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Background: Vasoactive intestinal peptide (VIP) is a neuronal peptide with prominent distribution along the enteric nervous system. While effects of VIP on intestinal motility, mucosal vasodilation, secretion, and mucosal immune cell function are well-studied, the direct impact of VIP on intestinal epithelial cell turnover and differentiation remains less understood. Intestinal stem and progenitor cells are essential for the maintenance of intestinal homeostasis and regeneration, and their functions can be modulated by factors of the stem cell niche, including neuronal mediators. Here, we investigated the role of VIP in regulating intestinal epithelial homeostasis and regeneration following irradiation-induced injury. Methods: Jejunal organoids were derived from male and female C57Bl6/J, Lgr5-EGFP-IRES-CreERT2 or Lgr5-EGFP-IRES-CreERT2/R26R-LSL-TdTomato mice and treated with VIP prior to analysis. Injury conditions were induced by exposing organoids to 6 Gy of irradiation (IR). To investigate protective effects of VIP in vivo, mice received 12 Gy of abdominal IR followed by intraperitoneal injections of VIP. Results: We observed that VIP promotes epithelial differentiation towards a secretory phenotype predominantly via the p38 MAPK pathway. Moreover, VIP prominently modulated epithelial proliferation as well as the number and proliferative activity of Lgr5-EGFP+ progenitor cells under homeostatic conditions. In the context of acute irradiation injury in vitro, we observed that IR injury renders Lgr5-EGFP+ progenitor cells more susceptible to VIP-induced modulations, which coincided with the strong promotion of epithelial regeneration by VIP. Finally, the observed effects translate into an in vivo model of abdominal irradiation, where VIP showed to prominently mitigate radiation-induced injury. Conclusions: VIP prominently governs intestinal homeostasis by regulating epithelial progenitor cell proliferation and differentiation and promotes intestinal regeneration following acute irradiation injury. [ABSTRACT FROM AUTHOR]

Background: Chronic liver diseases such as hepatic tumors can affect the brain through the liver–brain axis, leading to neurotransmitter dysregulation and behavioral changes. Cancer patients suffer from fatigue, which can be associated with sleep disturbances. Sleep is regulated via two interlocked mechanisms: homeostatic regulation and the circadian system. In mammals, the hypothalamic suprachiasmatic nucleus (SCN) is the key component of the circadian system. It generates circadian rhythms in physiology and behavior and controls their entrainment to the surrounding light/dark cycle. Neuron–glia interactions are crucial for the functional integrity of the SCN. Under pathological conditions, oxidative stress can compromise these interactions and thus circadian timekeeping and entrainment. To date, little is known about the impact of peripheral pathologies such as hepatocellular carcinoma (HCC) on SCN. Materials and Methods: In this study, HCC was induced in adult male mice. The key neuropeptides (vasoactive intestinal peptide: VIP, arginine vasopressin: AVP), an essential component of the molecular clockwork (Bmal1), markers for activity of neurons (c-Fos), astrocytes (GFAP), microglia (IBA1), as well as oxidative stress (8-OHdG) in the SCN were analyzed by immunohistochemistry at four different time points in HCC-bearing compared to control mice. Results: The immunoreactions for VIP, Bmal1, GFAP, IBA1, and 8-OHdG were increased in HCC mice compared to control mice, especially during the activity phase. In contrast, c-Fos was decreased in HCC mice, especially during the late inactive phase. Conclusions: Our data suggest that HCC affects the circadian system at the level of SCN. This involves an alteration of neuropeptides, neuronal activity, Bmal1, activation of glia cells, and oxidative stress in the SCN. [ABSTRACT FROM AUTHOR]

Inflammation with expression of interleukin 6 (IL-6) in the central nervous system (CNS) occurs in several neurodegenerative/neuroinflammatory conditions and may cause neurochemical changes to endogenous neuroprotective systems. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are two neuropeptides with well-established protective and anti-inflammatory properties. Yet, whether PACAP and VIP levels are altered in mice with CNS-restricted, astrocyte-targeted production of IL-6 (GFAP-IL6) remains unknown. In this study, PACAP/VIP levels were assessed in the brain of GFAP-IL6 mice. In addition, we utilised bi-genic GFAP-IL6 mice carrying the human sgp130-Fc transgene (termed GFAP-IL6/sgp130Fc mice) to determine whether trans-signalling inhibition rescued PACAP/VIP changes in the CNS. Transcripts and protein levels of PACAP and VIP, as well as their receptors PAC1, VPAC1 and VPAC2, were significantly increased in the cerebrum and cerebellum of GFAP-IL6 mice vs. wild type (WT) littermates. These results were paralleled by a robust activation of the JAK/STAT3, NF-κB and ERK1/2MAPK pathways in GFAP-IL6 mice. In contrast, co-expression of sgp130Fc in GFAP-IL6/sgp130Fc mice reduced VIP expression and activation of STAT3 and NF-κB pathways, but it failed to rescue PACAP, PACAP/VIP receptors and Erk1/2MAPK phosphorylation. We conclude that forced expression of IL-6 in astrocytes induces the activation of the PACAP/VIP neuropeptide system in the brain, which is only partly modulated upon IL-6 trans-signalling inhibition. Increased expression of PACAP/VIP neuropeptides and receptors may represent a homeostatic response of the CNS to an uncontrolled IL-6 synthesis and its neuroinflammatory consequences. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) signaling pathway is a powerful regulator of cell proliferation, growth, synapse maintenance and cell fate. While intensely studied for its role in cancer, the role of mTOR signaling is just beginning to be uncovered in specific cell types that are implicated in neurodevelopmental disorders. Previously, loss of the Tsc1 gene, which results in hyperactive mTOR, was shown to affect the function and molecular properties of GABAergic cortical interneurons (CINs) derived from the medial ganglionic eminence. To assess if other important classes of CINs could be impacted by mTOR dysfunction, we deleted Tsc1 in a caudal ganglionic eminence-derived interneuron group, the vasoactive intestinal peptide (VIP)+ subtype, whose activity disinhibits local circuits. Tsc1 mutant VIP+ CINs reduced their pattern of apoptosis from postnatal days 15-20, resulting in increased VIP+ CINs. The mutant CINs exhibited synaptic and electrophysiological properties that could contribute to the high rate of seizure activity in humans that harbor Tsc1 mutations.

Abstract Background Vasoactive intestinal peptide (VIP) is a neuronal peptide with prominent distribution along the enteric nervous system. While effects of VIP on intestinal motility, mucosal vasodilation, secretion, and mucosal immune cell function are well-studied, the direct impact of VIP on intestinal epithelial cell turnover and differentiation remains less understood. Intestinal stem and progenitor cells are essential for the maintenance of intestinal homeostasis and regeneration, and their functions can be modulated by factors of the stem cell niche, including neuronal mediators. Here, we investigated the role of VIP in regulating intestinal epithelial homeostasis and regeneration following irradiation-induced injury. Methods Jejunal organoids were derived from male and female C57Bl6/J, Lgr5-EGFP-IRES-CreERT2 or Lgr5-EGFP-IRES-CreERT2/R26R-LSL-TdTomato mice and treated with VIP prior to analysis. Injury conditions were induced by exposing organoids to 6 Gy of irradiation (IR). To investigate protective effects of VIP in vivo, mice received 12 Gy of abdominal IR followed by intraperitoneal injections of VIP. Results We observed that VIP promotes epithelial differentiation towards a secretory phenotype predominantly via the p38 MAPK pathway. Moreover, VIP prominently modulated epithelial proliferation as well as the number and proliferative activity of Lgr5-EGFP+ progenitor cells under homeostatic conditions. In the context of acute irradiation injury in vitro, we observed that IR injury renders Lgr5-EGFP+ progenitor cells more susceptible to VIP-induced modulations, which coincided with the strong promotion of epithelial regeneration by VIP. Finally, the observed effects translate into an in vivo model of abdominal irradiation, where VIP showed to prominently mitigate radiation-induced injury. Conclusions VIP prominently governs intestinal homeostasis by regulating epithelial progenitor cell proliferation and differentiation and promotes intestinal regeneration following acute irradiation injury.

