Signal Routing Research Articles

The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke.

Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines. Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke.

Hearing Aid in Vestibular-Schwannoma-Related Hearing Loss: A Review.

(1) Background: Several types of hearing aids are available for the rehabilitation of vestibular-schwannoma (VS)-related hearing loss. There is a lack of recently published papers regarding this theme. The aim of the present work is to organize current knowledge. (2) Methods: A review of the literature regarding the topics "vestibular schwannoma", "hearing loss", and "hearing aid" was performed. Nineteen studies were thus considered. (3) Results: Conventional hearing aids, contralateral routing of signal (CROS) aids, bone anchored hearing aids (BAHA), and others are available options for hearing rehabilitation in VS patients. The speech discrimination score (SDS) is considered the best measure to assess candidacy for rehabilitation with hearing aids. The best hearing rehabilitative conditions in VS patients when using conventional hearing aid devices are a mild-moderate hearing loss degree with good word recognition (more than 50% SDS). CROS-Aid and BAHA are reported to be beneficial. CROS-Aid expands on the area of receiving hearing. BAHA aids use direct bone-conduction stimulation. Unfortunately, there are no available studies focused specifically on VS patients that compare CROS and BAHA technologies. (4) Conclusions: Hearing aids, CROS, and BAHA are viable options for rehabilitating hearing impairment in VS, but require an accurate case-by-case audiological evaluation for rehabilitating hearing impairment in VS. Further studies are needed to prove if what is currently known about similar hearing illnesses can be confirmed, particularly in the case of VS.

Healthy mitochondrial DNA in balanced mitochondrial dynamics: A potential marker for neuro‑aging prediction (Review).

The mitochondrial genome or mitochondrial DNA (mtDNA) is released as a response to cellular stress. In mitochondrial biogenesis, active communication between the mitochondria genome and nucleus is associated with the mtDNA profile that affects the mitochondrial quality. The present review aimed to assess the molecular mechanism and potential roles of mitochondria in neuro-aging, including the importance of evaluating the health status of mtDNA via mitochondrial dynamics. The normal condition of mitochondria, defined as mitochondrial dynamics, includes persistent changes in morphology due to fission and fusion events and autophagy-mitophagy in the mitochondrial quality control process. The calculated copy number of mtDNA in the mitochondria genome represents cellular health, which can be affected by a long-term imbalance between the production and accumulation of reactive oxygen species in the neuroendocrine system, which leads to an abnormal function of mitochondria and mtDNA damage. Mitochondria health is a new approach to discovering a potential indicator for the health status of the nervous system and several types of neurodegenerative disorders. Mitochondrial dynamics is a key contributor to predicting neuro-aging development, which affects the self-renewal and differentiation of neurons in cell metabolism. Neuro-aging is associated with uncontrolled mitochondrial dynamics, which generates age-associated diseases via various mechanisms and signaling routes that lead to the mtDNA damage that has been associated with neurodegeneration. Future studies on the strategic positioning of mtDNA health profile are needed to detect early neurodegenerative disorders.

On the solitonic wave structures and stability analysis of the stochastic nonlinear Schrödinger equation with the impact of multiplicative noise

The nonlinear Schrödinger equation (NLSE) is a fundamental and significant physical model that plays a crucial role in demonstrating the dynamics of optical solitons in the theory optical fibers. The propagation of solitons in nonlinear optical fibers has garnered substantial interest due to its broad spectrum of applications, particularly in ultrafast signal routing systems and short light pulses for communications. This article focuses on investigating the impact of multiplicative noise on the solutions of this governing model. To achieve this, three distinct methods, namely the enhanced modified extended tanh expansion (METE) method, the generalized Kudryashov (GK) approach and the extended modified auxiliary equation mapping (EMAEM) method are employed to obtain a new variety of stochastic solutions. The perception of how noise intensity impacts the transmission of waves is a fundamental and critical issue in various fields. In the context of this study, an equation describes an exact wave pattern under the condition that s (representing noise intensity) equals zero. In such cases, the observed pattern remains undisturbed and matches the expected theoretical wave pattern. However, as the strength of noise s increases, the observed pattern begins to deviate from the ideal wave pattern and exhibits signs of damage or distortion. Furthermore, the stability analysis for the stochastic NLSE is performed, providing valuable insights into the behavior solutions as the strength of multiplicative noise increases. The validation of computational results through stability analysis enhances the confidence in the findings of the study. All the mathematical calculations, as well as graphical representations, have been meticulously achieved to present a comprehensive and detailed understanding of the impact of multiplicative on soliton propagation in nonlinear optical fibers.

