Fundamental Functions Research Articles

Regenerating Locus Coeruleus-Norepinephrine (LC-NE) Function: A Novel Approach for Neurodegenerative Diseases.

Pathological changes in the locus coeruleus-norepinephrine (LC-NE) neurons, the major source of norepinephrine (NE, also known as noradrenaline) in the brain, are evident during the early stages of neurodegenerative diseases (ND). Research on both human and animal models have highlighted the therapeutic potential of targeting the LC-NE system to mitigate the progression of ND and alleviate associated psychiatric symptoms. However, the early and widespread degeneration of the LC-NE system presents a significant challenge for direct intervention in ND. Recent advances in regenerative cell therapy offer promising new strategies for ND treatment. The regeneration of LC-NE from pluripotent stem cells (PSCs) could significantly broaden the scope of LC-NE-based therapies for ND. In this review, we delve into the fundamental background and physiological functions of LC-NE. Additionally, we systematically examine the evidence and role of the LC-NE system in the neuropathology of ND and psychiatric diseases over recent years. Notably, we focus on the significance of PSCs-derived LC-NE and its potential impact on ND therapy. A deeper understanding and further investigation into the regeneration of LC-NE function could pave the way for practical and effective treatments for ND.

Atomic fluorescence collection into planar photonic devices

Fluorescence collection from individual emitters plays a key role in state detection and remote entanglement generation, fundamental functionalities in many quantum platforms. Planar photonics have been demonstrated for robust and scalable addressing of trapped-ion systems, motivating consideration of similar elements for the complementary challenge of photon collection. Here, using an argument from the reciprocity principle, we show that far-field photon collection efficiency can be simply expressed in terms of the fields associated with the collection optic at the emitter position alone. We calculate collection efficiencies into ideal paraxial and fully vectorial focused Gaussian modes parameterized in terms of focal waist, and further quantify the modest enhancements possible with more general beam profiles, establishing design requirements for efficient collection. Toward practical implementation, we design, fabricate, and characterize two diffractive collection elements operating at λ = 397 nm; a forward emitting design is predicted to offer 0.25% collection efficiency into a single waveguide mode, while a more efficient reverse-emitting design offers 1.14% collection efficiency, albeit with more demanding fabrication requirements. Close agreement between simulated and measured emission for both designs indicates practicality of these collection efficiencies, and we indicate avenues to improved devices approaching the limits predicted for ideal beams. We point out a particularly simple integrated waveguide configuration for polarization-based remote entanglement generation enabled by integrated collection.

Sensorimnemonic decisions: choosing memories versus sensory information.

We highlight a fundamental psychological function that is central to many of our interactions in the environment - when to rely on memories versus sampling sensory information anew to guide behavior. By operationalizing sensorimnemonic decisions we aim to encourage and advance research into this pivotal process for understanding how memories serve adaptive cognition.

Agama Sebagai Institusi Sosial (Tinjauan Literatur Sosiologi Agama)

This study aims to explore the role of religion as a social institution in the context of the study of religious sociology literature. The research methodology applied in this study is qualitative, with an approach based on literature review. The findings of the study indicate that religion functions as a social phenomenon that is inseparable from people's lives, regardless of any level of culture. Religion will continue to maintain its existence in society, because of its fundamental function. Religion can be considered a social institution, considering its existence in society, where religion is an entity that is recognized, understood, obeyed, and respected by the community. The conflicts or tensions that arise due to religion are not caused by religion itself, but by the excessive fanaticism of its adherents or by the extreme changes that occur in their communities.

Identifying a non-conserved site for achieving allosteric covalent inhibition of CECR2.

The bromodomain (BRD) represents a highly conserved structural module that provides BRD proteins with fundamental functionality in modulating protein-protein interactions involved in diverse biological processes such as chromatin-mediated gene transcription, DNA recombination, replication and repair. Consequently, dysregulation of BRD proteins has been implicated in the pathogenesis of numerous human diseases. In recent years, considerable scientific endeavors have focused on unraveling the molecular mechanisms underlying BRDs and developing inhibitors that target these domains. While these inhibitors compete for binding with the acetylated lysine binding site of BRDs, achieving inhibition of BRD proteins via competitive pocket binding has proven challenging due to the conserved nature of these pockets. To address this limitation, the present study employed dynamic simulations for a comprehensive analysis, leading to the identification of a non-conserved pocket in CECR2 for achieving BRD family inhibition through allosteric modulation. Subsequently, the compound BAY 11-7085 was proven capable of covalently binding to C494 of this pocket after covalent docking and biological verification in vitro. The allosteric inhibition strategy of CECR2 was further verified by the structurally optimized compound LC-CE-7, which is an allosteric covalent CECR2 inhibitor with anti-cancer effects in MDA-MB-231 cells.