Attention deficit is one of the most prominent and disabling symptoms in Fragile X syndrome (FXS). Hypersensitivity to sensory stimuli contributes to attention difficulties by overwhelming and/or distracting affected individuals, which disrupts activities of daily living at home and learning at school. We find that auditory or visual distractors selectively impair visual discrimination performance in humans and mice with FXS but not in typically developing controls. In both species, males and females were examined. Vasoactive intestinal polypeptide (VIP) neurons were significantly modulated by incorrect responses in the poststimulus period during early distractor trials in WT mice, consistent with their known role as error signals. Strikingly, however, VIP cells from Fmr1 -/- mice showed little modulation in error trials, and this correlated with their poor performance on the distractor task. Thus, VIP interneurons and their reduced modulatory influence on pyramidal cells could be a potential therapeutic target for attentional difficulties in FXS.SIGNIFICANCE STATEMENT Sensory hypersensitivity, impulsivity, and persistent inattention are among the most consistent clinical features of FXS, all of which impede daily functioning and create barriers to learning. However, the neural mechanisms underlying sensory over-reactivity remain elusive. To overcome a significant challenge in translational FXS research we demonstrate a compelling alignment of sensory over-reactivity in both humans with FXS and Fmr1 -/- mice (the principal animal model of FXS) using a novel analogous distractor task. Two-photon microscopy in mice revealed that lack of modulation by VIP cells contributes to susceptibility to distractors. Implementing research efforts we describe here can help identify dysfunctional neural mechanisms associated not only with sensory issues but broader impairments, including those in learning and cognition.

En la actualidad, el comercio internacional de joyería está experimentando un repentino crecimiento lo que ha dado lugar a la celebración de ferias y exhibiciones en diversos países de todo el mundo. Esta situación ha originado una prolífica aparición de documentos técnicos y publicitarios, además del aumento exponencial de portales digitales que ofrecen información, documentación contractual o guías de compra. Todo ello ha convertido este ámbito de los negocios en un dominio especializado clave para el trabajo del traductor o intérprete, cuya labor es necesaria para la comunicación efectiva en el sector. La traducción al español de estos textos supone un reto desde el punto vista técnico debido a la extensa terminología especifica que suele estar presente en estos documentos y portales digitales y a la necesidad de manejar dicha terminología en reuniones y encuentros a través de comunicación oral. Nuestra propuesta en este trabajo plantea la búsqueda y compilación de documentos técnicos de catálogos de joyería en inglés y en español para elaborar, con la ayuda de las nuevas tecnologías, corpus textuales bilingües que sirvan de base para la compilación de glosarios terminológicos actualizados para la traducción e interpretación en este campo y, por ende, para su uso por el traductor o intérprete. Igualmente se analiza la tipología del contrato. El uso de las nuevas tecnologías en la traducción e interpretación, ha supuesto una aportación valiosa, y en este trabajo utilizaremos el sistema VIP. Dicho programa se ha creado en el grupo de investigación Lexytrad de la Universidad de Málaga, como herramienta de generación de corpus y glosarios que nos permitirá realizar un estudio de la terminología más frecuente en estos documentos, tanto desde el punto de vista técnico como jurídico, y la compilación de glosarios actualizados que surgirán como propuesta de ayuda para la traducción y la interpretación.

Vasoactive-intestinal peptide (Vip) is a pleiotropic peptide with a wide range of distribution and functions. Zebrafish possess 2 isoforms of Vip (a and b), in which Vipa is most homologous to the mammalian form. In female zebrafish, Vipa can stimulate LH secretion from the pituitary but is not essential for female reproduction, as vipa −/− females display normal reproduction. In contrast, we have found that vipa −/− males are severely subfertile and sex ratio of offspring is female-biased. By analyzing all aspects of male reproduction with wild-type (WT) males, we show that the testes of vipa −/− are underdeveloped and contain ∼70% less spermatids compared to WT counterparts. The sperm of vipa −/− males displayed reduced potency in terms of fertilization (by ∼80%) and motility span and duration (by ∼50%). In addition, vipa −/− male attraction to WT females was largely nonexistent, indicating decreased sexual motivation. We show that vipa mRNA and protein is present in Leydig cells and in developing germ cells in the testis of WT, raising the possibility that endogenous Vipa contributes to testicular function. Absence of Vipa in vipa −/− males resulted in downregulation of 3 key genes in the androgen synthesis chain in the testis, 3β-hsd, 17β-hsd1 , and cyp11c1 (11β-hydrogenase), associated with a pronounced decrease in 11-ketotestosterone production and, in turn, compromised reproductive fitness. Altogether, this study establishes a crucial role for Vipa in the regulation of male reproduction in zebrafish, like in mammals, with the exception that Vipa is also expressed in zebrafish testis. [ABSTRACT FROM AUTHOR]

In mammals, intrinsic 24 h or circadian rhythms are primarily generated by the suprachiasmatic nuclei (SCN). Rhythmic daily changes in the transcriptome and proteome of SCN cells are controlled by interlocking transcription‐translation feedback loops (TTFLs) of core clock genes and their proteins. SCN cells function as autonomous circadian oscillators, which synchronize through intercellular neuropeptide signalling. Physiological and behavioural rhythms can be severely disrupted by genetic modification of a diverse range of genes and proteins in the SCN. With the advent of next generation sequencing, there is unprecedented information on the molecular profile of the SCN and how it is affected by genetically targeted alteration. However, whether the expression of some genes is more readily affected by genetic alteration of the SCN is unclear. Here, using publicly available datasets from recent RNA‐seq assessments of the SCN from genetically altered and control mice, we evaluated whether there are commonalities in transcriptome dysregulation. This was completed for four different phases across the 24 h cycle and was augmented by Gene Ontology Molecular Function (GO:MF) and promoter analysis. Common differentially expressed genes (DEGs) and/or enriched GO:MF terms included signalling molecules, their receptors, and core clock components. Finally, examination of the JASPAR database indicated that E‐box and CRE elements in the promoter regions of several commonly dysregulated genes. From this analysis, we identify differential expression of genes coding for molecules involved in SCN intra‐ and intercellular signalling as a potential cause of abnormal circadian rhythms. [ABSTRACT FROM AUTHOR]

In this paper, we demonstrated a very competitive RGB tandem OLED based on ViP technology that showed low power consumption and long lifetime. Compared to the traditional single OLED for mass production, panels based on tandem OLED can reduce power consumption by 29% and increase lifetime by more than 3.3 times. In combination with ViP technology, 8% efficiency improvement was obtained by optimizing the light‐emitting layer positions of RGB tandem OLEDs and thickness of cathode and capping layer (CPL), respectively, achieving a white light emission current efficiency over 134 cd/A. [ABSTRACT FROM AUTHOR]

LTPO(Low Temperature Polycrystalline Oxide) is a hybrid backplane technology that combines low‐temperature polycrystalline silicon and oxide‐based TFT (thin‐film transistor). It is also one breakthrough technology that achieves ultra‐long standby time and stable battery life. This paper mainly discusses the key technical points of LTPO power saving [1][2] from the driver IC technology and screen technology solution, and also introduces the mass production results of Visionox LTPO technology, demonstrating the great potential of LTPO in low power comsumption. [ABSTRACT FROM AUTHOR]

