminal regions of BID, thus unleashing the highly active C-terminal segment to exert downstream pro-apoptotic effects. Consistently, PEITC promotes the cleavage and mitochondrial translocation of BID, leading to a strong induction of apoptosis. We further show that mutation of N-terminal cysteines impairs the N- and C-terminal interaction of BID, relieving the self-inhibition and enhancing its apoptotic activity. Overall, our chemical proteomics profiling and functional studies not only reveal BID as the principal target of PEITC in mediating upstream events for the induction of apoptosis, but also uncover a novel molecular mechanism involving N-terminal cysteines within the first helix of BID in regulating its pro-apoptotic potential.

A 24–30‐GHz Modified Gilbert‐Cell Downconverter With High Linearity and Isolation

ABSTRACTThis paper introduces a downconverter mixer employing a modified double‐balanced Gilbert‐cell topology, designed using IHP's 0.13‐m SiGe BiCMOS technology. Distinct from the conventional topology, a resonator was employed at the emitter of the transconductance stage, which enables the utilization of transconductance stage as an active balun, allowing for direct feeding of the single‐ended input without sacrificing the advantageous of the double‐balanced topology. The integration of the resonator reduces the amplitude and phase errors within the active balun segment, thereby enhancing port‐to‐port isolation. The area occupied by the resonator is approximately 1.7 times smaller than that of an RF transformer balun typically employed in conventional double‐balanced topologies. The LO and IF differential signals are converted to single‐ended ones through transformer baluns for measurement purposes. The frequencies of operation for RF, LO, and IF are 24–30, 18–24, and 6 GHz, respectively. The conversion loss is 7.7 dB at 26 GHz, with port‐to‐port isolations exceeding 35 dB. The input 1‐dB compression point is 5.7 dBm, while the circuit consumes 65‐mW power from a 3.3‐V voltage supply. Excluding the pads, the active area of the design spans 1 mm2.

An Efficient Algorithm for Exact Segmentation of Large Compositional and Categorical Time Series

ABSTRACTChange‐point detection, also known as signal segmentation, is an essential preprocessing step in many applications, ranging from industrial monitoring to bioinformatics. In short, it consists in finding the temporal boundaries of homogeneous regimes in long and non‐stationary time series. While this area of research is active, most existing methods are designed for Euclidean data. However, in many practical scenarios, the collected time series are compositional, meaning that each observation belongs to the probability simplex (the set of non‐negative vectors whose components sum to one). In this work, we propose an algorithm detecting change‐points in large compositional signals with an underlying piecewise stationary model. We cast the change‐point detection task as a discrete optimization problem, whose solution is shown to converge to the true change‐points. We introduce a new and time‐efficient dynamic programming algorithm that solves exactly this problem. To limit the number of operations, we describe a novel pruning rule that allows us to reduce the set of candidate change‐point indices. Our method is tested on a thorough simulation study, which confirms its efficiency. Additionally, we apply our method to a human activity segmentation task, highlighting the necessity for such novel techniques compared to standard algorithms.

ЗАДАЧИ ПО ПРЕДОТВРАЩЕНИЮ ПРИРОДНЫХ ЧРЕЗВЫЧАЙНЫХ СИТУАЦИЙ НА АКВАТОРИИ МОРЕЙ РОССИЙСКОЙ АРКТИКИ (ПО МАТЕРИАЛАМ МОРСКОЙ ДОКТРИНЫ РОССИЙСКОЙ ФЕДЕРАЦИИ)

This article provides an overview of the main organizational and managerial tasks to ensure protection from natural emergencies during marine activities in the Arctic zone of the Russian Federation. The main mechanism for ensuring the safety of maritime economic activity in the Arctic is called the prevention of emergency situations by forecasting them. The problems of natural (climatic extremes) emergencies are emphasized, the main directions of obtaining predictive information, scientific and scientific-technical activities, and the tasks of legal regulation are briefly outlined. The guideline for the presentation of the topic of the article is the Maritime doctrine of the Russian Federation – a strategic act of the Head of state, which contains the main provisions on the principles and mechanisms of maritime activities in the Russian Federation. The result of this study is the positioning of emergency forecasting as an inseparable segment of activity in the Arctic from the economy.