Contralateral Routing of Signal Disrupts Monaural Sound Localization.

In the absence of binaural hearing, individuals with single-sided deafness can adapt to use monaural level and spectral cues to improve their spatial hearing abilities. Contralateral routing of signal is the most common form of rehabilitation for individuals with single-sided deafness. However, little is known about how these devices affect monaural localization cues, which single-sided deafness listeners may become reliant on. This study aimed to investigate the effects of contralateral routing of signal hearing aids on localization performance in azimuth and elevation under monaural listening conditions. Localization was assessed in 10 normal hearing adults under three listening conditions: (1) normal hearing (NH), (2) unilateral plug (NH-plug), and (3) unilateral plug and CROS aided (NH-plug + CROS). Monaural hearing simulation was achieved by plugging the ear with E-A-Rsoft™ FX™ foam earplugs. Stimuli consisted of 150 ms high-pass noise bursts (3-20 kHz), presented in a random order from fifty locations spanning ±70° in the horizontal and ±30° in the vertical plane at 45, 55, and 65 dBA. In the unilateral plugged listening condition, participants demonstrated good localization in elevation and a response bias in azimuth for signals directed at the open ear. A significant decrease in performance in elevation occurs with the contralateral routing of signal hearing device on, evidenced by significant reductions in response gain and low r2 value. Additionally, performance in azimuth is further reduced for contralateral routing of signal aided localization compared to the simulated unilateral hearing loss condition. Use of the contralateral routing of signal device also results in a reduction in promptness of the listener response and an increase in response variability. Results suggest contralateral routing of signal hearing aids disrupt monaural spectral and level cues, which leads to detriments in localization performance in both the horizontal and vertical dimensions. Increased reaction time and increasing variability in responses suggests localization is more effortful when wearing the contralateral rerouting of signal device.

A Full-Custom Design Flow and a Top-Down RTL-to-GDS Flow for Adiabatic Quantum-Flux-Parametron Logic Using a Commercial EDA Design Suite

The adiabatic quantum-flux-parametron (AQFP) circuit is a superconductor digital logic family with extremely low power consumption. It consumes five orders less power than the state-of-the-art CMOS circuits and three orders of magnitude less power than RSFQ circuits, another competing digital superconductor technology. The computing resources required by society are increasing every year, and the AQFP circuit is a strong candidate for the next generation of computers. In previous research, a 4-bit MANA microprocessor and a 16-bit Kogge-Stone adder using AQFP logic were designed and demonstrated. These circuits were designed almost by hand, and the development environment needs to be improved to implement AQFP circuits for practical applications. So, we used Synopsys EDA tools typically used for CMOS design to create a full-custom design flow for logic cell design and a top-down flow to design combinational logic circuits automatically. We integrated a circuit design editor with simulation and verification tools for the full-custom design flow. For the top-down flow, we created an environment that automatically performs logic synthesis, path balancing, cell placement, and signal and excitation routing. 1024-bit adders with more than two million Josephson junctions (JJs) have been successfully designed.

Connective tissue growth factor: Role in trabecular meshwork remodeling and intraocular pressure lowering.