Transplantation of genome-edited retinal organoids restores some fundamental physiological functions coordinated with severely degenerated host retinas.

We have previously shown that the transplantation of stem cell-derived retinal organoid (RO) sheets into animal models of end-stage retinal degeneration can lead to host-graft synaptic connectivity and restoration of vision, which was further improved using genome-edited Islet1-/- ROs (gROs) with a reduced number of ON-bipolar cells. However, the details of visual function restoration using this regenerative therapeutic approach have not yet been characterized. Here, we evaluated the electrophysiological properties of end-stage rd1 retinas after transplantation (TP-rd1) and compared them with those of wild-type (WT) retinas using multi-electrode arrays. Notably, retinal ganglion cells (RGCs) in TP-rd1 retinas acquired light sensitivity comparable to that of WT retinas. Furthermore, RGCs in TP-rd1 retinas showed light adaptation to a photopic background and responded to flickering stimuli. These results demonstrate that transplantation of gRO sheets may restore some fundamental physiological functions, possibly coordinating with the remaining functions in retinas with end-stage degeneration.

Resurrection of a diatom after 7000years from anoxic Baltic Sea sediment.

Dormancy is a widespread key life history trait observed across the tree of life. Many plankton species form dormant cell stages that accumulate in aquatic sediments and, under anoxic conditions, form chronological records of past species and population dynamics under changing environmental conditions. Here we report on the germination of a microscopic alga, the abundant marine diatom Skeletonema marinoi Sarno et Zigone, that had remained dormant for up to 6871 ± 140years in anoxic sediments of the Baltic Sea and resumed growth when exposed to oxygen and light. Resurrected diatom strains, representing cohorts from six different time points of the past 6871 ± 140years, are genetically differentiated, and fundamental physiological functions such as growth and photosynthesis have remained stable through time despite distinct environmental dynamics. Showing that resurrection and full functional recovery, in comparison to 3 ± 2years of dormancy, is possible after millennial resting, we emphasize the relevance of dormancy and living sediment archives. For the future, sediment archives, together with the resurrection approach, would offer a powerful tool to trace adaptive traits over millennia under distinct climatic conditions and elucidate the underlying mechanisms.

DDX18 influences chemotherapy sensitivity in colorectal cancer by regulating genomic stability.

Chromosomal Instability (CIN) encompasses approximately 65%-70% of colorectal cancer (CRC) patients, playing a pivotal role in tumor progression. However, controversies persist regarding the molecular characteristics and treatment strategies associated with these patients. Integrative colorectal cancer proteogenomic analysis identified DDX18 in colorectal cancer. We investigated the molecular mechanisms underlying the regulation of colorectal cancer by the R-loop binding protein DDX18 using colon cancer tissues, cell lines and patient-derived organoids. Our findings revealed that DDX18 expression positively correlates with the expression of genomic instability marker R-loops. Moreover, heightened DDX18 expression delays the completion of DNA damage repair, leading to an increase in double-strand DNA breaks, thereby promoting genomic instability. Notably, the upregulation of DDX18 enhances sensitivity to DNA-damaging. This study elucidated DDX18 beyond participating in fundamental physiological functions, may play a crucial role in the regulation of genomic stability, and also provides a powerful resource for further functional exploration of DDX18 in cancer progression and therapeutic application.

Dynamic FeOx/FeWOx nanocomposite memristor for neuromorphic and reservoir computing.

Memristors are crucial in computing due to their potential for miniaturization, energy efficiency, and rapid switching, making them particularly suited for advanced applications such as neuromorphic computing and in-memory operations. However, these tasks often require different operational modes-volatile or nonvolatile. This study introduces a forming-free Ag/FeOx/FeWOx/Pt nanocomposite memristor capable of both operational modes, achieved through compliance current (CC) adjustment and structural engineering. Volatile switching occurs at low CC levels (<500 μA), transitioning to nonvolatile at higher levels (mA). Operating at extremely low voltages (<0.2 V), this memristor exhibits excellent uniformity, data retention, and multilevel switching, making it highly suitable for high-density data storage. The memristor successfully mimics fundamental biological synapse functions, exhibiting potentiation, depression, and spike-rate dependent plasticity (SRDP). It effectively emulates transitions from short-term memory (STM) to long-term memory (LTM) by varying pulse characteristics. Leveraging its volatile switching and STM features, the memristor proves ideal for reservoir computing (RC), where it can emulate dynamic reservoirs for sequence data classification. A physical RC system, implemented using digits 0 to 9, achieved a recognition rate of 93.4% in off-chip training with a deep neural network (DNN), confirming the memristor's effectiveness. Overall, the dual-mode switching capability of the Ag/FeOx/FeWOx/Pt memristor enhances its potential for AI applications, particularly in temporal and sequential data processing.

