Статті в журналах з теми "Catalyse relais"

Herein, we report a new approach to bio-inspired catalyst design. The molecular catalyst employed in these studies is based on the robust and selective Re(bpy)(CO)₃Cl-type (bpy = 2,2′-bipyridine) homogeneous catalysts, which have been extensively studied for their ability to reduce CO₂electrochemically or photochemically in the presence of a photosensitizer. These catalysts can be highly active photocatalysts in their own right. In this work, the bipyridine ligand was modified with amino acids and synthetic peptides. These results build on earlier findings wherein the bipyridine ligand was functionalized with amide groups to promote dimer formation and CO₂reduction by an alternate bimolecular mechanism at lower overpotential (ca.250 mV) than the more commonly observed unimolecular process. The bio-inspired catalysts were designed to allow for the incorporation of proton relays to support reduction of CO₂to CO and H₂O. The coupling of amino acids tyrosine and phenylalanine led to the formation of two structurally similar Re catalyst/peptide catalysts for comparison of proton transport during catalysis. This article reports the synthesis and characterization of novel catalyst/peptide hybrids by molecular dynamics (MD simulations of structural dynamics), NMR studies of solution phase structures, and electrochemical studies to measure the activities of new bio-inspired catalysts in the reduction of CO_2.

The proton transfer plays a crucial, yet not well-control, role in enhancing the oxygen evolution reaction (OER) performance of transition metal (TM) (oxy) hydroxide materials. Herein, we take Ce-doped FeCo layered double hydroxide (Ce-FeCo LDH) nanosheets in situ growth on spindle-like MIL-88A, as a model system to demonstrate enhancing OER activity through the promotion of proton transfer by forming the carboxylate ligands coordinated with TM atoms. The carboxyl group-functionalized MIL-88A@Ce-FeCo LDH core–shell hybrid catalyst, fabricated by the one-pot reflux method, is made up of Ce-FeCo LDH as active component and carboxylate ligands as a proton acceptor. Specifically, the uncoordinated carboxylate ligands serve as relays to promote proton transfer and deprotonation efficiency. As a result, this core–shell structured hybrid exhibits superior OER activity while maintaining excellent durability. This work provides a facile method to reserve carboxylates as the station of proton transfer on TM-based catalyst to promote water splitting.

Islam Nusantara gave rise to many perceptions in the midst of Indonesian Muslim society, both in terminological discourse and practical perception. This study presents the results of qualitative research on Islam Nusantara in the perception of East Kalimantan community leaders from the Regency of Paser Grogot, Kutai Kartanegara, Samarinda City and Berau. In their perception Islam Nusantara is perceived as a catalyst between Islam, nationality, plurality and eternal truth. This was stated in the form of understanding and practice by East Kalimantan community leaders in religious life. In terms of their understanding, Islam Nusantara is perceived as a functional instrument of mutualism between Islam and culture towards productive diversity. While in practice, Islam Nusantara is placed as a foothold or starting point in carrying out da'wah to realize the simplification of human relations and eternal truth

The reductive part of artificial photosynthesis, the reduction of protons into H2, is a two electron two proton process. It corresponds basically to the reactions occurring in natural photosystem I. We show in this review a selection of involved processes and components which are mandatory for making this light-driven reaction possible at all. The design and the performances of the water reduction catalysts is a main focus together with the question about electron relays or sacrificial electron donors. It is shown how an original catalyst is developed into better ones and what it needs to move from purely academic homogeneous processes to heterogeneous systems. The importance of detailed mechanistic knowledge obtained from kinetic data is emphasized.

When using binders in coatings, whose film formation process relays on the oxygen uptake to start the cross-linking reaction, the use of special metal salts, so called driers, can catalyze the process, accelerating the curing of the film and reducing the waiting time between the applications of the next layers of paint. In this work, three primary driers, based on cobalt, iron and manganese are compared, to determine which one is more efficient in drying of alkyd and boiled linseed oil based coating. The study has been done using FTIR spectroscopy to investigate the rate of drying for each drier. The obtained results confirm that using the cobalt drier, the film formation is faster than with the other two alternative driers.

Protein–protein assemblies are highly prevalent in all living cells. Considerable evidence has recently accumulated suggesting that particularly transient association/dissociation of proteins represent an important means of regulation of metabolism. This is true not only in the cytosol and organelle matrices, but also at membrane surfaces where, for example, receptor complexes, as well as those of key metabolic pathways, are common. Transporters also frequently come up in lists of interacting proteins, for example, binding proteins that catalyze the production of their substrates or that act as relays within signal transduction cascades. In this review, we provide an update of technologies that are used in the study of such interactions with mitochondrial transport proteins, highlighting the difficulties that arise in their use for membrane proteins and discussing our current understanding of the biological function of such interactions.

A trinuclear nickel complex with S-based ligands is reported as a bio-inspired model of the [NiFe] hydrogenases' active site. DFT calculations indicate that thiolate and thioether functions are involved as proton relays in the H₂ evolution mechanism.

La Bibliothèque Vaticane garde, sous la signature Vat. lat. 5730, un manuscrit roman enluminé du premier quart du XIIe siècle et de prove­nance catalane qui contient le commentaire de Florus de Lyon aux épîtres de Saint Paul. On considère qu'il fut copié et enluminé à l'abbaye de Santa Maria de Ripoll en référence au document du roy Lothaire (982) copié sur le dernier folio. Cette étude analyse les rapports existant entre les illustra­tions du Vat. 5730 et celles d'autres manuscrits romans catalans, comme le Beatus de Turin et, surtout ces de l'évangéliaire de Cuixà (Perpignan, Bi­bliothèque Municipale, ms. 1) avec lesquelles les rapports sont plus étroits. Aucun de ces manuscrits n'ayant été illustré à Ripoll, on suggère que peut­être le Vat. 5730 ait pu être exécuté dans un autre scriptorium catalan (Gi­rona?) et tranféré après à Ripoll ou le document a pu y être ajouté. Des rapports avec les manuscrits étrangers -l'un d'eux (Paris, Bibliothèque Na­tionale, ms. lat. 794) peut-être italien, et d'autres enluminés à Cîteaux au commencement du XIIº siècle- sont aussi considérés.

The Hsp70 family of molecular chaperones acts as a central ‘hub’ in the cell that interacts with numerous newly synthesized proteins to assist in their biogenesis. Apart from its central and well-established role in facilitating protein folding, Hsp70s also act as key decision points in the cellular chaperone network that direct client proteins to distinct biogenesis and quality control pathways. In this paper, we review accumulating data that illustrate a new branch in the Hsp70 network: the post-translational targeting of nascent membrane and organellar proteins to diverse cellular organelles. Work in multiple pathways suggests that Hsp70, via its ability to interact with components of protein targeting and translocation machineries, can initiate elaborate substrate relays in a sophisticated cascade of chaperones, cochaperones, and receptor proteins, and thus provide a mechanism to safeguard and deliver nascent membrane proteins to the correct cellular membrane. We discuss the mechanistic principles gleaned from better-studied Hsp70-dependent targeting pathways and outline the observations and outstanding questions in less well-studied systems.