Connective tissue growth factor (CTGF) is a distinct signaling molecule modulating many physiological and pathophysiological processes. This protein is upregulated in numerous fibrotic diseases that involve extracellular matrix (ECM) remodeling. It mediates the downstream effects of transforming growth factor beta (TGF-β) and is regulated via TGF-β SMAD-dependent and SMAD-independent signaling routes. Targeting CTGF instead of its upstream regulator TGF-β avoids the consequences of interfering with the pleotropic effects of TGF-β. Both CTGF and its upstream mediator, TGF-β, have been linked with the pathophysiology of glaucomatous optic neuropathy due to their involvement in the regulation of ECM homeostasis. The excessive expression of these growth factors is associated with glaucoma pathogenesis via elevation of the intraocular pressure (IOP), the most important risk factor for glaucoma. The raised in the IOP is due to dysregulation of ECM turnover resulting in excessive ECM deposition at the site of aqueous humor outflow. It is therefore believed that CTGF could be a potential therapeutic target in glaucoma therapy. This review highlights the CTGF biology and structure, its regulation and signaling, its association with the pathophysiology of glaucoma, and its potential role as a therapeutic target in glaucoma management.

Aqueous Two-Phase Systems within Selectively Permeable Vesicles.

An aqueous two-phase system (ATPS) encapsulated within a vesicle organizes the vesicle core as two coexisting phases that partition encapsulated solutes. Here, we use microfluidic technologies to produce vesicles that efficiently encapsulate mixtures of macromolecules, providing a versatile platform to determine the phase behavior of ATPSs. Moreover, we use compartmentalized vesicles to investigate how membrane permeability affects the dynamics of the encapsulated ATPS. Designing a membrane selectively permeable to one of the components of the ATPS, we show that out-of-equilibrium phase separations formed by a rapid outflow of water can be spontaneously reversed by a slower outflow of the permeating component across the vesicle membrane. This dynamics may be exploited advantageously by cells to separate and connect metabolic and signaling routes within their nucleoplasm or cytoplasm depending on external conditions.

Modes of Action of a Novel c-MYC Inhibiting 1,2,4-Oxadiazole Derivative in Leukemia and Breast Cancer Cells.

The c-MYC oncogene regulates multiple cellular activities and is a potent driver of many highly aggressive human cancers, such as leukemia and triple-negative breast cancer. The oxadiazole class of compounds has gained increasing interest for its anticancer activities. The aim of this study was to investigate the molecular modes of action of a 1,2,4-oxadiazole derivative (ZINC15675948) as a c-MYC inhibitor. ZINC15675948 displayed profound cytotoxicity at the nanomolar range in CCRF-CEM leukemia and MDA-MB-231-pcDNA3 breast cancer cells. Multidrug-resistant sublines thereof (i.e., CEM/ADR5000 and MDA-MB-231-BCRP) were moderately cross-resistant to this compound (<10-fold). Molecular docking and microscale thermophoresis revealed a strong binding of ZINC15675948 to c-MYC by interacting close to the c-MYC/MAX interface. A c-MYC reporter assay demonstrated that ZINC15675948 inhibited c-MYC activity. Western blotting and qRT-PCR showed that c-MYC expression was downregulated by ZINC15675948. Applying microarray hybridization and signaling pathway analyses, ZINC15675948 affected signaling routes downstream of c-MYC in both leukemia and breast cancer cells as demonstrated by the induction of DNA damage using single cell gel electrophoresis (alkaline comet assay) and induction of apoptosis using flow cytometry. ZINC15675948 also caused G2/M phase and S phase arrest in CCRF-CEM cells and MDA-MB-231-pcDNA3 cells, respectively, accompanied by the downregulation of CDK1 and p-CDK2 expression using western blotting. Autophagy induction was observed in CCRF-CEM cells but not MDA-MB-231-pcDNA3 cells. Furthermore, microarray-based mRNA expression profiling indicated that ZINC15675948 may target c-MYC-regulated ubiquitination, since the novel ubiquitin ligase (ELL2) was upregulated in the absence of c-MYC expression. We propose that ZINC15675948 is a promising natural product-derived compound targeting c-MYC in c-MYC-driven cancers through DNA damage, cell cycle arrest, and apoptosis.