Graphene Field‐Effect Transistors toward Study of Cardiac Ischemia at Early Stage

AbstractIschemia and reperfusion states are studied in a network of cardiomyocytes as a part of real‐state conditions of heart injuries and inflammations, specifically myocardial infractions. Arrays of graphene field‐effect transistors (GFETs) fabricated in this work are used for extracellular recordings of ischemia states of cardiac cells during the external triggering of the ischemia infarction. The low‐concentrated ischemic buffer solution allows to create a cell‐stress condition resulting in the reperfusion process. The results show that the action potentials recorded with the graphene transistors, especially their shape, and duration of the active segment in measured extracellular action potentials, can be used to characterize the real state of the studied cardiac cell culture. The unique property of GFETs to detect such small changes in the action potential of cells in cardiac healthy and unhealthy states provides prospects for building the next generation of ultrasensitive biosensors, enabling the detection of acute ischemic states at an early stage.

Dynamic Interplay of Loop Motions Governs the Molecular Level Regulatory Dynamics in Spleen Tyrosine Kinase: Insights from Molecular Dynamics Simulations.

The spleen tyrosine kinase (Syk) is a key regulator in immune cell signaling and is linked to various mechanisms in cancer and neurodegenerative diseases. Although most computational research on Syk focuses on novel drug design, the molecular-level regulatory dynamics remain unexplored. In this study, we utilized 5 × 1 μs all-atom molecular dynamics simulations of the Syk kinase domain, examining it in combinations of activation segment phosphorylated/unphosphorylated (at Tyr525, Tyr526) and the "DFG"-Asp protonated/deprotonated (at Asp512) states to investigate conformational variations and regulatory dynamics of various loops and motifs within the kinase domain. Our findings revealed that the formation and disruption of several electrostatic interactions among residues within and near the activation segment likely influenced its dynamics. The protein structure network analysis indicated that the N-terminal and C-terminal anchors were stabilized by connections with the nearby stable helical regions. The P-loop showed conformational variation characterized by movements toward and away from the conserved "HRD"-motif. Additionally, there was a significant correlation between the movement of the β3-αC loop and the P-loop, which controls the dimensions of the adenine-binding cavity of the C-spine region. Overall, understanding these significant motions of the Syk kinase domain enhances our knowledge of its functional regulatory mechanism and can guide future research.

Unveiling crustal deformation patterns along the north Tabriz fault from 2015 to 2022 using multi-temporal InSAR analysis

This paper presents a comprehensive study on the recognition of crustal deformation patterns surrounding the North Tabriz Fault in Northwestern Iran, utilizing Multi-Temporal InSAR analysis. The fault, despite its seismic inactivity for over two centuries, has a long history of ancient seismicity, with earthquake recurrence intervals exceeding two centuries. This makes it highly susceptible to future activity and the generation of significant and devastating earthquakes. However, limited research has been conducted on extracting and modeling deformation patterns of the North Tabriz Fault to identify its active segments. The primary objective of this study is to derive a general trend for fault displacement and investigate regions under pressure in terms of abnormal crustal movements. The results indicate that the Earth's crust in the surrounding regions of the central and northwest segments of the fault exhibits an upward movement ranging from approximately 2 to 10 millimeters per year from 2015 to 2022. In contrast, neighboring areas of the northwestern fault, as well as the northwestern, western, and southwestern parts of Tabriz County, experience ground subsidence with rates ranging from approximately 5 to 40 millimeters per year. These findings are consistent with GNSS-derived line-of-sight measurements obtained from some IPGN stations around the fault with an RMSE of 1.72 mm/yr. Furthermore, the study identifies critical points near the fault that exhibit varying and diverse displacement patterns over time, suggesting significant strain and notable stress within the subsurface environment. According to the analysis of time series data on crustal movements at the identified critical points, it has been found that the prevailing motion pattern of the Earth's crust within the fault zone largely conforms to a sinusoidal descending pattern. Additionally, recent earthquakes in the northwest vicinity of the fault have been observed to occur close to these critical points. Using line-of-sight (LOS) data acquired at these critical points, the study estimates a slip rate of 7.71 ± 0.01 mm/year and a locking depth of 11.27 ± 0.01 km, contributing to a better understanding of the fault's seismogenic behavior. These findings provide valuable insights into the crustal deformation patterns around the North Tabriz Fault, highlighting active segments and regions under pressure.

