Fundamental Functions Research Articles

Site suitability analysis of urban green parks in Ranchi city using GIS–AHP based multi-criteria decision analysis

Purpose The presence of green spaces plays a vital role in promoting urban sustainability. Urban green parks (UGPs) help create sustainable cities while providing fundamental ecological functions. However, rapid urbanization has destroyed crucial green areas in Ranchi City, endangering inhabitants’ health. This study aims to locate current UGPs and predict future UGP sites in Ranchi City, Jharkhand. Design/methodology/approach It uses geographic information system (GIS) and analytical hierarchical process (AHP) to evaluate potential UGP sites. It involves the active participation of urban communities to ensure that the UGPs are designed to meet dweller’s needs. The site suitability assessment is based on several parameters, including the normalized difference vegetation index (NDVI), land use and land cover (LULC), population distribution, PM 2.5 levels and the Urban Heat Island (UHI) effect. The integration of these factors enables an evaluation of potential UGP’s sites. Findings The findings of this research reveal that 54.39% of the evaluated areas are unsuitable, 15.55% are less suitable, 12.76% are moderately suitable, 11.52% are highly suitable and 5.78% are very highly suitable for UGPs site selection. These results emphasize that the middle and outer regions of Ranchi City are the most favorable locations for establishing UGPs. The NDVI is the most important element in UGP site appropriateness, followed by LULC, population distribution, PM 2.5 levels and the UHI effect. Originality/value This study improves the process of integrating AHP and GIS, and UGPs site selection maps help urban planners and decision-makers make better choices for Ranchi City’s sustainability and greenness.

323 Advances in using membrane vesicles for studying intestinal functions

Abstract Enterocytes are the major cell lineage of the small intestinal epithelia along the crypt-villus axis in gut mucosa. Enterocytes participate in the gut terminal nutrient digestion and absorption; and have essential roles in nutrient and metabolite recycling and efflux, nutrient and hormonal sensing, interactions with symbiotic microbiome and binding to infectious viruses, thus influencing the host homeostasis and whole-body physiological status. Intestinal membrane vesicles have been widely used for studying various gut functions in the past several decades. Villus enterocytic brush border membrane and the apical membrane vesicles along the crypt-villus axis in gut mucosa can be prepared and isolated by Mg2+- and Ca2+-precipitation and differential centrifugation procedures. Whereas, gut mucosal basolateral membrane vesicles can be prepared, fractionated and differentiated from other intracellular organelles such as the mitochondrial inner membrane by the Percoll gradient ultracentrifugation. Nutrient transport and exchange activities in the membrane vesicles in vitro are conducted often by rapid hand filtration, and in excess, in an automated fast sampling apparatus. Nutrient transport and exchange activity kinetics are derived according to the well-established classic Michaelis-Menten and the tracer inhibitory kinetic models with a simple linear diffusional component. Physiological and biochemical properties associated with various nutrient uptake systems such as pH optimum, requirements for co-transported ions (e.g., Na+, K+, Cl-), transporter affinity and substrate specificity can be effectively investigated in vitro with the membrane vesicles by altering the compositions of uptake buffers and intra-vesicular pre-loading buffers. Some of the fundamental gut functions are established via using the membrane vesicles in different mammalian species. And these include H+-peptide cotransport, Na+-cotransport and Na+-independent systems of hexose uptake across the apical membrane and the low-affinity Na+-independent hexose bidirectional uptake across the basolateral membrane that were characterized in rodents; Na+-dependent cotransport and Na+-independent systems of amino acid (AA) transport across the apical membrane that were revealed in rodents and pigs; as well as the Na+-hexose and AA cotransport and the co-expression of the coronavirus SARS-CoV-2 host epithelial apical membrane binding receptor, i.e., the angiotensin-converting enzyme-2 (ACE2), along the gut crypt-villus axis that were identified in liquid formula-fed piglets. In the post genomic and metagenomic sequencing era, further research efforts need to pursue understanding of expression and various functionality of the gut terminal hydrolases, nutrient transporters, nutrient exchangers, nutrient sensors, substrate and particle receptors, taste receptors, viral binding receptors such as ACE2 and hormonal receptors and their interactions with luminal factors such as nutrient, metabolites, symbiotic bacterial outer membrane vesicles etc., along the longitudinal and crypt-villus axes, through using the mammalian primary enterocytic apical and the basolateral membrane vesicles under various research settings.