An Optical 1×4 Power Splitter Based on Silicon-Nitride MMI Using Strip Waveguide Structures.

This paper presents a new design for a 1 × 4 optical power splitter using multimode interference (MMI) coupler in silicon nitride (Si3N4) strip waveguide structures. The main functionality of the proposed design is to use Si3N4 for dealing with the back reflection (BR) effect that usually happens in silicon (Si) MMI devices due to the self-imaging effect and the higher index contrast between Si and silicon dioxide (SiO2). The optimal device parameters were determined through numerical optimizations using the beam propagation method (BPM) and finite difference time domain (FDTD). Results demonstrate that the power splitter with a length of 34.6 μm can reach equal distribution power in each output port up to 24.3% of the total power across the O-band spectrum with 0.13 dB insertion loss and good tolerance MMI coupler parameters with a shift of ±250 nm. Additionally, the back reflection range over the O-band was found to be 40.25-42.44 dB. This demonstrates the effectiveness of the incorporation using Si3N4 MMI and adiabatic input and output tapers in mitigating unwanted BR to ensure that a good signal is received from the laser. This design showcases the significant potential for data-center networks, offering a promising solution for efficient signal distribution and facilitating high-performance and reliable optical signal routing within the O-band range. By leveraging the advantages of Si3N4 and the MMI coupler, this design opens possibilities for advanced optical network architectures and enables efficient transmission of optical signals in the O-band range.

Mast cells link immune sensing to antigen-avoidance behaviour

The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with immunoglobulin E (IgE), promote allergic diseases. Allergic symptoms may, however, facilitate expulsion of allergens, toxins and parasites and trigger future antigen avoidance1–3. Here, we show that antigen-specific avoidance behaviour in inbred mice4,5 is critically dependent on mast cells; hence, we identify the immunological sensor cell linking antigen recognition to avoidance behaviour. Avoidance prevented antigen-driven adaptive, innate and mucosal immune activation and inflammation in the stomach and small intestine. Avoidance was IgE dependent, promoted by Th2 cytokines in the immunization phase and by IgE in the execution phase. Mucosal mast cells lining the stomach and small intestine rapidly sensed antigen ingestion. We interrogated potential signalling routes between mast cells and the brain using mutant mice, pharmacological inhibition, neural activity recordings and vagotomy. Inhibition of leukotriene synthesis impaired avoidance, but overall no single pathway interruption completely abrogated avoidance, indicating complex regulation. Collectively, the stage for antigen avoidance is set when adaptive immunity equips mast cells with IgE as a telltale of past immune responses. On subsequent antigen ingestion, mast cells signal termination of antigen intake. Prevention of immunopathology-causing, continuous and futile responses against per se innocuous antigens or of repeated ingestion of toxins through mast-cell-mediated antigen-avoidance behaviour may be an important arm of immunity.

Rapid phosphorylation of glucose-6-phosphate dehydrogenase by casein kinase 2 sustains redox homeostasis under ionizing radiation

Exposure to ionizing radiation leads to oxidative damages in living cells. NADPH provides the indispensable reducing power to regenerate the reduced glutathione to maintain cellular redox equilibria. In mammalian cells, pentose phosphate pathway (PPP) is the major route to produce NADPH by using glycolytic intermediates, and the rate-limiting step of PPP is controlled by glucose-6-phosphate dehydrogenase (G6PD). Nevertheless, whether G6PD is timely co-opted under ionizing radiation to cope with oxidative stress remains elusive. Here we show that cellular G6PD activity is induced 30 min after ionizing radiation, while its protein expression is mostly unchanged. Mechanistically, casein kinase 2 (CK2) phosphorylates G6PD T145 under ionizing radiation, which consolidates the enzymatic activity of G6PD by facilitating G6PD binding with its substrate NADP+. Further, CK2-dependent G6PD T145 phosphorylation promotes NADPH production, decreases ROS level and supports cell proliferation under ionizing radiation. Our findings report a new anti-oxidative signaling route under ionizing radiation, by which CK2-mediated rapid activation of G6PD orchestrates NADPH synthesis to maintain redox homeostasis, thereby highlighting its potential value in the early treatment of ionizing radiation-induced injuries.