Relationship between physical activity, body posture and morbidity risk in the elderly population

Background Physical activity plays a crucial role in the health and well-being of older adults, positively influencing various aspects of their quality of life. This study aims to explore the relationship between physical activity and body segments, as well as the risk indices of non-communicable chronic diseases in healthy elderly individuals. Methods The analyzed variables include weekly physical activity, the Postural Correction Index (PCI), measured using the system developed by Portland State University (PSU), and predictors of non-communicable chronic diseases assessed through body mass index (BMI) and waist-to-hip ratio. Results The results reveal a moderate positive relationship between physical activity and the PCI (r=0.45; p≤0.05), with significant correlations in specific components of the PCI, such as thoracic depression (r=0.51; p<0.01), anteroposterior shoulder alignment (r=0.51; p<0.01), and upper back (r=0.53; p<0.001). Conclusions It is concluded that physical activity has a significant positive impact on the posture of older adults, particularly in the trunk, contributing 40% to the improvement of PCI components. The PCI values obtained, exceeding 82.67 in men and 84.67 in women according to the PSU evaluation, underscore the effectiveness of physical activity in postural correction and the prevention of issues associated with chronic diseases.

Tectonic Activity Analysis of the Laji-Jishi Shan Fault Zone: Insights from Geomorphic Indices and Crustal Deformation Data

Fault segmentation plays a critical role in assessing seismic hazards, particularly in tectonically complex regions. The Laji-Jishi Shan Fault Zone (LJSFZ), located on the northeastern margin of the Tibetan Plateau, is a key structure that accommodates regional tectonic stress. This study integrates geomorphic indices, cross-fault deformation rate profiles, and 3D crustal electrical structure data to analyze the varying levels of tectonic activity across different segments of the LJSFZ. We extracted 160 drainage basins along the strike of the LJSFZ from a 30 m resolution digital elevation model and calculated geomorphic indices, including the hypsometric integral (HI), stream length-gradient index (SL), and channel steepness index (ksn), to assess the variations in tectonic activity intensity along the strike of the LJSFZ. The basins were categorized based on river flow directions to capture potential differences across the fault zone. Our results show that the eastern basins of the LJSFZ exhibit the strongest tectonic activity, demonstrated by significantly higher SL and ksn values compared to other regions. A detailed segmentation analysis along the northern Laji Shan Fault and eastern Jishi Shan Fault identified distinct fault segments characterized by variations in SL and ksn indices. Segments with high SL values (>500) correspond to higher crustal uplift rates (~3 mm/year), while segments with lower SL values exhibit lower uplift rates (~2 mm/year), as confirmed by cross-fault deformation profiles derived from GNSS and InSAR data. This correlation demonstrates that geomorphic indices effectively reflect fault activity intensity. Additionally, 3D crustal electrical structure data further indicate that highly conductive mid- to lower-crustal materials originating from the interior of the Tibetan Plateau are obstructed at segment L3 of the LJSFZ. This obstruction leads to localized intense uplift and enhanced fault activity. These findings suggest that while the regional stress–strain pattern of the northeastern Tibetan Plateau is the primary driver of the segmented activity along the Laji-Jishi Shan belt, the direction of localized crustal flow is a critical factor influencing fault activity segmentation.

Recent and active faulting along the exposed front of the Northern Apennines (Italy): New insights from field and geochronological constraints

Establishing genetic links between active shallow faulting and deep seismogenic sources is challenging, especially in areas where seismogenic faults lack clear and readily interpretable geological evidence at the surface. The architecture of the Pedeapenninic margin of the Northern Apennines (Italy) reflects a regional-scale and complex NE-verging blind thrust system, which is dissected by transpressive/transtensive faults resulting from active NE-SW orogenic compression. The local geological framework is defined by allochthonous ocean-derived units resting atop Pliocene-to-present successions exposed along the Northern Apennines margin and to the NE of it, while the innermost chain sector mostly contains Adria-related units. We present results from field structural-geological investigations to identify and characterize potential active faults along the margin. There, the Pliocene-to-present units are faulted and folded, indicating that tectonic activity is still on-going, thus contributing to the local seismic hazard. Top-to-the NE and SW normal faults are common in the area and deform the Pliocene-to-present succession together with NE-SW strike-slip and transpressional/transtensional faults. Based on field evidence, we define four potentially active thrust segments affecting Middle Pleistocene to Holocene deposits exposed along the margin. Calcite U-Th dating on samples from faults extend the most recent datable tectonic activity back to the Middle Pleistocene. Paleostress analysis from inversion of fault-slip data from the most recent identified striated fault planes constrains a NE-SW shortening direction parallel to the Apennines regional migration direction. A distinct but coaxial extensional stress regime, recorded by structures measured within Plio-Pleistocene formations, was also identified. Our results offer a sound starting point for future investigations aimed at improving our understanding of active and seismogenic faulting in the area, so as to create robust Probabilistic Seismic and Fault Displacement Hazard Assessment (PSHA and PFDHA) models that can implement refined seismic hazard maps benefitting from structural-geological deterministic inputs in addition to the classic seismological constraints.