ViPTM (Visionox intelligent Pixelization) Technology is a novel RGB self‐aligned pixelization approach without Fine Metal Mask for OLED patterning. Since being released in May 2023, numerous breakthrough technical progress has been achieved. In this presentation, the recent results on panel performance and other advantages of ViPTM Technology will be discussed. [ABSTRACT FROM AUTHOR]

Due to the disposal of different wastewater into the water bodies, the rate of surface water pollution is increasing. The virginia initiative plant (VIP), one of the most efficient and economical wastewater treatment systems, was assessed. The experiments were carried out by a laboratory-scale VIP system used for this study, with a flow rate of 100 L/day and a solid retention time rate estimated at 10 days. The system works on three different ratios for internal rotation (100, 150, and 200%) and three for external rotation (80, 90, and 100%), and the effective volumes were 20, 40, and 60 L for anaerobic, anoxic, and oxic reactors, respectively. The results showed that the VIP system achieved the best removal efficiency of organic matter represented by COD, phosphorous, and ammonia (86, 94, and 93%, respectively). The impact of internal and external rotation ratios was tested by removing COD, phosphorous, and ammonia. The percentages of internal rotation significantly affect the biological removal of nitrates. The relationship between them is inverse, while the percentages of external rotation significantly impact the biological removal process of phosphorus. The relationship between them is positive, whereas the internal and external rotation percentages did not considerably affect the efficiency of removing both ammonia and COD. According to the research results, internal and external rotation ratios enhanced the removal efficiency of phosphorus and nitrates. The VIP system proved to be an effective method for domestic wastewater treatment with a flow conforming to Iraqi standards for draining wastewater with all organic matter, phosphorous, and nitrogenous compounds to rivers.

Gamma band synchronization can facilitate local and long-range neural communication. In the primary visual cortex, visual stimulus properties within a specific location determine local synchronization strength, while the match of stimulus properties between distant locations controls long-range synchronization. The neural basis for the differential control of local and global gamma band synchronization is unknown. Combining electrophysiology, optogenetics, and computational modeling, we found that VIP disinhibitory interneurons in mouse cortex linearly scale gamma power locally without changing its stimulus tuning. Conversely, they suppress long-range synchronization when two regions process non-matched stimuli, tuning gamma coherence globally. Modeling shows that like-to-like connectivity across space and specific VIP→SST inhibition capture these opposing effects. VIP neurons thus differentially impact local and global properties of gamma rhythms depending on visual stimulus statistics. They may thereby construct gamma-band filters for spatially extended but continuous image features, such as contours, facilitating the downstream generation of coherent visual percepts.

Several neuropeptides present in bone tissues, produced by nerve fibers and bone cells, have been reported to play a role in regulating the fine‐tuning of osteoblast and osteoclast functions to maintain bone homeostasis. This study aims to characterize the influence of the neuropeptide vasoactive intestinal peptide (VIP) on the differentiation process of human mesenchymal stem cells (MSCs) into osteoblasts and on their anabolic function. We describe the mRNA and protein expression profile of VIP and its receptors in MSCs as they differentiate into osteoblasts, suggesting the presence of an autocrine signaling pathway in these cells. Our findings reveal that VIP enhances the expression of early osteoblast markers in MSCs under osteogenic differentiation and favors both bone matrix formation and proper cytoskeletal reorganization. Finally, our data suggest that VIP could be exerting a direct modulatory role on the osteoblast to osteoclast signaling by downregulating the receptor activator of nuclear factor‐κB ligand/osteoprotegerin ratio. These results highlight the potential of VIP as an osteoinductive differentiation factor, emerging as a key molecule in the maintenance of human bone homeostasis. [ABSTRACT FROM AUTHOR]

The plasticity of inhibitory interneurons (INs) plays an important role in the organization and maintenance of cortical microcircuits. Given the many different IN types, there is an even greater diversity in synapse-type-specific plasticity learning rules at excitatory to excitatory (E!I), I!E, and I!I synapses. I!I synapses play a key disinhibitory role in cortical circuits. Because they typically target other INs, vasoactive intestinal peptide (VIP) INs are often featured in I!I!E disinhibition, which upregulates activity in nearby excitatory neurons. VIP IN dysregulation may thus lead to neuropathologies such as epilepsy. In spite of the important activity regulatory role of VIP INs, their long-term plasticity has not been described. Therefore, we characterized the phenomenology of spike-timing-dependent plasticity (STDP) at inputs and outputs of genetically defined VIP INs. Using a combination of wholecell recording, 2-photon microscopy, and optogenetics, we explored I!I STDP at layer 2/3 (L2/3) VIP IN outputs onto L5 Martinotti cells (MCs) and basket cells (BCs). We found that VIP IN!MC synapses underwent causal long-term depression (LTD) that was presynaptically expressed. VIP IN!BC connections, however, did not undergo any detectable plasticity. Conversely, using extracellular stimulation, we explored E!I STDP at inputs to VIP INs which revealed long-term potentiation (LTP) for both causal and acausal timings. Taken together, our results demonstrate that VIP INs possess synapsetype- specific learning rules at their inputs and outputs. This suggests the possibility of harnessing VIP IN long-term plasticity to control activity-related neuropathologies such as epilepsy. [ABSTRACT FROM AUTHOR]

Antagonist peptides (ANTs) of vasoactive intestinal polypeptide receptors (VIP-Rs) are shown to enhance T cell activation and proliferation in vitro, as well as improving T cell-dependent anti-tumor response in acute myeloid leukemia (AML) murine models. However, peptide therapeutics often suffer from poor metabolic stability and exhibit a short half-life/fast elimination in vivo. In this study, we describe efforts to enhance the drug properties of ANTs via chemical modifications. The lead antagonist (ANT308) is derivatized with the following modifications: N-terminus acetylation, peptide stapling, and PEGylation. Acetylated ANT308 exhibits diminished T cell activation in vitro, indicating that N-terminus conservation is critical for antagonist activity. The replacement of residues 13 and 17 with cysteine to accommodate a chemical staple results in diminished survival using the modified peptide to treat mice with AML. However, the incorporation of the constraint increases survival and reduces tumor burden relative to its unstapled counterpart. Notably, PEGylation has a significant positive effect, with fewer doses of PEGylated ANT308 needed to achieve comparable overall survival and tumor burden in leukemic mice dosed with the parenteral ANT308 peptide, suggesting that polyethylene glycol (PEG) incorporation enhances longevity, and thus the antagonist activity of ANT308. [ABSTRACT FROM AUTHOR]

Vasoactive intestinal peptide (VIP) is an important component of the suprachiasmatic nucleus (SCN) which relays circadian information to neuronal populations, including GnRH neurons. Human and animal studies have shown an impact of disrupted daily rhythms (chronic shift work, temporal food restriction, clock gene disruption) on both male and female reproduction and fertility. To date, how VIP modulates GnRH neurons remains unknown. Calcium imaging and electrophysiology on primary GnRH neurons in explants and adult mouse brain slice, respectively, were used to address this question. We found VIP excites GnRH neurons via the VIP receptor, VPAC2. The downstream signaling pathway uses both Gs protein/adenylyl cyclase/protein kinase A (PKA) and phospholipase C/phosphatidylinositol 4,5-bisphosphate (PIP2) depletion. Furthermore, we identified a UCL2077-sensitive target, likely contributing to the slow afterhyperpolarization current (IAHP), as the PKA and PIP2 depletion target, and the KCa3.1 channel as a specific target. Thus, VIP/VPAC2 provides an example of Gs protein-coupled receptor-triggered excitation in GnRH neurons, modulating GnRH neurons likely via the slow IAHP. The possible identification of KCa3.1 in the GnRH neuron slow IAHP may provide a new therapeutical target for fertility treatments. [ABSTRACT FROM AUTHOR]