Embryo sac development relies on symplastic signals from ovular integuments in Arabidopsis.

Ovules are female reproductive organs of angiosperms, consisting of sporophytic integuments surrounding female gametophytes, that is, embryo sacs. Synchronization between integument growth and embryo sac development requires intracellular communication. However, signaling routes through which cells of the two generations communicate are unclear. We report that symplastic signals through plasmodesmata (PDs) of integuments are critical for the development of female gametophytes. Genetic interferences of PD biogenesis either by functional loss of CHOLINE TRANSPORTER-LIKE1 (CTL1) or by integument-specific expression of a mutated CALLOSE SYNTHASE 3 (cals3m) compromised PD formation in integuments and reduced fertility. Close examination of pINO:cals3m or ctl1 ovules indicated that female gametophytic development was either arrested at various stages after the formation of functional megaspores. In both cases, defective ovules could not attract pollen tubes, leading to the failure of fertilization. Results presented here demonstrate a key role of the symplastic route in sporophytic control of female gametophytic development.

CRISPR gene technology—the next best thing in medicine

CRISPR gene technology—the next best thing in medicine

Molecular and genetic perspectives of cold tolerance in wheat.

Environmental variation is the most crucial problem as it is causing food insecurity and negatively impacts food availability, utilization, assessment, and stability. Wheat is the largest and extensively cultivated staple food crop for fulfilling global food requirements. Abiotic stresses including salinity, heavy metal toxicity, drought, extreme temperatures, and oxidative stresses being the primary cause of productivity loss are a serious threat to agronomy. Cold stress is a foremost ecological constraint that is extremely influencing plant development, and yield. It is extremely hampering the propagative development of plant life. The structure and function of plant cells depend on the cell's immune system. The stresses due to cold, affect fluid in the plasma membrane and change it into crystals or a solid gel phase. Plants being sessile in nature have evolved progressive systems that permit them to acclimatize the cold stress at the physiological as well as molecular levels. The phenomenon of acclimatisation of plants to cold stress has been investigated for the last 10 years. Studying cold tolerance is critical for extending the adaptability zones of perennial grasses. In the present review, we have elaborated the current improvement of cold tolerance in plants from molecular and physiological viewpoints, such as hormones, the role of the posttranscriptional gene, micro RNAs, ICE-CBF-COR signaling route in cold acclimatization and how they are stimulating the expression of underlying genes encoding osmoregulatory elements and strategies to improve cold tolerance in wheat.

OPTICAL 4:1 MULTIPLEXER USING SAGNAC SWITCHES

This paper presents the design and implementation of an Optical 4:1 Multiplexer using Sagnac Switches as Terahertz Optical Asymmetric Demultiplexers (TOADs). Optical multiplexers play a crucial role in modern communication systems by combining multiple signals onto a single optical channel. The proposed multiplexer architecture leverages the benefits of Sagnac Switches, such as low insertion loss, high extinction ratio, and low crosstalk, along with TOADs to achieve efficient signal routing and demultiplexing. The design is evaluated through simulations, demonstrating its performance in terms of insertion loss, extinction ratio, and crosstalk. The experimental validation of the multiplexer verifies its effectiveness in real-world scenarios. The Optical 4:1 Multiplexer using Sagnac Switches as TOADs offers a promising solution for optical communication networks, enabling efficient signal multiplexing and demultiplexing while maintaining high data integrity and low signal degradation.