Breast cancer tumor draining lymph nodes (TDLNs) display distinct morphologic changes depending on the breast cancer subtype. For triple-negative breast cancers (TNBC), draining LNs display a higher amount of secondary lymphoid follicles, which can be regarded as a surrogate marker for an activated humoral immune response. In the present study, we focus on PD1+ T-follicular helper cells (Tfh) in TDLNs of TNBC, since PD1+ Tfh are drivers of the germinal center (GC) reaction. We quantified PD1+ Tfh in 22 sentinel LNs with 853 GCs and interfollicular areas from 19 patients with TNBC by morphometry from digitalized immunostained tissue sections. Overall survival was significantly worse for patients with a higher number and area density of PD1+ Tfh within GCs of TDLNs. Further, we performed T-cell receptor gamma chain (TRG) analysis from microdissected tissue in the primary tumor and TDLNs. Eleven patients showed the same TRG clones in the tumor and the LN. Five patients shared the same TRG clones in the tumor and the GCs. In two patients, those clones were highly enriched inside the GCs. Enrichment of identical TRG clones at the tumor site vs. the TDLN was associated with improved overall survival. TDLNs are important relays of cancer immunity and enable surrogate approaches to predict the outcome of TNBC itself.

Eksekusi peraturan presiden Nomor 15/2018 di Waduk Jatiluhur melalui penertiban Keramba Jaring Apung (KJA) tidak hanya akan merubah tatanan ekonomi namun juga memiliki risiko sosial bagi masyarakat pemanfaat sumber daya perikanan waduk baik pemanfaat langsung maupun tidak langsung. Makalah ini bertujuan untuk menganalisis risiko sosial yang akan muncul akibat penertiban KJA tersebut. Penelitian dilakukan di Kabupaten Purwakarta pada tahun 2018 dengan menggunakan metode analisis deskriptif kualitatif. Hasil penelitian menunjukkan bahwa program penertiban KJA di Waduk Jatiluhurakan menghasilkan berbagai risiko sosial. Risiko sosial yang terjadi berupa culture shock masyarakat akibat perubahan pola kehidupan, kohesifitas masyarakat menurun sehingga rentan terhadap konflikhorizontal, hilangnya jaminan sosial, dan berbagai permasalahan demografi. Permasalahan demografi meliputi meningkatnya angka pengangguran, meningkatnya angka putus sekolah, meningkatnya angkakriminalitas, dan mobilitas teritorial berupa migrasi masyarakat keluar daerah. Salah satu alternatif yang dapat dilakukan sebagai upaya untuk menghilangkan risiko sosial dapat dimulai dari menghilangkansumber risiko dengan cara meningkatkan kapasitas masyarakat dalam menciptakan lapangan kerja baru, sosialisasi kebijakan agar masyarakat paham maksud dan tujuan kebijakan, menyediakan fasilitasi berupa rubrik konsultasi untuk menyelesaikan permasalahan sosial masyarakat terdampak. Selain itu perlu juga memperbaiki faktor katalis risiko berupa perbaikan kebijakan dengan mempertimbangkan sumber-sumber risiko berupa kondisi masyarakat, relasi usaha, dan historis pembangunan waduk dilihat dari aspek sosial.Title: Social Risk of Floating Cages Control Programin the Jatiluhur Reservoir fAs the implementation of Presidential Regulation No. 15/2018, the floating nets control in Jatiluhur Reservoir resulted not only in economic disorder but also in social risks for the direct and indirect beneficiaries of the reservoir. This paper aimed to analyzing the social risks as the result of the floating net control. The study was conducted in Purwakarta Regency in 2018 using qualitative descriptive methods. The Floating Nets Control Program in Jatiluhur Reservoir caused a variety of social risks. The social risks were culture shock due to life changes, decreased community cohesion that vulnerable to conflict, loss of social benefit, and demographic issues. The demographic issues included increased numberof unemployment, dropouts, crimes, and migration to outside the region. Some alternative solutions to eliminate these social risks are eliminating the risk sources by increasing community capacity to create new jobs, educating community regarding the objectives of the policies, providing consultation services to help people with solution of these social problems. In addition, it is necessary to fix the risk catalyst factor with policy improvement that consider community condition, business relation, and social aspect of historical reservoir development.

Eksekusi peraturan presiden Nomor 15/2018 di Waduk Jatiluhur melalui penertiban Keramba Jaring Apung (KJA) tidak hanya akan merubah tatanan ekonomi namun juga memiliki risiko sosial bagi masyarakat pemanfaat sumber daya perikanan waduk baik pemanfaat langsung maupun tidak langsung. Makalah ini bertujuan untuk menganalisis risiko sosial yang akan muncul akibat penertiban KJA tersebut. Penelitian dilakukan di Kabupaten Purwakarta pada tahun 2018 dengan menggunakan metode analisis deskriptif kualitatif. Hasil penelitian menunjukkan bahwa program penertiban KJA di Waduk Jatiluhurakan menghasilkan berbagai risiko sosial. Risiko sosial yang terjadi berupa culture shock masyarakat akibat perubahan pola kehidupan, kohesifitas masyarakat menurun sehingga rentan terhadap konflikhorizontal, hilangnya jaminan sosial, dan berbagai permasalahan demografi. Permasalahan demografi meliputi meningkatnya angka pengangguran, meningkatnya angka putus sekolah, meningkatnya angkakriminalitas, dan mobilitas teritorial berupa migrasi masyarakat keluar daerah. Salah satu alternatif yang dapat dilakukan sebagai upaya untuk menghilangkan risiko sosial dapat dimulai dari menghilangkansumber risiko dengan cara meningkatkan kapasitas masyarakat dalam menciptakan lapangan kerja baru, sosialisasi kebijakan agar masyarakat paham maksud dan tujuan kebijakan, menyediakan fasilitasi berupa rubrik konsultasi untuk menyelesaikan permasalahan sosial masyarakat terdampak. Selain itu perlu juga memperbaiki faktor katalis risiko berupa perbaikan kebijakan dengan mempertimbangkan sumber-sumber risiko berupa kondisi masyarakat, relasi usaha, dan historis pembangunan waduk dilihat dari aspek sosial.Title: Social Risk of Floating Cages Control Programin the Jatiluhur Reservoir fAs the implementation of Presidential Regulation No. 15/2018, the floating nets control in Jatiluhur Reservoir resulted not only in economic disorder but also in social risks for the direct and indirect beneficiaries of the reservoir. This paper aimed to analyzing the social risks as the result of the floating net control. The study was conducted in Purwakarta Regency in 2018 using qualitative descriptive methods. The Floating Nets Control Program in Jatiluhur Reservoir caused a variety of social risks. The social risks were culture shock due to life changes, decreased community cohesion that vulnerable to conflict, loss of social benefit, and demographic issues. The demographic issues included increased numberof unemployment, dropouts, crimes, and migration to outside the region. Some alternative solutions to eliminate these social risks are eliminating the risk sources by increasing community capacity to create new jobs, educating community regarding the objectives of the policies, providing consultation services to help people with solution of these social problems. In addition, it is necessary to fix the risk catalyst factor with policy improvement that consider community condition, business relation, and social aspect of historical reservoir development.