Missense mutation in the activation segment of the kinase CK2 models Okur-Chung neurodevelopmental disorder and alters the hippocampal glutamatergic synapse.

Exome sequencing has enabled the identification of causative genes of monogenic forms of autism, amongst them, in 2016, CSNK2A1, the gene encoding the catalytic subunit of the kinase CK2, linking this kinase to Okur-Chung Neurodevelopmental Syndrome (OCNDS), a newly described neurodevelopmental condition with many symptoms resembling those of autism spectrum disorder. Thus far, no preclinical model of this condition exists. Here we describe a knock-in mouse model that harbors the K198R mutation in the activation segment of the α subunit ofCK2. This region is a mutational hotspot, representing one-third of patients. These mice exhibit behavioral phenotypes that mirror patient symptoms. Homozygous knock-in mice die mid-gestation while heterozygous knock-in mice are born at half of the expected mendelian ratio and are smaller in weight and size than wildtype littermates. Heterozygous knock-in mice showed alterations in cognition and memory-assessing paradigms, enhanced stereotypies, altered circadian activity patterns, and nesting behavior. Phosphoproteome analysis from brain tissue revealed alterations in the phosphorylation status of major pre- and postsynaptic proteins of heterozygous knock-in mice. In congruence, we detect reduced synaptic maturation in hippocampal neurons and attenuated long-term potentiation in the hippocampus of knock-in mice. Taken together, heterozygous knock-in mice (CK2αK198R/+) exhibit significant face validity, presenting ASD-relevant phenotypes, synaptic deficits, and alterations in synaptic plasticity, all of which strongly validate this line as a mouse model of OCNDS.

Community Engagement in Development Planning in Jabon District

Background: Community participation is essential for effective development planning in rural areas. Specific Background: This study examines participation in development planning within a particular village. Knowledge Gap: Although existing literature recognizes community involvement, disparities in participation among different societal groups remain underexplored. Aims: The research aims to analyze community participation levels and highlight engagement differences. Results: Findings reveal uneven participation in oversight processes, with certain groups more engaged, potentially sidelining the interests of less active segments. Novelty: This study emphasizes the need for inclusive strategies to ensure diverse community voices are heard. Implications: Results call for initiatives that promote broader engagement in oversight activities, facilitating equitable representation and effective development planning that addresses the challenges of marginalized groups. Highlights : Engagement Disparities: Participation levels vary significantly among community groups. Inclusive Strategies: Effective planning requires ensuring all voices are heard. Representation Challenges: Underrepresented segments may have their interests overlooked. Keywords: community participation, development planning, oversight processes, engagement disparities, inclusive strategies

Analysis of electrode performance on amplitude integrated electroencephalography in neonates: evaluation of a new electrode aCUP-E vs. liquid gel electrodes.

Neonatologists and clinical neurophysiologists face challenges with the current electrodes used for long-duration amplitude-integrated electroencephalography (aEEG) in neonatal intensive care units (NICU), limiting the capacity to diagnose brain damage. The objectives of this study were to develop methods for comparing the performance of different electrodes to be used in aEEG. The comparison was done between a newly designed neonate-specific electrode, aCUP-E, with commercial liquid gel electrodes used in amplitude-integrated electroencephalography (aEEG). The comparison included impedance stability, electrode survival, recording quality, usability, and satisfaction of NICU staff. aEEG recordings with bipolar montage was used, with one hemisphere fitted with commercial electrodes and the other with aCUP-E electrodes, alternated among subjects. Continuous impedance and raw EEG data were collected over a minimum of 24 h, and signal processing was performed using Python and MATLAB. aCUP-E electrodes demonstrated superior performance, including: Increased impedance stability and electrode survival, enhanced recording quality with fewer artifacts, high correlation in signal capture between electrodes during optimal brain activity segments, higher signal-to-noise ratio (SNR) across varying impedance levels, greater staff satisfaction and ease of use. Moreover, Kaplan-Meier curves indicated a higher survival rate for aCUP-E electrodes over 24 h compared to commercial electrodes. Impedance variability analysis showed statistically significant stability improvements for aCUP-E. aCUP-E electrodes outperform commercial liquid gel electrodes in impedance stability, electrode survival, and recording quality. These results suggest that aCUP-E electrodes could significantly enhance aEEG utilization in diagnosing and treating neonatal brain conditions in NICUs. Future improvements to the aCUP-E electrode may further reduce artifacts and increase electrode longevity, potentially leading to a significant improvement in neonatal brain monitoring by means of aEEG.