A newly invented structure called Multi-Fin-based FinFET (M-FinFET) device is a promising candidate for future improvisation of the semiconductor industry. In this article, Multi-channel FinFET (Mch-FinFET) is proposed. A comparative investigation of various DC, analog/linearity attributes is studied for gate length variation and oxide thickness through a Sentaurus TCAD tool. The simulation study concluded that the increased number of channels (= 3no.) has enhanced ION by 409.71% compared to single-channel FinFET. The decreased value of Fin width and Fin height has shown an impressive improvement of sub-threshold swing (SS) and leakage current, which helps achieve a better switching ratio. Mch-FinFET device with lower oxide thickness (Tox=1 nm) enhances the transconductance (Gm), drain conductance (Gd), intrinsic gain (Av), and transconductance gain factor (TGF) by 52.42%, 41.17%, 85.03%, respectively. Various linearity parameters like higher-order harmonics (Gm2 and Gm3), voltage intercepts points (VIP2 and VIP3), and 1-dB compression point has improved by 32.32%, 110.71% 77%, 60.09%, 418.86%, 411.5% respectively gate length of 10 nm. Besides that, a symmetric dual spacer material is introduced to the proposed structure to analyze the importance of spacer engineering. The simulation study reveals that the Mch-FinFET device with HfO2 spacer has improved driving current by 21.42%. The optimization of various short channel effects (SCEs) such as threshold voltage roll-off, sub-threshold swing (SS), and leakage current is reflected in introducing HfO2 spacer material. This detailed study is expected to design low-power RF circuits that would benefit future CMOS technology. [ABSTRACT FROM AUTHOR]

Long-term potentiation (LTP) induced by theta-burst stimulation (TBS) undergoes postweaning developmental changes partially linked to GABAergic circuit maturation. Endogenous vasoactive intestinal peptide (VIP) acting on its VPAC1 receptor strongly influences LTP induced by theta-burst stimulation (TBS), an effect dependent on GABAergic transmission. Although VPAC1 receptor levels are developmentally regulated during embryogenesis, their variation along postweaning development is unknown, as is the VPAC1 modulation of LTP or its relation to hippocampal GABAergic circuit maturation. As such, we investigated how VPAC1 modulation of LTP adjusts from weaning to adulthood along with GABAergic circuit maturation. As described, LTP induced by mild TBS (5 bursts, 4 pulses delivered at 100 Hz) was increasingly greater from weaning to adulthood. The influence of the VPAC1 receptor antagonist PG 97-269 (100 nM) on TBS-induced LTP was much larger in juvenile (3-week-old) than in young adult (6–7-week-old) or adult (12-week-old) rats. This effect was not associated with a developmental decrease in synaptic VPAC1 receptor levels. However, an increase in pre and post-synaptic GABAergic synaptic markers suggests an increase in the number of GABAergic synaptic contacts that is more prominent than the one observed in glutamatergic connections during this period. Conversely, endogenous VPAC2 receptor activation did not significantly influence TBS-induced LTP. VPAC2 receptor levels enhance pronouncedly during postweaning development, but not at synaptic sites. Given the involvement of VIP interneurons in several aspects of hippocampal-dependent learning, neurodevelopmental disorders, and epilepsy, this could provide important insights into the role of VIP modulation of hippocampal synaptic plasticity during normal and altered brain development potentially contributing to epileptogenesis. [ABSTRACT FROM AUTHOR]

Diabetic keratopathy (DK) is a common ocular complication of diabetes, characterized by alteration of the normal wound-healing mechanism, reduction of epithelial hemidesmosomes, disruption of the basement membrane, impaired barrier function, reduced corneal sensitivity, corneal ulcers, and corneal edema. The limited number of clinical studies do not allow a full characterization of the pathophysiology of DK and, until now, effective therapeutic approaches have not been available. However, in recent years, neuropeptides gained great attention for their biochemical characteristics and therapeutic potential. This review focuses on the role of neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in the eye and, in particular, in the cornea, in physiological conditions, or during DK, by providing an overview of this diabetes mellitus complication. [ABSTRACT FROM AUTHOR]

Short-term plasticity is an important feature in the brain for shaping neural dynamics and for information processing. Short-term plasticity is known to depend on many factors including brain region, cortical layer, and cell type. Here we focus on vasoactive-intestinal peptide (VIP) interneurons (INs). VIP INs play a key disinhibitory role in cortical circuits by inhibiting other IN types, including Martinotti cells (MCs) and basket cells (BCs). Despite this prominent role, short-term plasticity at synapses to and from VIP INs is not well described. In this study, we therefore characterized the short-term plasticity at inputs and outputs of genetically targeted VIP INs in mouse motor cortex. To explore inhibitory to inhibitory (I → I) short-term plasticity at layer 2/3 (L2/3) VIP IN outputs onto L5 MCs and BCs, we relied on a combination of whole-cell recording, 2-photon microscopy, and optogenetics, which revealed that VIP IN→MC/BC synapses were consistently short-term depressing. To explore excitatory (E) → I short-term plasticity at inputs to VIP INs, we used extracellular stimulation. Surprisingly, unlike VIP IN outputs, E → VIP IN synapses exhibited heterogeneous short-term dynamics, which we attributed to the target VIP IN cell rather than the input. Computational modeling furthermore linked the diversity in short-term dynamics at VIP IN inputs to a wide variability in probability of release. Taken together, our findings highlight how short-term plasticity at VIP IN inputs and outputs is specific to synapse type. We propose that the broad diversity in short-term plasticity of VIP IN inputs forms a basis to code for a broad range of contrasting signal dynamics.

Class-B1 G-protein-coupled receptors (GPCRs) are an important family of clinically relevant drug targets that remain difficult to investigate via high-throughput screening and in animal models. Here, we engineered PAClight1P78A, a novel genetically encoded sensor based on a class-B1 GPCR (the human PAC1 receptor, hmPAC1R) endowed with high dynamic range (ΔF/F0 = 1100%), excellent ligand selectivity, and rapid activation kinetics (τON = 1.15 s). To showcase the utility of this tool for in vitro applications, we thoroughly characterized and compared its expression, brightness and performance between PAClight1P78A-transfected and stably expressing cells. Demonstrating its use in animal models, we show robust expression and fluorescence responses upon exogenous ligand application ex vivo and in vivo in mice, as well as in living zebrafish larvae. Thus, the new GPCR-based sensor can be used for a wide range of applications across the life sciences empowering both basic research and drug development efforts.

Background: Chronic liver diseases such as hepatic tumors can affect the brain through the liver–brain axis, leading to neurotransmitter dysregulation and behavioral changes. Cancer patients suffer from fatigue, which can be associated with sleep disturbances. Sleep is regulated via two interlocked mechanisms: homeostatic regulation and the circadian system. In mammals, the hypothalamic suprachiasmatic nucleus (SCN) is the key component of the circadian system. It generates circadian rhythms in physiology and behavior and controls their entrainment to the surrounding light/dark cycle. Neuron–glia interactions are crucial for the functional integrity of the SCN. Under pathological conditions, oxidative stress can compromise these interactions and thus circadian timekeeping and entrainment. To date, little is known about the impact of peripheral pathologies such as hepatocellular carcinoma (HCC) on SCN. Materials and Methods: In this study, HCC was induced in adult male mice. The key neuropeptides (vasoactive intestinal peptide: VIP, arginine vasopressin: AVP), an essential component of the molecular clockwork (Bmal1), markers for activity of neurons (c-Fos), astrocytes (GFAP), microglia (IBA1), as well as oxidative stress (8-OHdG) in the SCN were analyzed by immunohistochemistry at four different time points in HCC-bearing compared to control mice. Results: The immunoreactions for VIP, Bmal1, GFAP, IBA1, and 8-OHdG were increased in HCC mice compared to control mice, especially during the activity phase. In contrast, c-Fos was decreased in HCC mice, especially during the late inactive phase. Conclusions: Our data suggest that HCC affects the circadian system at the level of SCN. This involves an alteration of neuropeptides, neuronal activity, Bmal1, activation of glia cells, and oxidative stress in the SCN.