Development in Parliamentary Oversight of Government Work in Light of the 2020 Constitutional Amendment (Algeria)

In most comparative law systems, the role of parliament is not limited to issuing various types of legislation and improving the legislative framework. It goes beyond its fundamental function of legislating to include another important role: oversight, specifically the restraining role over the actions of government members in certain cases defined by the Constitution. Parliament exercises this oversight role alongside its legislative function. It is also important in maintaining public interest and evaluating the government’s work by questioning its members on the progress and execution of agreed-upon projects. Referring to the Algerian system, we find that the Algerian Parliament, which consists of two chambers—the National People’s Assembly (APN) and the Council of the Nation—exercises oversight over the government’s actions. The first chamber, the APN, primarily does this. Consequently, this type of oversight may sometimes lead to political accountability, which can result in either the resignation of the Prime Minister or the dissolution of the first chamber of parliament. These mechanisms include the motion of censure and the interpellation process.

Similar patterns of brain activity for holistic representation of working memory: a study in children and adults.

Working memory is the fundamental function of the various cognitive processes and abilities in the overall trajectory of development. Significant advances in multivariate analysis of human functional magnetic resonance imaging data have converged functional segregation models toward integrated representation-based models. However, due to the inherent limitations of the multi-voxel pattern analysis method, we are unable to determine whether the underlying neural representations are spatially similar in the brain. Our study attempts to answer this question by examining the spatial similarity of brain activity during the working memory task in children and adults. Our results reveal similar patterns of activity between the regions involved in working memory. This functional network of similar spatial patterns was observed in both normally developing children and adults. However, the between-region similarity was more pronounced in adults than in children and associated with better performance. We propose an exchange of similar information flows through the brain at an integrated level of working memory processes, underpinning the holistic nature of working memory representation.

Taylor theory in quantum calculus: a general approach

Let the function β be strictly increasing and continuous on an interval I ⊂ ℝ. The β-difference operator is defined by Dβ f (t) = (f(β(t)) − f(t)/(β(t) – t), where t ≠ β(t), and Dβ f (t) = f′ t(t) when t = s 0 is a fixed point of the function β. This quantum operator is a generalization of q-Jackson, Hahn, power and other quantum operators. As a convenience of the β-function: β(t) turns into the probability distribution function with the probability measure 1, and the sample space ℝ, in the case of its conditions are relaxed to be increasing and continuous from the right, that is, lim t →∞ β(t) = 1 and lim t →∞ β(t) = 0, and also by using the Lebesgue-Stieltjes measure of the interval [a, b] to be β(b) − β(a). In this paper, we investigate a β-Taylor’s formula associated with the operator Dβ when the function β has a unique fixed point s 0 ∈ I, which may allow for more flexible and accurate approximations of functions. An estimation of its remainder is given. Additionally, the β-power series is defined. Furthermore, as application, the β-expansion form of some fundamental functions is introduced. Finally, we find the unique solution of the β-shifting problem.

High-level L-Gln compromises intestinal amino acid utilization efficiency and inhibits protein synthesis by GCN2/eIF2α/ATF4 signaling pathway in piglets fed low-crude protein diets