Melatonin is the main pineal hormone that relays light/dark-cycle information to the circadian system. Recent studies have examined the intrinsic antitumor activity of melatonin in various cancers, including hepatocellular carcinoma (HCC), the primary life-threatening malignancy in both sexes in Taiwan. However, the detailed regulatory mechanisms underlying melatonin’s anti-HCC activity remain incompletely understood. Here, we investigated the mechanisms by which the anti-HCC activity of melatonin is regulated. Human hepatoma cell lines were treated with 1 and 2 mM melatonin, and functional assays were used to dissect melatonin’s antitumor effect in HCC; small-RNA sequencing was performed to identify the microRNAs (miRNAs) involved in the anti-HCC activity of melatonin; and quantitative RT-PCR and Western blotting were used to elucidate how miRNAs regulate melatonin-mediated HCC suppression. Melatonin treatment at both doses strongly inhibited the proliferation, migration and invasion capacities of Huh7 and HepG2 cell lines, and melatonin treatment markedly induced the expression of the miRNA let7i-3p in cells. Notably, transfection of cells with a let7i-3p mimic drastically reduced RAF1 expression and activation of mitogen-activated protein kinase signaling downstream from RAF1, and rescue-assay results demonstrated that melatonin inhibited HCC progression by modulating let7i-3p-mediated RAF1 suppression. Our findings support the view that melatonin treatment holds considerable promise as a therapy for HCC.

Mediator 25 (Med25) is a member of the mediator complex that relays signals from transcription factors to the RNA polymerase II machinery. Multiple transcription factors, particularly those involved in lipid metabolism, utilize the mediator complex, but how Med25 is involved in this context is unclear. We previously identified Med25 in a translatome screen of adult cardiomyocytes (CMs) in a novel cell type-specific model of LMNA cardiomyopathy. In this study, we show that Med25 upregulation is coincident with myocardial lipid accumulation. To ascertain the role of Med25 in lipid accumulation, we utilized iPSC-derived and neonatal CMs to recapitulate the in vivo phenotype by depleting lamins A and C (lamin A/C) in vitro. Although lamin A/C depletion elicits lipid accumulation, this effect appears to be mediated by divergent mechanisms dependent on the CM developmental state. To directly investigate Med25 in lipid accumulation, we induced adipogenesis in Med25-silenced 3T3-L1 preadipocytes and detected enhanced lipid accumulation. Assessment of pertinent mediators driving adipogenesis revealed that C/EBPα and PPARγ are super-induced by Med25 silencing. Our results indicate that Med25 limits adipogenic potential by suppressing the levels of master regulators that govern adipogenesis. Furthermore, we caution the use of early-developmental-stage cardiomyocytes to model adult-stage cells, particularly for dissecting metabolic perturbations emanating from LMNA mutations.

The neuromuscular junction (NMJ) is a crucial structure that connects the cholinergic motor neurons to the muscle fibers and allows for muscle contraction and movement. Despite the interruption of the supraspinal pathways that occurs in spinal cord injury (SCI), the NMJ, innervated by motor neurons below the injury site, has been found to remain intact. This highlights the importance of studying the NMJ in rodent models of various nervous system disorders, such as amyotrophic lateral sclerosis (ALS), Charcot–Marie–Tooth disease (CMT), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). The NMJ is also involved in myasthenic disorders, such as myasthenia gravis (MG), and is vulnerable to neurotoxin damage. Thus, it is important to analyze the integrity of the NMJ in rodent models during the early stages of the disease, as this may allow for a better understanding of the condition and potential treatment options. The spinal cord also plays a crucial role in the functioning of the NMJ, as the junction relays information from the spinal cord to the muscle fibers, and the integrity of the NMJ could be disrupted by SCI. Therefore, it is vital to study SCI and muscle function when studying NMJ disorders. This review discusses the formation and function of the NMJ after SCI and potential interventions that may reverse or improve NMJ dysfunction, such as exercise, nutrition, and trophic factors.

Traumatic brain injury (TBI) disrupts thalamic and cortical integrity. The effect of post-injury reorganization and plasticity in thalamocortical pathways on the functional outcome remains unclear. We evaluated whether TBI causes structural changes in the thalamocortical axonal projection terminals in the primary somatosensory cortex (S1) that lead to hyperexcitability. TBI was induced in adult male Sprague Dawley rats with lateral fluid-percussion injury. A virus carrying the fluorescent-tagged opsin channel rhodopsin 2 transgene was injected into the ventroposterior thalamus. We then traced the thalamocortical pathways and analyzed the reorganization of their axonal terminals in S1. Next, we optogenetically stimulated the thalamocortical relays from the ventral posterior lateral and medial nuclei to assess the post-TBI functionality of the pathway. Immunohistochemical analysis revealed that TBI did not alter the spatial distribution or lamina-specific targeting of projection terminals in S1. TBI reduced the axon terminal density in the motor cortex by 44% and in S1 by 30%. A nematic tensor-based analysis revealed that in control rats, the axon terminals in layer V were orientated perpendicular to the pial surface (60.3°). In TBI rats their orientation was more parallel to the pial surface (5.43°, difference between the groups p < 0.05). Moreover, the level of anisotropy of the axon terminals was high in controls (0.063) compared with TBI rats (0.045, p < 0.05). Optical stimulation of the sensory thalamus increased alpha activity in electroencephalography by 312% in controls (p > 0.05) and 237% (p > 0.05) in TBI rats compared with the baseline. However, only TBI rats showed increased beta activity (33%) with harmonics at 5 Hz. Our findings indicate that TBI induces reorganization of thalamocortical axonal terminals in the perilesional cortex, which alters responses to thalamic stimulation.