Light-sensitive neurons are located in the ventral and central core of the suprachiasmatic nucleus (SCN), whereas stably oscillating clock neurons are found mainly in the dorsal shell. Signals between the SCN core and shell are believed to play an important role in light entrainment. Core neurons express vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), and Neuroglobin (Ngb), whereas the shell neurons express vasopressin (AVP), prokineticin 2, and the VIP type 2 (VPAC2) receptor. In rodents, light has a phase-shifting capacity at night, which induces rapid and transient expression of the EGR1 and FOS in the SCN. Methods: The present study used immunohistochemical staining of FOS, EGR1, and phenotypical markers of SCN neurons (VIP, AVP, Ngb) to identify subtypes/populations of light-responsive neurons at early night. Results: Double immunohistochemistry and cell counting were used to evaluate the number of SCN neurons expressing FOS and EGR1 in the SCN. The number of neurons expressing either EGR1 or FOS was higher than the total number of neurons co-storing EGR1 and FOS. Of the total number of light-responsive cells, 42% expressed only EGR1, 43% expressed only FOS, and 15% expressed both EGR1 and FOS. Light-responsive VIP neurons represented only 31% of all VIP neurons, and EGR1 represents the largest group of light-responsive VIP neurons (18%). VIP neurons expressing only FOS represented 1% of the total lightresponsive VIP neurons. 81% of the Ngb neurons in the mouse SCN were light-responsive, and of these neurons expressing only EGR1 after light stimulation represented 44%, whereas 24% expressed FOS. Although most light-responsive neurons are found in the core of the SCN, 29% of the AVP neurons in the shell were light-responsive, of which 8% expressed EGR1, 10% expressed FOS, and 11% co-expressed both EGR1 and FOS after light stimulation. Discussion: Our analysis revealed cell-specific differences in light responsiveness between different peptidergic and Ngb-expressing neurons in different compartments of the mouse SCN, indicating that light activates diverse neuronal networks in the SCN, some of which participate in photoentrainment. [ABSTRACT FROM AUTHOR]

Epoxy/carbon fiber (CF) composites are widely used for structural applications owing to their exceptional mechanical and physical characteristics. The main aim of this work is to individually analyze the impact of multiwalled carbon nanotubes (MWCNTs) as nanofillers in epoxy/MWCNTs/CF composites prepared by vacuum infusion process (VIP) and hand layup followed by vacuum bagging technique (HLVB). Optimal Manufacturing Strategies were followed at various stages of manufacturing which include the selection of effective dispersion technique for MWCNTs, identification of optimal weight percentage of MWCNTs in epoxy/MWCNTs nanocomposites and preparation of epoxy/MWCNTs/CF composites. For HLVB samples, tensile and flexural strengths increased from 337.5 to 475 MPa and 615.40 to 677.09 MPa. For VIP samples tensile and flexural strengths increased from 371 to 521 MPa and 714.19 to 769.02 MPa. Thermogravimetric analysis (TGA) indicated improvement in the thermal stability of epoxy with the incorporation of MWCNTs/CF and improved weight percentage retention of 84.7% at 375°C. Fracture analysis of the epoxy/MWCNTs/CF composites prepared using VIP were analyzed by FE‐SEM and revealed that constant fiber rupture caused by better interface and improved bridging mechanism eventually led to enhanced mechanical performance. The predominant immediate fracture mechanism of MWCNTs also indicated this improved interfacial interaction. Highlights: Pull‐out fracture mechanism was predominantly seen in high viscous epoxy/MWCNTs compositesImmediate fracture mechanism of MWCNTs were predominant in low viscous epoxy/MWCNTs sampleConstant fiber rupture of VIP samples indicated improved fiber matrix interfaceIncorporation of MWCNTs showed improved weight percentage retention0.5 wt% MWCNTs incorporated VIP epoxy/CF composites showed improved performance [ABSTRACT FROM AUTHOR]

Super-insulation materials have become more commonplace as highly insulated building envelopes are required to reduce the energy demand of buildings aligned with the net zero targets. While several super insulation materials are available, their environmental impacts and practical on-site limitations hindered their large-scale adoption. The following paper investigates the feasibility of developing hollow-core vacuum insulated panels supported by an internal structural array with different configurations. The designed panel was simulated and measured to evaluate its performance as a thermal insulator for building applications. Panel samples were manufactured from polished stainless-steel plates separated by a PTFE structural array. The change in temperature and heat flux through the sample was measured in a vacuum chamber at a pressure of 0.01 Pa. Thermal conductance was obtained from gradual measurements of heat flux and temperature across the sample after a rapid increase in temperature. Numerical methods that combine molecular and macroscopic solvers were used to model unsteady behaviour recorded in empirical tests. Direct Simulation Monte Carlo (DSMC) was used to calculate the thermal conductivity of the rarefied gas, which was then used to solve the enthalpy equation for the multi-region model. Thermal resistance from empirical tests and numerical methods are in agreement within error bands, the greatest accuracy observed in high conductance models. Thermal resistance as low as 0.17 m 2 · K · W − 1 and as high as 4.75 m 2 · K · W − 1 was measured. Low conductance sample configurations were sensitive to thermal contact conductance from the structural array contact interfaces, accounting for at least 40% of transferred energy. Gas conduction at a pressure of 0.01 Pa transfers up to 4% of energy in low emissivity sample configurations. Radiative energy transfer in high conductance configurations was responsible for up to 95% of transferred energy. The paper provides a comprehensive feasibility study, providing a solid foundation for further design optimization of the technology. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) signaling pathway is a powerful regulator of cell proliferation, growth, synapse maintenance and cell fate. While intensely studied for its role in cancer, the role of mTOR signaling is just beginning to be uncovered in specific cell types that are implicated in neurodevelopmental disorders. Previously, loss of the Tsc1 gene, which results in hyperactive mTOR, was shown to affect the function and molecular properties of GABAergic cortical interneurons (CINs) derived from the medial ganglionic eminence. To assess if other important classes of CINs could be impacted by mTOR dysfunction, we deleted Tsc1 in a caudal ganglionic eminence-derived interneuron group, the vasoactive intestinal peptide (VIP)+ subtype, whose activity disinhibits local circuits. Tsc1 mutant VIP+ CINs reduced their pattern of apoptosis from postnatal days 15–20, resulting in increased VIP+ CINs. The mutant CINs exhibited synaptic and electrophysiological properties that could contribute to the high rate of seizure activity in humans that harbor Tsc1 mutations. [ABSTRACT FROM AUTHOR]