Gln, one of the most abundant amino acids (AA) in the body, performs a diverse range of fundamental physiological functions. However, information about the role of dietary Gln on AA levels, transporters, protein synthesis, and underlying mechanisms in vivo is scarce. The present study aimed to explore the effects of low-crude protein diet inclusion with differential doses of L-Gln on intestinal AA levels, transporters, protein synthesis, and potential mechanisms in weaned piglets. A total of 128 healthy weaned piglets (Landrace × Yorkshire) were randomly allocated into four treatments with four replicates. Pigs in the four groups were fed a low-crude protein diet containing 0%, 1%, 2%, or 3% L-Gln for 28 d. L-Gln administration markedly (linear, P < 0.05) increased Ala, Arg, Asn, Asp, Glu, Gln, His, Ile, Lys, Met, Orn, Phe, Ser, Thr, Tyr, and Val levels and promoted trypsin activity in the jejunal content of piglets. Moreover, L-Gln treatment significantly enhanced concentrations of colonic Gln and Trp, and serum Thr (linear, P < 0.01), and quadratically increased serum Lys and Phe levels (P < 0.05), and decreased plasma Glu, Ile, and Leu levels (linear, P < 0.05). Further investigation revealed that L-Gln administration significantly upregulated Atp1a1, Slc1a5, Slc3a2, Slc6a14, Slc7a5, Slc7a7, and Slc38a1 relative expressions in the jejunum (linear, P < 0.05). Additionally, dietary supplementation with L-Gln enhanced protein abundance of general control nonderepressible 2 (GCN2, P = 0.010), phosphorylated eukaryotic initiation factor 2 subunit alpha (eIF2α, P < 0.001), and activating transcription factor 4 (ATF4) in the jejunum of piglets (P = 0.008). These results demonstrated for the first time that a low crude protein diet with high-level L-Gln inclusion exhibited side effects on piglets. Specifically, 2% and 3% L-Gln administration exceeded the intestinal utilization capacity and compromised the jejunal AA utilization efficiency, which is independent of digestive enzyme activities. A high level of L-Gln supplementation would inhibit protein synthesis by GCN2/eIF2α/ATF4 signaling in piglets fed low-protein diets, which, in turn, upregulates certain AA transporters to maintain AA homeostasis.

Cerebral Synchronization Between Mothers and Their Newborns During Breastfeeding.

Introduction: Breastfeeding is a fundamental biological function in mammals, allowing the progeny to develop in a physiological way. A physical and emotional dialog between mothers and offspring during breastfeeding has been described as part of the attachment relationship, and a synchronicity between maternal and neonatal brains can be hypothesized. This study aimed to assess if neonatal and maternal cortical areas activated during breastfeeding are functionally synchronized since the second day of life. Materials and Methods: Twenty mothers and their term newborns were enrolled. Cortical activation during breastfeeding was identified by multichannel near-infrared spectroscopy, which detects changes in haemoglobin concentration from multiple cortical regions. Functional activity was simultaneously detected (hyperscanning) in mothers and newborns' frontal and motor/primary somatosensory cortical areas during the first 5 minutes of breastfeeding. Cluster analysis and Student's t test were used to detect oxygenated haemoglobin increase, as cortical activation estimate. Wavelet transform coherence (WTC) analysis was used to identify a possible synchronization between maternal and neonatal activated cortical regions. Results: Mothers showed an activation of the central motor/primary somatosensory cortex, above the sagittal fissure. In newborns, the bilateral frontal cortex was activated. WTC analysis revealed two different cyclical synchronizations between mothers and infants' activated cortical regions. Conclusions: Such evidence may reflect a very early common sharing of experiences, possibly associated with reciprocal dynamic motor adjustments, hormonal coregulation, and somatic stimulations and sensations. The observed cyclical neural synchronization, between the mother and her newborn's cortex during breastfeeding, may play an important role in promoting their bonding.

Нейровизуализационный подход для выявления биомаркеров рабочей памяти у больных с хронической ишемией мозга

Verbal working memory (VWM) is a fundamental function responsible for temporary storage and short-term handling of verbal information. The study was aimed to determine the working memory biomarker associated with imaging of the source of infra-slow electrical activity in patients with chronic cerebral ischemia (CCI). A total of 50 patients with CCI took part in the study: 16 males and 34 females aged 50–85 years. VWM was evaluated by the Luria test. The subjects were divided into two groups matched by age with the VWM below and above the average level for the studied sample. The infra-slow, below 0.1 Hz, electrical activity, otherwise known as the DC potentials (DCPs) of the brain, was recorded with five monopolar leads: frontal, central, occipital, right and left temporal. The resting state fMRI was used to analyze brain regions with the activated BOLD (blood-oxygen-level-dependent) signal that were associated with the brain regions responsible for VWM and the DCP generation sources recorded with the non-polarizable electrodes. The differences in BOLD signal activation and infra-slow activity amplitude were found in two VWM groups. These resting-state neural networks, VWM and the neural network responsible for DCP generation, overlapped in frontal regions. There were significant differences in DCP recorded with the frontal lead in two VWM groups (р = 0.00004). In patients with CCI, infra-slow activity, recorded with the frontal lead that is generated by the neural network fragment representing an intersection of the VWM network and the part of the brain responsible for DCP generation in the frontal region, is a VWM biomarker.