Proton‐coupled electron transfer (PCET) imparts an energetic advantage over solo electron transfer in activating inert substances. Natural PCET enzyme catalysis generally requires tripartite preorganization of proton relay, substrate‐bound active center, and redox mediator, making the processes efficient and precluding side reactions. Inspired by this, a heterogeneous photocatalytic PCET system was established to achieve higher PCET driving forces by modifying proton relays into anthraquinone‐based anionic coordination polymers. The proximally separated proton relays and photoredox‐mediating anthraquinone moiety allowed pre‐assembly of inert substrate between them, merging proton and electron into unsaturated bond by photoreductive PCET, which enhanced reaction kinetics than the counter catalyst without proton relay. This photocatalytic PCET method was applied to a broad‐scoped reduction of aryl ketones, unsaturated carbonyls, and aromatic compounds. The distinctive regioselectivities for the reduction of isoquinoline derivatives were found to occur on the carbon‐ring sides. PCET‐hydrogenated radical intermediate of quinoline could be trapped by alkene for proton relay‐assisted Minisci addition, forming the pharmaceutical aza‐acenaphthene scaffold within one step. When using heteroatom(X)–H/C–H compounds as proton‐electron donors, this protocol could activate these inert bonds through photooxidative PCET to afford radicals and trap them by electron‐deficient unsaturated compounds, furnishing the direct X–H/C–H functionalization.

Proton‐coupled electron transfer (PCET) imparts an energetic advantage over solo electron transfer in activating inert substances. Natural PCET enzyme catalysis generally requires tripartite preorganization of proton relay, substrate‐bound active center, and redox mediator, making the processes efficient and precluding side reactions. Inspired by this, a heterogeneous photocatalytic PCET system was established to achieve higher PCET driving forces by modifying proton relays into anthraquinone‐based anionic coordination polymers. The proximally separated proton relays and photoredox‐mediating anthraquinone moiety allowed pre‐assembly of inert substrate between them, merging proton and electron into unsaturated bond by photoreductive PCET, which enhanced reaction kinetics than the counter catalyst without proton relay. This photocatalytic PCET method was applied to a broad‐scoped reduction of aryl ketones, unsaturated carbonyls, and aromatic compounds. The distinctive regioselectivities for the reduction of isoquinoline derivatives were found to occur on the carbon‐ring sides. PCET‐hydrogenated radical intermediate of quinoline could be trapped by alkene for proton relay‐assisted Minisci addition, forming the pharmaceutical aza‐acenaphthene scaffold within one step. When using heteroatom(X)–H/C–H compounds as proton‐electron donors, this protocol could activate these inert bonds through photooxidative PCET to afford radicals and trap them by electron‐deficient unsaturated compounds, furnishing the direct X–H/C–H functionalization.

Integration of CO2 capture capability from flue gas and electrochemical CO2 reduction reaction (eCO2RR) active sites into a catalyst is a promising cost‐effective strategy for carbon neutrality, but is of great difficulty. Herein, combining the mixed gas breakthrough experiments and eCO2RR tests, we showed that a Ag12 cluster‐based metal‐organic framework (1−NH2, aka Ag12bpy−NH2), simultaneously possessing CO2 capture sites as "CO2 relays" and eCO2RR active sites, can not only utilize its micropores to efficiently capture CO2 from simulated flue gas (CO2:N2 = 15:85, at 298 K), but also catalyze eCO2RR of the adsorbed CO2 into CO with an ultra‐high CO2 conversion of 60%. More importantly, its eCO2RR performance (a Faradaic efficiency (CO) of 96% with a commercial current density of 120 mA cm−2 at a very low cell voltage of −2.3 V for 300 hours and the full‐cell energy conversion efficiency of 56%) under simulated flue gas atmosphere is close to that under 100% CO2 atmosphere, and higher than those of all reported catalysts at higher potential under 100% CO2 atmosphere. This work bridges the gap between CO2 enrichment/capture and eCO2RR.

Integration of CO2 capture capability from flue gas and electrochemical CO2 reduction reaction (eCO2RR) active sites into a catalyst is a promising cost‐effective strategy for carbon neutrality, but is of great difficulty. Herein, combining the mixed gas breakthrough experiments and eCO2RR tests, we showed that a Ag12 cluster‐based metal‐organic framework (1−NH2, aka Ag12bpy−NH2), simultaneously possessing CO2 capture sites as "CO2 relays" and eCO2RR active sites, can not only utilize its micropores to efficiently capture CO2 from simulated flue gas (CO2:N2 = 15:85, at 298 K), but also catalyze eCO2RR of the adsorbed CO2 into CO with an ultra‐high CO2 conversion of 60%. More importantly, its eCO2RR performance (a Faradaic efficiency (CO) of 96% with a commercial current density of 120 mA cm−2 at a very low cell voltage of −2.3 V for 300 hours and the full‐cell energy conversion efficiency of 56%) under simulated flue gas atmosphere is close to that under 100% CO2 atmosphere, and higher than those of all reported catalysts at higher potential under 100% CO2 atmosphere. This work bridges the gap between CO2 enrichment/capture and eCO2RR.

In this paper the author poses and seeks an answer to the question, “Is music an effective tool in secondary and post-secondary foreign language learning classrooms?” By observing articles and research ranging from the historic intertwinement of language and music to its use as a medium for learner choice, the author details music’s benefits on foreign language learner cognition, affect, motivation, and identity as well as the challenges involved. Additionally, the author presents some possible ways the introduction of music into the classroom can be a catalyst for learner and teacher autonomy.

AbstractHow to put together a comprehensive water oxidation design is the long‐term problem for the generation of sustainable fuels. In nature, plants are equipped with a complex mechanism (the Calvin cycle) in the stroma that, over the billions of years, efficiently takes CO2 and converts it to sugar. This reductive process needs electrons from an oxygen‐evolving complex (OEC) in the core of photosystem II, where a water oxidation reaction (WOR) releases molecular oxygen. The initial function of proton relays in natural WOR happens when Tyrosine Yz is oxidized by light harvested P680 through a proton‐coupled electron transfer reaction. The second and main one, is composed of water‐included polypeptide channels from and to CaMn4O5. These channels were created utilizing hydrogen‐bonded networks (HBN). HBN is crucial in providing water substrate and removing the released protons to prevent the accumulation of protons and preserve the stability of the catalytic center. This concept summarizes the challenges in employing biomimicry to create artificial leaves from the viewpoint of proton relays, with the main purpose being providing structural functionality to assist the quick proton hopping.

Abstract First-row transition metal-based catalysts have been developed for the oxygen evolution reaction (OER) during the past years, however, such catalysts typically operate at overpotentials (η) significantly above thermodynamic requirements. Here, we report an iron/nickel terephthalate coordination polymer on nickel form (NiFeCP/NF) as catalyst for OER, in which both coordinated and uncoordinated carboxylates were maintained after electrolysis. NiFeCP/NF exhibits outstanding electro-catalytic OER activity with a low overpotential of 188 mV at 10 mA cm−2 in 1.0 KOH, with a small Tafel slope and excellent stability. The pH-independent OER activity of NiFeCP/NF on the reversible hydrogen electrode scale suggests that a concerted proton-coupled electron transfer (c-PET) process is the rate-determining step (RDS) during water oxidation. Deuterium kinetic isotope effects, proton inventory studies and atom-proton-transfer measurements indicate that the uncoordinated carboxylates are serving as the proton transfer relays, with a similar function as amino acid residues in photosystem II (PSII), accelerating the proton-transfer rate.