Bacillus thuringiensis Berliner (Bt) and B. cereus sensu stricto Frankland and Frankland are closely related species of aerobic, spore-forming bacteria included in the B. cereus sensu lato group. This group is one of the most studied, but it remains also the most mysterious species of bacteria. Despite more than a century of research on the features of these ubiquitous bacteria, there are a lot of questionable issues related to their taxonomy, resistance to external influences, endophytic existence, their place in multidimensional relationships in the ecosystem, and many others. The review summarizes current data on the mutualistic relationships of Bt and B. cereus bacteria with plants, the structure of the phytomicrobiomes including Bt and B. cereus, and the abilities of plant-associated and endophytic strains to improve plant resistance to various environmental factors and its productivity. Key findings on the possibility of the use of Cry gene promoter for transcription of the target dsRNA and simultaneous release of pore-forming proteins and provocation of RNA-interference in pest organisms allow us to consider this group of microorganisms as unique tools of genetic engineering and biological control. This will open the prospects for the development and direct change of plant microbiomes, and possibly serve as the basis for the regulation of the entire agroecosystem. [ABSTRACT FROM AUTHOR]

Neuropeptides are among the most abundant chemical messengers produced in the brain that can function as neurotransmitters or hormones. Neuropeptides are synthesized and used by a neuron. There are over one hundred known neuropeptides, representing the largest and most diverse class of signaling molecules in the nervous system. Neuropeptides are often co-released with other neuropeptides and neurotransmitters in a single neuron, yielding a multitude of effects. The focus of this review is their role in cancer in general and mainly sarcomas. Neuropeptides and their receptors are no exception when it comes to their pro or antitumorigenic diverse functions defined by cellular and disease content. The molecular targets, pathways, and epigenetic regulation of sarcoma growth by neuropeptides are highlighted to better understand the importance of these molecules and suggest future alternative therapies for this challenging disease with unmet cancer needs. [ABSTRACT FROM AUTHOR]

The plasticity of inhibitory interneurons (INs) plays an important role in the organization and maintenance of cortical microcircuits. Given the many different IN types, there is an even greater diversity in synapse-type-specific plasticity learning rules at excitatory to excitatory (E→I), I→E, and I→I synapses. I→I synapses play a key disinhibitory role in cortical circuits. Because they typically target other INs, vasoactive intestinal peptide (VIP) INs are often featured in I→I→E disinhibition, which upregulates activity in nearby excitatory neurons. VIP IN dysregulation may thus lead to neuropathologies such as epilepsy. In spite of the important activity regulatory role of VIP INs, their long-term plasticity has not been described. Therefore, we characterized the phenomenology of spike-timing-dependent plasticity (STDP) at inputs and outputs of genetically defined VIP INs. Using a combination of whole-cell recording, 2-photon microscopy, and optogenetics, we explored I→I STDP at layer 2/3 (L2/3) VIP IN outputs onto L5 Martinotti cells (MCs) and basket cells (BCs). We found that VIP IN→MC synapses underwent causal long-term depression (LTD) that was presynaptically expressed. VIP IN→BC connections, however, did not undergo any detectable plasticity. Conversely, using extracellular stimulation, we explored E→I STDP at inputs to VIP INs which revealed long-term potentiation (LTP) for both causal and acausal timings. Taken together, our results demonstrate that VIP INs possess synapse-type-specific learning rules at their inputs and outputs. This suggests the possibility of harnessing VIP IN long-term plasticity to control activity-related neuropathologies such as epilepsy.

Vasoactive intestinal peptide (VIP) is an important component of the suprachiasmatic nucleus (SCN) which relays circadian information to neuronal populations, including GnRH neurons. Human and animal studies have shown an impact of disrupted daily rhythms (chronic shift work, temporal food restriction, clock gene disruption) on both male and female reproduction and fertility. To date, how VIP modulates GnRH neurons remains unknown. Calcium imaging and electrophysiology on primary GnRH neurons in explants and adult mouse brain slice, respectively, were used to address this question. We found VIP excites GnRH neurons via the VIP receptor, VPAC2. The downstream signaling pathway uses both Gs protein/adenylyl cyclase/protein kinase A (PKA) and phospholipase C/phosphatidylinositol 4,5-bisphosphate (PIP2) depletion. Furthermore, we identified a UCL2077-sensitive target, likely contributing to the slow afterhyperpolarization current (IAHP), as the PKA and PIP2 depletion target, and the KCa3.1 channel as a specific target. Thus, VIP/VPAC2 provides an example of Gs protein-coupled receptor-triggered excitation in GnRH neurons, modulating GnRH neurons likely via the slow IAHP. The possible identification of KCa3.1 in the GnRH neuron slow IAHP may provide a new therapeutical target for fertility treatments.

ViP™ (Visionox intelligent Pixelization) Technology is a novel RGB pixelization approach without Fine Metal Mask for OLED patterning. ViP™technology was released in May 2023. In this paper, some key features of display performance and mass production outlook of ViP™ Technology will be discussed. [ABSTRACT FROM AUTHOR]

Alzheimer’s Disease (AD) represents a significant neurodegenerative challenge with current therapeutic strategies primarily focused on symptomatic management. This review explores the relationship between disrupted circadian rhythms, AD and the critical involvement of vasoactive intestinal peptide (VIP) and adenylate cyclase-activating polypeptide (PACAP) signaling pathways. These pathways hold promise for new drug development and provide insights into the complex pathogenesis of AD. Enhancement of brain bioavailability through advanced drug delivery systems is proposed and reviewed.

Light-sensitive neurons are located in the ventral and central core of the suprachiasmatic nucleus (SCN), whereas stably oscillating clock neurons are found mainly in the dorsal shell. Signals between the SCN core and shell are believed to play an important role in light entrainment. Core neurons express vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), and Neuroglobin (Ngb), whereas the shell neurons express vasopressin (AVP), prokineticin 2, and the VIP type 2 (VPAC2) receptor. In rodents, light has a phase-shifting capacity at night, which induces rapid and transient expression of the EGR1 and FOS in the SCN.Methods: The present study used immunohistochemical staining of FOS, EGR1, and phenotypical markers of SCN neurons (VIP, AVP, Ngb) to identify subtypes/populations of light-responsive neurons at early night.Results: Double immunohistochemistry and cell counting were used to evaluate the number of SCN neurons expressing FOS and EGR1 in the SCN. The number of neurons expressing either EGR1 or FOS was higher than the total number of neurons co-storing EGR1 and FOS. Of the total number of light-responsive cells, 42% expressed only EGR1, 43% expressed only FOS, and 15% expressed both EGR1 and FOS. Light-responsive VIP neurons represented only 31% of all VIP neurons, and EGR1 represents the largest group of light-responsive VIP neurons (18%). VIP neurons expressing only FOS represented 1% of the total light-responsive VIP neurons. 81% of the Ngb neurons in the mouse SCN were light-responsive, and of these neurons expressing only EGR1 after light stimulation represented 44%, whereas 24% expressed FOS. Although most light-responsive neurons are found in the core of the SCN, 29% of the AVP neurons in the shell were light-responsive, of which 8% expressed EGR1, 10% expressed FOS, and 11% co-expressed both EGR1 and FOS after light stimulation.Discussion: Our analysis revealed cell-specific differences in light responsiveness between different peptidergic and Ngb-expressing neurons in different compartments of the mouse SCN, indicating that light activates diverse neuronal networks in the SCN, some of which participate in photoentrainment.