Dramatic Function of Soundtrack Film Message Model

The soundtrack was characterized by a dramatic function that played an essential role in building the cinematic and dramatic landscape and centered on how to support and support the event and film scene with multiple and varied functions in the (message film) film and emphasize the foundations on which the soundtrack served as a fundamental dramatic function in the artistic content and film event. Chapter I included the methodological framework in which the research problem of research arose after the researcher conducted a field survey of some films in which the soundtrack had a dramatic function that played a key role in the construction of the film scene. In this sense, the researcher seeks to raise the question of what is the dramatic function of the soundtrack in the film message? Hence the importance of research from which we mention1:- Highlight the elements of the soundtrack and its relationship to the film's scene event Then the goal of the research centered on the dramatic function of the soundtrack in the film and the research is determined by the music of the film. E-The first chapter of the chapter came with researchers who specialized the first elements and components of the soundtrack I only the second was entitled the dramatic effect of the soundtrack musician Then the theoretical framework was marked and then chapter III was followed by research procedures and analysis of the soundtrack models of the music of the message film.

Inhibitory Control Training Improves Cold but Not Warm Cognition in Typically Developing Preschoolers.

Inhibitory control, as a fundamental executive function, has been found to be associated with a range of cognitive processes. In this study, our objective was to enhance inhibitory control through a targeted training program and assess its impact on attention, executive function, delay discounting and risky decision making. Thirty-two typically-developing children (age mean 6.89 ± 0.32years) were recruited in a random clinical trial design in two equal intervention and active control groups. Go/No-Go, Flanker, continuous performance, delay discounting, and balloon analogue risk tasks were used for assessment in three baseline, post- intervention, and 3-months follow-up sessions. The intervention group received the program for attentive rehabilitation of inhibition and selective attention (PARISA) and the active control group participated in a story telling class, both in 12 sessions. The results of the study indicate significant improvements in sustained attention, interference control, and prepotent inhibition among participants in the intervention group. However, there were no significant changes observed in delay discounting and risky decision making. These findings suggest that the inhibitory control training primarily enhances aspects of cold cognition and attentional processes. However, the observed improvements did not extend to reward processing or warm cognition.

Optimizing Fractional Differential Equation Solutions with Novel Müntz Space Basis Functions

This paper introduces innovative basis functions derived from Müntz spaces, aimed at addressing the computational challenges of Fractional Differential Equations (FDEs). Our primary focus is the creation of these functions using singular indices linked to the solutions of FDEs. We thoroughly investigate the properties of these fundamental functions to understand their operational potential. These functions are particularly adept at capturing initial singular indices, making them highly suitable for solving FDEs. The proposed numerical method is distinguished by its rapid convergence rates, showcasing its efficiency in computational evaluations. We validate our approach by presenting numerical examples that highlight its accuracy and reliability. These examples confirm the effectiveness and efficiency of the new basis functions from Müntz spaces in accurately solving FDEs. This research advances numerical methods for FDEs and serves as a valuable resource for researchers seeking robust and reliable techniques

Cotton Pectate Lyase GhPEL48_Dt Promotes Fiber Initiation Mediated by Histone Acetylation.