Nanosecond time‐resolved X‐ray (tr‐XAS) and optical transient absorption spectroscopy (OTA) are applied to study 3 multimolecular photocatalytic systems with [Ru(bpy)3]2+photoabsorber, ascorbic acid electron donor and Co catalysts with methylene (1), hydroxomethylene (2) and methyl (3) amine substituents in pure water. OTA and tr‐XAS of 1 and 2 show that the favored catalytic pathway involves reductive quenching of the excited photosensitizer and electron transfer to the catalyst to form a CoII square pyramidal intermediate with a bonded aqua molecule followed by a CoI square planar derivative that decays within ~8 µs. By contrast, a CoI square pyramidal intermediate with a longer decay lifetime of ~35 µs is formed from an analogous CoII geometry for 3 in H2O. These results highlight the protonation of CoI to form the elusive hydride species to be the rate limiting step and show that the catalytic rate can be enhanced through hydrogen containing pendant amines that act as H‐H bond formation proton relays.

The reaction kinetics of photocatalytic CO 2 reduction is highly dependent on the transfer rate of electrons and protons to the CO 2 molecules adsorbed on catalytic centers. Studies on uncovering the proton effect in catalysts on photocatalytic activity of CO 2 reduction are significant but rarely reported. In this paper, we, from the molecular level, revealed that the photocatalytic activity of CO 2 reduction is closely related to the proton availability in catalysts. Specifically, four dinuclear Co(II) complexes based on Robson-type ligands with different number of carboxylic groups (– n COOH; n = 0, 2, 4, 6) were designed and synthesized. All these complexes show photocatalytic activity for CO 2 reduction to CO in a water-containing system upon visible-light illumination. Interestingly, the CO yields increase positively with the increase of the carboxylic-group number in dinuclear Co(II) complexes. The one containing –6COOH shows the best photocatalytic activity for CO 2 reduction to CO, with the TON value reaching as high as 10,294. The value is 1.8, 3.4, and 7.8 times higher than those containing –4COOH, –2COOH, and –0COOH, respectively. The high TON value also makes the dinuclear Co(II) complex with –6COOH outstanding among reported homogeneous molecular catalysts for photocatalytic CO 2 reduction. Control experiments and density functional theory calculation indicated that more carboxylic groups in the catalyst endow the catalyst with more proton relays, thus accelerating the proton transfer and boosting the photocatalytic CO 2 reduction. This study, at a molecular level, elucidates that more carboxylic groups in catalysts are beneficial for boosting the reaction kinetics of photocatalytic CO 2 reduction.

AbstractThe increasing concentration of CO2 in the atmosphere and its impact on the climate are matters of significant concern. Extensive research is being conducted on molecular catalysts to electrochemically reduce CO2 into valuable products to disrupt the unidirectional carbon flow. This study compares two manganese bipyridine catalysts, tailored with four or two benzylic diethylamine groups in the secondary coordination sphere. Either of these amine‐bearing scaffolds positioned close to the Mn center serves as effective proton relays to facilitate the formation of the corresponding Mn hydride intermediate. Alongside competitive H2 evolution, the reaction of this crucial intermediate with CO2 leads to formate. Our findings underscore the pronounced influence of external Brønsted acids on product selectivity. Notably, when employing the catalyst bearing four amine groups, the HCOO−/H2 ratio varies from 81 : 3 with 1.0 M iPrOH to 16 : 64 with 1.0 M PhOH, while the Mn complex adorned with two amine pendant groups consistently favors HCOO−, irrespective of the utilized proton sources. Infrared spectroelectrochemistry and density‐functional theory calculations unveil distinct disparities in the reactivity of the Mn hydrides toward CO2 due to the change of ligand bulkiness in the two cases. This work substantiates the importance of modulating spatial accessibility while modifying the second sphere encompassing molecular catalysts.

ABSTRACT The human pathogen Clostridioides difficile is increasingly tolerant of multiple antibiotics and causes infections with a high rate of recurrence, creating an urgent need for new preventative and therapeutic strategies. The stringent response, a universal bacterial response to extracellular stress, governs antibiotic survival and pathogenesis in diverse organisms but has not previously been characterized in C. difficile. Here, we report that the C. difficile (p)ppGpp synthetase RSH is incapable of utilizing GTP or GMP as a substrate but readily synthesizes ppGpp from GDP. The enzyme also utilizes many structurally diverse metal cofactors for reaction catalysis and remains functionally stable at a wide range of environmental pHs. Transcription of rsh is stimulated by stationary-phase onset and by exposure to the antibiotics clindamycin and metronidazole. Chemical inhibition of RSH by the ppGpp analog relacin increases antibiotic susceptibility in epidemic C. difficile R20291, indicating that RSH inhibitors may be a viable strategy for drug development against C. difficile infection. Finally, transcriptional suppression of rsh also increases bacterial antibiotic susceptibility, suggesting that RSH contributes to C. difficile antibiotic tolerance and survival. IMPORTANCE Clostridioides difficile infection (CDI) is an urgent public health threat with a high recurrence rate, in part because the causative bacterium has a high rate of antibiotic survival. The (p)ppGpp-mediated bacterial stringent response plays a role in antibiotic tolerance in diverse pathogens and is a potential target for development of new antimicrobials because the enzymes that metabolize (p)ppGpp have no mammalian homologs. We report that stationary-phase onset and antibiotics induce expression of the clostridial ppGpp synthetase RSH and that both chemical inhibition and translational suppression of RSH increase C. difficile antibiotic susceptibility. This demonstrates that development of RSH inhibitors to serve as adjuvants to antibiotic therapy is a potential approach for the development of new strategies to combat CDI.