Despite the prevalence of diabetic retinopathy, the majority of adult diabetic patients develop visually debilitating corneal complications, including impaired wound healing. Unfortunately, there is limited treatment for diabetes-induced corneal damage. The current project investigates a novel, peptide-based combination therapy, thymosin beta-4 and vasoactive intestinal peptide (Tβ4/VIP), against high-glucose-induced damage to the corneal epithelium. Electric cell–substrate impedance sensing (ECIS) was used for real-time monitoring of barrier function and wound healing of human corneal epithelial cells maintained in either normal glucose (5 mM) or high glucose (25 mM) ± Tβ4 (0.1%) and VIP (5 nM). Barrier integrity was assessed by resistance, impedance, and capacitance measurements. For the wound healing assay, cell migration was also monitored. Corneal epithelial tight junction proteins (ZO-1, ZO-2, occludin, and claudin-1) were assessed to confirm our findings. Barrier integrity and wound healing were significantly impaired under high-glucose conditions. However, barrier function and cell migration significantly improved with Tβ4/VIP treatment. These findings were supported by high-glucose-induced downregulation of tight junction proteins that were effectively maintained similar to normal levels when treated with Tβ4/VIP. These results strongly support the premise that Tβ4 and VIP work synergistically to protect corneal epithelial cells against hyperglycemia-induced damage. In addition, this work highlights the potential for significant translational impact regarding the treatment of diabetic patients and associated complications of the cornea. [ABSTRACT FROM AUTHOR]

Marketing scholars have extensively examined the role of altruistic and ecological personal values and pro‐environmental identity in ethical consumption decisions. Conversely, the role of egoistic personal values and other identities has received scant attention from researchers. This research examines the role of altruistic, egoistic, and ecological personal values in triggering two types of identities: pro‐environmental and car‐authority. The effects of values and identities on personal norms and attitudes toward electric cars were also examined. A sample of Egyptian consumers responded to an electronic survey, and collected data were analyzed using SEM. The findings generally support the VIP framework, where biospheric values significantly affect pro‐environmental identity, and pro‐environmental identity affects personal norms. Furthermore, personal norms affected attitudes positively. A different path was obtained which starts with biospheric and altruistic values affecting car authority positively and negatively, respectively. Car authority identity was found to affect attitudes directly, although this is accepted at lower confidence levels. A discussion of research findings, implications, and research limitations were also presented. [ABSTRACT FROM AUTHOR]

Long-term potentiation (LTP) induced by theta-burst stimulation (TBS) undergoes postweaning developmental changes partially linked to GABAergic circuit maturation. Endogenous vasoactive intestinal peptide (VIP) acting on its VPAC1 receptor strongly influences LTP induced by theta-burst stimulation (TBS), an effect dependent on GABAergic transmission. Although VPAC1 receptor levels are developmentally regulated during embryogenesis, their variation along postweaning development is unknown, as is the VPAC1 modulation of LTP or its relation to hippocampal GABAergic circuit maturation. As such, we investigated how VPAC1 modulation of LTP adjusts from weaning to adulthood along with GABAergic circuit maturation. As described, LTP induced by mild TBS (5 bursts, 4 pulses delivered at 100 Hz) was increasingly greater from weaning to adulthood. The influence of the VPAC1 receptor antagonist PG 97-269 (100 nM) on TBS-induced LTP was much larger in juvenile (3-week-old) than in young adult (6–7-week-old) or adult (12-week-old) rats. This effect was not associated with a developmental decrease in synaptic VPAC1 receptor levels. However, an increase in pre and post-synaptic GABAergic synaptic markers suggests an increase in the number of GABAergic synaptic contacts that is more prominent than the one observed in glutamatergic connections during this period. Conversely, endogenous VPAC2 receptor activation did not significantly influence TBS-induced LTP. VPAC2 receptor levels enhance pronouncedly during postweaning development, but not at synaptic sites. Given the involvement of VIP interneurons in several aspects of hippocampal-dependent learning, neurodevelopmental disorders, and epilepsy, this could provide important insights into the role of VIP modulation of hippocampal synaptic plasticity during normal and altered brain development potentially contributing to epileptogenesis.

Spinal cord injury (SCI) is a debilitating condition that results in significant impairment of motor function and sensation. Despite the ongoing efforts to develop effective treatments, there are currently very limited options available for patients with SCI. Celastrol, a natural anti-inflammatory compound extracted from Tripterygium wilfordii, has been shown to exhibit anti-inflammatory and anti-apoptotic properties. In this study, we aimed to explore the therapeutic potential of celastrol for SCI and elucidate the underlying molecular mechanisms involved. We found that local tissue often experiences a significant decrease in cAMP content and occurrs apoptosis after SCI. However, the treatment of celastrol could promote the production of cAMP by up-regulating the VIP-ADCYAP1R1-GNAS pathway. This could effectively inhibit the phosphorylation of JNK and prevent apoptosis, ultimately improving the exercise ability after SCI. Together, our results reveal celastrol may be a promising therapeutic agent for the treatment of SCI.

Migraine is a debilitating neurological condition affecting millions of people worldwide. Until a few years ago, preventive migraine treatments were based on molecules with pleiotropic targets, developed for other indications, and discovered by serendipity to be effective in migraine prevention, although often burdened by tolerability issues leading to low adherence. However, the progresses in unravelling the migraine pathophysiology allowed identifying novel putative targets as calcitonin gene-related peptide (CGRP). Nevertheless, despite the revolution brought by CGRP monoclonal antibodies and gepants, a significant percentage of patients still remains burdened by an unsatisfactory response, suggesting that other pathways may play a critical role, with an extent of involvement varying among different migraine patients. Specifically, neuropeptides of the CGRP family, such as adrenomedullin and amylin; molecules of the secretin family, such as pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP); receptors, such as transient receptor potential (TRP) channels; intracellular downstream determinants, such as potassium channels, but also the opioid system and the purinergic pathway, have been suggested to be involved in migraine pathophysiology. The present review provides an overview of these pathways, highlighting, based on preclinical and clinical evidence, as well as provocative studies, their potential role as future targets for migraine preventive treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: PACAP and VIP are peptides produced and released in the central and peripheral nervous systems and in a variety of peripheral organs and tissues. PACAP and VIP, which share high amino acidic sequence homology, bind to three different G-protein-coupled receptors, PAC1, VPAC1 and VPAC2, through which they activate signaling cascades to regulate important body metabolic and homeostatic physiological processes. The PACAP and VIP pathways have been linked to the regulation of body weight and fat mass accumulation, and to the development of obesity and metabolic syndrome. In this review article, PACAP and VIP regulation of appetite/satiety, feeding behavior, metabolism, body homeostasis and orexigenic and anorexigenic hormones is discussed. The overwhelming increase in the prevalence of obesity and related disorders in recent years is one of the greatest threats to the global healthcare system since it generates immense healthcare costs. As the prevalence of obesity approaches epidemic proportions, the importance of elucidating the mechanisms regulating appetite, satiety, body metabolism, energy balance and adiposity has garnered significant attention. Currently, gastrointestinal (GI) bariatric surgery remains the only approach capable of achieving successful weight loss. Appetite, satiety, feeding behavior, energy intake and expenditure are regulated by central and peripheral neurohormonal mechanisms that have not been fully elucidated yet. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Vasoactive Intestinal Polypeptide (VIP) are members of a family of regulatory peptides that are widely distributed in parallel with their specific receptors, VPAC1R, VPAC2R and PAC1R, in the central nervous system (CNS) and in the periphery, such as in the gastrointestinal tract and its associated organs and immune cells. PACAP and VIP have been reported to play an important role in the regulation of body phenotype, metabolism and homeostatic functions. The purpose of this review is to present recent data on the effects of PACAP, VIP, VPAC1R, VPAC2R and PAC1R on the modulation of appetite, satiety, metabolism, calorie intake and fat accumulation, to evaluate their potential use as therapeutic targets for the treatment of obesity and metabolic syndrome. [ABSTRACT FROM AUTHOR]