GhPEL48_Dt, a Pectate lyase (PEL, EC4.2.2.2), is a crucial enzyme involved in cell-wall modification and pectin degradation. Studies have shown that the GhPEL48_Dt also plays a significant role in cotton-fiber development; however, the specific function and regulatory mechanism of GhPEL48_Dt in cotton-fiber development are still not fully understood. Here, we found that the histone deacetylase inhibitor-Trichostatin A significantly reduces the transcript levels of GhPEL48_Dt and its enzyme activity. Further, silencing of GhPEL48_Dt significantly inhibits the initiation and elongation of cotton fibers by promoting pectin degradation, and the heterologous expression of GhPEL48_Dt promotes the development of trichomes and root hairs in Arabidopsis, which suggests that GhPEL48_Dt plays a positive and conserved role in single cell i.e., fiber, root hair, and leaf trichome development. Collectively, this paper provides a comprehensive analysis of the fundamental characteristics and functions of GhPEL48_Dt in fiber development, including the regulatory role of histone acetylation on GhPEL48_Dt, which contributes to the understanding of pectin degradation pathways and establishes a theoretical foundation for elucidating its regulatory mechanism.

Generalization of ZZ Transform and Its Applications

ZZ integral transformation was presented via Zain UI A. Zafar in year (2016), [1,6], In this research paper, a generalized form of ZZ integral transform has been proposed, the general transform is introduced as a new integral transform called the " general ZZ integral Transform". The general ZZ Transform has been studied and proven for some fundamental functions It's applicability and ability to evaluate the exact solution have been proven via utilizing the transformation in solving n^th order ordinary differential equations.

Arc and BDNF mediated effects of hippocampal astrocytic glutamate uptake blockade on spatial memory stages

Glutamate is involved in fundamental functions, including neuronal plasticity and memory. Astrocytes are integral elements involved in synaptic function, and the GLT–1 transporter possesses a critical role in glutamate uptake. Here, we study the role of GLT-1, specifically located in astrocytes, in the consolidation, expression, reconsolidation and persistence of spatial object recognition memory in rats. Administration of dihydrokainic acid (DHK), a selective GLT-1 inhibitor, into the dorsal hippocampus around a weak training which only induces short-term memory, promotes long-term memory formation. This promotion is prevented by hippocampal administration of protein-synthesis translation inhibitor, blockade of Activity-regulated cytoskeleton-associated protein (Arc) translation or Brain-Derived Neurotrophic Factor (BDNF) action, which are plasticity related proteins necessary for memory consolidation. However, DHK around a strong training, which induces long-term memory, does not affect memory consolidation. Administration of DHK before the test session impairs the expression of long-term memory, and this effect is dependent of Arc translation. Furthermore, DHK impairs reconsolidation if applied before a reactivation session, and this effect is independent of Arc translation. These findings reveal specific consequences on spatial memory stages developed under hippocampal GLT-1 blockade, shedding light on the intricate molecular mechanisms, governed in part for the action of glia.

Unveiling the electrodynamics of the first nonlinearly charged rotating black hole

After many years of efforts, the first nonlinearly charged rotating black hole has been finally reported by García-Diaz in two recent works. This is an important result that was pending in General Relativity since nonlinear generalizations of the Kerr–Newman solution were not yet known. Unfortunately, the Lagrangian supporting this configuration cannot be expressible in terms of the standard invariants using elementary functions. In the present work we circumvent this problem by using the formulations of nonlinear electrodynamics in terms of mixed electromagnetic eigenvalues, introduced by Salazar, García-Diaz, and Plebański almost four decades ago. In doing so, we prove that the underlying theory becomes fully determined, and hence the new nonlinearly charged stationary axisymmetric spacetimes found correspond to exact solutions of a well-defined self-gravitating nonlinear electrodynamics whose fundamental structural functions are provided here.

A Flexible Memristor Based on CsPbCl3 Nanocrystals for an Artificial Nociceptor.