Working-memory load decoding model inspired by brain cognition based on cross-frequency coupling.

Working memory, a fundamental cognitive function of the brain, necessitates the evaluation of cognitive load intensity due to limited cognitive resources. Optimizing cognitive load can enhance task performance efficiency by preventing resource waste and overload. Therefore, identifying working memory load is an essential area of research. Deep learning models have demonstrated remarkable potential in identifying the intensity of working memory load. However, existing neural networks based on electroencephalogram (EEG) decoding primarily focus on temporal and spatial characteristics while neglecting frequency characteristics. Drawing inspiration from the role of cross-frequency coupling in the hippocampal region, which plays a crucial role in advanced cognitive processes such as working memory, this study proposes a Multi-Band Multi-Scale Hybrid Sinc Convolutional Neural Network (MBSincNex). This model integrates multi-frequency and multi-scale Sinc convolution to facilitate time-frequency conversion and extract time-frequency information from multiple rhythms and regions of the EEG data with the aim of effectively model the cross-frequency coupling across different cognitive domains. Due to its unique structural design, the proposed model proficiently extracts features in temporal, frequency, and spatial domains while its feature extraction capability is validated through post-hoc interpretability techniques. On our collected three-class working memory dataset, the proposed model achieved higher classification accuracy compared to other state-of-the-art methods. Furthermore, by analyzing the model's classification performance during different stages of working memory processes, this study emphasizes the significance of the encoding phase and confirms that behavioral response does not accurately reflect cognitive load.

High grazing pressure accelerates changes in community assembly over time in a long-term grazing experiment in the desert steppe of northern China.

Although numerous studies have shown that grazing gives rise to community succession from the communities or even species perspective, there is a lack of discussion about how grazing drives community assembly based on plant functional traits in a long-term experiment. We find different grazing intensities lead to temporal effects on trait-mediated multidimensional community assembly processes, including community-weighted trait mean (CWM), trait filtering, and trait distribution (divergence/convergence). CWM, trait filtering, and trait distribution of different traits transformed over the 16-year grazing experiment. Major findings include the following: (1) CWM changed rapidly under higher grazing intensity, and the removal of unsuitable traits from communities over time was accelerated with higher grazing intensity, such as higher specific leaf area (SLA), rich epidermal appendages (PAP), deep root system (RD), and growth form (shrub and subshrub) and dispersal mode (DM, e.g., insect spread) with higher scores. (2) Patterns of trait filtering strongly depended on grazing intensity and trait types, most traits, such as SLA, DM, PAP, RD, and onset of flowering (OFL), were filtered at high grazing intensity area, and effects of trait filtering in the community assembly process strengthened with grazing time. (3) Traits related to the cycling of biological matter, such as leaf area (LA), SLA, reproductive height (RH), photosynthetic (PHO), and GF more frequently diverged after long-term grazing, especially in higher grazing areas. Community assembly in intensely grazed ecosystems takes over a decade to support fundamental functions, highlighting the need for grazing intensity thresholds for sustainable grassland use.

Enhancing User Experience in Insurance Applications: Adopting Microservices Architecture and Innovative Methods

In this study, the transition to microservices architecture is addressed with the aim of improving user experience and increasing operational efficiency in the insurance sector. Within the scope of the project, fundamental functions such as online sales, video calls, and biometric verification were restructured as independent microservices. This transformation enabled systems to become more scalable, flexible, and manageable. The goal was to enhance user security and interaction through innovative features. The online sales module allowed transactions to be completed quickly. The successful completion of the project was recognized with prestigious awards and acknowledged as a significant example of digital transformation and user-focused solutions in the insurance sector. As a result, the study demonstrated how microservices increase modularity, ease of maintenance, and development speed, highlighting the potential for creating more user-friendly and efficient insurance platforms.