KLK4 affects the biological behavior of oral squamous cell carcinoma through Wnt/β catenin and PI3K/Akt signaling pathways

Purpose: To investigate the effect of kallikrein 4 (KLK4) on oral squamous cell carcinoma (OSCC), and its mechanism of action.&#x0D; Method: Human tongue SCC cell line TCA-8113 was cultured, and the interference fragment and irrelevant sequence fragment of KLK4 gene were designed and synthesized. These fragments were constructed into pgcsi-h1 plasmid. Then, the TCA-8113 cells were cultured for 24 h, followed by transfection, after which TCA-8113-NC and TCA-8113-siKLK4 cells were obtained. The mRNA expression of KLK4 was determined using quantitative real-time-polymerase chain reaction (PCR). Proliferative potential was assessed using MTT method, while apoptosis was determined by flow cytometry. Furthermore, cell migration was evaluated by scratch test, and Transwell cell invasion experiment was used to determine cell invasion. Immunoblot assay was applied to determine the expressions of E- and N-cadherins, vimentin, uPA, Wnt1, β-Catenin, p-pi3k and p-Akt.&#x0D; Result: Compared with TCA-8113-nc, the expression of KLK4 in TCA-8113-siKLK4 cells was significantly down-regulated, while, relative to TCA-8113-NC, TCA-8113-siKLK4 cells had significantly reduced cell proliferation, invasion and migration, and enhanced apoptosis (p &lt; 0.05). Moreover, there was significant up-regulation of E- and N-cadherins, vimentin, uPA, Wnt1, β-Catenin, p-pi3k and p-Akt in TCA-8113-siKLK4 group, relative to TCA-8113-NC (p &lt; 0.05).&#x0D; Conclusion: KLK4 enhances the multiplication, metastasis and invasive potential of OSCC cells, but suppresses apoptotic changes via activation of Wnt/β-catenin/PI3K/Akt signal route. The potential of Kallikrein-4 as biomarker for OSCC cells should be determined in suitable animal models.

On the dynamics of a dual space–time fractional nonlinear Schrödinger model in optical fibers

The nonlinear Schrödinger equation (NLSE) is a significant nonlinear complex model known as the most important struture to represent light pulse propagation in optical fibers, which plays a key role in demonstrating the proliferation specifically short pulse in optical fibers and have large appliances in telecommunication system and ultra fast signal routing in nonlinear optics. In this study, we look into explicit solutions of a coupled fractional NLSE for a dual space–time, which reflect numerous explicit travelling wave solutions, as well as their physical interpretation. We use the fractional complex transform to obtain multiple exact answers using the unified technique and the extended simple equation method. These exact answers include trigonometric function solutions as well as dark, bright, singular, periodic, and optical soliton solutions. For a set of appropriate parameters, Mathematica is used to represent the dynamics of various wave structures as 3D, 2D, and contour visualizations. These findings show that the proposed methodologies are simple, prolific, and capable of studying the nature of numerous physical models of complex phenomena in modern science.

Cross-shape reconfigurable field effect transistor for flexible signal routing

Cross-shape reconfigurable field effect transistor for flexible signal routing

Integrated Power Distribution Network Synthesis for Mixed Macro Blocks and Standard Cells

Power distribution network (PDN) requires more routing resources as wire resistance increases with technology scaling but IR drop constraint does not scale. We address post-placement PDN synthesis for mixed macro blocks and standard cells. Macro blocks already have partial PDN, while standard cells do not. So the design, which has been placed, is divided into a number of partitions: each macro block in its own partition, and standard cell area into a number of partitions. Multi-layer PDN synthesis is performed in each partition one by one; the goal of this problem is to insert minimum number of metal straps (in irregular pitches) while IR drop and electromigration (EM) constraints are respected. This is formulated as mixed integer quadratically constrained programming (MIQCP) and a heuristic algorithm is proposed for practical application. Experimental results with some test circuits indicate that the proposed approach achieves on average of 26% reduction in PDN straps, which helps reduce congestion overflow of signal routing by 15%, compared to popular approach in which PDN straps are located in regular pitch period.