Simple Summary: The downstream signaling mechanisms and importance of the autocrine secretion of the vasoactive intestinal peptide (VIP) in cancer remains poorly understood. We hypothesized that VIP expression may promote cancer-associated signaling pathways. We analyzed gene sequencing data from cancer and healthy tissues based on the co-expression data of the VIP with 760 cancer-related genes. We identified a meaningful and novel association between the VIP and transcription factor ZEB1 in healthy and malignant human gastrointestinal tissues. ZEB1 is a known regulator of cancer EMT (epithelial–mesenchymal transition). Gene set analysis further supports the overlap in the EMT and cell cycle pathways. Our results identify a potentially novel function of the autocrine VIP as an important signaling peptide and biomarker of ZEB1-mediated EMT. VIP (vasoactive intestinal peptide) is a 28-amino acid peptide hormone expressed by cancer and the healthy nervous system, digestive tract, cardiovascular, and immune cell tissues. Many cancers express VIP and its surface receptors VPAC1 and VPAC2, but the role of autocrine VIP signaling in cancer as a targetable prognostic and predictive biomarker remains poorly understood. Therefore, we conducted an in silico gene expression analysis to study the mechanisms of autocrine VIP signaling in cancer. VIP expression from TCGA PANCAN tissue samples was analyzed against the expression levels of 760 cancer-associated genes. Of the 760 genes, 10 (MAPK3, ZEB1, TEK, NOS2, PTCH1 EIF4G1, GMPS, CDK2, RUVBL1, and TIMELESS) showed statistically meaningful associations with the VIP (Pearson's R-coefficient > |0.3|; p < 0.05) across all cancer histologies. The strongest association with the VIP was for the epithelial–mesenchymal transition regulator ZEB1 in gastrointestinal malignancies. Similar positive correlations between the VIP and ZEB1 expression were also observed in healthy gastrointestinal tissues. Gene set analysis indicates the VIP is involved in the EMT and cell cycle pathways, and a high VIP and ZEB1 expression is associated with higher median estimate and stromal scores These findings uncover novel mechanisms for VIP- signaling in cancer and specifically suggest a role for VIP as a biomarker of ZEB1-mediated EMT. Further studies are warranted to characterize the specific mechanism of this interaction. [ABSTRACT FROM AUTHOR]

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most common and severe manifestations of lupus; however, its pathogenesis is still poorly understood. While there is sparse evidence suggesting that the ongoing autoimmunity may trigger pathogenic changes to the central nervous system (CNS) microvasculature, culminating in inflammatory/ischemic damage, further evidence is still needed. In this study, we used the spontaneous mouse model of SLE (NZBWF1 mice) to investigate the expression of genes and proteins associated with endothelial (dys)function: tissue and urokinase plasminogen activators (tPA and uPA), intercellular and vascular adhesion molecules 1 (ICAM-1 and VCAM-1), brain derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 4 (KLF4) and neuroprotection/immune modulation: pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), PACAP receptor (PAC1), VIP receptors 1 and 2 (VPAC1 and VPAC2). Analyses were carried out both in the hippocampus and striatum of SLE mice of two different age groups (2 and 7 months old), since age correlates with disease severity. In the hippocampus, we identified a gene/protein expression profile indicative of mild endothelial dysfunction, which increased in severity in aged SLE mice. These alterations were paralleled by moderate alterations in the expression of VIP, PACAP and related receptors. In contrast, we report a robust upregulation of endothelial activation markers in the striatum of both young and aged mice, concurrent with significant induction of the VIP/PACAP system. These data identify molecular signatures of endothelial alterations in the hippocampus and striatum of NZBWF1 mice, which are accompanied by a heightened expression of endogenous protective/immune-modulatory neuropeptides. Collectively, our results support the idea that NPSLE may cause alterations of the CNS micro-vascular compartment that cannot be effectively counteracted by the endogenous activity of the neuropeptides PACAP and VIP. [ABSTRACT FROM AUTHOR]

Manipulation of genetic diversity is significant for developing new varieties in crop breeding programs. The success of elite varieties in the last decade may be narrowing genetic diversity among original populations down to an ideotype genome under human demands. However, it is unclear how genetic diversity is shaped to maximize the genetic potential for human demands. Understanding of genomic changes during crop breeding programs for the establishment of elite varieties will drive genetic diversity for the development of new varieties to meet future demands. We will be more concerned on genetic diversity. Now, we can see genetic diversity among plant materials using the methods using next generation sequencing. Here, we propose one strategy, which is common over crop species; visualization of genetic diversity for ideal phenotype (VIP). VIP can be applied in common for various crop species with ploidy level, pollination habit, genome size, and the history of their breeding programs. VIP would accelerate the development of new elite varieties to meet future challenges from the world's increasing population, global climate change, and sustainability in agriculture. [ABSTRACT FROM AUTHOR]

The ViP technology has been evaluated on an internal AMOLED phone display platform with a ppi of 458 by the Gen6 line. In this technology, ViP replaced FMM (Fine Metal Mask) for deposition and patterning. Characterization, simulation, advantages, and future applications of ViP have been discussed. [ABSTRACT FROM AUTHOR]

Abstract Background Gastrointestinal (GI) functions are controlled by the enteric nervous system (ENS) in vertebrates, but data on snakes are scarce, as most studies were done in mammals. However, the feeding of many snakes, including Crotalus atrox, is in strong contrast with mammals, as it consumes an immense, intact prey that is forwarded, stored, and processed by the GI tract. We performed immunohistochemistry in different regions of the GI tract to assess the neuronal density and to quantify cholinergic, nitrergic, and VIPergic enteric neurons. We recorded motility patterns and determined the role of different neurotransmitters in the control of motility. Neuroimaging experiments complemented motility findings. Results A well-developed ganglionated myenteric plexus (MP) was found in the oesophagus, stomach, and small and large intestines. In the submucous plexus (SMP) most neurons were scattered individually without forming ganglia. The lowest number of neurons was present in the SMP of the proximal colon, while the highest was in the MP of the oesophagus. The total number of neurons in the ENS was estimated to be approx. 1.5 million. In all regions of the SMP except for the oesophagus more nitric oxide synthase+ than choline-acetyltransferase (ChAT)+ neurons were counted, while in the MP ChAT+ neurons dominated. In the SMP most nerve cells were VIP+, contrary to the MP, where numerous VIP+ nerve fibers but hardly any VIP+ neuronal cell bodies were seen. Regular contractions were observed in muscle strips from the distal stomach, but not from the proximal stomach or the colon. We identified acetylcholine as the main excitatory and nitric oxide as the main inhibitory neurotransmitter. Furthermore, 5-HT and dopamine stimulated, while VIP and the ß-receptor-agonist isoproterenol inhibited motility. ATP had only a minor inhibitory effect. Nerve-evoked contractile responses were sodium-dependent, insensitive to tetrodotoxin (TTX), but sensitive to lidocaine, supported by neuroimaging experiments. Conclusions The structure of the ENS, and patterns of gastric and colonic contractile activity of Crotalus atrox are strikingly different from mammalian models. However, the main excitatory and inhibitory pathways appear to be conserved. Future studies have to explore how the observed differences are an adaptation to the particular feeding strategy of the snake.

This research aimed to study the preventive and relieving outcomes of kiwi berry on constipation. The administration of kiwi berries to mice resulted in a significant increase in body weight gain of 148.2% compared to mice that were constipated. The number of stools and the water content of stools both increased by 138.5% and 106.5%, respectively. The gastrointestinal transit rate increased by 45.3%, and the time it took for the first dark stool to form decreased by 57.5%. The levels of the excitability neurotransmitters were found to be higher in the group that had been given kiwi berries in comparison to the group that had been given loperamide. The opposite results were produced by vasoactive intestinal peptide (VIP) and aquaporin-3 (AQP3). In addition, kiwi berry consumption may lessen epithelial cell apoptosis and promote colon health. All the results point to kiwi berries as an extremely promising food supplement for the prevention and relief of constipation in the future since they successfully prevent and alleviate constipation brought on by loperamide.