DEGRADED FAMILY AS A CAUSE OF JUVENILE DELINQUENCY

Degraded family refers to a family structure that has experienced significant breakdowns in its fundamental roles and functions. This degradation is often manifested in various forms, such as domestic violence, neglect, substance abuse, or severe financial instability. Such family environments lack emotional support, supervision, and social norms typically provided by a stable family. As a result, children growing up in such families may develop behavioral issues, lack proper role models, and have limited access to education or positive social interactions. The author first addresses the etiology of juvenile delinquency, emphasizing that the deficient and degraded family is a fundamental and decisive cause of delinquency among young people. In addition to highlighting the accepted definitions and understanding of deficient and degraded families, the paper emphasizes the degradation of the family in a broader sense, indicating that the degradation of the family as a core social institution is a contributing factor to juvenile delinquency. The causal relationship between juvenile delinquency and family dynamics is illustrated by some statistical data from Serbia and the USA. In the conclusion, the author emphasizes the degradation of the family as a natural institution, which serves as a fertile ground for a degraded family in the criminological context. Finally, the author sees a return to traditional, conservative values as a possible path to the 'healing' of the modern family.

New Axes of Interaction in Circ_0079593/miR-516b-5p Network in Melanoma Metastasis Cell Lines.

microRNAs (miRNAs) and circular RNA (circRNAs) show a close interconnection in the control of fundamental functions, such as cell proliferation and tumor development. A full understanding of this complex and interconnected network is essential for better understanding the mechanisms underlying cancer progression. Hsa_circ_0079593 is a circRNA highly expressed in melanoma and is associated with increased metastasis and progression of malignancy, whereas miR516b-5p is a microRNA whose expression is lower in several tumor types, including melanoma; its overexpression inhibits cell proliferation, migration, and invasion. In this study, we tested whether circ_0079593 is involved in the progression of melanoma aggressiveness by regulating CHAF1B and MCAM via the inhibition of miR-516b-5p. We first verified the expression of the key components in both healthy melanocyte lines and melanoma metastases, subsequently using in vitro assays such as scratch tests, Western blot, qRT-PCR, and dual luciferase report assay; we verified their interconnected regulatory effect. Our results showed that circ_0079593-miR516b-5p interactions are involved in the increase in the migration of metastasis melanoma cells by exploiting their binding to MCAM and CHAF1B mRNAs. This study provides two other regulatory networks in which circ_0079593 may exert its oncogenic function by increasing the speed of movement of metastatic cells through the sponge of miR-516b-5p, which cannot regulate MCAM and CHAF1B expression.

Measuring Livelihood Resilience in Multi-Hazard Regions: A Case Study of the Khuzestan Province in the Persian Gulf Coast

Assessing community-level resilience and implementing strategies to enhance it are essential for maintaining fundamental community functions, coping with and mitigating risks, effectively reducing hazards, and promoting sustainable regional development. Accordingly, this study aimed to measure hazard exposure and livelihood resilience in the counties of Khuzestan Province. Hazard exposure to earthquakes, flooding, and drought was evaluated using decision-making techniques within a geographic information system (GIS). Additionally, a multi-criteria decision-making approach incorporating eight indicators was employed to calculate the integrated livelihood resilience indicator for the counties. The results indicated that the northern and northeastern counties exhibit the highest potential for flooding and earthquake hazards, whereas the southern and southwestern counties are most vulnerable to flooding and drought. Moreover, Dezful, Shadegan, and Ahvaz counties demonstrated the highest levels of livelihood resilience, while Lali, Haftkel, and Andika counties exhibited the lowest levels. Assessing hazard exposure and livelihood resilience represents critical steps in risk reduction management programs and initiatives. Evaluating community-level livelihood resilience in multi-hazard areas is a vital component in advancing the global objectives of the Sendai Framework for Disaster Risk Reduction and the Sustainable Development Goals.

THE WILLMORE ENERGY VARIATIONS AND ENERGY EFFICIENT ARCHITECTURE

Since the shape is an important feature of objects and can be immensely useful in characterizing objects, it should point out the shape analysis considering the variation of magnitudes that characterize the shape itself. One of the fundamental functionals that measure the bending of a surface is the Willmore energy. In view of the meaning of ruled surfaces in aesthetics, statics, scale and manufacturing technologies, we point out the possibility of a mathematical analysis in the case of infinitesimal deformations by considering the variations of the Willmore energy on Gaudi surface under infinitesimal bending in R3. Application could be connected with energy efficient building design.

Working memory updating in the macaque lateral prefrontal cortex.