Halide perovskites (HPs) based memristors show great potential in the simulation of biological neurons. Herein, a memristor with Ag/PMMA&CsPbCl3/ITO structure is developed by incorporating CsPbCl3 nanocrystals (NCs) into poly(methyl methacrylate) (PMMA) as the functional layer. The device exhibits typical bipolar resistive behavior, low operating voltage, good endurance of more than 400 cycles, consistent and excellent ON/OFF ratio (≈ 103), and high mechanical bending stability (bending times = 1000). The RS mechanism has been well explained by the electric field induced formation and rupture of Ag filaments in the PMMA&CsPbCl3 layer. More importantly, the memristor successfully displays fundamental nociceptive functions including threshold, nonadaptation, relaxation, and sensitization (allodynia and hyperalgesia). To demonstrate the feasibility of the artificial nociceptor, a pressure nociceptor system is constructed using the Ag/PMMA&CsPbCl3/ITO device. These results provide new perspectives for the development of next-generation, high-performance HPs based neural morphology devices.

Fluorinated macromolecular amphiphiles as prototypic molecular drones.

The advent of drones has revolutionized various aspects of our lives, and in the realm of biological systems, molecular drones hold immense promise as "magic bullets" for major diseases. Herein, we introduce a unique class of fluorinated macromolecular amphiphiles, designed in the shape of jellyfish, serving as exemplary molecular drones for fluorine-19 MRI (19F MRI) and fluorescence imaging (FLI)-guided drug delivery, status reporting, and targeted cancer therapy. Functioning akin to their mechanical counterparts, these biocompatible molecular drones autonomously assemble with hydrophobic drugs to form uniform nanoparticles, facilitating efficient drug delivery into cells. The status of drug delivery can be tracked through aggregation-induced emission (AIE) of FLI and 19F MRI. Furthermore, when loaded with a heptamethine cyanine fluorescent dye IR-780, these molecular drones enable near-infrared (NIR) FL detection of tumors and precise delivery of the photosensitizer. Similarly, when loaded with doxorubicin (DOX), they enable targeted chemotherapy with fluorescence resonance energy transfer (FRET) FL for real-time status updates, resulting in enhanced therapeutic efficacy. Compared to conventional drug delivery systems, molecular drones stand out for their simplicity, precise structure, versatility, and ability to provide instantaneous status updates. This study presents prototype molecular drones capable of executing fundamental drone functions, laying the groundwork for the development of more sophisticated molecular machines with significant biomedical implications.

Chinese formula Guben-Jiannao Ye alleviates the dysfunction of circadian and sleep rhythms in APP/PS1 mice implicated in activation of the PI3K/AKT/mTOR signaling pathway

Ethnopharmacological relevanceThe Chinese formula Guben-Jiannao Ye (GBJNY) formula has a long history of usage in traditional Chinese medicine (TCM) for the treatment of learning and memory disorders as well as senile insomnia. This formulation is derived from Sun Simiao's five tonic pills. Furthermore, modern pharmacological investigations have revealed its ability to improve cognitive impairment and ameliorate sleep-wake circadian rhythm disorders. However, the precise mechanism underlying its efficacy remains elusive. Aim of the studyThe current research explored the modulatory effects and possible mechanisms of GBJNY in circadian rhythm sleep-wake disorders and cognitive dysfunction in Alzheimer's disease using transcriptome sequencing and experimental validation. Materials and methodsThe LC-MS/MS tandem technology was utilized to qualitatively discern the active components present in GBJNY. The APP/PS1 mice received continuous treatment with GBJNY or Melatonin for 3 months. The learning and memory abilities of mice were assessed utilizing the Morris water maze (MWM) test, while sleep changes were studied utilizing the electroencephalogram (EEG) and electromyogram (EMG). Concurrently, mice's hippocampus clock gene rhythmicity was investigated. Subsequently, we employed HE staining, Golgi staining, and immunofluorescence to observe GBJNY's impact on synaptic damage and neuronal loss. We performed high-throughput sequencing to analyze the mRNA expression profiles of mice, aiming to identify differentially expressed genes (DEGs). Subsequently, we conducted GO and KEGG enrichment analyses to explore associated signaling pathways. Furthermore, we evaluated the expression levels of proteins involved in the PI3K/AKT/mTOR pathway and Aβ deposition in the hippocampus of mice. Through this comprehensive approach, we sought to elucidate and validate the potential mechanisms of action of GBJNY in APP/PS1 mice. ResultsResults showed 216 DEGs. Following this, we conducted GO enrichment and KEGG pathway analyses to delve deeper into the distinctions and fundamental functions of the mRNA target genes. The enrichment analysis underscored the prominence of the PI3K/Akt/mTOR signaling pathway as the most pivotal among them. Through in vivo experiments, it was further demonstrated that the administration of GBJNY enhanced memory and learning capacities in APP/PS1 mice. Additionally, GBJNY treatment resulted in alterations in the sleep-wake circadian rhythm, characterized by reduced wakefulness and an increase in non-rapid eye movement (NREM) sleep. Moreover, alterations in the peak expression of Per1, Per2, Clock, Cry1, Cry2, and Bmal1 mRNA were noted in the hippocampus of treated mice. Particularly noteworthy were the observed reductions in amyloid-beta (Aβ) deposition within the hippocampus, improvements in neuronal synaptic integrity, and upregulation of mTOR, Akt, and PI3K protein expression in the hippocampal region. These findings underscore the critical involvement of the PI3K/Akt/mTOR signaling pathway in mitigating disturbances in sleep-wake circadian rhythms. ConclusionsGBJNY enhanced the cognitive performance of APP/PS1 mice and altered clock gene expression patterns, alleviating sleep-wake circadian rhythm disruptions. The fundamental mechanism appears to be linked to the PI3K/Akt/mTOR pathway regulation, offering a foundation for potential clinical applications.