Discussing the interaction between representation and narrative structures, Anthony Mandal argues that the Gothic has always been “an intrinsically intertextual genre” (Mandal 350). From its inception, the intertextuality of the Gothic has taken many and varied incarnations, from simple references and allusions between texts—dates, locations, characters, and “creatures”—to intricate and evocative uses of style and plot organisation. And even though it would be unwise to reduce the Gothic “text” to a simple master narrative, one cannot deny that, in the midst of re-elaborations and re-interpretations, interconnections and interpolations also appear, a collective gathering of ideas and writing practices that construct what is known as “the Gothic intertext” (Mishra 235). As far as storytelling, characterisation, and symbolism are concerned, the Gothic finds strength in its ability to develop as well as negate expectation, re-moulding the culturally known and the aesthetically acceptable in order to present its audience with a multi-faceted and multi-layered narrative. Although the Gothic has traditionally found fertile ground in literary works—a connection that is now a legacy as much as an origin—other contemporary media, such as animation, have offered the Gothic a privileged chance for growth and adaptation. An evocative example of the mergence between the Gothic mode and the animated medium is Alex Hirsch’s Gravity Falls. This visual text provides an example of the reach of the Gothic within popular culture, where intersecting hideous creatures and interconnected narrative structures, although simple and “for children” on the surface, reveal the presence of a dense and intertextual Gothic network. Those interlacings are, of course, never disconnected from the wider cultural framework, and clearly occupy an important part in unravelling the insidious aspects of human nature, from the difficulties of finding “oneself” to the loneliness of the everyday. Gravity Falls is an animated television series created by Alex Hirsch. It premiered on the Disney Channel in the United States on 15 June 2012. Now scheduled for its second season of running, Gravity Falls follows the adventures of 12-year-old twin siblings Dipper and Mabel Pines while on their summer vacation in the small town of Gravity Falls, Oregon. The choice of “twins” as main characters reveals, even at such an embryonic level, a connection to Gothicised structures, as the mode itself, as Vijay Mishra suggests, finds an affinity with doublings and “specular identifications” that “confuse the norm” (63). The presence of twins makes the double nature of character, traditionally a metaphorical and implicit idea in the Gothic, a very obvious and explicit one. Dipper and Mabel are staying with their eccentric and money-grabbing Great Uncle Stan—often referred to as “Grunkle Stan”—who runs the local curiosity shop known as the Mystery Shack. It becomes very obvious from the very beginning that an air of mystery truly surrounds the Shack, which quickly lives up to its name, and the eponymous town. In an aptly Gothic manner, things are definitely not what they seem and the twins are caught in odd plots, eerily occurrences, and haunted/haunting experiences on a daily basis. The instigator for the twins’ interest in the odd manifestations is the finding of a mysterious journal, a manual the relays detailed descriptions of the creatures that inhabit the forest in the town of Gravity Falls. The author of the journal remains unknown, and is commonly known only as “3”, an unexplained number that marks the cover of the book itself. Although the connection between the Gothic and animation may be obscure, it is in fact possible to identify many common and intersecting elements—aesthetically, narratively, and conceptually—that highlight the two as being intrinsically connected. The successful relation that the Gothic holds with animation is based in the mode’s fundamental predilection for not only subversion, excess and the exploration of the realm of the “imagination”, but also humour and self-reflexivity. These aspects are shared with animation which, as a medium, is ideally placed for exploring and presenting the imaginative and the bizarre, while pushing the boundaries of the known and the proper. Julia Round suggests that the Gothic “has long been identified as containing a dual sense of play and fear” (7). The playfulness and destabilisation that are proper to the mode find a fertile territory in animation in view of not only its many genres, but also its style and usually sensational subject matter. This discourse becomes particularly relevant if one takes into consideration matters of audienceship, or, at least, receivership. Although not historically intended for younger viewers, the animation has evolved into a profoundly children-orientated medium. From cinema to television, animated features and series are the domain of children of various ages. Big production houses such as Disney and Warner Bros have capitalised on the potential of the medium, and established its place in broadcasting slots for young viewers. Not unlike comics—which is, in a way, its ancestral medium—animation is such a malleable and contextual form that it requires a far-reaching and inclusive approach, one that is often interdisciplinary in scope; within this, where the multi-faceted nature of the Gothic opens up the way for seeing animated narratives as the highly socio-historical mediums they are. And not unlike comics, animation shares a common ground with the Gothic in requiring a vast scope of analysis, one that is intrinsically based on the conceptual connections between “texts”. Round has also aptly argued that, like comics, animated series lend themselves to malleable and mouldable re-elaboration: “from the cultural to the aesthetic, the structural to the thematic”, graphic media always reflect the impact of “intertextual and historical references” (8). Animation’s ability to convey, connect, and revolutionise ideas is, therefore, well-matched to the aesthetic and conceptual idiosyncrasies of Gothic tropes. Dipper and Mabel’s vacation in the town of Gravity Falls is characterised by the appearance of numerous super- and preter-natural creatures. The list of “monsters” encountered by the twins is long and growing, from gnomes, goblins, mermaids and zombies, to ghosts, clones, and a wide and colourful variety of demons. And although, at first glance, this list would appear to be a simple and simplistic grouping of bizarre and creatively assembled creatures, it is made quickly apparent that these “monsters” are all inspired, often very directly, by “existing”—or, at least, well-known—Gothic creatures, and their respective contexts of development. Indeed, the links to the Gothic in contemporary popular culture are unavoidable. The creatures in Gravity Falls are presented with subtle references to Gothic literature and cinema, from John Carpenter’s Halloween (1978) and Joe Dante’s Gremlins (1984), to Stephen King’s The Shining (1977) and Needful Things (1991). Borrowing from these texts, the creatures in the series all have strange names that rely on play-on-words and re-inventions, and the rubric twists that they undertake are part of a system of both homage and conceptual interdependency. One can find, for instance, “Manotaurs”—creatures that are half-bull and half-man, and that value “manliness” in their society above all else—and the “Gremlobin” – a gigantic monster somewhere in between, we are told, a “gremlin” and a “goblin”, whose eyes can show “your worst nightmares”. But the range extends to other bizarre “creatures” that are clearly very spooky, such as the “Summewrween Trickster”—a large, shadowy, purple/orange monster with a “jack-o’-melon” mask – the living “mailbox”—a sentient and omniscient object—and the truly haunting Bill Cipher—a mind demon that can be summoned through an incantation and enter a person’s subconscious. The connection to the Gothic in popular culture is instrumental for the construction of the Gothic intertext in Gravity Falls. In episode One, “Tourist Trapped” (1.01), Mabel is kidnapped by a tribe of gnomes, who are set on making her their queen. The gnomes are incongruous creatures: on the one hand, they are vengeful and spiteful, recalling the horror monsters found in