Working memory updating is an important executive process. Here, we study the single-neuron mechanisms involved in updating versus protecting memory from distractors in the macaque prefrontal cortex. We recorded single-neuron activity from the lateral prefrontal cortex (LPFC) and prearcuate cortex (PAC) while male monkeys performed a task that required them to update their memory of target locations while ignoring distractors. Our findings revealed that neurons in the PAC signaled updated memory locations approximately ∼100 ms after stimulus onset, significantly faster than the ∼400 ms observed in the LPFC. Additionally, PAC neurons exhibited longer encoding of distractor information. Population decoding analyses further indicated that distractor information was maintained in orthogonal subspaces from target information in both regions, minimizing interference. These results demonstrate the distinct temporal dynamics in memory updating processes between the PAC and LPFC and highlight the interplay between robust memory maintenance and updating, suggesting that local neural mechanisms may contribute to these processes.Significance Statement Working memory is a fundamental cognitive function. It stored information in the short term, and this information can be manipulated to allow intelligent behaviors. The lateral prefrontal cortex is involved in this process, but the mechanisms of working memory manipulation remain unclear. Here, we studied one type of manipulation; working memory updating, which refers to the exchange of one memory for another. We found that two adjacent regions in the lateral prefrontal cortex show different updating times: while a posterior region updates memory content very fast, the more anterior region takes significantly longer. These results show that working memory updating may involve multiple operations, such as updating of memory or attention versus updating of motor plans.

Conformational response of αIIbβ3 and αVβ3 integrins to force.

As major adhesion receptors, integrins transmit biochemical and mechanical signals across the plasma membrane. These functions are regulated by transitions between bent and extended conformations and modulated by force. To understand how force on integrins mediates cellular mechanosensing, we compared two highly homologous integrins, αIIbβ3 and αVβ3. These integrins, expressed in circulating platelets vs. solid tissues, respectively, share the β3 subunit, bind similar ligands and have similar bent and extended conformations. Here, we report that in cells expressing equivalent levels of each integrin, αIIbβ3 mediates spreading on softer substrates than αVβ3. These effects correlate with differences in structural dynamics of the two integrins under force. All-atom simulations show that αIIbβ3 is more flexible than αVβ3 due to correlated residue motions within the α subunit domains. Single molecule measurements confirm that αIIbβ3 extends faster than αVβ3. These results reveal a fundamental relationship betweenprotein function and structural dynamics in cell mechanosensing.

The Role of the Serotonergic System in Time Perception: A Systematic Review.

Time perception is a fundamental cognitive function essential for adaptive behavior and shared across species. The neural mechanisms underlying time perception, particularly its neuromodulation, remain debated. In this review, we examined the role of the serotonergic system in time perception (at the scale of seconds and minutes), building a translational bridge between human and non-human animal studies. The literature search was conducted according to the PRISMA statement in PubMed, APA PsycINFO, and APA PsycARTICLES. Sixty papers were selected for full-text review, encompassing both human (n = 10) and animal studies (n = 50). Summarizing the reviewed literature, we revealed consistent evidence for the role of serotonin in timing behavior, highlighting its complex involvement across retrospective, immediate, and prospective timing paradigms. Increased serotonergic activation appears to accelerate internal time speed, which we interpret through the dual klepsydra model as accelerated discharge of the temporal accumulator. However, some findings challenge this framework. Additionally, we link impulsivity-associated with decreased serotonergic functioning in our review-to a slower internal time speed. Variability in prospective timing tasks underscores the need for further research into how serotonin modulates reward-based temporal decisions, using novel approaches to disentangle internal time speed, response inhibition, and other factors.

Formation Of the Commissioner Judge Institution as A Court Supervision Policy (Judicial Scrutiny) Indonesian Criminal Justice System

The idea of the concept of commissioner judges as Preliminary Examination Judge Institutions is the influence of the development of the times, as well as the ratification of the International Covenant on Civil and Political Rights by Indonesia, so that protection of the rights of suspects/defendants becomes the country's main priority in efforts to enforce the law through law enforcement officers. The fundamental function of Criminal Procedure Law is to seek material truth, so it is felt that the Preliminary Examination Judge as a new institution that emerged in the Criminal Procedure Code Bill is a new breakthrough to maintain the Due Process of Law so that it can continue to run according to expectations. It is also hoped that in the future there will be no innocent people who are sentenced without ignoring the interests of the victim. This scientific writing uses the Sociological Legal Research method (socio legal research).