Zinc Supplementation Reduces the Formation of Neutrophil Extracellular Traps by Decreasing the Expression of Peptidyl Arginine Deiminase 4.

Neutrophils play a decisive role during the immediate defense against infections. However, as observed during rheumatoid arthritis, activated neutrophils can also cause tissue damage. Previous studies indicate that zinc supplementation may alter certain neutrophil functions. However, precise underlying mechanisms and possible effects of zinc deficiency remain incompletely understood. The objective of this study is to investigate the effects of changes in zinc status on formation of neutrophil extracellular traps (NETs) and other fundamental neutrophil functions. Interleukin (IL)-17 and tumor necrosis factor (TNF)-α are used to simulate the inflammatory environment observed in autoimmune diseases. The study analyzes the impact of the zinc status on NETs release, using a fluorescence plate reader, and on the expression of peptidylarginine deiminase 4 (PAD4), S100A8/A9, and certain cytokines by PCR and western blot. These results show that zinc supplementation significantly reduces NETs formation and downregulates PAD4 protein expression. Zinc supplementation results in increased protein expression of interleukin-1 receptor antagonist (IL-1RA) and IL-8 in stimulated cells. The results suggest that changes in extracellular zinc availability may influence the functions of neutrophils. Therefore, maintaining an appropriate zinc level is advisable for preserving innate immunity and to prevent hyper-activation of neutrophils.

Legal Position of the Surrogate as a Substitute For a Signature In a Notarial Deed

A handwritten signature on an authentic deed serves a fundamental legal function as an identifier and acknowledgment to legalize all rights and obligations outlined in the deed. According to the regulation concerning the Notary Public Functional Position (Undang-Undang Jabatan Notaris), an authentic deed must contain the signatures of all parties involved (the notary public, witnesses, and the first and second parties) as mentioned in the deed. However, this regulation can create issues when one of the parties is unable to provide a signature on the authentic deed. This research analyzes how notarial deeds are signed for people who cannot sign. This research is normative legal research using a statutory approach and a conceptual approach. The results of this study show that there are three procedures for using a Surrogate in authentic deeds First procedure: If the individual cannot read or write but has no physical disabilities (they have all their fingers and can make a signature), a fingerprint will be used as the Surrogate. This should be noted and attached to the last page of the authentic deed; Second procedure: If the individual can read and write but has issues with their fingers (due to an injury or the absence of fingers), the Surrogate can be used, but it must be accompanied by an official medical letter from a doctor or hospital. This should also be noted and attached to the last page of the authentic deed. Third procedure: If the individual has visual impairments (is blind), the Surrogate can be used, but it must be accompanied by an official medical letter from a doctor or hospital. This should be noted and attached to the last page of the authentic deed.