movies such as the questionable Blood Gnome (2004). On the other, however, they wear red pointy hats and white beards, and their friendly smiles recall the harmless appearance of actual garden gnomes. When the gnomes grow upset, they throw up rainbows; this strange fact destroys their potential as a Gothic horror icon, and makes them accessible and amusing. This subversion of iconography takes place with a number of other “creatures” in Gravity Falls, with the Summerween Trickster—subverting the “terror” of Hallowe’en—being another fitting example. When the gnomes are attempting to woe Mabel, they do not appear to her in their real form: they camouflage themselves into a teenage boy— one who is moody, brooding, and mysterious—and become Mabel’s boyfriend; the “boy’s” interest in her, however, is so intense, that Dipper suspects him to be a member of “The Undead”, a category of monster that is closely described in 3’s journal: due to their “pale skin” and “bad attitudes”, they are often mistaken for “teenagers”. Clues to Dipper’s doubts include the teenage boy’s hand “falling off” while he is hugging Mabel, a clear sign—it would seem—that the boy is obviously a decaying, zombie corpse. The intertextual connection to several horror visual narratives where limbs “fall off” the undead and the monstrous is clear here, with apt film examples being Dawn of the Dead (1978), The Fly (1986), horror comedy Army of Darkness (1992), and, more recently, television’s The Walking Dead (2010-). The references to well-known horror films are scattered throughout the series, and comprise the majority of the lampooned cultural context in which the creatures appear. In spite of Dipper’s suspicions, the situation is revealed to have a rather different outcome. When the boyfriend tells Mabel he has a big secret to reveal, her mind wanders into another direction, choosing a different type of undead, as she expectantly thinks: “Please be a vampire…please be a vampire”. It is not difficult to spot the conceptual connection here to narratives such as Stephenie Meyer’s Twilight saga (2005-2008), both in its literary and cinematic variations, where brooding and mysterious teenage boys find ideal incarnations as the undead creature. The romanticised nature of teenage fictional narratives such as the Twilight saga is also mirrored in Mabel’s distinctive love-centred interest in the potential vampire, revealing an intertextual and highly contextual association to seeing the creature as part of an amorous relationship, as opposed to a blood-thirsty murderer. Mabel’s dreams of vampric love are unfortunately shattered when the boyfriend is revealed to be several gnomes carefully assembled to operate a human-like body, rather than one immortal lover. Irrespective of its desire to parody the Gothic, however, Gravity Falls still maintains unavoidable links to the notion of terror. Clear evidence of this is to be found in the fact that all “creatures” in the series present a level of anthropomorphism about them, and this is interpreted by the characters—and the viewers—as one of their scariest aspects. Leigh Blackmore suggests that a special brand of terror can be found in “anthropomorphic beings” that are in fact not human (Blackmore 95). Most of the creatures in the series are humanoid in shape, and can speak like humans. From gnomes to mermaids, mailboxes and demons, the creatures act as humans, but they are in fact something “other”, something that only recalls the human itself. This idea of being “almost human”, but “not quite”, is disturbing in itself, and connects the presentation of the creatures to the Gothic via the notion of the uncanny: “a crisis of the natural, touching upon everything that one might have thought was ‘part of nature’ […] human nature, the nature of reality and the world” (Royle 1). The uncanny nature of the creatures in Gravity Falls is maintained through their profound inhumanity, and their simultaneous links to human ways of acting, speaking, and even thinking. Indeed, most of the creatures are presented as petty, bitter, and childish, and often seen as greedy and sulking. In a way, the creatures lampoon some of the most intrinsic qualities of the human species, what separates us from animals. The supernatural creatures operate here as a critique of the humans themselves, exposing, as the Gothic often does, the most disturbing parts of humanity. The creatures are presented initially as scary, recalling—albeit very briefly—notions of terror and horror, but that façade is quickly destroyed as their “real nature” is exposed. They are de-terrorised by not only making them common, but also ridiculing their habits and de-constructing their thinly-veiled Gothic personas. The creatures in Gravity Falls are a subversion of the subversion, a re-thinking of the Gothic through parody that allows their conceptual, and culturally relevant, function to be rapidly exposed. The impact of the Gothic intertext in Gravity Falls is not only visible in its representational forms—its monsters and “creatures”—but also extends to its structural organisation. Jerrold Hogle has argued that, although they maintain a heterogeneous construction of texts and contexts, there are certain qualities applicable to “Gothic texts”: an antiquated space (often decaying); a concealed secret from the historical past; a physical or psychological haunting; and an oscillation between “reality” and the “supernatural” (3). Although Hogle’s pinpointing of what he calls the “Gothic matrix” (3) is mainly focused on the literary world, a broader and more wide-reaching understanding of the Gothic text allows these qualities to be clearly identifiable in other narrative mediums, such as an animated series. Indeed, Gravity Falls presents the main elements of the “Gothic matrix”: the Mystery Shack is an old and isolated place, physically crumbling and in constant state of disrepair; it is made clear that the Shack harbours many secrets—filled as it is with hidden passageways and underground vaults—connected to the shady past of Grunkle Stan and its unresolved connections to mysticism and magic; there are plenty of hauntings to be found in the series: from physical ones—in the form of demons and ghosts—to psychological ones, condensed in Dipper and Mabel’s difficulties with their approaching puberties and “growing up”; finally, the line between reality and supernatural is constantly challenged by the appearance of multiple creatures that are clearly not of this world, and even though several characters doubt their existence within the story, their very presence challenges the stability of the boundaries between real and unreal. On the surface, the series is presented as a standard linear narrative, where the linear journey of each 20-minute episode culminates with the resolution of the main “haunting”, and the usual destruction or appeasing of the “creature”. And while the series’ use of cliff-hangers is, in true television style, a common presence, they also expose and recall the unresolved nature of the narrative. Indeed, the story’s structure in Gravity Falls is reliant on narrative undertellings and off-shoots that often lie underneath the logical “line” of the plot. Sub-plots reign supreme, and multiple motives for the characters’ actions are introduced but not expanded upon, leaving the series impregnated with an aura of uncertainty and chaos. The focus of the storytelling is also denied; one moment, it appears to be Dipper’s desire to discover the “secrets” of the forest; the other, it is Grunkle Stan’s long-time battle with his arch-nemesis Gideon over the ownership of the Shack. This plot confusion in Gravity Falls continues to expose its narrative debt to the Gothic intertext, since “structural multiplicity”, as Round suggests, is “a defining feature of the Gothic” (19). The series’ narrative structure is based on numerous multiplicities, an open denial of linear journeys that is dependant, paradoxically, on the illusion of resolution. The most evocative example of Gravity Falls’ denial of clear-cut structures is arguably to be found in the narrative underlayers added by 3’s monster manual. It is obvious from the beginning that 3’s stay in the town of Gravity Falls was riddled with strange experiences, and that his sojourn intersected, at one point or the other, with the lives and secrets of Grunkle Stan and his enemies. It is also made clear that 3’s journal is not a solitary presence in the narrative, but is in fact only one in a triad of mystical books—these books, it is suggested, have great power once put together, but the resolution to this mystery is yet to be revealed. As Grunkle Stan and Gideon fight (secretly) over the possession of the three books, it is openly suggested that several uncovered stories haunt the main narrative in the series and, unknown Dipper and Mabel, are responsible for many of the strange occurrences during their stay at the Shack. Jean-Jacques Lecercle has long argued that one of the defining characteristics of the Gothic, and its intertextual structure, is the presence of “embedded narratives” (72). In Gravity Falls, the use of 3’s manual as not only an initiator of the plot, but also as a continuous performative link to the “haunted” past, uncovers the series’ re-elaboration of the traditional structure of Gothic narratives. As a paratextual presence in the story—one that is, however, often responsible for the development of the main narrative—3’s manual draws attention to the importance of constructing layered stories in order to create the structures of terror, and subsequent horror, that are essential to the Gothic itself. Although it often provides Dipper with information for solving the mysteries of the Shack, and subduing the supernatural creatures that overtake it, 3’s manual is, in reality, a very disruptive presence in the story. It creates confusion as it begins storytelling without concluding it, and opens the way to narrative pathways that are never fully explored. This is of course in keeping with the traditional narrative structures of the Gothic mode, where ancient books and stories— belonging to “antiquity”—are used as a catalyst for the present narrative to take place, but are also strangely displaced from it. This notion recalls Victor Sage’s suggestion that, in Gothic narratives, ancient books and stories paradoxically “disrupt” the main narrative, starting a separate dialogue with a storytelling structure that is inevitably unexplored and left unanswered (86). Canonical examples such as Ann Radcliffe’s The Mysteries of Udolpho (1794) and Emily Brontë’s Wuthering Heights (1847) inevitably come to mind here, but also more recent cinematic examples such as the Evil Dead franchise (1978-), where ancient books and old storytellers uncover hoary secrets that instigate, as well as obscure, the main narrative. In Gravity Falls, the interaction with 3’s manual is inherently performative, and continuously intertextual, but it is also deeply confusing, adding to the feeling of strangeness and mystery that is the conceptual basis for the series itself. The intertextual connections that drive the narrative in Gravity Falls construct lampooned versions of both the traditional concepts of Gothic horror and Gothic terror. Hogle has suggested that Gothic terror is apparent in the construction of suspense, achieved through an exploration of psychological hauntings, human nature and its un/limitations, and that which is kept out sight, the expected “hidden secrets” (3). Gothic horror, on the other hand, is characterised by the consequences of these occurrences; the physical manifestation of the “haunting”, so to speak, is achieved through the presentation of something repulsive and horrific, the monstrous in its various incarnations (Hogle 3). In Gravity Falls, the connection to the traditional Gothic intertext is made clear through both elicitations of “terror”, and subsequent manifestations of “horror”. Indeed, the “hidden secrets” of the Shack, and to some extent, the fears and insecurities of the characters, are mediated through the appearance of horrific machinery and creatures. The Shack always conceals something hidden, a magical element of sort that is kept secret by intricate passageways. The shadowy nature of the building – evoking the psychological hauntings of Gothic terror – inevitably causes the appearance of something physically disturbing, finding its apogee in a Gothic horror experience. A clear example of this can be found in the episode “Double Dipper” (1.07). Desperate to impress his co-worker and secret love-interest Wendy, and “haunted” by his lack of self-worth, Dipper roams the rooms of the Shack and discovers a very old and enchanted photocopier machine; the machine copies “people”, making clones of the original. The “clones” themselves are a manifestation of horror, a presence that breaks the boundaries of propriety, and worries its viewers in view of its very existence. The cloning copy machine is strongly intertextual as it not only provides conceptual links to numerous cinematic and literary examples where a “haunted machine” threats to destroy humanity— in examples such as Stephen King’s Christine (1983) —but also evokes the threat of “doubles”, another powerfully Gothic conduit (Royle). As it is often the case in Gravity Falls, Dipper loses control of the situation, and the dozens of clones he unwittingly created take over his life and threaten to annihilate him. Dipper must destroy the “horror” —the clones—and confront the “terror”—his haunting insecurities and personal secrets—in order to restore the original balance. This intertextual dynamic validates Hogle’s contention that, in Gothic narratives, both the physical and the psychological “hauntings” rise from view “within the antiquated space” and “manifest unresolved conflicts that can no longer be successfully buried from view” (Hogle 2). The “hidden secrets” of Gravity Falls, and their manifestations through both Gothic horror and terror, are clearly connected to explorations of human nature and deeply existentialist crises that are put forward through humour and parody. These range from Grunkle Stan’ inability to commit to a relationship—and his feeling that life is slipping away in his old age—to the twins’ constant insecurities about pre-teen amorous encounters. Not to mention the knowledge that, in reality, Dipper and Mabel were “abandoned” by their mother in the care of Stan, as she had other plans for the summer. As Round has argued, the Gothic’s most significant development seems to have been the “transvaluation of moral issues”, as notions of “monsters have become less clear cut” (18). The series’ successful engagement with the wider “monstrous” intertext, and its connection to moral issues and “hidden” preoccupations, uncovers the ability of the Gothic, as Catherine Spooner puts it, to act as “commodity”, no longer a marginalised cultural presence, but a fully purchasable item in consumer-capitalist systems (Spooner 2007). The evocations of both horror and terror in Gravity Falls are, naturally, unavoidably diluted, a homage as much as a direct encounter. The use of the monstrous and the haunted in the series is domesticated, made accessible so that it can be presented to a younger and more commercial audience. The profound interlacings with the Gothic intertext remain, however, unchanged, as the series reconciles its subversive, uncanny elements with the inevitably conventional, Disney-fied context in which it is placed. References Blackmore, Leigh. “Marvels and Horrors: Terry Dowling’s Clowns at Midnight”. 21st Century Gothic: Great Gothic Novels Since 2000, ed. Danel Olson. Lanham: Rowman & Littlefield, 2011. 87-97. Gravity Falls. Disney Television. Disney Channel, Los Angeles. 2012-2014. Hogle, Jerrold. “Introduction: The Gothic in Western Culture”. The Cambridge Companion of Gothic Fiction, ed. Jerrold Hogle. Cambridge: Cambridge University Press, 2002. 1-20. Lecercle, Jean-Jacques. “The Kitten’s Nose: Dracula and Witchcraft”. The Gothic, ed. Fred Botting. D.S Brewer: Cambridge, 2001. 71-86. Mandal, Anthony. “Intertext”. The Encyclopaedia of the Gothic, ed. David Punter, Bill Hughes and Andrew Smith. Basingstoke: Wiley, 2013. 350-355. Mishra, Vijay. The Gothic Sublime. Albany: State University of New York Press, 1994. Round, Julia. Gothic in Comics and Graphic Novels. Jefferson: McFarland, 2014. Royle, Nicholas. The Uncanny. Manchester: Manchester University Press, 2003. Sage, Victor. “Irish Gothic: C.R. Maturin and J.S. LeFanu. A Companion to the Gothic, ed. David Punter. Oxford; Blackwell, 2001. 81-93. Spooner, Catherine. Contemporary Gothic. London: Reaktion, 2007.